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

 

ANBL1821 - A Phase 2 Randomized Study of Irinotecan/Temozolomide/Dinutuximab With or Without Eflornithine (DFMO) in Children With Relapsed, Refractory or Progressive Neuroblastoma

Open

ANBL1821 - A Phase 2 Randomized Study of Irinotecan/Temozolomide/Dinutuximab With or Without Eflornithine (DFMO) in Children With Relapsed, Refractory or Progressive Neuroblastoma

Go to family friendly version

DiagnosisHigh Risk, Recurrent, or Refractory NeuroblastomaStudy StatusOpen
PhaseII
Age1 Year and olderRandomisationYES
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationBiological: Dinutuximab (Given Intravenous (IV)) Drug: Irinotecan Hydrochloride (Given Intravenous (IV)) Biological: Sargramostim (Given Intravenous (IV) or Subcutaneous (SC)) Drug: Temozolomide (Given orally or via NG or G tube) Drug: Eflornithine Hydrochloride (Given orally or via NG or G tube) may or may not be given
Last Posted Update2023-09-28
ClinicalTrials.gov #NCT03794349
International Sponsor
Children's Oncology Group
Principal Investigators for Canadian Sites
The Hospital for Sick Children - Dr. Daniel Morgenstern
CancerCare Manitoba - Dr. Ashley Chopek
CHU Quebec - Dr. Bruno Michon
CHU Sherbrooke - Dr. Josée Brossard
Hamilton Health Sciences Centre (McMaster) - Dr. Uma H. Athale
IWK Health Centre - Dr. Craig Erker
Montreal Children's Hospital - Dr. Sharon Abish
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. Magimairajan Vanan
Social worker/patient navigator contact
Rhéanne Bisson
 
Clinical research contact
Rebekah Hiebert
Megan Ridler
Kathy Hjalmarsson

 

 

Medical contact
Raoul Santiago
 
Social worker/patient navigator contact
Isabelle Audet
 
Clinical research contact
Barbara Desbiens
 

 

Medical contact
Dr. Carol Portwine
 
Social worker/patient navigator contact
Jane Cassano 
 
Clinical research contact
Sabrina Millson
 
 
Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 
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. Josee Brossard 
Social worker/patient navigator contact
Please Contact Site Directly
 
Clinical research contact
Please Contact Site Directly 
 

 

 

Study Description

This phase II trial studies how well irinotecan hydrochloride, temozolomide, and dinutuximab work with or without eflornithine in treating patients with neuroblastoma that has come back (relapsed) or that isn't responding to treatment (refractory). Drugs used in chemotherapy, such as irinotecan hydrochloride and temozolomide, 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. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Eflornithine blocks the production of chemicals called polyamines that are important in the growth of cancer cells. Giving eflornithine with irinotecan hydrochloride, temozolomide, and dinutuximab, may work better in treating patients with relapsed or refractory neuroblastoma.

