Clinical trial NCT03625505: A Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Participants With Relapsed/Refractory Acute Myeloid Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Keywords: Cancer
Acute Myeloid Leukemia (AML)
Relapsed or Refractory AML
Pharmacokinetics
venetoclax
gilteritinib
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
name: Genentech, Inc.
First posted: 2018-08-10
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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.

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.

Primary outcomes:
measure: Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs
timeFrame: Up to approximately 6 months after the last participant is enrolled
measure: Modified Composite Complete Remission (CRc)
timeFrame: Up to approximately 6 months after the last participant is enrolled
Secondary outcomes:
measure: Pharmacokinetics - Cmax of Venetoclax
timeFrame: Approximately 16 days after first dose of study drug
measure: Pharmacokinetics - Cmax of Gilteritinib
timeFrame: Approximately 16 days after first dose of study drug
measure: Pharmacokinetics - Tmax of Venetoclax
timeFrame: Approximately 16 days after first dose of study drug
measure: Pharmacokinetics - Tmax of Gilteritinib
timeFrame: Approximately 16 days after first dose of study drug
measure: Pharmacokinetics - AUCt of Venetoclax
timeFrame: Approximately 16 days after first dose of study drug
measure: Pharmacokinetics - AUCt of Gilteritinib
timeFrame: Approximately 16 days after first dose of study drug
measure: Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Venetoclax
timeFrame: Approximately 16 days after first dose of study drug
measure: Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Gilteritinib
timeFrame: Approximately 16 days after first dose of study drug
measure: Composite Complete Remission (CRc) Rate
timeFrame: Up to approximately 6 months after the last participant is enrolled
measure: Duration of Response (DOR) of Modified Composite Complete Remission (CRc)
timeFrame: Up to approximately 6 months after the last participant is enrolled
measure: Complete Remission (CR) + with Partial Hematologic Recovery (CRh)
timeFrame: Up to approximately 6 months after the last participant is enrolled
measure: Duration of Response (DOR) of Complete Remission (CR) + Complete Remission with Partial Hematologic Recovery (CRh)
timeFrame: Up to approximately 6 months after the last participant is enrolled
measure: Number of Participants With Adverse Events
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicin /ID# 200166
state: California
city: San Francisco
country: United States
facility: UC San Francisco Medical Center-Parnassus /ID# 200205
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer /ID# 200268
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital /ID# 200230
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute /ID# 200623
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University /ID# 200349
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic - Rochester /ID# 200346
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack Univ Med Ctr /ID# 200229
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College /ID# 200109
state: New York
city: Philadelphia
country: United States
facility: Hosp of the Univ of Penn /ID# 200348
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center at Texas Medical Center /ID# 206686
state: Texas
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: 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.