A Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Participants With Relapsed/Refractory Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03625505
• Other study ID #: M16-802
• Status: Completed
• Phase: Phase 1
• Start date: October 18, 2018
• Est. completion date: August 31, 2021

Study information

• Verified date: September 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: August 31, 2021
• Est. primary completion date: August 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Venetoclax
tablet, oral
• Gilteritinib
tablet, oral

Locations

Country	Name	City	State
United States	Johns Hopkins University /ID# 200349	Baltimore	Maryland
United States	Northwestern Memorial Hospital /ID# 200230	Chicago	Illinois
United States	Hackensack Univ Med Ctr /ID# 200229	Hackensack	New Jersey
United States	MD Anderson Cancer Center at Texas Medical Center /ID# 206686	Houston	Texas
United States	David Geffen School of Medicin /ID# 200166	Los Angeles	California
United States	Norton Cancer Institute /ID# 200623	Louisville	Kentucky
United States	Sylvester Comprehensive Cancer /ID# 200268	Miami	Florida
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	Mayo Clinic - Rochester /ID# 200346	Rochester	Minnesota
United States	UC San Francisco Medical Center-Parnassus /ID# 200205	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
AbbVie	Astellas Pharma Inc, Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Pharmacokinetics - Cmax of Venetoclax	Maximum observed plasma concentration (Cmax) of study drug.	Approximately 16 days after first dose of study drug
Secondary	Pharmacokinetics - Cmax of Gilteritinib	Maximum observed plasma concentration (Cmax) of study drug.	Approximately 16 days after first dose of study drug
Secondary	Pharmacokinetics - Tmax of Venetoclax	Time to maximum plasma concentration (Tmax) of study drug.	Approximately 16 days after first dose of study drug
Secondary	Pharmacokinetics - Tmax of Gilteritinib	Time to maximum plasma concentration (Tmax) of study drug.	Approximately 16 days after first dose of study drug
Secondary	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.	Approximately 16 days after first dose of study drug
Secondary	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.	Approximately 16 days after first dose of study drug
Secondary	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.	Approximately 16 days after first dose of study drug
Secondary	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.	Approximately 16 days after first dose of study drug
Secondary	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).	Up to approximately 6 months after the last participant is enrolled
Secondary	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.	Up to approximately 6 months after the last participant is enrolled
Secondary	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).	Up to approximately 6 months after the last participant is enrolled
Secondary	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.	Up to approximately 6 months after the last participant is enrolled
Secondary	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.	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)

External Links

•   This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.