Inclusion Criteria
  • Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines (i.e. > 2 x upper limit of normal [ULN]), at the time of initial diagnosis.
  • For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound as intended to treat high-risk disease. The doses of chemotherapy must be comparable to those used in frontline high-risk neuroblastoma therapies (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, and ANBL1531). Patients must have ONE of the following:
    • First episode of recurrent high-risk disease following completion of aggressive multi-drug frontline high-risk therapy.
    • First episode of progressive high-risk disease during aggressive multi-drug frontline therapy.
    • Primary resistant/refractory disease (less than partial response by International Neuroblastoma Response Criteria [INRC]) detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, ANBL1531, etc.).
  • Patients must have at least ONE of the following at the time of enrollment:
    • Measurable tumor on magnetic resonance imaging (MRI) or computed tomography (CT) scan. Measurable is defined as >= 10 mm in at least one dimension on spiral/helical CT that is metaiodobenzylguanidine (MIBG) avid or demonstrates increased fludeoxyglucose F-18 (FDG) uptake on positron emission tomography (PET) scan.
    • MIBG-avid lesion detected on MIBG scan with positive uptake at a minimum of one site. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction.
    • Patients with resistant/refractory soft tissue disease that is not MIBG avid or does not demonstrate increased FDG uptake on PET scan must undergo biopsy to document the presence of viable neuroblastoma. Biopsy is not required for patients who have a new site of soft tissue disease (radiographic evidence of disease progression) regardless of whether progression occurs while receiving therapy or after completion of therapy.
    • Patients with bone marrow disease only will be eligible if they have more than 5% disease involvement (documented neuroblastoma cells) in at least one sample from bilateral bone marrow biopsies.
    • Note: Patients with elevated catecholamines (i.e. > 2 x ULN) only are NOT eligible for this study.
  • 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.
  • Primary refractory/resistant patients must have received at least 4 cycles of frontline high-risk chemotherapy. Frontline therapy may also have included surgery, chemotherapy, autologous stem cell transplantation (SCT) +/- MIBG, immunotherapy, radiotherapy, and retinoids but must NOT have received second line therapy for resistant/refractory, relapsed, or progressive disease. Patients who received intensified therapy for poor induction response or refractory disease (e.g. MIBG) will be considered to have received second line therapy and will not be eligible.
  • At least 14 days must have elapsed since completion of myelosuppressive therapy.
  • Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent.
  • Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1.
  • No interim time prior to study entry is required following prior radiation therapy (RT) for non-target lesions. However, patients must not have received radiation for a minimum of 4 weeks prior to study entry at the site of any lesion that will be identified as a target lesion to measure tumor response. Lesions that have been previously radiated cannot be used as target lesions unless there is radiographic evidence of progression at the site following radiation or a biopsy done following radiation shows viable neuroblastoma. Palliative radiation while on study is not permitted.
  • Patients are eligible >= 6 weeks after autologous stem cell transplants or stem cell infusions (including stem cell infusions given as supportive care following 131 I-MIBG therapy) as long as hematologic and other eligibility criteria have been met.
  • Patients are eligible >= 6 weeks after therapeutic 131 I-MIBG provided that all other eligibility criteria are met.
  • Subjects who have previously received anti-GD2 monoclonal antibodies with or without retinoids for biologic therapy are eligible unless they have had progressive disease while receiving prior anti-GD2 therapy or progressed/relapsed within 3 months of receiving anti-GD2 therapy. However, eligible patients may NOT have received anti-GD2 monoclonal antibodies in combination with chemotherapy.
  • Subjects who have received autologous marrow infusions or autologous stem cell infusions that were purged using monoclonal antibody linked to beads are eligible.
  • Subjects who have previously received DFMO are eligible for this study provided they have not had progressive disease while receiving DFMO or progressed/relapsed within 3 months of completing DFMO.
  • Patients must not have received long-acting myeloid growth factors (e.g. pegfilgrastim) within 14 days of entry on this study. Seven days must have elapsed since administration of a short-acting myeloid growth factor.
  • For patients with solid tumors (without marrow involvement) including status post SCT: peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to enrollment).
  • For patients with solid tumors (without marrow involvement) including status post SCT: platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
  • Patients known to have bone marrow involvement with neuroblastoma are eligible provided that minimum ANC and transfusion independent platelet count criteria are met (as above). However, these patients are not evaluable for hematological toxicity.
  • Creatinine clearance or radioisotope GFR >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
    • 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
    • 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
    • 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
    • 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
    • 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
    • >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to enrollment).
  • Total bilirubin =< 1.5 x ULN for age (within 7 days prior to enrollment).
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5.0 x ULN for age (=< 225 U/L). For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment).
  • Shortening fraction of >= 27% by echocardiography (ECHO) (within 7 days prior to enrollment).
  • Ejection fraction of >= 50% by ECHO or gated radionuclide study (within 7 days prior to enrollment).
  • No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry > 94% if there is a clinical indication for pulse oximetry. Normal pulmonary function tests in patients who are capable of cooperating with testing (including diffusion capacity of the lung for carbon monoxide [DLCO)] are required if there is a clinical indication for determination. For patients who do not have respiratory symptoms, full pulmonary function tests (PFTs) are NOT required.
  • Patients with a history of central nervous system (CNS) disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment.
  • Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsants.
  • CNS toxicity =< grade 2.

Other inclusion and exclusion criteria may apply and will be reviewed by your treating team.

Exclusion Criteria
  • Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study. Based on the established teratogenic potential of alkylating agents, pregnant women will be excluded from this study. Because of potential risks to breastfed infants due to drug metabolites that could be excreted in breast milk, female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study. Females of childbearing potential must have a negative pregnancy test to be eligible for this study.
  • Patients with only elevated catecholamines (i.e. > 2 x ULN) are NOT eligible for this study.
  • Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment. Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions. The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency.
  • Patients on any other immunosuppressive medications (e.g. cyclosporine, tacrolimus) are not eligible.
  • Patients must not have received prior treatment with irinotecan and temozolomide.
  • Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to study enrollment. Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic acid, or levetiracetam will be eligible.
  • Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment are not eligible.
  • Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma.
  • Patients with symptoms of congestive heart failure are not eligible.
  • Patients must not have >= grade 2 diarrhea.
  • Patients who are unable to tolerate oral/nasogastric/gastrostomy medications will not be eligible for this trial. Additionally, patients with significant malabsorption will not be eligible for this trial.
  • Patients must not have uncontrolled infection.
  • Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy are not eligible.
  • Patients 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 study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible.

Other inclusion and exclusion criteria may apply and will be reviewed by your treating team.

SNDX-5613-0700 - AUGMENT-101: A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX 5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation

Open

SNDX-5613-0700 - AUGMENT-101: A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX 5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation

Go to family friendly version

DiagnosisAcute Myeloid Leukemia Acute Lymphoblastic Leukemia Mixed Lineage Acute Leukemia Mixed Phenotype Acute Leukemia Acute Leukemia of Ambiguous LineageStudy StatusOpen
PhaseI/II
Ageup to 18 YearsRandomisationNO
Line of treatmentFirst line treatment, Disease relapse or progression
Routes of Treatment AdministrationDrug: SNDX-5613 (given orally) Drug: Cobicistat (Patients in Phase 1 Arm C patients will receive 150 mg cobicistat daily)
Last Posted Update2023-09-28
ClinicalTrials.gov #NCT04065399
International Sponsor
Syndax Pharmaceuticals
Principal Investigators for Canadian Sites
The Hospital for Sick Children - Dr. Jim Whitlock
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

Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of SNDX-5613 in patients with acute leukemia. There are 3 arms in Phase 1 as follows: 

  • Arm A: Patients not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/ inducers.
  • Arm B: Patients receiving strong cytochrome P450 3A4 (CY3A4) inhibitors for antifungal prophylaxis.
  • Arm C: Patients receiving SNDX-5613 in combination with cobicistat.

