This is a Phase I/II, multicenter, open-label, multi-arm study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of idasanutlin, administered as a single agent or in combination with chemotherapy or venetoclax, in pediatric and young adult participants with acute leukemias or solid tumors.
This study is divided into three parts: Part 1 will begin with dose escalation of idasanutlin as a single agent in pediatric participants with relapsed or refractory solid tumors to identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and to characterize dose-limiting toxicities (DLTs). Following MTD/MAD identification, three separate safety run-in cohorts in neuroblastoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) will be conducted to identify the recommended Phase 2 dose (RP2D) of idasanutlin in each combination, with chemotherapy or venetoclax. Part 2 will evaluate the safety and early efficacy of idasanutlin in combination with chemotherapy or venetoclax in newly enrolled pediatric and young adult participants in neuroblastoma, AML,and ALL cohorts at idasanutlin RP2D. Part 3 will potentially be conducted as an additional expansion phase of the idasanutlin combination cohorts in neuroblastoma, AML, or ALL for further response and safety assessment.
Condition or disease | Intervention/treatment | Phase |
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Acute Myeloid Leukemia (AML) Acute Lymphoblastic Leukemia (ALL) Neuroblastoma Solid Tumors | Drug: Idasanutlin Drug: Venetoclax Drug: Cyclophosphamide Drug: Topotecan Drug: Fludarabine Drug: Cytarabine Drug: Intrathecal Chemotherapy | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 183 participants |
Allocation: | Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I/II, Multicenter, Open-Label, Multi-Arm Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemias or Solid Tumors |
Actual Study Start Date : | January 27, 2020 |
Estimated Primary Completion Date : | May 16, 2024 |
Estimated Study Completion Date : | May 16, 2024 |
Arm | Intervention/treatment |
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Experimental: Dose Escalation: Solid Tumors: Idasanutlin Single Agent |
Drug: Idasanutlin
Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.
Other Name: RG7388
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Experimental: Neuroblastoma: Idasanutlin + Venetoclax |
Drug: Idasanutlin
Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.
Other Name: RG7388
Drug: Venetoclax Venetoclax will be administered orally at the adult dose equivalent (adjusted by body weight) of 400 milligrams (mg) in participants with neuroblastoma and the adult dose equivalent of 600 mg in participants with leukemia.
Other Names:
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Experimental: Neuroblastoma: Idasanutlin + Cyclophosphamide + Topotecan |
Drug: Idasanutlin
Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.
Other Name: RG7388
Drug: Cyclophosphamide Cyclophosphamide will be administered once daily on Days 1-5 of each 28-day cycle at 250 milligrams per meter squared of body surface area (mg/m^2) as an intravenous (IV) infusion.
Drug: Topotecan Topotecan will be administered once daily on Days 1-5 of each 28-day cycle at 0.75 mg/m^2 as an IV infusion.
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Experimental: AML: Idasanutlin + Venetoclax |
Drug: Idasanutlin
Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.
Other Name: RG7388
Drug: Venetoclax Venetoclax will be administered orally at the adult dose equivalent (adjusted by body weight) of 400 milligrams (mg) in participants with neuroblastoma and the adult dose equivalent of 600 mg in participants with leukemia.
Other Names:
Drug: Intrathecal Chemotherapy All participants with leukemia, irrespective of arm, will receive intrathecal chemotherapy on Day 1 of each 28-day treatment cycle. Intrathecal chemotherapy will consist of either single-agent cytarabine or methotrexate, or a combination of methotrexate, cytarabine, and hydrocortisone, at appropriate age-based dosing as specified in the protocol.
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Experimental: AML: Idasanutlin + Fludarabine + Cytarabine |
Drug: Idasanutlin
Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.
Other Name: RG7388
Drug: Fludarabine Fludarabine will be administered once daily on Days 1-5 of each 28-day treatment cycle at 30 mg/m^2 as an IV infusion.
Drug: Cytarabine Cytarabine will be administered once daily on Days 1-5 of each 28-day treatment cycle at 2000 mg/m^2 as an IV infusion.
