Acute Myeloid Leukemia Clinical Trial

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

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.

View Eligibility Criteria

Eligibility Criteria

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 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 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 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

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

183

Study ID:

NCT04029688

Recruitment Status:

Recruiting

Sponsor:

Hoffmann-La Roche

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There are 19 Locations for this study

See Locations Near You

Phoenix Children's Hospital
Phoenix Arizona, 85016, United States
Arkansas Children's Hospital Research Institute
Little Rock Arkansas, 72202, United States
Lucile Packard Children's Hospital at Stanford University; Thoracic Oncology
Palo Alto California, 94304, United States
Arnold Palmer Hosp-Children
Orlando Florida, 32806, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States
Penn State Hershey Children's Hospital
Hershey Pennsylvania, 17033, United States
The University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States
University of Texas Health Science Center at San Antonio
San Antonio Texas, 78229, United States
Huntsman Cancer Institute at The University of Utah
Salt Lake City Utah, 84112, United States
Alberta Children'S Hospital
Calgary Alberta, T3B 6, Canada
Centre Leon Berard
Lyon CEDEX 08 , 69373, France
Institut Curie
Paris , 75005, France
CHU de Brabois
Vandoeuvre Les Nancy , 54511, France
Gustave Roussy
Villejuif CEDEX , 94800, France
Hospital Sant Joan De Deu
Esplugues De Llobregas Barcelona, 08950, Spain
Hospital Infantil Universitario Nino Jesus
Madrid , 28009, Spain
Birmingham Children's Hospital
Birmingham , B4 6N, United Kingdom
The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit
Newcastle Upon Tyne , NE1 4, United Kingdom
Royal Marsden Hospital; Pediatric Unit
Surrey , SM2 5, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

183

Study ID:

NCT04029688

Recruitment Status:

Recruiting

Sponsor:


Hoffmann-La Roche

How clear is this clinincal trial information?

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