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Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric/Young Adult Participants With Relapsed/Refractory Acute Leukemias or Solid Tumors

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

  • Clinical Trial Information

    Trial Contact: El-Shami, Jessica; Leffin, Melissa; Spinelli, Jennifer; Cevallos, Claudia

  • IRB No: 19.244.09

    Protocol Abbrev: GO40871

    Principal Investigator: Amy A Smith, MD

    Phase: Drug: Phase I

    Age Group: Pediatric

    Secondary Protocol No: GO40871

    Treatment: Drug: Idasanutlin Drug: Venetoclax Drug: Cyclophosphamide Drug: Topotecan Drug: Fludarabine Drug: Cytarabine Drug: Intrathecal Chemotherapy

    Therapies Involved: Medication

    ClinicalTrials.gov ID: NCT04029688

  • Objective

    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.

  • Key Eligibility

    •  Study Part 1 (single-agent therapy dose escalation): histologically confirmed diagnosis of neuroblastoma or other solid tumor that has progressed or recurred despite standard therapy, and for which there is no therapy proven to prolong survival with an acceptable quality of life
    •  Study Part 1 (combination safety run-in), Study Part 2 (initial expansion), and Study Part 3 (additional expansion): histologically confirmed diagnosis of neuroblastoma, AML, or precursor-B ALL that has progressed or recurred despite, or is refractory to, standard therapy
    •  Adequate performance status: Participants <16 years of age: Lansky greater than or equal to (≥)50%; Patients ≥16 years of age: Karnofsky ≥50%
    •  Adequate hematologic and end-organ function
    •  Able to swallow tablets or liquid
    •  For females of childbearing potential: agreement to remain abstinent, use contraception, agreement to refrain from donating eggs. Females must remain abstinent or use two methods of contraception with a failure rate of <1% per year during the treatment and follow-up period (variable depending on the combination agent) or in accordance with national prescribing information guidance regarding abstinence, contraception
    •  For males: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, with a female partner of childbearing potential or pregnant female partner, males must remain abstinent or use a condom during the treatment period and for follow-up period (variable, depending on the combination agent) or in accordance with national prescribing information guidance regarding abstinence, contraception

    Additional Inclusion Criteria for Participants with Solid Tumors (including Neuroblastoma)
    •  At least one evaluable or measurable radiological site of disease as defined by standard criteria for the participant's tumor type, or measurable bone marrow disease by morphology
    •  Adequate hematologic function
    •  Tumor tissue from relapsed disease

    Additional Inclusion Criteria for Patients with Leukemia
    •  Bone marrow with ≥5% lymphoblasts by morphologic assessment at screening
    •  Available bone marrow aspirate or biopsy from screening