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98 results found

Title
Status

 

F8394-201 - A Phase 2 Master Protocol to Assess the Efficacy and Safety of FORE8394, an Inhibitor of BRAF Class 1 and Class 2 Alterations, in Participants With Cancer Harboring BRAF Alterations

Open

F8394-201 - A Phase 2 Master Protocol to Assess the Efficacy and Safety of FORE8394, an Inhibitor of BRAF Class 1 and Class 2 Alterations, in Participants With Cancer Harboring BRAF Alterations

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DiagnosisCancer Harboring BRAF AlterationsStudy StatusOpen
PhaseII
Age10 Years and olderRandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationDrug: Plixorafenib (Oral tablets) Drug: Cobicistat (Oral tablets)
Last Posted Update2024-08-21
ClinicalTrials.gov #NCT05503797
International Sponsor
Fore Biotherapeutics
Principal Investigators for Canadian Sites
Sunnybrook Health Sciences Centre - Dr. Mary Jane Lim-Fay
CHU Ste. Justine - Dr. Sébastien Perreault
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
N/A
Social worker/patient navigator contact
N/A
Clinical research contact

   

 

 

Study Description

 

The objective of this study is to evaluate the efficacy of plixorafenib in participants with locally advanced or metastatic solid tumors, or recurrent or progressive primary central nervous system (CNS) tumors harboring BRAF fusions, or in participants with recurrent high-grade glioma (HGG) harboring BRAF V600E mutation. This will be conducted as two single arm open-label subprotocols (F8394-201A; F8394-201B) under one master protocol.

Inclusion Criteria

Group A: 

  • Male and female, ≥10 years of age, and weighing ≥30 kg.
  • Histologic diagnosis of a solid tumor or primary CNS tumor.
  • Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically validated test by DNA sequencing or RNA (transcriptome) sequencing at CLIA or CLIA-equivalent laboratory or sponsor-designated central laboratory.
  • Have an archival tissue sample at less than 24 months from date of screening available with sufficient tumor for central next generation sequencing (NGS) testing and biomarker analyses, or >24 months if the participant has never received targeted therapy. If an archival tissue sample is not available, a newly obtained (before treatment) tumor biopsy may be submitted instead.
  • Consent to provide scan(s) prior to baseline to assess change in tumor trajectory (at least 2 preferred). For participants with LGG, every effort should be made to provide 3 to 4 pre-baseline scans to the central imaging vendor whenever feasible.
  • Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.
  • All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline except for
    • Alopecia (Grade ≤2)
    • Sensory neuropathy (Grade ≤2)
    • Other adverse events that have resolved to Grade ≤2 that, according to the clinical judgment of the investigator, do not constitute a safety risk to the participant.

Group B: 

  • Male and female, ≥10 years of age, and weighing ≥30 kg.
  • Histological diagnosis of a primary CNS tumor, including but not limited to the following:
    • Adults (≥18 years) with Grade 1-4 glioma or glioneuronal tumor (including glioblastoma, anaplastic astrocytoma, high grade astrocytoma with piloid features, pilocytic astrocytoma, gliosarcoma, anaplastic pleomorphic xanthoastrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, not otherwise specified [NOS], ganglioglioma, or recurrent LGG).
    • Pediatric patients (10-17 years of age) with a Grade 3 or 4 glioma or glioneuronal tumor, including those with a prior, histologically confirmed, diagnosis of a low-grade glioma or glioneuronal tumor and now have radiographic or histopathological findings consistent with WHO [2021] Grade 3 or 4 primary CNS tumor.
    • Participants must have unresectable, locally advanced or metastatic disease that:
      • Had prior treatment with radiotherapy and/or first-line chemotherapy or concurrent chemoradiation therapy OR
      • Is intolerant to available therapies OR iii. The investigator has determined that treatment with standard therapy is not appropriate.
      • Note: Participants who have a WHO Grade 3 or 4 glioma for whom chemotherapy and/or radiotherapy is not considered standard of care may remain eligible for the study. Consult the Medical Lead to discuss and determine if participant is eligible for enrollment.
  • Documented BRAF V600E mutation in tumor and/or blood detected by an analytically validated test by NGS or polymerase chain reaction (PCR) methods and locally approved assays at CLIA or CLIA-equivalent laboratory approved by sponsor or sponsor-designated central test. Sponsor review of the report is required, and testing of BRAF alteration is required at sponsor's central laboratory.
  • An archival tissue sample at less than 24 months from date of screening available with sufficient tumor for central NGS testing* and biomarker analyses, or >24 month if the participant has never received a targeted therapy, or fresh biopsy is required if the archival sample is not available for retrospective confirmation test. Tissue obtained most proximal to initiating this subprotocol is preferred.
  • Measurable disease based upon RANO HGG for high-grade tumors or RANO LGG for the low grade tumors, as determined by the radiographic BICR.
  • All adverse events related to prior therapies (eg, chemotherapy, radiotherapy, surgery) must have resolved to Grade 1 or baseline except for:
    • Alopecia (Grade ≤2)
    • Sensory neuropathy (Grade ≤2)
    • Other adverse events that have resolved to Grade ≤2 that, according to the clinical judgment of the investigator, do not constitute a safety risk to the participant
  • Participants who are receiving corticosteroid treatment must be on a stable or decreasing dose of ≤8 mg/day of dexamethasone or equivalent corticosteroid treatment for 7 days prior to first dose of study treatments.
Exclusion Criteria

