Canadian clinical trial registry

Search results

Information is also accessible through the patient and families tab. Family friendly summaries are created and reviewed by our advocacy partners. The information is updated to the best of our knowledge but might not reflect the latest information. Note that most studies are only available at a limited number of sites, please click on ‘further information’ for details. Studies, particularly early phase trials, may also temporarily close to enrolment or not have slots available for all treatment groups. In all cases, study teams at individual C17 centres will have the most up-to-date information.

75 results found

Title
Status

 

TPX-0005-07 - A Phase 1/2, Open-Label, Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity Study of Repotrectinib in Pediatric and Young Adult Subjects With Advanced or Metastatic Malignancies Harboring ALK, ROS1, NTRK1-3 Alterations

Open

TPX-0005-07 - A Phase 1/2, Open-Label, Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity Study of Repotrectinib in Pediatric and Young Adult Subjects With Advanced or Metastatic Malignancies Harboring ALK, ROS1, NTRK1-3 Alterations

Go to family friendly version

DiagnosisNon-Hodgkin Lymphoma, solid tumours, CNS tumours with eligible genetic changesStudy StatusOpen
PhaseI/II
AgeChild, Adult - (Up to 25 Years)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationRepotrectinib: Oral
Last Posted Update2023-12-13
ClinicalTrials.gov #NCT04094610
International Sponsor
Turning Point Therapeutics, Inc.
Principal Investigators for Canadian Sites
Stollery Children's Hospital - Dr. Sunil Desai
Centres
Medical contact
Dr. Sarah McKillop
Dr. Sunil Desai

 

 

Social worker/patient navigator contact
Danielle Sikora
 Michelle Woytiuk 
Jaime Hobbs
Clinical research contact
Amanda Perreault

 

 

Study Description

Brief Summary:

Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D).- PHASE 1 IS NOW CLOSED

Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric subjects with advanced or metastatic malignancies harboring ALK, ROS1, or NTRK1-3 alterations.

Detailed Description:

Enrollment of subjects into Phase 1 will proceed concurrently by age as follows:

  • Subjects <12 years old will initially be enrolled in the Phase 1 part to determine the pediatric RP2D for this age group; once the pediatric RP2D is determined, subjects age <12 years old may be enrolled into the Phase 2 part of the study.
  • Subjects 12 to 25 years old will be directly enrolled into the Phase 2 part concurrent with Phase 1 enrollment.

Phase 1:

Approximately 12 pediatric subjects with locally advanced or metastatic solid tumors, including a primary central nervous system (CNS) tumor, or anaplastic large cell lymphoma (ALCL), with disease progression or who are non-responsive or intolerant to available therapies and for which no standard or available curative therapy exists.

Phase 2:

Subjects will be enrolled in one of 3 cohorts as follows:

Cohort 1: approximately 10-20 subjects with solid tumors characterized by NTRK fusion, TRK tyrosine kinase inhibitor (TKI)-naïve, and centrally confirmed measurable disease at baseline.

Cohort 2: approximately 23 subjects with solid tumors characterized by NTRK fusion, TRK TKI-pretreated, and centrally confirmed measurable disease at baseline.

Cohort 3: approximately 20 subjects with solid tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease not otherwise eligible for Cohort 1 or 2.

Inclusion Criteria

Key Inclusion Criteria:

  1. Documented genetic ALK, ROS1, or NTRK1-3 alteration (point mutation, fusion, amplification) as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
  2. Age <12 years.
  3. Prior cytotoxic chemotherapy is allowed.
  4. Prior immunotherapy is allowed.
  5. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
  6. All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology Criteria (RANO) criteria at time of enrollment.
  7. Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 14 days prior to enrollment.
  8. Subjects must have a Lansky (< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
  9. Life expectancy greater than or equal to 12 weeks.
  10. Adequate hematologic, renal and hepatic function.

Phase 2 Inclusion Criteria:

  1. Age 12 to <25 years
  2. Cohort Specific Inclusion Criteria:

    • Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
    • Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
    • Cohort 3: subjects with tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease or not otherwise eligible for Cohort 1 or 2.
  3. Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment.
Exclusion Criteria
  1. Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
  2. Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
  3. Known active infections (bacterial, fungal, viral including HIV positivity).
  4. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
  5. Any of the following cardiac criteria:

    • Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) > 470 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
    • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec)
    • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
  6. Peripheral neuropathy of CTCAE ≥grade 2.
  7. Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.

DCL-17-001 - An Open-Label, Dose Escalation, Efficacy, and Safety Study of CLR 131 in Children and AYA with Select Solid Tumors, Lymphoma, and Malignant Brain Tumors (CLOVER-2) and Expansion in Children, AYA with Relapsed or Refractory High Grade Glioma

Open

DCL-17-001 - An Open-Label, Dose Escalation, Efficacy, and Safety Study of CLR 131 in Children and AYA with Select Solid Tumors, Lymphoma, and Malignant Brain Tumors (CLOVER-2) and Expansion in Children, AYA with Relapsed or Refractory High Grade Glioma

Go to family friendly version

DiagnosisGlioblastoma, Astrocytoma, Oligodendroglioma, Mixed Glioma, Pleomorphic Xanthoastrocytoma, Ganglioglioma, DIPG, Ependymoma Study StatusOpen
PhaseI/II
AgeChild, Adult - (10 years to 25 years)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationCLR 131 administered intravenously, fractionated dose Arm 1: two planned cycles, 20 mCi/m2 on day 1 and day 15 Arm 2: three planned cycles, 10mCi/m2 on day 1 and day 15
Last Posted Update2023-11-10
ClinicalTrials.gov #NCT03478462
International Sponsor
Cellectar Biosciences, Inc.
Principal Investigators for Canadian Sites
The Hospital for Sick Children - Dr. Daniel Morgenstern
Centres
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

 

 

Study Description

Brief Summary:

The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or refractory High Grade Glioma (HGG) for which there are no standard treatment options with curative potential.

