Relapsed/refractory acute leukemias (AL) and solid tumors. MedDRA version: 21.0 Level: LLT Classification code 10000835 Term: Acute leukemia System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: idasanutlin
Product Code: RO5503781/F26
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: idasanutlin
CAS Number: 1229705-06-9
Current Sponsor code: RO5503781, RO5503781-000
O
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 50%; Patients >= 16 years of age: Karnofsky >= 50% - Adequate end-organ function - Able to swallow tablets or liquid - 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 = 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: 200 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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/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, and 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the safety and tolerability of idasanutlin as a single agent, in combination with chemotherapy, and in combination with venetoclax and to determine the maximum tolerated dose/ maximum administered dose of idasanutlin administered as a single agent; and to define the recommended Phase II doses of idasanutlin in combination with either chemotherapy or venetoclax • To evaluate the anti-cancer activity of idasanutlin in combination with chemotherapy or venetoclax for Neuroblastoma and Leukemia.;Secondary Objective: • To characterize the pharmacokinetic (PK) profile of idasanutlin as a single agent and in combination with chemotherapy or venetoclax on basis of plasma concentration of idasanutlin when administered as a single agent, and in combination with chemotherapy or venetoclax at specified timepoints • To characterize the PK profile of venetoclax in combination with idasanutlin on basis of plasma concentration of venetoclax at specified timepoints • To evaluate the anti-cancer activity of idasanutlin as single agent, in combination with chemotherapy, and in combination with venetoclax. ;Primary end point(s): Safety 1. Incidence and severity of adverse events with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 2. Changes from baseline in physical findings 3. Changes from baseline in targeted clinical laboratory test results and ECG parameters 4. Incidence of DLTs assessed during the first cycle of study treatment of single-agent idasanutlin and again with idasanutlin in combination with chemotherapy or venetoclax. Efficacy 5. Objective response rate (Neuroblastoma) 6. Complete remission rate (Leukemias) 7. For patients with ALL: MRD-negative rate.;Timepoint(s) of evaluation of this end point: 1. Up to 30 days after the last dose of study treatment 2-3. Baseline (Day-28 to-1) to study discontinuation 4. 28 days (one cycle duration) 5-7. Up to study d | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetics 1. Area under the concentration-time curve (AUC) of idasanutlin, 2. Maximum concentration (Cmax) of idasanutlin 3. Minimum concentration (Cmin) of idasanutlin 4. Total clearance (Cl)of idasanutlin 5. Volume of distribution at steady-state (Vss) of idasanutlin 6. terminal half-life (t1/2 ) of idasanutlin 7. Plasma concentration of venetoclax at specified timepoints Efficacy Neuroblastoma: 8. Clinical benefit rate 9. Duration of objective response 10. Progression-free survival 11. Overall survival 12. Objective response rate Leukemia(s): 13. Number of patients receiving transplant after study treatment 14. Event-free survival 15. Complete remission rate 16. For patients with AML: MRD-negative rate.;Timepoint(s) of evaluation of this end point: 1-6. Day 1, 2, 5, 8,15, 22 of Cycle 1; Day 1 of Cycles 2, 3, 8, 12, 16, and every 8 cycles thereafter (28 days each) and at study treatment discontinuation visit 7. Day 1, 2, 5, 15 of Cycle 1; Day 1 of Cycles 2, 3, 8, 12, 16, and every 8 cycles thereafter (28 days each) and at study treatment discontinuation visit 8-16. Up to study discontinuation. | — |
Countries
Canada, France, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed