A Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Participants With Relapsed/Refractory Acute Myeloid Leukemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Escalation Venetoclax + Gilteritinib Different combinations of dose levels for venetoclax in combination with gilteritinib will be administered to determine the recommended phase 2 dose (RPTD). |
Drug: Venetoclax
tablet, oral
Other Names:
Drug: Gilteritinib
tablet, oral
Other Names:
|
| Experimental: Dose Expansion Venetoclax + Gilteritinib Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion. |
Drug: Venetoclax
tablet, oral
Other Names:
Drug: Gilteritinib
tablet, oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- Pharmacokinetics - Cmax of Venetoclax [Approximately 16 days after first dose of study drug]
Maximum observed plasma concentration (Cmax) of study drug.
- 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.
- 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 - 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.
- 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.
- 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).
- 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.
- 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).
- 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.
- 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.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | David Geffen School of Medicin /ID# 200166 | Los Angeles | California | United States | 90095 |
| 2 | UC San Francisco Medical Center-Parnassus /ID# 200205 | San Francisco | California | United States | 94143-2202 |
| 3 | Sylvester Comprehensive Cancer /ID# 200268 | Miami | Florida | United States | 33136-1002 |
| 4 | Northwestern Memorial Hospital /ID# 200230 | Chicago | Illinois | United States | 60611-2927 |
| 5 | Norton Cancer Institute /ID# 200623 | Louisville | Kentucky | United States | 40202-3700 |
| 6 | Johns Hopkins University /ID# 200349 | Baltimore | Maryland | United States | 21287 |
| 7 | Mayo Clinic - Rochester /ID# 200346 | Rochester | Minnesota | United States | 55905-0001 |
| 8 | Hackensack Univ Med Ctr /ID# 200229 | Hackensack | New Jersey | United States | 07601 |
| 9 | Weill Cornell Medical College /ID# 200109 | New York | New York | United States | 10065 |
| 10 | Hosp of the Univ of Penn /ID# 200348 | Philadelphia | Pennsylvania | United States | 19104 |
| 11 | MD Anderson Cancer Center at Texas Medical Center /ID# 206686 | Houston | Texas | United States | 77030-4000 |
Sponsors and Collaborators
- AbbVie
- Astellas Pharma Inc
- Genentech, Inc.
Investigators
- Study Director: ABBVIE INC., AbbVie
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- M16-802