In Phase 2, patients will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of SNDX-5613. There are 3 cohorts in Phase 2 as follows: 

  • Cohort 2A: Patients with MLLr acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL).
  • Cohort 2B: Patients with MLLr AML.
  • Cohort 2C: Patients with NPM1c AML.
Inclusion Criteria

Patients must have active acute leukemia (bone marrow blasts ≥ 5% or reappearance of blasts in peripheral blood) as defined by the National Comprehensive Cancer Network (NCCN) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020).

  • Phase 1: Documented R/R acute leukemia harboring MLL rearrangement or NPM1c mutation.

    • Arm A: Patients not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducers.
    • Arm B: Patients receiving strong cytochrome P450 3A4 inhibitors for antifungal prophylaxis.
    • Arm C: Patients receiving SNDX-5613 in combination with cobicistat.
  • Phase 2:

    • Cohort 2A: Documented R/R ALL/MPAL with an MLLr translocation.
    • Cohort 2B: Documented R/R AML with an MLLr translocation.
    • Cohort 2C: Documented R/R AML with NPM1c.
  • WBC must be below 50,000/ μL at time of enrollment. Patients may receive cytoreduction prior to enrollment.
  • Male or female patient aged ≥30 days old.
  • Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or Karnofsky/Lansky score ≥40.
  • Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 neuropathy or alopecia.
  • Radiation Therapy: At least 60 days from prior total body irradiation (TBI), craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
  • Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion (DLI) without conditioning.
  • Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T cell therapy.
  • Myelosuppressive Chemotherapy: At least 14 days since the completion of cytotoxic/myelosuppressive therapy.
  • Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
  • Biologics: At least 7 days or 5 half-lives, whichever is longer, since the completion of therapy with a biologic agent.
  • Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy.
  • Adequate organ function.
  • If of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
Exclusion Criteria
  • Active diagnosis of acute promyelocytic leukemia.
  • Isolated extramedullary relapse.
  • Known CNS involvement (cytologic or radiographic).
  • Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Patients with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment.
  • Hepatitis B or C.
  • Pregnant or nursing women.
  • Cardiac Disease: Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
    • - QTc >450 msec for males and QTc >450 msec for females.
  • Gastrointestinal Disease:

    • Chronic diarrhea or other gastrointestinal issue that might affect oral drug absorption or ingestion (ie, short-gut syndrome, gastroparesis, etc).
    • Cirrhosis with a Child-Pugh score of B or C.
  • Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant patients must have been off all systemic immunosuppressive therapy and calcineurin inhibitors for at least 4 weeks prior to enrollment. Patients may be on physiological doses of steroids.
  • Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in complete remission or no evidence of disease during this timeframe.
  • Participation in another therapeutic interventional clinical study within 30 days of enrollment.

DAY101-001 (FIREFLY-1) - FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With BRAF-Altered, Recurrent or Progressive Low-Grade Glioma

Open

DAY101-001 (FIREFLY-1) - FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With BRAF-Altered, Recurrent or Progressive Low-Grade Glioma

Go to family friendly version

DiagnosisLow-grade glioma or solid tumors with RAF alterationsStudy StatusOpen
PhaseII
AgeChild, Adult - (6 Months to 25 Years)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationDay101: oral (tablet formulation)
Last Posted Update2023-09-28
ClinicalTrials.gov #NCT04775485
International Sponsor
Day One Biopharmaceuticals, Inc.
Principal Investigators for Canadian Sites
Montreal Children's Hospital – Dr. Nada Jabado
CHU Ste-Justine – Dr. Sebastien Perreault
CHU de Quebec – Dr. Valerie Larouche

Centres
Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 
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
 
Medical contact
Raoul Santiago
 
Social worker/patient navigator contact
Isabelle Audet
 
Clinical research contact
Barbara Desbiens
 

 

 

 

Study Description

Brief Summary:

FIREFLY-1 is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma harboring a known BRAF alteration.

Detailed Description:

Approximately 60 pediatric patients will be treated with DAY101, an oral pan-RAF inhibitor, for a planned period of 26 cycles will be treated with DAY101 for a planned period of 26 cycles (approximately 24 months).

DAY101 will be administered at the recommended Phase 2 dose (RP2D) of 420 mg/m2 (not to exceed 600 mg) orally once weekly (QW) for each 28-day treatment cycle.

Treatment cycles will repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients will undergo radiographic evaluation of their disease at the end of every third cycle. Patients will continue on DAY101 until radiographic evidence of disease progression by RANO criteria as determined by treating investigator, unacceptable toxicity, patient withdrawal of consent, or death.

Patients who have radiographic evidence of disease progression may be allowed to continue DAY101 if, in the opinion of the investigator and approval by the Sponsor, the patient is deriving clinical benefit from continuing study treatment. Disease assessments for patients being treated beyond progression should continue as per regular schedule.