Part A for Solid Tumors, Lymphoma, and Malignant  Brain Tumors is now closed. This study is exclusively enrolling on Part B for HGG

 

Detailed Description:

Even with standard, highly toxic multimodality therapies and salvage regimen, most pediatric patients with primary metastatic or relapsed solid tumors are confronted with a poor prognosis. For these patients there is currently no accepted successful treatment regimen. There is a need for new drugs, including targeted radiopharmaceuticals, preferably with cancer-specific uptake and broad applicability for these rare pediatric malignancies.

CLR 131 is a radioiodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). CLR 131 has demonstrated tumor selective uptake across numerous adult and pediatric cancer cell types. Therapeutic efficacy has been demonstrated in various pediatric and adult-type cancer xenograft models, confirming the ability of CLR 131 to target tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in relapsed pediatric cancers and initial preclinical and clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 1 pediatric trial.

Inclusion Criteria
  • Previously confirmed (histologically or cytologically) HGG that is clinically or radiographically suspected to be relapsed, refractory, or recurrent. Patients with DIPG are exempt from histologic verification if they have typical MRI findings of DIPG (i.e., hypo- or isointense on T1-weighted imaging, hyperintense on FLAIR or T2-weighted imaging, epicenter in the pons, greater than 50% of pons involved) and the risk of tumor biopsy is prohibitive
  • Patient is ≥ 10 years and ≤ 25 years of age at time of consent/assent
  • Patients ≥ age 16 years must have a Karnofsky performance status of ≥ 60. Patients < age 16 years must have a Lansky performance status of ≥ 60
  • Patients must meet the following lab criteria:
    • Platelets ≥ 75,000/µL [75 x 109 /L] (last transfusion, if any, must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
    • Absolute neutrophil count ≥ 750/µL [0.75 x109/L]
    • Hemoglobin ≥ 8 g/dL [80 g/L] (last transfusion must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
    • Using the bedside Schwartz formula [Schwartz 2009], estimated GFR (creatinine clearance) > 60 ml/min/1.73m2
    • Alanine aminotransferase < 3 × ULN
    • Bilirubin < 2 × ULN
  • At least 1 measurable intracranial lesion with longest diameter of at least 10 mm on any imaging sequence.
  • Patients with previously known neurological deficits must be clinically stable at time of enrollment and able to complete all study related procedures. Patients with documented or newly diagnosed neurological deficits will be enrolled at the investigator’s discretion.
  • If patient receives steroids for neurological symptom control, the dose must be stable (unchanged for three weeks prior to registration) or on a steroid tapering regimen. Initiation of steroids per routine care immediately prior to CLR 131 dosing is acceptable.
  • Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol.
  • Patient or his or her legal representative has the ability to read, understand, and provide written informed consent for the initiation of any study-related procedures.
  • Female patients of childbearing potential must have a negative pregnancy test at screening and within 24 hours of dosing. It is recommended that female caregivers of childbearing potential have a negative pregnancy test within one week of dosing.
  • Patients of childbearing potential must practice an effective method of birth control while participating on this study to avoid possible harm to the fetus.

 

Exclusion Criteria
  • Antitumor therapy or investigational therapy, within three-half-lives of the agent preceding the present study. For certain types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to skull-based metastases is not considered craniospinal radiation for the purposes of this study]), at least 3 months must have elapsed. Palliative focal radiation to non-target lesions should be completed at least 2 weeks prior to dosing. NOTE: Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial.
  • History of hypersensitivity to thyroid protection medication (e.g., potassium iodide, Lugol’s solution, etc.)
  • Any other concomitant serious illness or organ system dysfunction (including cardiac and pulmonary dysfunction) that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
  • Major surgery within 6 weeks of enrollment unless delay in therapy poses unacceptable risk to the patient due to clinical progression (enrollment of such patients should be discussed with Medical Monitor).
  • Known history of human immunodeficiency virus or uncontrolled, serious, active infection.
  • Pregnancy or breastfeeding
     

AREN1921 - Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT)

Open

AREN1921 - Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT)

Go to family friendly version

DiagnosisAnaplastic Wilms Tumor, Recurrent Wilms TumorStudy StatusOpen
PhaseII
Ageup to 30 YearsRandomisationNO
Line of treatmentFirst line treatment, Disease relapse or progression
Routes of Treatment AdministrationChemotherapy medications, all given intravenously (Carboplatin, Cyclophosphamide, Doxorubicin, Etoposide, Ifosfamide, Irinotecan, Topotecan, Vincristine)
Last Posted Update2023-11-09
ClinicalTrials.gov #NCT04322318
International Sponsor
Children's Oncology Group
Principal Investigators for Canadian Sites
Alberta Children's Hospital
BC Children's Hospital - Dr. David Dix
CancerCare Manitoba - Dr. Ashley Chopek
McMaster Children's Hospital - Dr. Uma Athale
Stollery Children's Hospital - Dr. Sarah McKillop
Western Children's Hospital - Dr. Shayna Zelcer
Children's Hospital of Eastern Ontario (CHEO) - Dr. Donna Johnston
Hospital for Sick Children - Dr. Daniel Morgenstern
Montreal Children's Hospital - Dr. Sharon Abish
CHU Quebec - Dr. Bruno Michon
CHU Ste. Justine - Dr. Yvan Samson
IWK Health Centre - Dr. Craig Erker
Centres
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