Group A: 

  • Participants with known co-occurring NF1 alteration and/or RAS-related mutations.
  • Participants with evidence of subclonal mutations or heterogeneity that are indicative of a prior treatment effect instead of a driver mutation.
  • Prior treatment with RAF/BRAF inhibitors active for Class 2 BRAF alterations for advanced unresectable or metastatic disease (including but not limited to tovorafenib [formerly known as DAY 101, TAK 580, and MLN 2480], KIN-2787, BGB-3245, and CFT1946).
    • Note: Participants with pediatric-type LGGs (molecular classification by WHO2021; diagnosed at ≤25 years of age) who had received prior treatment(s) with RAF/BRAF inhibitors are eligible for enrollment, provided there was no evidence of tumor progression on that therapy or within 4 weeks of discontinuation, based upon radiographic assessment.
  • Prior treatment with a MEK inhibitor.
  • Tyrosine kinase inhibitor(s) and/or targeted therapies are allowed (other than BRAF/MAPK pathway inhibitors per Exclusion Criteria 3 and 4) and will be restricted to no more than the number of lines of therapy that are consistent with standard treatment guidelines. NOTE: There is no restriction on the number of lines of chemotherapy or immunotherapy.
  • Malignancy with co-occurring activating RAS mutation(s) at any time.
  • Uncontrolled intercurrent illness that would limit compliance with study requirements.
  • Current or planned participation in a study of an investigational agent or device.
  • Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral plixorafenib or cobicistat (such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, and small bowel resection).
  • Are currently receiving (within 7 days of Cycle 1 Day 1) or are planning to receive during participation:
    • Agents that are known strong inducers or inhibitors of CYP3A4 (other than cobicistat). Restrictions include foods or herbal medications, including grapefruit juice and grapefruit/grapefruit related citrus fruits (eg, Seville oranges, pomelos), and St. John's Wort.
    • Agents that are contraindicated with cobicistat. Note: For participants with no other option except agents with potential drug interactions with cobicistat, but which are not contraindicated, the dose of that agent must be altered or the regimen must follow the cobicistat prescribing information and be approved by the medical monitor.

Group B: 

  • Prior treatment with BRAF, ERK, and/or MEK inhibitor(s).
  • Known or suspected neurofibromatosis-1 (NF-1) and/or Ras related gene alterations.
  • Uncontrolled intercurrent illness that would limit compliance with study requirements.
  • Active infection requiring systemic therapy.
  • Current or planned participation in a study of an investigational agent or device.
  • Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral plixorafenib or cobicistat (such as ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
  • Grade ≥ 2 changes in AST, ALT, gamma-glutamyl transaminase (GGT), or bilirubin attributed to prior immune checkpoint inhibitor treatment are exclusionary, even if resolved.
  • Are currently receiving (within 7 days of Cycle 1 Day 1) or are planning to receive during participation:
    • Agents that are known strong inducers or inhibitors of CYP3A4 (other than cobicistat). Restrictions include foods or herbal medications, including grapefruit juice, grapefruit/grapefruit related citrus fruits (eg, Seville oranges, pomelos), and St. John's Wort.
    • Agents that are contraindicated with cobicistat Note: For participants with no other option except agents with potential drug interactions with cobicistat, but which are not contraindicated, the dose of that agent must be altered or the regimen must follow the cobicistat prescribing information and be approved by the medical monitor.
  • Progressively worsening in frequency or severity seizures indicative of rapid tumor progression, or seizures poorly controlled with available therapy.