DAY101 is an oral pan-RAF inhibitor administered as an oral tablet at 420 mg/m2 (not to exceed 600 mg).

Inclusion Criteria
  • Age 6 months to 25 years with a relapsed or progressive LGG or solid tumor with known activating RAF alteration (BRAF or CRAF/RAF1 fusion or BRAF V600 mutations (LGG only))
  • Confirmation of histopathologic diagnosis of LGG or solid tumor and molecular diagnosis of activating RAF alteration (BRAF or CRAF/RAF1 fusion or BRAF V600 mutations (LGG only))
  • Must have received at least one line of systemic therapy and have evidence of radiographic progression
  • Must have at least 1 measurable lesion as defined by RANO criteria
Exclusion Criteria
  • Patient's tumor has additional previously-known activating molecular alterations
  • Patient has symptoms of clinical progression in the absence of radiographic progression
  • Known or suspected diagnosis of neurofibromatosis type 1 (NF-1)
  • Other inclusion/exclusion criteria as stipulated by protocol may apply

2215-CL-0603 (ASP2215) - A Phase 1/2, Multicenter, Open-Label, Single Arm, Dose Escalation and Expansion Study of Gilteritinib (ASP2215) Combined With Chemotherapy in Children, Adolescents and Young Adults With FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)

Open

2215-CL-0603 (ASP2215) - A Phase 1/2, Multicenter, Open-Label, Single Arm, Dose Escalation and Expansion Study of Gilteritinib (ASP2215) Combined With Chemotherapy in Children, Adolescents and Young Adults With FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)

Go to family friendly version

DiagnosisAcute Myeloid LeukemiaStudy StatusOpen
PhaseI/II
AgeChild, Adult - (6 Months to 21 Years)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationOral for gilteritinib ; other drugs as usually administered for leukemia therapy
Last Posted Update2023-09-28
ClinicalTrials.gov #NCT04240002
International Sponsor
Astellas Pharma Global Development, Inc.
Principal Investigators for Canadian Sites
CHU Ste Justine - Dr. Henrique Bittencourt
Centres
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 the phase 1 portion (dose escalation) of the study will be to establish an optimally safe and biologically active recommended phase 2 dose (RP2D) and/or to determine maximum tolerated dose (MTD) for gilteritinib in sequential combination with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). The purpose of the phase 2 portion (dose expansion) is to determine complete remission (CR) rates and composite complete remission (CRc) rates after two cycles of therapy. The study will also assess safety, tolerability and toxicities of gilteritinib in combination with FLAG, evaluate FLT3 inhibition, assess pharmacokinetics (PK), perform serial measurements of minimal residual disease, obtain preliminary estimates of 1-year event free survival (EFS) and overall survival (OS) rate and assess the acceptability as well as palatability of the formulation.

One cycle is defined as 28 days of treatment. A participant completing 2 cycles in phase 1 or 2 will have the option to participate in long term treatment (LTT) with gilteritinib (for up to 2 years).

Inclusion Criteria
  • Subject is aged ≥ 6 months and < 21 years of age at the time of signing informed consent and/or assent, as applicable.

    • For phase 2: Enrollment of subjects from 6 months to less than 1 year and 1 year to less than 2 years will be dependent on the establishment of recommended phase 2 dose (RP2D) in the respective for age groups during phase 1.
  • Subject has a diagnosis of acute myeloid leukemia (AML) according to The French-American-British (FAB) classification with ≥ 5% blasts in the bone marrow, with or without extramedullary disease (except subjects with active central nervous system [CNS] leukemia).

    • In the phase 1 portion of the study, subject must be in first or greater relapse or refractory to induction therapy with no more than 1 attempt at remission induction.
    • For the phase 2 portion of the study, subject must be in first relapse.
  • Subject has fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

    • Myelosuppressive chemotherapy:

      • For subject who relapses while receiving cytotoxic therapy, at least 21 days must have elapsed since the completion of cytotoxic therapy and prior to screening.
      • Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of systemic protocol therapy (cycle 1 day -1). Subject may also receive low dose cytarabine (100 mg/m^2 per dose once daily for 5 days) for cytoreduction until 24 hours prior to cycle 1 day -1.
      • Subject who has received other FLT3 inhibitors (e.g., lestaurtinib, sorafenib, etc) is eligible for this study.
    • Hematopoietic growth factors: at least 7 days must have elapsed since the completion of therapy with a growth factor and prior to screening.
    • Biologic (anti-neoplastic agent): at least 7 days must have elapsed since the completion of therapy with a biologic agent and prior to screening. For agents that have known adverse events (AEs) occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur.
    • X-ray treatment (XRT):

      • 14 days must have elapsed for local palliative XRT for CNS chloromas and prior to screening; no washout period is necessary for other chloromas;
      • Prior to screening, 90 days must have elapsed if the subject had a prior traumatic brain injury or has received craniospinal XRT.
  • For subject undergoing hematopoietic stem cell transplant (HSCT), at least 90 days must have elapsed since HSCT and subject must not have active graft-versus-host disease (GVHD).
  • Subject has Karnofsky score ≥ 50 (if the subject is of ≥ 16 years of age) or Lansky score of ≥ 50 (if the subject is < 16 years of age). A score < 50 is acceptable if related to the subject's leukemia.
  • Subject must meet the following criteria as indicated on the clinical laboratory tests.

    • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit normal (ULN) for age
    • Total serum bilirubin ≤ 1.5 x ULN for age
    • Serum creatinine ≤ 1.5 x ULN for age or an estimated glomerular filtration rate of > 60 mL/min/1.73 m^2.
  • A female subject is eligible to participate if she is not pregnant and at least 1 of the following conditions applies:

    • Not a woman of childbearing potential (WOCBP) OR
    • WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 180 days after the final study drug administration.
  • Female subject must agree not to breastfeed starting at Screening, and throughout the study period and for 60 days after the final study drug administration.
  • Female subject must not donate ova starting at Screening and throughout the study, and for 180 days after the final study drug administration.
  • A male subject with female partner(s) of childbearing potential must agree to use contraception during the treatment period and for at least 180 days after the final study drug administration. (in United Kingdom, Germany and Canada)
  • A male subject must not donate sperm during the treatment period and for at least 120 days after the final study drug administration.
  • Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 180 days after the final study drug administration. (United Kingdom, Germany and Canada)
  • Subject and subject's parent(s) or legal guardian agrees not to participate in another interventional study while on treatment.
  • In United Kingdom, Germany and Canada: Live Vaccines - At least 6 weeks must have elapsed since the administration of the last dose of a live vaccine and prior to the initiation of study treatment (cycle 1, day -1)
  • Phase 1: Subject is positive for FLT3 (ITD and/or tyrosine kinase domain [TKD]) mutation in bone marrow or blood as determined by the local institution.
  • Phase 2: Subject is positive for the FLT3 (ITD) mutation in bone marrow or blood as determined by the local institution.
Exclusion Criteria
  • Subject has active CNS leukemia.
  • Subject has uncontrolled or significant cardiovascular disease, including:

    • Diagnosed or suspected congenital long QT syndrome or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes (TdP)); any history of arrhythmia will be discussed with the sponsor prior to subject's entry into the study
    • Prolonged Fridericia's Correction Formula (QTcF) interval on pre-entry electrocardiogram (ECG) (≥ 450 ms)
    • Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)
    • Heart rate < 50 beats/minute on pre-entry ECG
    • Uncontrolled hypertension
    • Complete left bundle branch block
  • Subject 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 subject needs to be off pressors and have negative blood cultures for 48 hours.
  • Subject is receiving or plans to receive concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
  • Subject has active clinically significant graft-versus-host disease (GVHD) or is on treatment with systemic corticosteroids and is receiving > 0.5 mg/kg of prednisone (or equivalent) daily dose for GVHD.
  • Subject has active malignant tumors other than AML.
  • Subject has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance; interfere with consent, study participation, follow-up or interpretation of study results.
  • Subject has hypokalemia and/or hypomagnesemia at Screening (defined as values below institutional lower limit of normal [LLN]). Repletion of potassium and magnesium levels during the screening period is allowed.
  • Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A/P-glycoprotein (P-gp).
  • Subject is known to have human immunodeficiency virus infection.
  • Subject has active hepatitis B or C, or other active hepatic disorder.
  • Subject must wait for at least 5 half-lives after stopping therapy with any investigational agent and before starting gilteritinib.
  • In United Kingdom, Germany and Canada: Subject has a known or suspected hypersensitivity to gilteritinib, cytarabine, fludarabine, granulocyte colony-stimulating factor (G-CSF) or any components of the formulation used.

NMTRC012 - A Study Using Molecular Guided Therapy With Induction Chemotherapy Followed by a Randomized Controlled Trial of Standard Immunotherapy With or Without DFMO Followed by DFMO Maintenance for Subjects With Newly Diagnosed High-Risk Neuroblastoma

Open

NMTRC012 - A Study Using Molecular Guided Therapy With Induction Chemotherapy Followed by a Randomized Controlled Trial of Standard Immunotherapy With or Without DFMO Followed by DFMO Maintenance for Subjects With Newly Diagnosed High-Risk Neuroblastoma

Go to family friendly version

DiagnosisNeuroblastomaStudy StatusOpen
PhaseII
AgeChild, Adult - (up to 22 Years )RandomisationYES
Line of treatmentFirst line treatment
Routes of Treatment AdministrationDFMO - oral Other drugs are given as usually administered for neuroblastoma therapy
Last Posted Update2023-09-28
ClinicalTrials.gov #NCT02559778
International Sponsor
Giselle Sholler
Principal Investigators for Canadian Sites
CHU Ste-Justine – Dr. Pierre Teira
Montreal Children's Hospital -
Centres
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
 
Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 

 

 

Study Description

A prospective open label, multicenter study to evaluate the feasibility and acute toxicity of using molecularly guided therapy in combination with standard therapy followed by a Randomized Controlled Trial of standard immunotherapy with or without DFMO followed by DFMO maintenance for Subjects with Newly Diagnosed High-Risk Neuroblastoma.

Inclusion Criteria

Part A:

  1. 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 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.

  2. Subjects must be age ≤ 21 years at initial diagnosis
  3. Subjects must not 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.
  4. Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.
  5. Ability to tolerate 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.

