TerminatedPhase 1/2

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

Stopped: Study was terminated by the sponsor based on insufficient tolerability and efficacy to proceed beyond Part 1b.

United States38 participantsStarted 2020-01-27

Plain-language 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.

Who can participate

Age range0 Years – 30 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * The participants ages are \< 18 for part 1a, \< 30 for Parts 1b. 2 and 3 * 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 end-organ function, as defined in the protocol * 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 co…

What they're measuring

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)

Timeframe: From screening up to 30 days after study treatment discontinuation (approximately 7 months)

Parts 1a and 1b: Number of Participants With Dose-Limiting Toxicities (DLTs)

Timeframe: Cycle 1 (one cycle is 28 days)

Part 1b: Objective Response Rate (ORR) in Participants With TP53 Wild-Type (WT) Neuroblastoma Assessed According to International Neuroblastoma Response Criteria (INRC)

Timeframe: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

Parts 2 and 3: ORR in Participants With TP53 WT Neuroblastoma Assessed According to INRC

Timeframe: Up to approximately 29 months

Parts 2 and 3: Complete Remission Rate (CRR) in Participants With TP53 WT Leukemia

Timeframe: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)

Parts 2 and 3: Minimal Residual Disease (MRD) - Negative Rate in Participants With ALL

Timeframe: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)

Trial details

NCT IDNCT04029688

SponsorHoffmann-La Roche

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2024-05-06

Results submitted2024-11-04

View on ClinicalTrials.gov More Acute Myeloid Leukemia (AML) trials

Plain-language summary

Who can participate

Age range0 Years – 30 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Timeframe: From screening up to 30 days after study treatment discontinuation (approximately 7 months)

Parts 1a and 1b: Number of Participants With Dose-Limiting Toxicities (DLTs)

Timeframe: Cycle 1 (one cycle is 28 days)

Part 1b: Objective Response Rate (ORR) in Participants With TP53 Wild-Type (WT) Neuroblastoma Assessed According to International Neuroblastoma Response Criteria (INRC)

Timeframe: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

Parts 2 and 3: ORR in Participants With TP53 WT Neuroblastoma Assessed According to INRC

Timeframe: Up to approximately 29 months

Parts 2 and 3: Complete Remission Rate (CRR) in Participants With TP53 WT Leukemia

Timeframe: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)

Parts 2 and 3: Minimal Residual Disease (MRD) - Negative Rate in Participants With ALL

Timeframe: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)