Medical contact
Rebecca Deyell

 

Social worker/patient navigator contact
Ilana Katz 

 

Clinical research contact
Hem/Onc/BMT Clinical Trials Unit

 

Medical contact
Dr. Magimairajan Vanan
Social worker/patient navigator contact
Rhéanne Bisson
 
Clinical research contact
Rebekah Hiebert
Megan Ridler
Kathy Hjalmarsson

 

 

Medical contact
Dr. Carol Portwine
 
Social worker/patient navigator contact
Jane Cassano 
 
Clinical research contact
Sabrina Millson
 
 
Medical contact
Dr. Donna Johnston
Dr. Lesleigh Abbott
Dr. Doaa Abdel Fattah
 
Social worker/patient navigator contact
Sherley Telisma
 
Clinical research contact
Carol Duchenne
 
Medical contact
Dr. Alexandra Zorzi
Dr. Shayna Zelcer
 
Social worker/patient navigator contact
Cindy Milne Wren
Jessica Mackenzie Harris
 
Clinical research contact
Mariam Mikhail
Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 
Medical contact
Dr. Victor Lewis

 

Social worker/patient navigator contact
Wendy Pelletier
Clinical research contact
Debra Rich
Medical contact
Raoul Santiago
 
Social worker/patient navigator contact
Isabelle Audet
 
Clinical research contact
Barbara Desbiens
 

 

Medical contact
Dr. Sarah McKillop
Dr. Sunil Desai

 

 

Social worker/patient navigator contact
Danielle Sikora
 Michelle Woytiuk 
Jaime Hobbs
Clinical research contact
Amanda Perreault
Medical contact
Dr. Henrique Bittencourt
Dr. Monia Marzouki
Dr. Sebastien Perreault (neuro-onc)
 
Social worker/patient navigator contact
Marie-Claude Charrette
 
Clinical research contact
Marie Saint-Jacques
 

 

 

Study Description

This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan) and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with 3 or more drugs for the initial WT).

 

PRIMARY OBJECTIVES:

I. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/ carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the event-free survival (EFS) of patients with newly diagnosed stage 4 diffuse anaplastic Wilms tumor (DAWT) as compared to historical controls.

II. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the EFS of patients with standard-risk relapsed favorable histology Wilms tumor (SRrFHWT) as compared to historical controls.

SECONDARY OBJECTIVES:

I. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the overall survival (OS) of patients with newly diagnosed stage 4 DAWT as compared to historical controls.

II. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the OS of patients with SRrFHWT as compared to historical controls.

III. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the EFS and OS of patients with newly diagnosed stage 2 and 3 DAWT as compared to historical controls.

IV. To establish EFS and OS for high-risk (HRrFHWT) and very high risk (VHRrFHWT) relapsed favorable histology Wilms tumor treated with ifosfamide/carboplatin/etoposide alternating with cyclophosphamide/ topotecan.

EXPLORATORY OBJECTIVES:

I. To describe renal toxicity of ifosfamide/carboplatin/etoposide in HRrFHWT and VHRrFHWT patients using conventional and novel biomarkers of renal toxicity (urine NGAL, cystatin C and Kim1) in the context of the chemotherapy regimens used on this study.

II. To collect and bank serial blood and urine samples in patients with newly diagnosed DAWT or relapsed FHWT and tumor tissue in patients with relapsed FHWT, for future analysis.

III. To assess the impact of p53 gene and protein expression on outcome for patients with newly diagnosed DAWT.

IV. To determine EFS/OS in the subsets of patients with newly diagnosed DAWT or relapsed FWHT who undergo gross total resection at all disease sites at diagnosis or after neoadjuvant chemotherapy.

V. To describe the rate of regional lymph node sampling at the time of nephrectomy with the use of a pre-operative surgical checklist for patients with newly diagnosed DAWT.

VI. To determine the feasibility of intensity modulated radiation therapy (IMRT) with central quality assurance (QA) monitoring to reduce radiation induced toxicity to the heart, thyroid, breast and solitary kidney for children with lung and liver metastases (part of an overarching aim in this study and across frontline favorable histology Wilms tumor studies).

 

Inclusion Criteria
  • Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN03B2 and have risk assignment or final pathology classification (if at delayed nephrectomy) results available prior to enrollment on AREN1921. Enrollment on AREN03B2 is not applicable for patients with relapsed favorable histology Wilms tumor
  • Patients with the following diagnoses are eligible for this study:
    • Newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor as confirmed by central review
    • Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must have previously achieved remission for their initial FHWT diagnosis to be eligible for this study. The relapse risk groups are defined as follows, regardless of radiation therapy:
      • Standard-Risk relapse: Patients who received two chemotherapy agents for frontline therapy; primarily actinomycin D and vincristine
      • High-Risk relapse: Patients who received three chemotherapy agents for frontline therapy; primarily vincristine, actinomycin D and doxorubicin or vincristine, actinomycin D and irinotecan
      • Very High-Risk relapse: Patients who received four or more chemotherapy agents as part of initial therapy; primarily Regimen M or its variations
  • Patients with newly diagnosed DAWT must have had histologic verification of the malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but not required
    • Note: for relapsed FHWT patients, an institutional pathology report confirming favorable histology Wilms tumor (from relapse, if available, or from original diagnosis) must be available for upload prior to initiation of protocol therapy
  • Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN1921 within 2 weeks of the first tumor-directed surgery or biopsy procedure (surgery/biopsy is day 0), except for patients who received prior therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse anaplastic Wilms tumor at subsequent review
  • Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least 1 lymph node sampled prior to study enrollment
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients must have a life expectancy of >= 8 weeks
  • Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have had no prior systemic therapy, except in the following situations:
    • Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks of pre nephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms tumor at delayed nephrectomy.
    • Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of chemotherapy following upfront nephrectomy or biopsy for presumed favorable histology Wilms tumor based on institutional review, but subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2 initial risk assignment results.
    • Treatment consisting of vincristine/doxorubicin/ cyclophosphamide initiated on an emergent basis and within allowed timing as described
    • Patients who received prior therapy for presumed favorable histology Wilms tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must begin study treatment starting at cycle 3 (week 7) of regimen UH 3. For treatment details specific to this group of patients. Patients who received emergency radiation to preserve organ function are eligible as noted
  • Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In addition, patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
    • Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study
    • Radiation therapy (RT): >= 2 weeks (wks) must have elapsed for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 wks must have elapsed if other substantial BM radiation. Patients with relapsed favorable histology Wilms tumor who received emergency radiation to preserve organ function are eligible and do not need to washout with the above criteria
  • Patients may not be receiving any other investigational agents (within 4 weeks prior to study enrollment)
  • Peripheral absolute neutrophil count (ANC) >= 750/uL (performed within 7 days prior to enrollment)
  • Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)
  • Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed within 7 days prior to enrollment)
  • Patients with high-risk or very high-risk relapsed FHWT who will be treated with Regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or radioisotope glomerular filtration rate (GFR) and meet the following requirement:
    • Creatinine clearance or radioisotope GFR >= 60 mL/min/1.73 m^2 (performed within 7 days prior to enrollment)
  • Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be treated with Regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR (meeting the above criteria of GFR >= 60 mL/min/1.73 m^2), or an adequate serum creatinine as per the following table:
    • Age: Maximum Serum Creatinine (mg/dL)
    • 1 month to < 6 months: 0.4 (male and female)
    • 6 months to < 1 year: 0.5 (male and female)
    • 1 to < 2 years: 0.6 (male and female)
    • 2 to < 6 years: 0.8 (male and female)
    • 6 to < 10 years: 1 (male and female)
    • 10 to < 13 years: 1.2 (male and female)
    • 13 to < 16 years: 1.5 (male), 1.4 (female)
    • >= 16 years: 1.7 (male), 1.4 (female)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =< ULN for patients whose total bilirubin > 1.5 x ULN (performed within 7 days prior to enrollment)
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age or =< 5 x ULN for patients with liver metastases (performed within 7 days prior to enrollment)
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram (performed within 7 days prior to enrollment)
Exclusion Criteria
  • Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
  • Patients with any uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, or symptomatic congestive heart failure (defined as grade 2 or higher heart failure per Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
  • Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk FHWT initially observed without chemotherapy) or received only one chemotherapy agent for frontline therapy
  • For patients with high-risk or very high-risk relapsed FHWT:
    • Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate < 16 mmol/L and serum phosphate =< 2 mg/dL (or < 0.8 mmol/L) without supplementation
  • For stages 2-4 DAWT and standard-risk relapsed FHWT patients:
    • Chronic inflammatory bowel disease and/or bowel obstruction
    • Concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
  • Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

ACNS1422 - A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

Open

ACNS1422 - A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

Go to family friendly version

DiagnosisMedulloblastomaStudy StatusOpen
PhaseII
Age3 Years to 21 YearsRandomisationNO
Line of treatmentFirst line treatment
Routes of Treatment AdministrationChemotherapy: Cisplatin (Given IV), Cyclophosphamide (Given IV), Lomustine (Given PO), Vincristine Sulfate (Given IV or via minibag) Radiation: Radiation Therapy
Last Posted Update2023-11-09
ClinicalTrials.gov #NCT02724579
International Sponsor
Children's Oncology Group
Principal Investigators for Canadian Sites
Alberta Children's Hospital - Dr. Victor Lewis
BC Children's Hospital - Dr. David Dix
CancerCare Manitoba - Dr. Ashley Chopek
Janeway Child Health Centre - Dr. Lisa Goodyear
IWK Health Centre - Dr. Craig Erker
McMaster Children's Hospital at Hamilton Health Sciences - Dr. Uma Athale
Western Children's Hospital - Dr. Shayna Zelcer
Children's Hospital of Eastern Ontario - Dr. Donna Johnston
Hospital for Sick Children - Dr. Vijay Ramaswamy
Montreal Children's Hospital - Dr. Genevieve Legault
Saskatoon Cancer Centre - Dr. Kathleen Felton
Centres
Medical contact
Dr. Victor Lewis

 

Social worker/patient navigator contact
Wendy Pelletier
Clinical research contact
Debra Rich
Medical contact
Rebecca Deyell

 

Social worker/patient navigator contact
Ilana Katz 

 

Clinical research contact
Hem/Onc/BMT Clinical Trials Unit

 

Medical contact
Dr. Magimairajan Vanan
Social worker/patient navigator contact
Rhéanne Bisson
 
Clinical research contact
Rebekah Hiebert
Megan Ridler
Kathy Hjalmarsson

 

 

Medical contact
Dr. Paul Moorehead
 
Social worker/patient navigator contact
Stephanie Eason
 
Clinical research contact
Bev Mitchell
 
Medical contact
Dr. Craig Erker
Dr. Conrad Fernandez 
Dr. Ketan Kulkarni 
 
Social worker/patient navigator contact
Rhonda Brophy
 
Clinical research contact
Tina Bocking
 
Medical contact
Dr. Carol Portwine
 
Social worker/patient navigator contact
Jane Cassano 
 
Clinical research contact
Sabrina Millson
 
 
Medical contact
Dr. Alexandra Zorzi
Dr. Shayna Zelcer
 
Social worker/patient navigator contact
Cindy Milne Wren
Jessica Mackenzie Harris
 
Clinical research contact
Mariam Mikhail
Medical contact
Dr. Donna Johnston
Dr. Lesleigh Abbott
Dr. Doaa Abdel Fattah
 
Social worker/patient navigator contact
Sherley Telisma
 
Clinical research contact
Carol Duchenne
 
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 
Medical contact
Dr. Chris Mpofu

 

 

Social worker/patient navigator contact
Jillian Galambos
La Rae Beebe

 

Clinical research contact
Susan Kaban

 

 

 

Study Description

This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.

