A Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Participants With Relapsed/Refractory Acute Myeloid Leukemia
- Conditions
- Acute Myeloid Leukemia (AML)
- Interventions
- Registration Number
- NCT03625505
- Lead Sponsor
- AbbVie
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 61
- 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 2.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Venetoclax + Gilteritinib Venetoclax Different combinations of dose levels for venetoclax in combination with gilteritinib will be administered to determine the recommended phase 2 dose (RPTD). Dose Escalation Venetoclax + Gilteritinib Gilteritinib Different combinations of dose levels for venetoclax in combination with gilteritinib will be administered to determine the recommended phase 2 dose (RPTD). Dose Expansion Venetoclax + Gilteritinib Venetoclax Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion. Dose Expansion Venetoclax + Gilteritinib Gilteritinib Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion.
- Primary Outcome Measures
Name Time Method Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs 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) 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 Outcome Measures
Name Time Method Pharmacokinetics - Cmax of Venetoclax Approximately 16 days after first dose of study drug Maximum observed plasma concentration (Cmax) of study drug.
Pharmacokinetics - AUCt of Venetoclax Approximately 16 days after first dose of study drug Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Gilteritinib Approximately 16 days after first dose of study drug Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-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 DOR of modified CRc will be defined as time from the first date achieving modified CRc to disease progression (including morphologic relapse) or death from any cause whichever is earlier.
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 DOR of CR + CRh will be defined as time from the first date achieving CR and/or CRh to disease progression (including morphologic relapse) or death from any cause whichever is earlier.
Pharmacokinetics - AUCt of Gilteritinib Approximately 16 days after first dose of study drug Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Venetoclax Approximately 16 days after first dose of study drug Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug.
Composite Complete Remission (CRc) Rate Up to approximately 6 months after the last participant is enrolled CRc is defined as the proportion of participants with documented CR + CRp + CRi based on guidelines adapted from the International Working Group (IWG) for Acute Myeloid Leukemia (AML).
Complete Remission (CR) + with Partial Hematologic Recovery (CRh) Up to approximately 6 months after the last participant is enrolled It is defined as the proportion of participants achieving CR or CRh based on guidelines adapted from the International Working Group (IWG) for Acute Myeloid Leukemia (AML).
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) An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Pharmacokinetics - Cmax of Gilteritinib Approximately 16 days after first dose of study drug Maximum observed plasma concentration (Cmax) of study drug.
Pharmacokinetics - Tmax of Venetoclax Approximately 16 days after first dose of study drug Time to maximum plasma concentration (Tmax) of study drug.
Pharmacokinetics - Tmax of Gilteritinib Approximately 16 days after first dose of study drug Time to maximum plasma concentration (Tmax) of study drug.
Trial Locations
- Locations (11)
Northwestern Memorial Hospital /ID# 200230
🇺🇸Chicago, Illinois, United States
Sylvester Comprehensive Cancer /ID# 200268
🇺🇸Miami, Florida, United States
David Geffen School of Medicin /ID# 200166
🇺🇸Los Angeles, California, United States
UC San Francisco Medical Center-Parnassus /ID# 200205
🇺🇸San Francisco, California, United States
Johns Hopkins University /ID# 200349
🇺🇸Baltimore, Maryland, United States
Hackensack Univ Med Ctr /ID# 200229
🇺🇸Hackensack, New Jersey, United States
Norton Cancer Institute /ID# 200623
🇺🇸Louisville, Kentucky, United States
Weill Cornell Medical College /ID# 200109
🇺🇸New York, New York, United States
Hosp of the Univ of Penn /ID# 200348
🇺🇸Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center at Texas Medical Center /ID# 206686
🇺🇸Houston, Texas, United States
Mayo Clinic - Rochester /ID# 200346
🇺🇸Rochester, Minnesota, United States