A Multicenter, Open-Label Phase 1b Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 61
- Locations
- 11
- Primary Endpoint
- Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs
Study Overview
Brief Summary
A dose-escalation study evaluating the safety, tolerability, pharmacokinetics (PK) and efficacy of venetoclax, in combination with gilteritinib, in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have failed to respond to, and/or have relapsed or progressed after at least 1 prior therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Should have an established, confirmed diagnosis of Acute Myeloid Leukemia (AML) by World Health Organization (2016).
- •Should have failed at least 1 line of prior therapy (defined as failure to respond to therapy, and/or progression during or after therapy).
- •Should have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Should have adequate hematologic, kidney and liver function as described in the protocol.
- •For participants enrolling into the Expansion Cohort only: a documented FMS-like Tyrosine Kinase (FLT3) mutation in bone marrow or peripheral blood, as described in the protocol.
Exclusion Criteria
- •Has a diagnosis of acute promyelocytic leukemia (APL) or BCR-ABL-positive leukemia.
- •Has a history of other malignancies within 2 years prior to study entry, with exceptions as described in the protocol.
- •Has active central nervous system leukemia.
- •Has a history of chronic New York Heart Association (NYHA) class IV heart failure.
- •Has a corrected QT interval of > 450 ms.
- •Has a chronic respiratory disease that requires continuous oxygen use.
Arms & Interventions
Dose Escalation Venetoclax + Gilteritinib
Different combinations of dose levels for venetoclax in combination with gilteritinib will be administered to determine the recommended phase 2 dose (RPTD).
Intervention: Venetoclax (Drug)
Dose Escalation Venetoclax + Gilteritinib
Different combinations of dose levels for venetoclax in combination with gilteritinib will be administered to determine the recommended phase 2 dose (RPTD).
Intervention: Gilteritinib (Drug)
Dose Expansion Venetoclax + Gilteritinib
Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion.
Intervention: Venetoclax (Drug)
Dose Expansion Venetoclax + Gilteritinib
Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion.
Intervention: Gilteritinib (Drug)
Outcomes
Primary Outcomes
Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs
Time Frame: Up to approximately 6 months after the last participant is enrolled
The RPTD of co-administered venetoclax and gilteritinib will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.
Modified Composite Complete Remission (CRc)
Time Frame: Up to approximately 6 months after the last participant is enrolled
Modified CRc rate is defined as the proportion of participants with documented complete response (CR) + CR with partial blood count recovery (CRp) + CR with incomplete blood count recovery (CRi) plus Morphologic Leukemia-Free State (MLFS) based on guidelines adapted from the International Working Group (IWG) for Acute Myeloid Leukemia (AML).
Secondary Outcomes
- Pharmacokinetics - Cmax of Venetoclax(Approximately 16 days after first dose of study drug)
- Pharmacokinetics - AUCt of Venetoclax(Approximately 16 days after first dose of study drug)
- Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Gilteritinib(Approximately 16 days after first dose of study drug)
- Duration of Response (DOR) of Modified Composite Complete Remission (CRc)(Up to approximately 6 months after the last participant is enrolled)
- Duration of Response (DOR) of Complete Remission (CR) + Complete Remission with Partial Hematologic Recovery (CRh)(Up to approximately 6 months after the last participant is enrolled)
- Pharmacokinetics - AUCt of Gilteritinib(Approximately 16 days after first dose of study drug)
- Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Venetoclax(Approximately 16 days after first dose of study drug)
- Composite Complete Remission (CRc) Rate(Up to approximately 6 months after the last participant is enrolled)
- Complete Remission (CR) + with Partial Hematologic Recovery (CRh)(Up to approximately 6 months after the last participant is enrolled)
- Number of Participants With Adverse Events(From first dose of study drug until 30 days or 5 half-lives after discontinuation of study drug administration will be collected (up to approximately 4 years))
- Pharmacokinetics - Cmax of Gilteritinib(Approximately 16 days after first dose of study drug)
- Pharmacokinetics - Tmax of Venetoclax(Approximately 16 days after first dose of study drug)
- Pharmacokinetics - Tmax of Gilteritinib(Approximately 16 days after first dose of study drug)