    Part A and B both:

  6. Adequate Cardiac Function Defined As:

    1. Shortening fraction of ≥ 27% by echocardiogram, or
    2. Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram.
  7. Adequate liver function must be demonstrated, defined as:

    c. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND d. ALT (SGPT) < 10 x upper limit of normal (ULN) for age

  8. 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 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5 1 to < 2 years 0.6 0.6 2 to < 6 year 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

  9. A negative serum pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)
  10. Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
  11. Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines.

    Part B:

  12. All patients must have a pathologically confirmed diagnosis of neuroblastoma, be age ≤ 21 years at initial diagnosis, and classified as high risk by the criteria used by COG or SIOPEN at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
  13. Previous Therapy- subjects must fit into one of the strata categories listed in section 10.5 to be eligible to enroll on Part B of this study.
  14. Pre-enrollment tumor survey:

    Prior to enrollment on Part B, a determination of mandatory disease staging must be performed. Tumor imaging studies including CT or MRI, MIBG or PET, and VMA/HVA (PET scan should be done for patients with prior disease that was MIBG non-avid). Bone marrow aspirates and biopsies are required.

    This disease assessment is required for eligibility and should be done preferably within 2 weeks, but must be done within a maximum of 4 weeks before first dose of study drug.

  15. Timing- Enrollment to occur prior to Day + 120 post-transplant, preferably when the subject is within 28 days after completing local radiation therapy (if given).
Exclusion Criteria
  1. Subjects who are 12-18 months of age with INSS Stage 4 and all stage 3 subjects with favorable biologic features (ie, nonamplified MYCN, favorable pathology, and DNA index > 1) are not eligible.
  2. Lactating females are not eligible unless they have agreed not to breastfeed their infants.
  3. Subjects receiving any investigational drug concurrently.
  4. 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

D0816C00025 - A Phase I, Open-label, Parallel Group Study to Investigate Olaparib Safety and Tolerability, Efficacy and Pharmacokinetics in Paediatric Patients With Solid Tumours

Open

D0816C00025 - A Phase I, Open-label, Parallel Group Study to Investigate Olaparib Safety and Tolerability, Efficacy and Pharmacokinetics in Paediatric Patients With Solid Tumours

Go to family friendly version

DiagnosisSolid TumoursStudy StatusOpen
PhaseI
Age6 Months to 18 Years RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationDrug: Olaparib (Oral)
Last Posted Update2023-09-28
ClinicalTrials.gov #NCT04236414
International Sponsor
AstraZeneca
Principal Investigators for Canadian Sites
Montreal Children's Hospital - Dr. Sharon Abish
Centres
Medical contact
Clinical Research Unit
 
Social worker/patient navigator contact
Clinical Research Unit
 
Clinical research contact
Stephanie Badour
 

 

 

Study Description

A Phase I open-label, multicentre study to determine the RP2D of olaparib monotherapy in the paediatric population, and to evaluate the safety, tolerability, PK, PDx and preliminary efficacy of olaparib monotherapy in paediatric patients from ≥6 months to <18 years of age at enrolment, with relapsed or refractory solid or primary CNS tumours (excluding lymphoid malignancies) for whom there are no standard treatment options. It is anticipated that eligible patients fulfilling all of the inclusion criteria and none of the exclusion criteria, will include but will not be limited to those with osteosarcoma, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, Ewing Sarcoma, neuroblastoma, medulloblastoma and glioma.

Inclusion Criteria
  • Provision of Informed Consent
  • Male and female patients who are ≥6 months to <18 years of age at consent
  • Pathologically confirmed relapsed or refractory solid or primary CNS tumours (excluding lymphoid malignancies), with a HRR deficiency/gene mutation, and for whom there are no standard treatment options. Eligible patients may include but not be limited to those with osteosarcoma, rhabdomyosarcoma, non rhabdomyosarcoma soft tissue sarcoma, Ewing Sarcoma, neuroblastoma, medulloblastoma and glioma
  • For dose finding phase only: recruitment will be open to all patients with HRR deficiency, based on a local test. For the signal identification phase: recruitment will be open only to patients with documented evidence of a deleterious or suspected deleterious germline or tumour HRR gene mutation that meets the AZ HRR rules
  • A formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer (all patients) suitable for central HRR testing and a blood sample (patients ≥2 years old) for central germline BRCA testing must be provided for each patient
  • For all non-neuroblastoma tumours, patients must have at least 1 radiographical assessable lesion (measurable and/or non-measurable). For neuroblastoma tumours, patients must have radiographical assessable disease with at least 1 lesion (measurable and/or non measurable) OR disease evidenced by uptake of meta-iodobenzylguanidine- (MIBG) or fluorodeoxyglucose positron emission tomography (FDG-PET) scans
  • Adequate performance status, organ, and marrow function and adequate weight to obtain blood samples for both safety laboratory assessments and PK analysis.
  • Ability to swallow tablets
Exclusion Criteria
  • Patients with MDS/AML or with features suggestive of MDS/AML
  • Patients unable to swallow orally administered medication
  • Unresolved toxicity from previous anticancer therapy
  • Unstable or untreated CNS disease (i.e., symptomatic uncontrolled brain metastases or untreated spinal cord compression)
  • Previous treatment with a PARP inhibitor, including olaparib
  • Receipt of any radiotherapy for cancer treatment (except for palliative reasons) within 30 days prior to first dose of study treatment or receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, monoclonal antibodies, etc) within 21 days prior to the first dose of study treatment
  • Concomitant use of known strong or moderate CYP3A inhibitors or concomitant use of known strong or moderate CYP3A inducers
  • Whole blood transfusions in the last 120 days prior to screening (packed red blood cells and platelet transfusions are acceptable)

