A Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Participants With Relapsed/Refractory Acute Myeloid Leukemia
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
1 other identifier
interventional
61
1 country
11
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2018
Typical duration for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 8, 2018
CompletedFirst Posted
Study publicly available on registry
August 10, 2018
CompletedStudy Start
First participant enrolled
October 18, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2021
CompletedSeptember 14, 2021
September 1, 2021
2.9 years
August 8, 2018
September 7, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
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).
Up to approximately 6 months after the last participant is enrolled
Secondary Outcomes (13)
Pharmacokinetics - Cmax of Venetoclax
Approximately 16 days after first dose of study drug
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
Pharmacokinetics - AUCt of Venetoclax
Approximately 16 days after first dose of study drug
- +8 more secondary outcomes
Study Arms (2)
Dose Escalation Venetoclax + Gilteritinib
EXPERIMENTALDifferent 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
EXPERIMENTALParticipants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion.
Interventions
tablet, oral
tablet, oral
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AbbVielead
- Astellas Pharma Inccollaborator
- Genentech, Inc.collaborator
Study Sites (11)
David Geffen School of Medicin /ID# 200166
Los Angeles, California, 90095, United States
UC San Francisco Medical Center-Parnassus /ID# 200205
San Francisco, California, 94143-2202, United States
Sylvester Comprehensive Cancer /ID# 200268
Miami, Florida, 33136-1002, United States
Northwestern Memorial Hospital /ID# 200230
Chicago, Illinois, 60611-2927, United States
Norton Cancer Institute /ID# 200623
Louisville, Kentucky, 40202-3700, United States
Johns Hopkins University /ID# 200349
Baltimore, Maryland, 21287, United States
Mayo Clinic - Rochester /ID# 200346
Rochester, Minnesota, 55905-0001, United States
Hackensack Univ Med Ctr /ID# 200229
Hackensack, New Jersey, 07601, United States
Weill Cornell Medical College /ID# 200109
New York, New York, 10065, United States
Hosp of the Univ of Penn /ID# 200348
Philadelphia, Pennsylvania, 19104, United States
MD Anderson Cancer Center at Texas Medical Center /ID# 206686
Houston, Texas, 77030-4000, United States
Related Publications (1)
Daver N, Perl AE, Maly J, Levis M, Ritchie E, Litzow M, McCloskey J, Smith CC, Schiller G, Bradley T, Tiu RV, Naqvi K, Dail M, Brackman D, Siddani S, Wang J, Chyla B, Lee P, Altman JK. Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia. J Clin Oncol. 2022 Dec 10;40(35):4048-4059. doi: 10.1200/JCO.22.00602. Epub 2022 Jul 18.
PMID: 35849791DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
ABBVIE INC.
AbbVie
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
August 8, 2018
First Posted
August 10, 2018
Study Start
October 18, 2018
Primary Completion
August 31, 2021
Study Completion
August 31, 2021
Last Updated
September 14, 2021
Record last verified: 2021-09
Data Sharing
- IPD Sharing
- Will not share