DAY101-102 - A Phase 1b/2, Open Label Study of DAY101 Monotherapy or Combination With Other Therapies for Patients With Recurrent, Progressive, or Refractory Solid Tumors Harboring MAPK Pathway Aberrations (FIRELIGHT)

Closed

DAY101-102 - A Phase 1b/2, Open Label Study of DAY101 Monotherapy or Combination With Other Therapies for Patients With Recurrent, Progressive, or Refractory Solid Tumors Harboring MAPK Pathway Aberrations (FIRELIGHT)

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DiagnosisNon-hematological tumours (solid and brain) with relevant biomarkerStudy StatusClosed
PhaseI/II
Age12 Years and olderRandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationDrug: DAY101 (Oral tablet) Drug: Pimasertib Hydrochloride (Oral capsule) - Sub-study B only.
Last Posted Update2024-07-31
ClinicalTrials.gov #NCT04985604
International Sponsor
Day One Biopharmaceuticals, 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

 

This is a Phase 1b/2, multi-center, open label umbrella study of patients ≥12 years of age with recurrent or progressive solid (including CNS) tumors with alterations in the key proteins of the RAS/RAF/MEK/ERK pathway, referred to as the MAPK pathway. Study DAY101-102 (master study) and sub-studies will consist of a screening period, a treatment period, a safety follow-up period, and a long-term follow-up period where survival, status and subsequent anticancer therapies are collected.

DAY101 will be evaluated alone (sub-study A) or combined with a different targeted therapy (sub-study B) in each sub-study. The Phase 1b part of each sub-study will evaluate the safety of the combination and select the dose for the Phase 2 part. The Phase 2 part of each sub-study will evaluate anti-tumor activity.

Inclusion Criteria
  • Signed assent for patients ≥ 12 up to < 18 years of age
  • Patients must have a histologically confirmed diagnosis of non-hematological tumor with concurrent MAPK pathway alteration as assessed by sequencing, PCR, FISH, or another clinically accepted molecular diagnostic method recognized by local laboratory or regulatory agency
  • Patients must have radiographically-recurrent or radiographically-progressive disease that is measurable using the appropriate tumor response criteria (e.g. RECIST version 1.1)
  • Archival tumor tissue (preferably less than 3 years old) or fresh tumor tissue for correlative studies is required
  • If brain metastases are present, they must have been previously treated and be stable as assessed by radiographic imaging

Other inclusion criteria may apply

Exclusion Criteria
  • Known presence of concurrent activating mutation
  • Patients with current evidence or a history of central serous retinopathy (CSR), retinal vein occlusion (RVO)

Substudy A-specific exclusion criterion:

  • Prior therapy of any RAS- RAF-, MEK-, or ERK-directed inhibitor therapy

Substudy B-specific exclusion criterion:

  • Prior receipt of any Type-II pan-RAF inhibitor therapy (e.g., LXH254/naporafenib, BGB- 283, BGB-3245, belvarafenib)

Other exclusion criteria may apply 

BP42573 - An Open-label, Multicenter, Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RO7428731 in Participants With Glioblastoma Expressing Mutant Epidermal Growth Factor Receptor Variant III

Open

BP42573 - An Open-label, Multicenter, Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RO7428731 in Participants With Glioblastoma Expressing Mutant Epidermal Growth Factor Receptor Variant III

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DiagnosisGlioblastomaStudy StatusOpen
PhaseI
Age18 Years and olderRandomisationNO
Line of treatmentFirst line treatment, Disease relapse or progression
Routes of Treatment AdministrationDrug: RO7428731, intravenously (IV)
Last Posted Update2024-06-21
ClinicalTrials.gov #NCT05187624
International Sponsor
Hoffmann-La Roche
Principal Investigators for Canadian Sites
Princess Margaret Cancer Centre
Centres
Medical contact

    CNS - Dr. Julie Bennett

     julie.bennett@sickkids.ca

     Sarcoma - Dr. Abha Gupta

     abha.gupta@uhn.ca

     Leukemia & Lymphoma - Dr. Dawn Maze

     dawn.maze@uhn.ca

Social worker/patient navigator contact

Please contact medical team for further information.

Clinical research contact

     CNS Trials - On Yee Jones

     onyee.jones@uhn.ca

     Sarcoma Trials - Hagit Peretz Soroka

     hagit.peretz@uhn.ca

     Leukemia & Lymphoma Trials - Deborah Sanfelice 

     deborah.Sanfelice@uhn.ca

 

 

Study Description

 

This is an open-label, multicenter study to assess safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary efficacy of RO7428731 administered as a monotherapy in participants with newly diagnosed or recurrent epidermal growth factor receptor variant III (EGFRvIII)-positive glioblastoma (GBM).

 

Experimental: Part I: Dose Escalation

Participants with newly diagnosed GBM will receive RO7428731, intravenously (IV), up to one year or until disease progression, withdrawal of consent, unacceptable toxicity, or death, whichever occurs first.

Experimental: Part II: Dose-Expansion(s)

Participants with newly diagnosed GBM will receive RO7428731, IV, in maximum of two dose expansion cohorts at a dose(s) not exceeding the maximum tolerated dose (MTD) established in Part I.

Experimental: Part III: Safety Run-in

Participants with recurrent GBM will receive RO7428731, IV in a dosing schedule determined in Part I. At the end of the Safety Run-in period, a decision will be made as to whether to open the Dose-Expansion Cohort Part IVA or open a second Safety Run-in Cohort at a lower dose.

Experimental: Part IV A: Dose-Expansions Cohort

Participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules.

Inclusion Criteria

Inclusion criteria for all participants:

  • Life expectancy of greater than or equal to 12 weeks, in the opinion of the Investigator
  • Diagnosis of GBM based on World Health Organization (WHO) classification of central nervous system (CNS) tumors, 5th edition
  • Participants must have confirmed EGFRvIII-expression
  • Karnofsky Performance Status (KPS) Score of >=70%
  • Adequate organ functions prior to start of study treatment
  • Willingness to abide by contraceptive measures for the duration of the study.

Inclusion criteria for Part I and Part II only:

  • Participants whose tumors have an unmethylated (Part I and Part II) or methylated (Part I only) O6-methylguanine-DNA methyltransferase (MGMT) promotor status based on local assessment
  • Participants (in Part I): Adult participants with newly diagnosed EGFRvIII-positive GBM with unmethylated MGMT promotor status who have completed standard of care therapy with surgical resection and adjuvant radiotherapy with or without concomitant temozolomide. Participants are allowed to have received any number of cycles of temozolomide maintenance. Adult participants with newly diagnosed EGFRvIII-positive GBM with methylated MGMT promotor status who have completed standard of care with surgical resection and adjuvant radiotherapy with concomitant and maintenance temozolomide or discontinued temozolomide maintenance due to reasons other than progressive disease.
  • Participants (in Part II): Adult participants with newly diagnosed EGFRvIII-positive GBM with unmethylated MGMT promotor status who have completed standard of care therapy with surgical resection and adjuvant radiotherapy with or without concomitant temozolomide.

Inclusion criteria for Part III and Part IV A only:

  • Documented first or second recurrence of GBM
  • At least one measurable GBM lesion as per Response Assessment in Neuro-Oncology (RANO) criteria prior to initiation of study treatment.
Exclusion Criteria

Exclusion criteria for all participants:

  • Participants with infratentorial tumors and tumors primarily located in or close to critical structures (e.g., brain stem)
  • Presence of extracranial metastatic or leptomeningeal disease
  • Known hypersensitivity to immunoglobulins or to any other component of the investigational medicinal product formulation
  • Active bleeding or pathological condition that carries a high risk of bleeding, including inherited and acquired coagulopathies
  • Participants unable to undergo an MRI with contrast.

Exclusion criteria for Part I and Part II only:

  • Recurrent malignant gliomas
  • Any prior anti-tumor treatment for GBM: tumor resection, adjuvant radiotherapy with or without concomitant temozolomide and temozolomide maintenance (Part I only) must be the only tumor-directed treatment that the participant has received for GBM.

Exclusion criteria for Part III and Part IV A only:

  • More than two recurrences of GBM
  • Prior anti-EGFRvIII-targeting agents (including vaccines), anti-angiogenic therapy, and/or gene therapy for the treatment of GBM and gliomas.

NETTER-P - A Multicenter Open-label Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With Somatostatin Receptor Positive Gastroenteropancreatic Neuroendocrine (GEP-NET) Tumors, Pheochromocytoma and Paragangliomas (PPGL)

Open

NETTER-P - A Multicenter Open-label Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With Somatostatin Receptor Positive Gastroenteropancreatic Neuroendocrine (GEP-NET) Tumors, Pheochromocytoma and Paragangliomas (PPGL)

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DiagnosisGastroenteropancreatic Neuroendocrine Tumors, Pheochromocytoma, ParagangliomaStudy StatusOpen
PhaseII
Age12 to 17 Years OldRandomisationNO
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationDrug: Lutetium [177Lu] oxodotreotide/dotatate (Other Name: Lutathera) Radiopharmaceutical solution for infusion (7.4 GBq of Lutathera per 30 ml vial)
Last Posted Update2024-06-21
ClinicalTrials.gov #NCT04711135
International Sponsor
Advanced Accelerator Applications
Principal Investigators for Canadian Sites
CHU de Québec – Université Laval – Dr François-Alexandre Buteau
Centres
Medical contact
Raoul Santiago
 
Social worker/patient navigator contact
Isabelle Audet
 
Clinical research contact
Barbara Desbiens
 

 

 

 

Study Description

 

This is a multicenter, open-label, single-arm study to evaluate the safety and dosimetry of Lutathera in adolescent patients 12 to <18 years old with somatostatin receptor positive GEP-NETs and PPGLs. The study will enroll at least 8 patients in the GEP-NET cohort and as many adolescents with PPGL as possible in the exploratory PPGL cohort.

The study schedule for each patient consists of the screening period (up to 2 weeks) followed by the treatment period (4 treatment administrations at 8-week interval), and the follow-up period (5 years).

