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

NCT03625505

Description:

A dose-escalation study evaluating the safety, tolerability, pharmacokinetics (PK) and efficacy of venetoclax, in combination with gilteritinib, in subjects 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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Acute Promyelocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Subjects 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

DrugSynonymsArms
VenetoclaxABT-199, GDC-0199Venetoclax + Gilteritinib
GilteritinibASP-2215Venetoclax + Gilteritinib

Purpose

A dose-escalation study evaluating the safety, tolerability, pharmacokinetics (PK) and efficacy of venetoclax, in combination with gilteritinib, in subjects 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

NameTypeDescriptionInterventions
Venetoclax + GilteritinibExperimentalVenetoclax and gilteritinib will be administered in combination. Different combinations of dose levels for venetoclax and gilteritinib will be explored.
  • Venetoclax
  • Gilteritinib

Eligibility Criteria

        Inclusion Criteria:

          -  Subject should have an established, confirmed diagnosis of Acute Myeloid Leukemia
             (AML) by World Health Organization (2016).

          -  Subject should have failed at least 1 line of prior therapy (defined as failure to
             respond to therapy, and/or progression during or after therapy).

          -  Subject should have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0, 1, or 2.

          -  Subject should have adequate hematologic, kidney and liver function as described in
             the protocol.

          -  For subjects 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:

          -  Subject has a diagnosis of acute promyelocytic leukemia (APL) or BCR-ABL-positive
             leukemia.

          -  Subject has a history of other malignancies within 2 years prior to study entry, with
             exceptions as described in the protocol.

          -  Subject has active central nervous system leukemia.

          -  Subject has a history of chronic New York Heart Association (NYHA) class IV heart
             failure.

          -  Subject has a corrected QT interval of > 450 ms.

          -  Subject 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 subject 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
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
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
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
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:Duration of Response (DOR) of Composite Complete Remission (CRc)
Time Frame:Up to approximately 6 months after the last subject is enrolled
Safety Issue:
Description:DOR of CRc will be defined as time from the first date achieving CRc to disease progression (including morphologic relapse) or death from any cause whichever is earlier.
Measure:Duration of Complete Remission (CR) + Complete Remission with incomplete hematologic recovery (CRh)
Time Frame:Up to approximately 6 months after the last subject 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:Complete Remission (CR) + with incomplete hematologic recovery (CRh)
Time Frame:Up to approximately 6 months after the last subject 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).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Cancer
  • Acute Myeloid Leukemia (AML)
  • Relapsed or Refractory AML
  • Pharmacokinetics
  • venetoclax
  • gilteritinib

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