NCT04029688

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

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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 38 (actual)
• Sponsor: Hoffmann-La Roche · Industry
• Sex: All
• Age: 0 Years – 30 Years
• Healthy volunteers: Not accepted

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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Idasanutlin	Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.
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.
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.
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.

Timeline

• Start date: 2020-01-27
• Primary completion: 2024-05-06
• Completion: 2024-05-06
• First posted: 2019-07-23
• Last updated: 2024-12-20
• Results posted: 2024-12-20

Locations

14 sites across 6 countries: United States, Canada, France, Netherlands, Spain, United Kingdom

Regulatory

• FDA-regulated drug study