Inclusion Criteria
  • Patients must be newly diagnosed and have:

    • Eligibility confirmed by rapid central pathology and molecular screening review on APEC14B1:

      • Classical histologic type (non LC/A) WNT medulloblastoma
      • Positive nuclear beta-catenin by immunohistochemistry (IHC)
      • Positive for CTNNB1 mutation
      • Negative for MYC and MYCN by fluorescence in situ hybridization (FISH)
  • Patient must have negative lumbar cerebrospinal fluid (CSF) cytology
    • Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF; ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status; patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated; patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively
  • Patients must have eligibility confirmed by Rapid Central Imaging Review on APEC14B1; patients must have =< 1.5 cm^2 maximal cross-sectional area of residual tumor; whole brain magnetic resonance imaging (MRI) with and without gadolinium and spine MRI with gadolinium must be performed
  • Patients must be enrolled, and protocol therapy must be projected to begin, no later than 36 days after definitive diagnostic surgery (day 0)
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 100,000/uL (transfusion independent)
  • Hemoglobin >= 10.0 g/dL (may receive red blood cell [RBC] transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
    • 3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males and females)
    • 6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)
    • 10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)
    • 13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL (females)
    • >= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
      • The threshold creatinine values were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
  • Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
  • Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3x ULN); for the purpose of this study, the ULN for SGPT is 45 U/L
  • Central nervous system function defined as:
    • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
    • Patients must not be in status epilepticus, a coma or on assisted ventilation at the time of study enrollment
  • Patients must have receptive and expressive language skills in English, French, or Spanish to complete the QoL and neurocognitive assessments; if a patient meets these criteria but the parent/guardian speaks a language other than English, French, or Spanish, the patient may still be enrolled and tested, and the parent-report measures should be omitted
  • All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria
  • Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
  • Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids
  • Pregnancy and Breast Feeding
    • Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies
    • Lactating females are not eligible unless they have agreed not to breastfeed their infants
    • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
    • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
  • Patients with a history of moderate to profound intellectual disability (i.e., intelligence quotient [Q)]=< 55) are not eligible for enrollment; PLEASE NOTE: Children with a prior history of attention deficit hyperactivity disorder (ADHD) or a specific learning disability (e.g., dyslexia) are eligible for this study

Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team.

AALL1521 - A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia

Closed to enrollment

AALL1521 - A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia

Go to family friendly version

DiagnosisALL, B-cell acute lymphoblastic leukemiaStudy StatusClosed to enrollment
PhaseII
AgeChild, Adult - (2 years to 21 years)RandomisationN/A
Line of treatmentFirst line treatment
Routes of Treatment AdministrationRuxolitinib - oral; Other drugs are given as usually administered for leukemia therapy
Last Posted Update2023-11-09
ClinicalTrials.gov #NCT02723994
International Sponsor
Incyte Corporation
Principal Investigators for Canadian Sites
BC Children's Hospital – Dr. David Dix
Montreal Children's Hospital – Dr. Sharon Abish
Alberta Children's Hospital – Dr. Victor Lewis
The Hospital for Sick Children – Dr. Ute Bartels
Hamilton Health Sciences Centre, McMaster University - Dr. Carol Portwine
CHU Ste Justine - Dr. Thai Tran


Centres
Medical contact
Rebecca Deyell

 

Social worker/patient navigator contact
Ilana Katz 

 

Clinical research contact
Hem/Onc/BMT Clinical Trials Unit

 

Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

Medical contact
Dr. Victor Lewis

 

Social worker/patient navigator contact
Wendy Pelletier
Clinical research contact
Debra Rich
Medical contact
Dr. Carol Portwine
 
Social worker/patient navigator contact
Jane Cassano 
 
Clinical research contact
Sabrina Millson
 
 
Medical contact
Dr. Henrique Bittencourt
Dr. Monia Marzouki
Dr. Sebastien Perreault (neuro-onc)
 
Social worker/patient navigator contact
Marie-Claude Charrette
 
Clinical research contact
Marie Saint-Jacques
 

 

 

Study Description

Brief Summary:

This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent chemotherapy regimen for the treatment of B-cell acute lymphoblastic leukemia. Part 1 of the study will optimize the dose of study drug (ruxolitinib) in combination with the chemotherapy regimen. Part 2 will evaluate the efficacy of combination chemotherapy and ruxolitinib at the recommended dose determined in Part 1.

