A 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.
- Conditions
- Relapsed/refractory acute leukemias (AL) and solid tumors.MedDRA version: 21.0Level: LLTClassification code 10000835Term: Acute leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004579-11-NL
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 183
- Age < 18 years for Part 1a; < 30 years for Parts 1b, 2, and 3
- Study Part 1a (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 1b (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: Patients < 16 years of age: Lansky >= 50%; Patients >= 16 years of age: Karnofsky >= 50%
- Adequate end-organ function
- 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 Patients with Solid Tumors (including Neuroblastoma)
- At least one evaluable or measurable radiological site of disease as defined by standard criteria for the patient’s tumor type, or measurable bone marrow disease by morphology
- Adequate hematologic end-organ function
- 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 183
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 17
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
- 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/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
- Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the patient
- 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 & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method