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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
61
tablet, oral
tablet, oral
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
Sylvester Comprehensive Cancer /ID# 200268
Miami, Florida, United States
Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs
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.
Time frame: Up to approximately 6 months after the last participant is enrolled
Modified Composite Complete Remission (CRc)
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).
Time frame: Up to approximately 6 months after the last participant is enrolled
Pharmacokinetics - Cmax of Venetoclax
Maximum observed plasma concentration (Cmax) of study drug.
Time frame: Approximately 16 days after first dose of study drug
Pharmacokinetics - Cmax of Gilteritinib
Maximum observed plasma concentration (Cmax) of study drug.
Time frame: Approximately 16 days after first dose of study drug
Pharmacokinetics - Tmax of Venetoclax
Time to maximum plasma concentration (Tmax) of study drug.
Time frame: Approximately 16 days after first dose of study drug
Pharmacokinetics - Tmax of Gilteritinib
Time to maximum plasma concentration (Tmax) of study drug.
Time frame: Approximately 16 days after first dose of study drug
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Northwestern Memorial Hospital /ID# 200230
Chicago, Illinois, United States
Norton Cancer Institute /ID# 200623
Louisville, Kentucky, United States
Johns Hopkins University /ID# 200349
Baltimore, Maryland, United States
Mayo Clinic - Rochester /ID# 200346
Rochester, Minnesota, United States
Hackensack Univ Med Ctr /ID# 200229
Hackensack, New Jersey, 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
...and 1 more locations
Pharmacokinetics - AUCt of Venetoclax
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.
Time frame: Approximately 16 days after first dose of study drug
Pharmacokinetics - AUCt of Gilteritinib
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.
Time frame: Approximately 16 days after first dose of study drug
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Venetoclax
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug.
Time frame: Approximately 16 days after first dose of study drug
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Gilteritinib
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug.
Time frame: Approximately 16 days after first dose of study drug
Composite Complete Remission (CRc) Rate
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).
Time frame: Up to approximately 6 months after the last participant is enrolled
Duration of Response (DOR) of Modified Composite Complete Remission (CRc)
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.
Time frame: Up to approximately 6 months after the last participant is enrolled
Complete Remission (CR) + with Partial Hematologic Recovery (CRh)
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).
Time frame: 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)
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.
Time frame: Up to approximately 6 months after the last participant is enrolled
Number of Participants With Adverse Events
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.
Time frame: 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)