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

ARST2031 - A Randomized Phase 3 Trial of Vinorelbine, Dactinomycin, and Cyclophosphamide (VINO-AC) Plus Maintenance Chemotherapy With Vinorelbine and Oral Cyclophosphamide (VINO-CPO) vs Vincristine, Dactinomycin and Cyclophosphamide (VAC) Plus VINO-CPO Maintenance in Patients With High Risk Rhabdomyosarcoma (HR-RMS)

Open

ARST2031 - A Randomized Phase 3 Trial of Vinorelbine, Dactinomycin, and Cyclophosphamide (VINO-AC) Plus Maintenance Chemotherapy With Vinorelbine and Oral Cyclophosphamide (VINO-CPO) vs Vincristine, Dactinomycin and Cyclophosphamide (VAC) Plus VINO-CPO Maintenance in Patients With High Risk Rhabdomyosarcoma (HR-RMS)

Go to family friendly version

DiagnosisRhabdomyosarcomaStudy StatusOpen
PhaseIII
Ageup to 50 YearsRandomisationYES
Line of treatmentFirst line treatment
Routes of Treatment AdministrationChemotherapy medications (Cyclophosphamide, Dactinomycin, Vincristine, Vinorelbine), all given intravenously, except for cyclophosphamide that will be taken by mouth too Patients will also receive radiation therapy when participating to this study.
Last Posted Update2023-09-28
ClinicalTrials.gov #NCT04994132
International Sponsor
Children's Oncology Group
Principal Investigators for Canadian Sites
The Hospital for Sick Children - Dr. Paul Nathan
Hamilton Health Sciences Centre - Dr. Uma H. Athale
Children’s Hospital of Eastern Ontario (CHEO) - Dr. Donna L. Johnston
Children's Hospital of Western Ontario – Dr. Shayna Zelcer

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. 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

 

 

Study Description

This phase III trial compares the effect of vinorelbine with vincristine, dactinomycin, and cyclophosphamide (VAC) followed by vinorelbine and cyclophosphamide versus VAC followed by vinorelbine and cyclophosphamide for the treatment of high risk rhabdomyosarcoma. Chemotherapy drugs, such as vinorelbine, vincristine, dactinomycin, and cyclophosphamide, 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 vinorelbine and VAC may kill more tumor cells. Adding maintenance therapy (vinorelbine and cyclophosphamide) after VAC therapy, with or without vinorelbine, may help get rid of the cancer and/or lower the chance that the cancer comes back.

PRIMARY OBJECTIVE:

I. To compare event-free survival (EFS) of patients with high-risk rhabdomyosarcoma (HR-RMS) treated with vinorelbine, dactinomycin and cyclophosphamide (VINO AC) followed by 24 weeks of vinorelbine and oral cyclophosphamide (VINO-CPO) maintenance therapy to that of patients treated with vincristine, dactinomycin and cyclophosphamide (VAC) followed by 24 weeks of VINO-CPO maintenance therapy.

SECONDARY OBJECTIVES:

I. To assess the safety and feasibility of administering VINO-AC in newly diagnosed patients with HR-RMS.

II. To describe the toxicity experience of patients with HR-RMS treated with VINO-AC compared to VAC.

III. To compare overall survival (OS) of patients with HR-RMS treated with VINO AC followed by 24 weeks of VINO-CPO maintenance therapy to that of patients treated with VAC followed by 24 weeks of VINO-CPO maintenance therapy.

IV. To compare objective radiologic response rates at week 12 between patients with HR-RMS treated with VINO-AC to those treated with VAC.

V. To determine whether the addition of 24 weeks of VINO-CPO maintenance therapy improves EFS in patients with HR-RMS when compared to historical controls.

EXPLORATORY OBJECTIVE:

I. To collect serial blood samples and tumor tissue for banking at baseline, during treatment, at the end of therapy, and at the time of progression for future tumor and liquid biopsy studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

  • ARM A: Patients receive vincristine sulfate intravenously (IV) on days 1, 8 and 15 of cycles 1-4, 7, 8, 11, and 12, and day 1 of cycles 6, 9, 10, 13, and 14. Patients also receive dactinomycin IV over 1-15 minutes on day 1 of cycles 1-5 and 8-14, and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on weeks 13 and 40.
  • ARM B: Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8, vincristine sulfate IV on day 15, dactinomycin IV over 1-15 minutes on day 1 of cycles 1-5 and 8-14, and cyclophosphamide IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on weeks 13 and 40.

 

MAINTENANCE: All patients receive vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15, and cyclophosphamide orally (PO) on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for year 1, every 4 months for years 2-3, and every 6 months for year 4.