Inclusion Criteria
  • Eligible for study when participant is 1 year to 21 years at the time of diagnosis
  • Eligible Ages in Australia and Canada; 2 years to 21 years
  • De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present at diagnosis:

    • Age ≥ 10 years
    • White blood cell (WBC) ≥ 50 × 10^3/μL
    • CNS3 leukemia at diagnosis
    • Systemic steroid pretreatment without presteroid WBC documentation
  • Diagnostic bone marrow or peripheral blood sample must have gene expression profiling and downstream genetic testing performed by submitting diagnostic specimens under the COG AALL08B1 or APEC14B1 biology studies, or AALL1131 or its successor study. Specimens must demonstrate a Ph-like expression profile (ie, LDA-positive) as tested by low density microarray testing at the COG ALL reference laboratory or TriCore laboratory at the University of New Mexico AND must contain 1 of the following genetic lesions: (determined at COG ALL reference laboratories, or equivalent CAP/CLIA-certified laboratories approved by the medical monitor:

    1. CRLF2 rearrangement* with confirmed JAK1 or JAK2 mutation (JAK+)
    2. CRLF2 rearrangement* without JAK mutation
    3. Other JAK pathway alterations (eg, JAK2 fusions, EPOR fusions, SH2B3 deletions, IL7RA mutations) with or without CRLF2-R, or CRLF2-R with unknown JAK status*† as determined by a COG ALL Reference Laboratory
  • Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or its successor study, or as per the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed
  • Male and female subjects of reproductive non childbearing potential or willing to take appropriate precautions to avoid pregnancy or fathering a child for the duration of study participation
Exclusion Criteria
  • Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment
  • Trisomy 21 (Down syndrome)
  • BCR-ABL1-rearranged (Ph+) ALL
  • Calculated creatinine clearance or radioisotope glomerular filtration rate < 70 mL/min/1.73 m^2
  • Alanine aminotransferase ≥ 5 × upper limit of normal (ULN) for age
  • Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN)
  • History or evidence of cirrhosis
  • Platelet count < 75 × 10^3/μL
  • Absolute neutrophil count (ANC) < 750/μL
  • Positive screen for hepatitis B or C
  • Known human immunodeficiency virus infection

M20-429 - A Single Arm, Open-Label, Phase 1b Trial of Epcoritamab in Pediatric Patients With Relapsed/Refractory Aggressive Mature B-cell Neoplasms

Open

M20-429 - A Single Arm, Open-Label, Phase 1b Trial of Epcoritamab in Pediatric Patients With Relapsed/Refractory Aggressive Mature B-cell Neoplasms

Go to family friendly version

DiagnosisNon-hodgkin LymphomaStudy StatusOpen
PhaseI
Age1 to 25 Years OldRandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationDrug: Epcoritamab Subcutaneous Injection (SC) Other Name: ABBV-GMAB-3013
Last Posted Update2023-10-18
ClinicalTrials.gov #NCT05206357
International Sponsor
AbbVie
Principal Investigators for Canadian Sites
The Hospital for Sick Children - Dr. Sarah Alexander
CHU Sainte-Justine - Dr. Henrique Bittencourt
Centres
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

Medical contact
Dr. Henrique Bittencourt
Dr. Monia Marzouki
Dr. Sebastien Perreault (neuro-onc)
 
Social worker/patient navigator contact
Marie-Claude Charrette
 
Clinical research contact
Marie Saint-Jacques
 

 

 

Study Description

The purpose of this study is to assess the safety and tolerability of epcoritamab in pediatric participants with relapsed/refractory aggressive mature B-cell neoplasms and young adult participants with Burkitt's or Burkitt-like lymphoma/leukemia. Adverse events and change in disease activity will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of relapsed/refractory aggressive mature B-cell neoplasms. Participants will receive subcutaneous (SC) of epcoritamab. Approximately 15 pediatric participants with a diagnosis of relapsed/refractory aggressive mature B-cell neoplasms and and young adult participants, ages of 18-25, with a diagnosis of Burkitt's or Burkitt-like lymphoma/leukemia will be enrolled at 50 sites globally.

Participants will receive subcutaneous epcoritamab in 28-day cycles. Participants will be followed for a minimum of 3 years after enrollment.

 

Inclusion Criteria
  • Participants >= 1 and < 18 years old at time of primary diagnosis with Burkitt's or Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma (DLBCL), or other aggressive mature (CD20+) B-cell lymphomas. Participants up to 25 years of age with Burkitt's or Burkitt-like lymphoma/leukemia are also eligible.
  • Disease pathologically confirmed (tumor tissue) by local testing.
  • Relapsed or primary refractory disease meeting any of the following criteria:

    • Progressive disease at any time during second-line chemoimmunotherapy (CIT).
    • Best response of stable disease (SD) after a minimum of 2 cycles of second-line CIT.
    • Best response of partial response (PR) after a minimum of 3 cycles of second-line CIT.
    • Complete Response (CR) after a minimum of 3 cycles of second-line CIT therapy but unfit or ineligible for consolidation with cell therapy.
    • Not in CR and unable to initiate or tolerate (i.e., must discontinue) second-line CIT.
    • Have received cell therapy (allogeneic or autologous transplant or chimeric antigen receptor T-cell (CAR-T) therapy) as consolidation but have not obtained or maintained a CR.
  • Recovery from toxic effects of prior chemoimmunotherapy.
  • Performance status by Lansky (< 16 years old at evaluation) or Karnofsky (>= 16 years old at evaluation) score >= 50 or Eastern Cooperative Oncology Group (ECOG) score <= 2 .
  • Adequate bone marrow, hepatic, and renal function.

Other inclusion criteria may apply

Exclusion Criteria
  • Known central nervous system (CNS) involvement by lymphoma at screening as confirmed by screening magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET) brain scans (participants with evidence of CNS disease only in the cerebrospinal fluid (CSF) will be eligible).
  • Other malignancy requiring therapy.
  • Currently receiving anti-cancer therapy, including chemotherapy (excluding intrathecal therapy), radiotherapy, small molecules, monoclonal antibodies, cell therapy, or other investigational agents.