The treatment period will consist of 4 Lutathera treatments administered at 8-week intervals. Lutathera administration will occur on Week 1 Day 1 of each cycle. Each patient will receive a total of 4 doses of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8 weeks; cumulative dose: 29.6 GBq/800 mCi). An infusion of 2.5% Lysine - Arginine amino acid (AA) solution will be co-administered with each Lutathera dose for renal protection according to the approved Lutathera local prescribing information. An antiemetic will be administered prior to infusion of the AA solution for prevention of infusion-related nausea and vomiting.

The dosimetry and PK assessments will be performed during the first week after the 1st Lutathera dose, i.e. one time during the study treatment period for each patient. The dosimetry analysis will allow for estimation from the 1st Lutathera administration of the cumulative absorbed radiation dose from 4 Lutathera doses and also for taking a decision on the next dose levels. In the exceptional circumstances when dosimetry cannot be performed in a particular patient after the first Lutathera dose, it should be completed as soon as feasible upon a later dose. In order to minimize risk for each study subject, an accelerated analysis of dosimetry and safety data will be performed for each patient in the study, to enable the Investigator to take a decision for the subsequent Lutathera doses. The results of dosimetry assessments (imaging and blood dosimetry) will be provided to the investigators for their evaluation prior to administration of subsequent therapeutic cycles in each patient.

A total follow-up period of 5 years (60 months) after the last Lutathera dose will take place for each patient who received at least one dose of Lutathera. This follow-up period will be comprised of a short-term follow-up of 6 months to evaluate cumulative Lutathera toxicities, followed by a long-term follow up of another 54 months.

Inclusion Criteria
  • GEP-NET cohort: presence of metastasized or locally advanced, inoperable (curative intent), histologically proven, G1 or G2 (Ki-67 index =< 20%), well differentiated GEP-NET.

    or PPGL cohort: presence of metastasized or locally advanced, inoperable (curative intent), histologically proven PPGL.

  • Patients from 12 to < 18 years of age at the time of enrollment.
  • Expression of somatostatin receptors confirmed by a somatostatin receptor imaging (SRI) modality within 3 months prior to enrollment, with tumor uptake Laboratory parameters:observed in the target lesions more or equal to the normal liver uptake.
  • Performance status as determined by Karnofsky score >= 50 or Lansky Play-Performance Scale score >= 50.
  • Parent's ability to understand and the willingness to sign a written informed consent document for adolescents as determined by local regulations. Adolescents will sign assent along with parental/legal guardian consent or will co-sign consent with parent/legal guardian in accordance with local regulation, prior to participation in the study.

Other inclusion and exclusion criteria may apply and will be discussed with you by the study team. 

Exclusion Criteria
  • Laboratory parameters:
    • Estimated creatinine clearance calculated by the Cockroft-Gault method < 70 mL/min
    • Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L; platelets <75x109/L.
    • Total bilirubin >3 x ULN for age.
    • Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
  • Established or suspected pregnancy.
  • Breastfeeding female patients unless they accept to discontinue breastfeeding from the 1st dose until 3 months after the last administration of study drug.
  • Female patients of child-bearing potential, unless they are using highly effective methods of contraception during treatment and for 6 months after the last dose of Lutathera.
  • Sexually active male patients, unless they agree to remain abstinent or be willing to use effective methods of contraception.
  • Patients for whom in the opinion of the investigator other therapeutic options are considered more appropriate than the therapy offered in the study, based on patient and disease characteristics.
  • Current spontaneous urinary incontinence.
  • Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
  • Hypersensitivity to the study drug active substance or to any of the excipients.
  • Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
  • Patient with known incompatibility to CT Scans with I.V. contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded.
  • Patients who received any investigational agent within the last 30 days.

Other inclusion and exclusion criteria may apply and will be discussed with you by the study team. 

BO41932 (TAPISTRY) - Tumor-Agnostic Precision Immunooncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial

Open

BO41932 (TAPISTRY) - Tumor-Agnostic Precision Immunooncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial

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DiagnosisSolid tumors with eligible genetic changeStudy StatusOpen
PhaseII
AgeChild (Under 18 Years)RandomisationNO
Line of treatmentFirst line treatment, Disease relapse or progression
Routes of Treatment AdministrationEntrectinib - oral Atezolizumab - IV Ipatasertib - oral Alectinib - oral Trastuzumab - IV GDC-0077 (Inavolisib) - oral Belvarafenib - oral Pralsetinib - oral
Last Posted Update2024-06-11
ClinicalTrials.gov #NCT04589845
International Sponsor
Hoffmann-La Roche
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

TAPISTRY is a Phase II, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in rational, specified combinations in participants with unresectable, locally advanced or metastatic solid tumors determined to harbor specific oncogenic genomic alterations or who are tumor mutational burden (TMB)-high as identified by a validated next-generation sequencing (NGS) assay.

Participants with solid tumors will be treated with a drug or drug regimen tailored to their NGS assay results at screening.

Participants will be assigned to the appropriate cohort based on their genetic alteration(s). Treatment will be assigned on the basis of relevant oncogenotype, will have cohort-specific inclusion/exclusion criteria, and, unless otherwise specified, will continue until disease progression, loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first.

Cohort A: ROS1 fusion-positive tumors - Closed to Accrual

Participants with metastatic or advanced solid tumors, with the exception of NSCLC will receive entrectinib once daily in repeated 28-day cycles at a dose of 600 milligram per day (mg/day) for pediatric participants with a body surface area (BSA) >/= 1.51 m2

Cohort B: Cohort B: NTRK1/2/3 fusion-positive tumors - Open

Participants with metastatic or advanced solid tumors will receive entrectinib once daily in repeated 28-day cycles at a dose of 600 mg/day for adults and pediatric participants with a BSA >/= 1.51 m2

Cohort C: ALK fusion-positive tumors (excluding NSCLC) - Closed to Accrual

Participants with metastatic or advanced solid tumors, with the exception of NSCLC, will receive alectinib at a dosage of 600 mg orally twice a day (BID), taken with food, in repeated 28-day cycles.

Cohort D: TMB-high tumors - Closed to Accrual

Participants with metastatic or advanced solid tumors will receive atezolizumab intravenously (IV) at a dose of 15 mg/kg (maximum 1200 mg) for participants aged < 18 years on Day 1 of each 21-day cycle.

Cohort E: AKT1/2/3 mutant-positive tumors - Closed to Accrual

Participants with metastatic or advanced solid tumors will receive ipatasertib orally once daily (QD). For participants 12-17 years of age, ipatasertib will be administered at the starting dose of 200 mg for participants <35 kg, 300 mg for participants >/= 35 and <45 kg, 400 mg for those >/=45 kg orally QD in repeated 28-day cycles until the participant experiences disease progression, intolerable toxicity, or withdraws consent.

Cohort F: HER2 mutant-positive tumors - Closed to Accrual

Participants with metastatic or advanced solid tumors will receive trastuzumab emtansine IV at a dose of 3.6 mg/kg every 21 days. This dosage and administration method also applies for pediatric participants 12-17 years of age.

Cohort H: PIK3CA multiple mutant-positive tumors - Closed to Accrual

Participants with metastatic or advanced solid tumors will receive GDC-0077 daily at a starting dose of 9 mg by mouth (PO) in repeated 28-day cycles. This dosage and administration method also applies for pediatric participants 12-17 years of age.

Cohort I: BRAF class II mutant or fusion-positive tumors - Closed to Accrual

Participants with BRAF class II mutant/fusion-positive tumors (adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib by mouth (PO) BID (twice a day) with adequate water (more than 200 mL). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle.

Cohort J: BRAF class III mutant-positive tumors - Closed to Accrual

Participants with BRAF class III mutant-positive tumors (adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib by mouth (PO) BID (twice a day) with adequate water (more than 200 mL). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle.

Cohort K: RET fusion-positive tumors - Closed to Accrual

Participants with RET fusion-positive tumors will self-administer Pralsetinib orally at home (except on clinic days) on a continuous daily dosing regimen at a dose of 400 mg/day (four 100-mg capsules per day) for adult and pediatric patients ≥ 12 and < 18 years of age. A treatment cycle consists of 4 weeks (28 days).

Inclusion Criteria
  • In addition to the general inclusion criteria below, participants must meet all of the cohort-specific inclusion criteria for the respective cohort
  • Briefly - for arm A, a ROS1 fusion is required; for arm B, a NTRK1/2/3 fusion is required; for arm D, a TMB >16mut/Mb is required; for arm E: specific mutations in the AKT gene are required; for arm F: specific mutations in the HER2 gene are required; for arm H, specific mutations in the PIK3CA gene are required; for arm I, a BRAF Class II mutation or fusion is required; for arm J, a BRAF Class III mutation is required; for Cohort K; a RET fusion is required. 
  • Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)
  • Performance status as follows: Participants aged >= 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Participantss aged 16 to < 18 years: Karnofsky score >= 50%; Participants aged < 16 years: Lansky score >= 50%
  • For participants aged >= 18 and <18 years: adequate hematologic and end-organ function
  • Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
  • Adequate recovery from most recent systemic or local treatment for cancer
  • Life expectancy >= 8 weeks
  • Ability to comply with the study protocol, in the investigator's judgment
  • For female participants of childbearing potential: Negative serum pregnancy test <= 14 days prior to initiating study treatment; agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period
  • For male participants: Willingness to remain abstinent or use acceptable methods of contraception as defined in the cohort-specific inclusion criteria
Exclusion Criteria
  • Current participation or enrollment in another therapeutic clinical trial
  • Any anticancer treatment within 2 weeks or 5 half-lives prior to start of study treatment
  • Whole brain radiotherapy within 14 days prior to start of study treatment
  • Stereotactic radiosurgery within 7 days prior to start of study treatment
  • Pregnant or breastfeeding, or intending to become pregnant during the study
  • History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study or confounds the ability to interpret data from the study
  • Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or higher), myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina
  • History of another active cancer within 5 years prior to screening that may interfere with the determination of safety or efficacy of study treatment with respect to the qualifying solid tumor malignancy
  • In addition to the general exclusion criteria above, in order to be enrolled in a treatment cohort of the study, participants must not meet any of the cohort-specific exclusion criteria