Drug: Intrathecal Chemotherapy All participants with leukemia, irrespective of arm, will receive intrathecal chemotherapy on Day 1 of each 28-day treatment cycle. Intrathecal chemotherapy will consist of either single-agent cytarabine or methotrexate, or a combination of methotrexate, cytarabine, and hydrocortisone, at appropriate age-based dosing as specified in the protocol.
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Experimental: ALL: Idasanutlin + Venetoclax |
Drug: Idasanutlin
Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.
Other Name: RG7388
Drug: Venetoclax Venetoclax will be administered orally at the adult dose equivalent (adjusted by body weight) of 400 milligrams (mg) in participants with neuroblastoma and the adult dose equivalent of 600 mg in participants with leukemia.
Other Names:
Drug: Intrathecal Chemotherapy All participants with leukemia, irrespective of arm, will receive intrathecal chemotherapy on Day 1 of each 28-day treatment cycle. Intrathecal chemotherapy will consist of either single-agent cytarabine or methotrexate, or a combination of methotrexate, cytarabine, and hydrocortisone, at appropriate age-based dosing as specified in the protocol.
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Ages Eligible for Study: | up to 30 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Additional Inclusion Criteria for Participants with Solid Tumors (including Neuroblastoma)
Additional Inclusion Criteria for Patients with Leukemia
Exclusion Criteria:
Contact: Reference Study ID Number: GO40871 www.roche.com/about_roche/roche_worldwide.htm | 888-662-6728 (U.S. Only) | global-roche-genentech-trials@gene.com |
Study Director: | Clinical Trials | Hoffmann-La Roche |
Tracking Information | |||||
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First Submitted Date ICMJE | July 19, 2019 | ||||
First Posted Date ICMJE | July 23, 2019 | ||||
Last Update Posted Date | June 2, 2021 | ||||
Actual Study Start Date ICMJE | January 27, 2020 | ||||
Estimated Primary Completion Date | May 16, 2024 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | A Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias or Solid Tumors | ||||
Official Title ICMJE | A Phase I/II, Multicenter, Open-Label, Multi-Arm Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemias or Solid Tumors | ||||
Brief Summary |
This is a Phase I/II, multicenter, open-label, multi-arm study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of idasanutlin, administered as a single agent or in combination with chemotherapy or venetoclax, in pediatric and young adult participants with acute leukemias or solid tumors. This study is divided into three parts: Part 1 will begin with dose escalation of idasanutlin as a single agent in pediatric participants with relapsed or refractory solid tumors to identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and to characterize dose-limiting toxicities (DLTs). Following MTD/MAD identification, three separate safety run-in cohorts in neuroblastoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) will be conducted to identify the recommended Phase 2 dose (RP2D) of idasanutlin in each combination, with chemotherapy or venetoclax. Part 2 will evaluate the safety and early efficacy of idasanutlin in combination with chemotherapy or venetoclax in newly enrolled pediatric and young adult participants in neuroblastoma, AML,and ALL cohorts at idasanutlin RP2D. Part 3 will potentially be conducted as an additional expansion phase of the idasanutlin combination cohorts in neuroblastoma, AML, or ALL for further response and safety assessment. |
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Detailed Description | Not Provided | ||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
183 | ||||
Original Estimated Enrollment ICMJE |
220 | ||||
Estimated Study Completion Date ICMJE | May 16, 2024 | ||||
Estimated Primary Completion Date | May 16, 2024 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Additional Inclusion Criteria for Participants with Solid Tumors (including Neuroblastoma)
Additional Inclusion Criteria for Patients with Leukemia
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | up to 30 Years (Child, Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Canada, France, Netherlands, Spain, United Kingdom, United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT04029688 | ||||
Other Study ID Numbers ICMJE | GO40871 2018-004579-11 ( EudraCT Number ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Hoffmann-La Roche | ||||
Study Sponsor ICMJE | Hoffmann-La Roche | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | Hoffmann-La Roche | ||||
Verification Date | May 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |