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Completed

NCT Number: NCT03625505

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

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.

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Key information

Conditions

Acute Myeloid Leukemia (AML) Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

David Geffen School of Medicin /ID# 200166, Los Angeles, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Venetoclax

Drug

tablet, oral

Other names: ABT-199, GDC-0199

Gilteritinib

Drug

tablet, oral

Other names: ASP-2215

Primary outcomes

  1. Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs

    Time frame: 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.

  2. Modified Composite Complete Remission (CRc)

    Time frame: 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 outcomes

  1. Pharmacokinetics - Cmax of Venetoclax

    Time frame: Approximately 16 days after first dose of study drug

    Maximum observed plasma concentration (Cmax) of study drug.

  2. Pharmacokinetics - Cmax of Gilteritinib

    Time frame: Approximately 16 days after first dose of study drug

    Maximum observed plasma concentration (Cmax) of study drug.

  3. Pharmacokinetics - Tmax of Venetoclax

    Time frame: Approximately 16 days after first dose of study drug

    Time to maximum plasma concentration (Tmax) of study drug.

  4. Pharmacokinetics - Tmax of Gilteritinib

    Time frame: Approximately 16 days after first dose of study drug

    Time to maximum plasma concentration (Tmax) of study drug.

  5. Pharmacokinetics - AUCt of Venetoclax

    Time frame: 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.

  6. Pharmacokinetics - AUCt of Gilteritinib

    Time frame: 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.

  7. Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Venetoclax

    Time frame: 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.

  8. Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Gilteritinib

    Time frame: 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.

  9. Composite Complete Remission (CRc) Rate

    Time frame: 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).

  10. Duration of Response (DOR) of Modified Composite Complete Remission (CRc)

    Time frame: 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.

  11. Complete Remission (CR) + with Partial Hematologic Recovery (CRh)

    Time frame: 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).

  12. 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

    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.

  13. 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)

    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.

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Collaborators

  • Astellas Pharma Inc
  • Genentech, Inc.

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Aug 10, 2018
Registry last updated
Sep 14, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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