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

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

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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 Update2024-06-03
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. Patients with a diagnosis of ependymoma may enroll with prior Sponsor approval.
    • Refractory is defined as:
      • Lack of response (stable disease) or disease progression while on therapy
      • Disease progression within 3 months of cessation of therapy
  • 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 for one week prior to enrollment and be able to complete all study related procedures
  • If patient receives steroids for neurological symptom control, the dose must be stable (unchanged for one week prior to enrollment) 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
     

LOGGIC/FIREFLY-2 - LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy

Open

LOGGIC/FIREFLY-2 - LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy

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DiagnosisLow-grade GliomaStudy StatusOpen
PhaseIII
Ageup to 25 YearsRandomisationYES
Line of treatmentFirst line treatment
Routes of Treatment AdministrationExperimental: Arm #1 - Tovorafenib (DAY101), oral
Last Posted Update2024-05-31
ClinicalTrials.gov #NCT05566795
International Sponsor
Sponsor:
Day One Biopharmaceuticals, Inc.

Collaborator:
SIOPe Brain Tumor Group LOGGIC Consortium
Principal Investigators for Canadian Sites
The Hospital for Sick Children
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

This is a 2-arm, randomized, open-label, multicenter, global, Phase 3 trial to evaluate the efficacy, safety, and tolerability of tovorafenib monotherapy versus standard of care (SoC) chemotherapy in patients with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring front-line systemic therapy.

Approximately 400 treatment-naïve low-grade glioma patients will be randomized 1:1 to either tovorafenib (Arm 1) or an Investigator's choice of SoC chemotherapy (Arm 2).

Arm 1 (tovorafenib): treatment cycles will repeat every 28 days in the absence of disease progression. Patients will continue tovorafenib until any of the following occurs: disease progression based on Response Assessment in Neuro-Oncology (RANO-LGG) criteria, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Arm 2 (Investigator's Choice of SoC Chemotherapy): patients will receive one of 3 SoC chemotherapy options selected by the treating Investigator: Children's Oncology Group - Vincristine/Carboplatin (COG-V/C) regimen, International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C) regimen, or vinblastine (VBL) regimen. The choice of SoC chemotherapy regimen will be selected prior to patient randomization. Treatment will continue until completion of therapy or until any of the following occurs: disease progression based on RANO-LGG criteria, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Patients who discontinue treatment due to disease progression will have (1) radiographic evidence of progressive disease based on RANO-LGG, as determined by the Investigator and confirmed by the IRC, or (2) clinical progression based on RANO-LGG criteria determined by the Investigator. Investigators are encouraged to discuss cases of clinical progression and early radiographic progression without clinical symptom with the Sponsor Medical Monitor prior to treatment discontinuation or initiation of a different form of treatment for the malignancy. Patients may continue therapy beyond progressive disease

Inclusion Criteria
  • Less than 25 years of age with LGG with known activating RAF alteration
  • Histopathologic diagnosis of glioma or glioneuronal tumor
  • At least one measurable lesion as defined by RANO criteria
  • Meet indication for first-line systemic therapy
Exclusion Criteria
  • Patient has any of the following tumor-histological findings:

    1. Schwannoma
    2. Subependymal giant cell astrocytoma (Tuberous Sclerosis)
    3. Diffuse intrinsic pontine glioma, even if histologically diagnosed as World Health Organization (WHO) Grade I-II
  • Patient's tumor has additional pathogenic molecular alterations
  • Known or suspected diagnosis of neurofibromatosis Type 1 or 2 (NF-1/NF-2)
  • Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/intravenous targeted therapy) including radiation

APAL2020D - A Randomized Phase 3 Trial of Fludarabine/Cytarabine/Gemtuzumab Ozogamicin With or Without Venetoclax in Children With Relapsed AML

Open

APAL2020D - A Randomized Phase 3 Trial of Fludarabine/Cytarabine/Gemtuzumab Ozogamicin With or Without Venetoclax in Children With Relapsed AML