Inclusion Criteria
  • Patients must be =< 50 years of age at the time of enrollment
  • Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification are eligible to enroll on the study based upon Stage, Group, and age, as below. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) Classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants
    • ERMS
      • Stage 4, group IV, >= 10 years of age
    • ARMS
      • Stage 4, group IV Patients will be eligible to remain on protocol therapy based upon stage, group, and age
  • Bone marrow metastatic disease is based on morphologic evidence of RMS based on hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
  • 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:
    • Age; Maximum serum creatinine (mg/dL)
    • 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
    • 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
    • 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
    • 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
    • 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
    • 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
    • 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
    • >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
    • If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x ULN for age
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Additional inclusion and exclusion criteria may apply 

Exclusion Criteria
  • Patients with evidence of uncontrolled infection are not eligible
  • RMS that is considered a second malignancy and previous cancer(s) that were treated with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is allowed
  • Patients with central nervous system involvement of RMS as defined below:
    • Malignant cells detected in cerebrospinal fluid
    • Intra-parenchymal brain metastasis separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed).
    • Diffuse leptomeningeal disease
  • Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment.
    • Note: the following exception:
      • Patients requiring emergency radiation therapy for RMS. These patients are eligible, provided they are consented to ARST2031 prior to administration of radiation
    • Note: Patients who have received or are receiving chemotherapy or radiation for non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy
  • Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment
  • 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

Additional inclusion and exclusion criteria may apply 

PLAT-05 - Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-05: A Phase 1 Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia

Open

PLAT-05 - Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-05: A Phase 1 Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia

Go to family friendly version

DiagnosisLeukemia, ALL, Acute Lymphoblastic LeukemiaStudy StatusOpen
PhaseI
AgeChild, Adult - (up to 30 Years)RandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationIV
Last Posted Update2023-09-28
ClinicalTrials.gov #NCT03330691
International Sponsor
Seattle Children's Hospital
Principal Investigators for Canadian Sites
BC Children's Hospital – Dr. Kirk Schultz
Centres
Medical contact
Rebecca Deyell

 

Social worker/patient navigator contact
Ilana Katz 

 

Clinical research contact
Hem/Onc/BMT Clinical Trials Unit

 

 

 

Study Description

Patients with relapsed or refractory leukemia often develop resistance to chemotherapy and some patients who relapse following CD19 directed therapy relapse with CD19 negative leukemia. For this reason, the investigators are attempting to use T-cells obtained directly from the patient, which can be genetically modified to express two chimeric antigen receptors (CARs). One is to recognize CD19 and the other is to recognize CD22, both of which are proteins expressed on the surface of the leukemic cell in patients with CD19+CD22+ leukemia. The CAR enables the T-cell to recognize and kill the leukemic cell through recognition of CD19 and CD22. This is a phase 1 study designed to determine the safety of the CAR+ T-cells and the feasibility of making enough to treat patients with CD19+CD22+ leukemia.

Inclusion Criteria
  • First 2 subjects: male and female subjects age ≥18 and < 27 years (as of 2/16/18 the first 2 subjects were enrolled and treated); subsequent subjects: male and female subjects age ≥12 months of age and <27 years.
  • Diagnosis of CD19+22+ leukemia
  • Disease status:

    • If post allogeneic HCT: Confirmed CD19+CD22+ leukemia recurrence defined as at least 0.01% disease following allogeneic HCT
    • If relapse/refractory status with no prior history of allogeneic HCT, one of the following:
    • Second or greater marrow relapse, with or without extramedullary disease
    • First marrow relapse at end of first month or re-induction with marrow having at least 0.01 % blasts by morphology and/or MPF
    • Primary refractory as defined as greater than 5% blasts by multi-parameter flow after at least 2 separate induction regimens.
    • Subject has indication for HCT but has been deemed ineligible, inclusive of persistent MRD prior to HCT
  • Asymptomatic from CNS involvement, if present, and in the opinion of the Principal Investigator with a reasonable expectation that disease burden can be controlled in the interval between enrollment and T-cell infusion. Subjects with significant neurologic deterioration will not be eligible for T-cell infusion until stabilized.
  • Free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks prior to enrollment
  • Lansky or Karnofsky performance score of at least 50
  • Life expectancy of at least 8 weeks
  • Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy
  • At least 7 days post last chemotherapy administration (excluding intrathecal maintenance chemotherapy)
  • At least 7 das post last systemic corticosteroids administration (unless physiologic replacement dosing)
  • No prior genetically modified cell therapy that is still detectable or virotherapy
  • Adequate organ function
  • Adequate laboratory values
  • Willing to participate in long-term follow-up for up to 15 years, if enrolled in the study and receive T cell infusion
  • Patients of childbearing/fathering potential must agree to use highly effective contraception from the time of initial T cell infusion through 12 months following the last T cell infusion
Exclusion Criteria
  • Presence of active clinically significant CNS dysfunction
  • Pregnant or breast-feeding
  • Unable to tolerate apheresis procedure
  • Presence of active malignancy other than CD19+CD22+ leukemia
  • Presence of active severe infection
  • Presence of any concurrent medical condition that, in the opinion of the Principal Investigator, would prevent the patient from undergoing protocol-specified therapy