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

  • End date
    May 16, 2024
  • participants needed
  • sponsor
    Hoffmann-La Roche
Updated on 17 October 2022
bone marrow procedure
solid tumour
solid tumor
bone marrow disease


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 Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Neuroblastoma, Solid Tumors
Treatment cyclophosphamide, Topotecan, cytarabine, Fludarabine, venetoclax, Idasanutlin, Intrathecal Chemotherapy
Clinical Study IdentifierNCT04029688
SponsorHoffmann-La Roche
Last Modified on17 October 2022


Yes No Not Sure

Inclusion Criteria

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
The participants ages are < 18 for part 1a, < 30 for Parts 1b. 2 and 3
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 end-organ function, as defined in the protocol
Adequate performance status: Participants <16 years of age: Lansky greater than or equal to (≥)50%; Patients ≥16 years of age: Karnofsky ≥50%
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
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 end-organ function, as defined in the protocol
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

Exclusion Criteria

Primary Central Nervous System (CNS) tumors
Symptomatic CNS metastases that result in a neurologically unstable clinical state or require increasing doses of corticosteroids or local CNS-directed therapy to control the CNS disease
CNS3 leukemia
Acute promyelocytic leukemia
White blood cell count >50 × 10^9 cells/Liter (L)
Down syndrome, Li-Fraumeni syndrome, history of severe aplastic anemia, or any known bone marrow failure predisposition syndrome
Burkitt-type acute lymphoblastic leukemia
T-cell lymphoblastic leukemia
Prior treatment with a MDM2 antagonist
Prior treatment with venetoclax (if potential for enrollment in a venetoclax arm)
Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the participant
Any uncontrolled medical condition or other identified abnormality that precludes the patient's safe participation in and completion of the study
Systemic anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to initiation of study treatment
Treatment with monoclonal antibodies, antibody drug conjugates, or cellular therapy for anti-neoplastic intent within 30 days prior to initiation of study treatment
I-131 meta-iodobenzylguanidine (MIBG) therapy within 6 weeks prior to initiation of study treatment
Myeloablative therapy with autologous or allogeneic hematopoietic stem cell rescue within 100 days of study treatment initiation
Immunosuppressive therapy for treatment of graft-versus-host disease within 2 weeks of study treatment initiation
Radiotherapy within 3 weeks prior to study treatment initiation
Specific restrictions are applicable for patients treated with drugs interacting with CYP2C8, CYP3A4, OATP1B1/B3, and P-gp
Received anti-coagulant or anti-platelet agent within 7 days or 5 half-lives prior to study treatment initiation
Underwent major surgical procedure within 21 days of study treatment initiation, or anticipate need for major surgical procedure during the course of the study
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