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DiagnosisAcute Myeloid LeukemiaStudy StatusOpen
PhaseIII
Age29 Days to 21 YearsRandomisationYES
Line of treatmentDisease relapse or progression
Routes of Treatment AdministrationDrug: Fludarabine - Intravenous (IV) infusion Drug: Cytarabine - Intravenous (IV) infusion Drug: Gemtuzumab Ozogamicin - Intravenous (IV) infusion Drug: Azacitidine - Intravenous (IV) infusion or subcutaneous injection Experimental Arm Drug: Venetoclax - Orally via tablet or powder suspension
Last Posted Update2024-05-10
ClinicalTrials.gov #NCT05183035
International Sponsor
LLS PedAL Initiative, LLC
Principal Investigators for Canadian Sites
BC Children's Hospital
CancerCare Manitoba
IWK Health Center
Children's Hospital of Eastern Ontario (CHEO)
SickKids - 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

 

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. Craig Erker
Dr. Conrad Fernandez 
Dr. Ketan Kulkarni 
 
Social worker/patient navigator contact
Rhonda Brophy
 
Clinical research contact
Tina Bocking
 
Medical contact
Dr. Donna Johnston
 
Dr. Lesleigh Abbott
 
Dr. Nirav Thacker
 
Social worker/patient navigator contact
Sherley Telisma
 
Clinical research contact
Isabelle Laforest
 

 

 

Study Description

Relapse of AML is driven by chemotherapy resistant stem cells. One mechanism of chemotherapeutic resistance in AML is the overexpression of the protein B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein which sequesters intracellular activators of apoptosis. Venetoclax is a selective, potent, orally bioavailable, small molecule inhibitor of B-cell lymphoma (BCL)-2 that restores programmed cell death in cancer cells.

This is a trial for children, adolescents and young adults with 2nd relapsed AML or 1st relapsed AML unable to receive additional anthracycline.

This is randomized trial of venetoclax in combination with intensive chemotherapy (fludarabine/cytarabine/gemtuzumab ozogamicin) for the first two cycles that would inform and evaluate if this agent is an effective option for this population to improve its poor prognosis. Participants can receive up to two cycles of induction chemotherapy before hematopoietic stem cell transplantation (HSCT). Participants benefiting from treatment and who are not able to proceed to HSCT have the possibility to continue to receive azacitidine in monotherapy (Arm A, control arm) or in combination with venetoclax (Arm B, experimental arm).

Inclusion Criteria
  • Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/LLS territory).
  • Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
  • Participants must have one of the following:
    • Children, adolescents, and young adults with acute myeloid leukemia without FLT3/internal tandem duplication (ITD) mutation in:
      • Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
      • First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy.
  • Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score)
  • Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
    • Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
    • Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
    • Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
    • Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
    • Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
    • Radiation therapy (RT) (before start of protocol treatment):
      • ≥ 14 days have elapsed for local palliative RT (small port);
      • ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis;
      • ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
    • Stem Cell Infusions (before start of protocol treatment):
      • ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation [TBI]) or boost infusion (any stem cell product; not including donor lymphocyte infusion [DLI])
      • No evidence of active graft versus host disease (GVHD).
    • Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment
    • Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.) before start of protocol treatment.
    • Participants with prior exposure to venetoclax are eligible in this trial
  • Adequate organ function:
    • Adequate Renal Function defined as:
      • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m^2, or
      • Normal serum creatinine based on age/sex
    • Adequate Liver Function defined as:
      • Direct bilirubin < 1.5 x upper limit of normal (ULN), and
      • Alkaline phosphatase ≤ 2.5 x ULN, and
      • Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
    • Cardiac performance: Minimum cardiac function defined as:
      • No history of congestive heart failure in need of medical treatment
      • No pre-treatment diminished left ventricular function on echocardiography (shortening fraction [SF] < 25% or ejection fraction [EF] < 40%)
      • No signs of congestive heart failure at presentation of relapse.
  • Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation.
Exclusion Criteria
  • Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible.
  • Participants with Down syndrome.
  • Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML).
  • Participants with isolated CNS3 disease or symptomatic CNS3 disease.
  • Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax.
  • Participants who are currently receiving another investigational drug (GO is not considered investigational in this study).
  • Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome.
  • Participants with known prior allergy to any of the medications used in protocol therapy.
  • Participants with documented active, uncontrolled infection at the time of study entry.
  • No known human immunodeficiency virus (HIV) infection.
  • Post menarchal female participants with positive pregnancy test.
  • Concomitant Medications
    • Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment.
    • Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment.
    • Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC).
  • Pregnancy or Breast-Feeding:
    • Participants who are pregnant or breast-feeding.
    • Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy.
    • Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy.

Additional criteria to receive a gemtuzumab ozogamicin infusion:

Gemtuzumab ozogamicin should not be given:

  • to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4
  • to participants with history of VOD/SOS grade 3
  • to participants with CD33 negative leukemic blasts (determined at local lab)

Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.