Other exclusion criteria may apply

AC220-A-U202-ADVL1822 - A Phase 1/2, Multicenter, Dose-Escalating Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy Of Quizartinib Administered in Combination With Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to <18 Years (and Young Adults Aged up to 21 Years) With FLT3-ITD Mutations

Open

AC220-A-U202-ADVL1822 - A Phase 1/2, Multicenter, Dose-Escalating Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy Of Quizartinib Administered in Combination With Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to <18 Years (and Young Adults Aged up to 21 Years) With FLT3-ITD Mutations

Go to family friendly version

DiagnosisAcute Myeloid Leukemia, AMLStudy StatusOpen
PhaseI/II
AgeChild, Adult - (1 Month to 21 Years)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationQuizartinib by mouth; other drugs are given as usually administered for leukemia therapy.
Last Posted Update2023-10-10
ClinicalTrials.gov #NCT03793478
International Sponsor
Daiichi Sankyo, Inc.
Principal Investigators for Canadian Sites
Montreal Children's Hospital – Dr. Sharon Abish
The Hospital for Sick Children - Dr Ute Bartels
BC Children's Hospital - Dr. David Dix
Centres
Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 
Medical contact

Dr. Daniel Morgenstern

daniel.morgenstern@sickkids.ca

Social worker/patient navigator contact

Karen Fung 

karen.fung@sickkids.ca

Clinical research contact

New Agent and Innovative Therapies (NAIT) 

nait.info@sickkids.ca

 

Medical contact
Rebecca Deyell

 

Social worker/patient navigator contact
Ilana Katz 

 

Clinical research contact
Hem/Onc/BMT Clinical Trials Unit

 

 

 

Study Description

Brief Summary:

Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research.

Children or young adults with a certain kind of blood cancer (FLT3-ITD AML) might be able to join this study if it has come back after remission or is not responding to treatment.

Detailed Description:

The medical condition being investigated is relapsed or refractory AML in participants aged ≥1 month to ≤21 years with Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutations (FLT3-ITD AML), following failure of front-line intensive chemotherapy.

The trial will be conducted in multiple phases. An independent data monitoring committee (DMC) will protect the rights, safety, and well-being of participants by monitoring the progress and results. The DMC will comprise qualified physicians and scientists who are not Investigators in the study and not otherwise directly associated with the Sponsor and will be convened at the end of Phase 1.

A. Dose Escalation/De-escalation Phase:

Number of participants is determined by age group. Participants will be enrolled by dose-level to determine the recommended Phase 2 dose (RP2D) of quizartinib for pediatric participants that provides similar exposure to adult patients treated at the target adult dose of 60 mg orally once daily.

B. Dose-Expansion Phase:

Participants will receive the RP2D of quizartinib for their respective age group.

During both dose escalation and dose expansion phases, participants will receive:

Re-Induction Therapy

  • Intrathecal (IT) triple chemotherapy prophylaxis prior to and between cycles
  • In re-induction Cycles 1 and 2, fludarabine/cytarabine (FLA) followed by quizartinib as a single agent

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Period:

After re-induction therapy, participants will be evaluated for eligibility to undergo allogeneic hematopoietic stem cell transplant (HSCT). Eligible participants may receive a single 28-day cycle of consolidation therapy (standard of care chemotherapy with or without quizartinib) if an allogeneic HSCT is not available immediately. The options for consolidation therapy are as follows:

  • High intensity chemotherapy with quizartinib, or
  • Low intensity chemotherapy alone, or
  • Low intensity therapy with quizartinib as a single agent

Continuation Therapy:

Participants in remission after HSCT, or who are not eligible for HSCT but achieve at least a partial remission (PR) after re-induction, will receive up to 12 continuous 28-day cycles of quizartinib continuation therapy at the same dose received during re-induction in the dose expansion phase.

Long-term Follow-up:

The long-term follow-up phase begins upon completion of 12 cycles of quizartinib Continuation Therapy or permanent discontinuation of quizartinib at any time. After completion of the 30-day safety follow-up visit, subsequent visits will occur at the following frequencies to assess survival and anti-leukemic treatments:

  • every 3 months for the first 2 years, and then
  • once a year thereafter until the last participant enrolled has been followed for three years from the date of enrollment
Inclusion Criteria
  • Has diagnosis of AML according to the World Health Organization (WHO) 2008 classification with >5% blasts in bone marrow, with or without extramedullary disease
  • Is in first relapse or refractory to first-line high-dose chemotherapy with no more than 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction - prior HSCT is permitted
  • Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood as defined in the protocol
  • Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is signed
  • Has protocol-defined adequate performance status score
  • Has fully recovered from the acute clinically significant toxicity effects of all prior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines
  • Has protocol-defined adequate renal, hepatic and cardiac functions
  • If of reproductive potential, is permanently sterile or agrees to use highly effective birth control upon enrollment, during the period of therapy, and for 6 months following the last dose of study drug or cytarabine, whichever is later
  • If female of child-bearing potential, tests negative for pregnancy and agrees not to breast feed
  • Participant/legal representative is capable of understanding the investigational nature of the study, potential risks, and benefits, and the patient (and/or legal representative) signs a written assent/informed consent
  • Meets protocol-specified guidelines before inclusion in the continuation therapy phase
Exclusion Criteria
  • Has been diagnosed with isolated central nervous system relapse, certain kinds of leukemia, or with myeloid proliferations related to Down syndrome
  • Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the protocol
  • Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient must be off vasopressors and have negative blood cultures for at least 48 hours prior to the start of systematic protocol therapy.
  • Has known active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)
  • Has known history of human immunodeficiency virus (HIV)
  • Has history of hypersensitivity to any of the study medications or their excipients
  • Is receiving or is anticipated to receive concomitant chemotherapy, radiation, or immunotherapy other than as specified in the protocol
  • Has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance, interfere with consent/assent, study participation, follow up, or interpretation of study results
  • Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)
  • Is otherwise considered inappropriate for the study by the Investigator

BCC018 - A Phase II Study of Naxitamab Added to Induction Therapy for Subjects With Newly Diagnosed High-Risk Neuroblastoma

Open

BCC018 - A Phase II Study of Naxitamab Added to Induction Therapy for Subjects With Newly Diagnosed High-Risk Neuroblastoma

Go to family friendly version

DiagnosisHigh-risk NeuroblastomaStudy StatusOpen
PhaseII
Age12 Months to 21 YearsRandomisationNO
Line of treatmentFirst line treatment
Routes of Treatment AdministrationDrug: Naxitamab (Intravenous (IV)) Additionally for patients with ALK aberration: Drug: Ceritinib (Oral)
Last Posted Update2023-09-28
ClinicalTrials.gov #NCT05489887
International Sponsor
Wake Forest University Health Sciences
Principal Investigators for Canadian Sites
CHU Quebec - Dr.Bruno Michon
Centres
Medical contact
Raoul Santiago
 
Social worker/patient navigator contact
Isabelle Audet
 
Clinical research contact
Barbara Desbiens
 

 

 

 

Study Description

This is a prospective, multicenter clinical trial in subjects with newly diagnosed high-risk neuroblastoma to evaluate the efficacy and safety of administering naxitamab with standard induction therapy.

All subjects will be followed for disease response, event free survival, overall survival and toxicity. Extent of disease will be measured and assessed for changes throughout the course of the study. All efficacy analyses will be performed on the evaluable population which will consist of all enrolled subjects (subjects who initiate treatment with naxitamab in combination with GM-CSF plus standard induction therapy) and who have measurable disease at baseline.

The initial chemotherapy Induction regimen will utilize sequential administration of 5 cycles of multi-agent chemotherapy. Naxitamab will be added to all 5 Induction cycles.

Subjects with an activating ALK mutation or ALK amplification will have ceritinib added to their treatment regimen as soon as results are available.

Stem cell mobilization and collection will occur after the 2nd cycle of induction.

Surgical resection of the primary tumor will ideally occur after the 4th cycle of Induction but may be delayed until after the 5th cycle of Induction if medically necessary.

Disease status evaluations will occur at the following time points: (1) pre-treatment, (2) post Cycle 2 Induction (3) Prior to surgical resection (if performed), (4) End of Induction (which includes surgery and 5 cycles of chemotherapy), and (5) End of Additional/Salvage Therapy as needed.

The current standard of care for high-risk neuroblastoma involves 5-7 cycles of induction chemotherapy with surgical removal of the tumor after 4-5 cycles of chemotherapy, followed by high-dose chemotherapy plus autologous stem cell transplant, then radiation to the primary tumor bed, followed by anti-GD2 immunotherapy and cis retinoic acid. This results in a less than 60% disease free survival for high-risk NB, a survival rate that still greatly needs improvement. Two areas in which improvements can be made include: 1) to improve response rate to induction chemotherapy and 2) to improve EFS by improving maintenance therapy to prevent relapse.

We hypothesize that the addition of anti-GD2 therapy to induction chemotherapy will result in improved end of induction responses and improved survival.

Inclusion Criteria
  • Diagnosis: Subjects must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Subjects with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:

a) Subjects with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) Stage 4 are eligible with the following: i. Age > 18 months (> 547 days) regardless of biologic features or ii. Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or iii. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.

b) Subjects with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following: i. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or ii. Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status.

c) Subjects with newly diagnosed neuroblastoma with INSS Stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.

  • Subjects must be age ≤ 21 years at initial diagnosis
  • Subjects must be >12 months of age at enrollment
  • Ability to tolerate Peripheral blood stem cell (PBSC) collection: No known contraindication to PBSC collection. Examples of contraindications would include a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.
  • Adequate Cardiac Function Defined As:
    • Shortening fraction of ≥ 27% by echocardiogram, or
    • Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram.
  • Adequate liver function must be demonstrated, defined as:
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
    • ALT (SGPT) < 5 x upper limit of normal (ULN) for age
  • Subjects must have adequate renal function defined as a serum creatinine based on age/gender as follows:
    • Age Maximum Serum Creatinine (mg/dL), Male/Female

      • 1 to < 2 years 0.6 0.6

      • 2 to < 6 years 0.8 0.8

      • 6 to < 10 years 1 1

      • 10 to < 13 years 1.2 1.2

      • 13 to < 16 years 1.5 1.4

      • ≥ 16 years 1.7 1.4

  • A negative serum pregnancy test is required for female participants of childbearing potential (≥13 years of age or after onset of menses)
  • Both male and female post-pubertal study subjects must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of <1% per year when used consistently and correctly) from the time of informed consent until 6 months after study treatment discontinuation. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence.
  • Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria
  • Subjects who are less than 1 year of age
  • Subjects who are 12-18 months of age with INSS Stage 4 and all stage 3 subjects with favorable biologic features (i.e., nonamplified MYCN, favorable pathology, and DNA index > 1) are not eligible.
  • Subjects who have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification status and histology.
  • Treatment with immunosuppressive treatment (local steroids excluded) within 4 weeks prior to enrollment
  • Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry < 94% and/or abnormal pulmonary function tests if these assessments are clinically indicated.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
  • Subjects receiving any investigational drug concurrently.
  • Subjects with any other medical condition, including but not limited to malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study.
  • Subjects with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of investigational medicinal products (IMPs) or to significantly increase the severity of the toxicities experienced from trial treatment.