Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
M16-802
- NCT ID:
NCT03625505
Conditions
- Acute Myeloid Leukemia (AML)
Interventions
| Drug | Synonyms | Arms |
|---|
| Venetoclax | ABT-199, GDC-0199 | Dose Escalation Venetoclax + Gilteritinib |
| Gilteritinib | ASP-2215 | Dose Escalation Venetoclax + Gilteritinib |
Purpose
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 Arms
| Name | Type | Description | Interventions |
|---|
| Dose Escalation Venetoclax + Gilteritinib | Experimental | Different 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 | Experimental | Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion. | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs |
| Time Frame: | Up to approximately 6 months after the last participant is enrolled |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Pharmacokinetics - Cmax of Venetoclax |
| Time Frame: | Approximately 16 days after first dose of study drug |
| Safety Issue: | |
| Description: | Maximum observed plasma concentration (Cmax) of study drug. |
| Measure: | Pharmacokinetics - Cmax of Gilteritinib |
| Time Frame: | Approximately 16 days after first dose of study drug |
| Safety Issue: | |
| Description: | Maximum observed plasma concentration (Cmax) of study drug. |
| Measure: | Pharmacokinetics - Tmax of Venetoclax |
| Time Frame: | Approximately 16 days after first dose of study drug |
| Safety Issue: | |
| Description: | Time to maximum plasma concentration (Tmax) of study drug. |
| Measure: | Pharmacokinetics - Tmax of Gilteritinib |
| Time Frame: | Approximately 16 days after first dose of study drug |
| Safety Issue: | |
| Description: | Time to maximum plasma concentration (Tmax) of study drug. |
| Measure: | Pharmacokinetics - AUCt of Venetoclax |
| Time Frame: | Approximately 16 days after first dose of study drug |
| Safety Issue: | |
| Description: | Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug. |
| Measure: | Pharmacokinetics - AUCt of Gilteritinib |
| Time Frame: | Approximately 16 days after first dose of study drug |
| Safety Issue: | |
| Description: | Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug. |
| Measure: | Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Venetoclax |
| Time Frame: | Approximately 16 days after first dose of study drug |
| Safety Issue: | |
| Description: | Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug. |
| Measure: | Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Gilteritinib |
| Time Frame: | Approximately 16 days after first dose of study drug |
| Safety Issue: | |
| Description: | Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug. |
| Measure: | Composite Complete Remission (CRc) Rate |
| Time Frame: | Up to approximately 6 months after the last participant is enrolled |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Duration of Response (DOR) of Modified Composite Complete Remission (CRc) |
| Time Frame: | Up to approximately 6 months after the last participant is enrolled |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Complete Remission (CR) + with Partial Hematologic Recovery (CRh) |
| Time Frame: | Up to approximately 6 months after the last participant is enrolled |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Duration of Response (DOR) of Complete Remission (CR) + Complete Remission with Partial Hematologic Recovery (CRh) |
| Time Frame: | Up to approximately 6 months after the last participant is enrolled |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Number of Participants With Adverse Events |
| 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) |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | AbbVie |
Trial Keywords
- Cancer
- Acute Myeloid Leukemia (AML)
- Relapsed or Refractory AML
- Pharmacokinetics
- venetoclax
- gilteritinib
Last Updated
August 2, 2021
