A Study Evaluating the Safety, Tolerability, Pharmacokinetics and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in Treatment of Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias or Solid Tumors

Part of paid clinical trials in Little Rock, Arkansas.

Sponsor
Hoffmann-La Roche
Study ID
NCT04029688
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

  • Acute Lymphoblastic Leukemia (ALL)
  • Acute Myeloid Leukemia (AML)
  • Neuroblastoma
  • Solid Tumors

Eligibility Criteria

Sex
ALL
Age
0 Years - 30 Years
Healthy Volunteers
Not accepted

Interventions

  • Idasanutlin — DRUG
    Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.
  • Venetoclax — DRUG
    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.
  • Cyclophosphamide — DRUG
    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.
  • Topotecan — DRUG
    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.
  • Fludarabine — DRUG
    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.
  • Cytarabine — DRUG
    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.
  • Intrathecal Chemotherapy — DRUG
    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.

Study Details

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 Dates

Start date
Jan 27, 2020
Status verified
Dec 2024
Primary completion
May 6, 2024
Completion
May 6, 2024

Study Design

Enrollment
38 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose Escalation: Solid Tumors: Idasanutlin Single Agent
  • Experimental: Neuroblastoma: Idasanutlin + Venetoclax
  • Experimental: Neuroblastoma: Idasanutlin + Cyclophosphamide + Topotecan
  • Experimental: AML: Idasanutlin + Venetoclax
  • Experimental: AML: Idasanutlin + Fludarabine + Cytarabine
  • Experimental: ALL: Idasanutlin + Venetoclax

Primary Outcome Measure

Part 1a and 1b: Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0) [ Time Frame: From screening up to 30 days after study treatment discontinuation (approximately 7 months) ]

Locations (5)

FacilityCityStateZIPSite coordinators
Arkansas Children's Hospital Research InstituteLittle RockArkansas72202-
Lucile Packard Children's Hospital at Stanford University; Thoracic OncologyPalo AltoCalifornia94304-
Arnold Palmer Hosp-ChildrenOrlandoFlorida32806-
Memorial Sloan Kettering Cancer CenterNew YorkNew York10065-
University of Texas Health Science Center at San AntonioSan AntonioTexas78229-

Find similar trials in Little Rock, AR

By condition
Neuroblastoma
By specialty
OncologyPediatric oncology
By research site
Arkansas Children's Hospital Research Institute· Little Rock, ARLucile Packard Children's Hospital at Stanford University; Thoracic Oncology· Palo Alto, CAArnold Palmer Hosp-Children· Orlando, FLMemorial Sloan Kettering Cancer Center· New York, NYUniversity of Texas Health Science Center at San Antonio· San Antonio, TX

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