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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03625505
Recruitment Status : Completed
First Posted : August 10, 2018
Last Update Posted : September 14, 2021
Sponsor:
Collaborators:
Astellas Pharma Inc
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Study Description
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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
Acute Myeloid Leukemia (AML) Drug: Venetoclax Drug: Gilteritinib Phase 1

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 18, 2018
Actual Primary Completion Date : August 31, 2021
Actual Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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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:
  • ABT-199
  • GDC-0199

Drug: Gilteritinib
tablet, oral
Other Name: ASP-2215
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:
  • ABT-199
  • GDC-0199

Drug: Gilteritinib
tablet, oral
Other Name: ASP-2215


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03625505


Locations
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United States, California
David Geffen School of Medicin /ID# 200166
Los Angeles, California, United States, 90095
UC San Francisco Medical Center-Parnassus /ID# 200205
San Francisco, California, United States, 94143-2202
United States, Florida
Sylvester Comprehensive Cancer /ID# 200268
Miami, Florida, United States, 33136-1002
United States, Illinois
Northwestern Memorial Hospital /ID# 200230
Chicago, Illinois, United States, 60611-2927
United States, Kentucky
Norton Cancer Institute /ID# 200623
Louisville, Kentucky, United States, 40202-3700
United States, Maryland
Johns Hopkins University /ID# 200349
Baltimore, Maryland, United States, 21287
United States, Minnesota
Mayo Clinic - Rochester /ID# 200346
Rochester, Minnesota, United States, 55905-0001
United States, New Jersey
Hackensack Univ Med Ctr /ID# 200229
Hackensack, New Jersey, United States, 07601
United States, New York
Weill Cornell Medical College /ID# 200109
New York, New York, United States, 10065
United States, Pennsylvania
Hosp of the Univ of Penn /ID# 200348
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
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
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Study Director: ABBVIE INC. AbbVie
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03625505    
Other Study ID Numbers: M16-802
First Posted: August 10, 2018    Key Record Dates
Last Update Posted: September 14, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Cancer
Acute Myeloid Leukemia (AML)
Relapsed or Refractory AML
 Pharmacokinetics
venetoclax
gilteritinib
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
 Neoplasms
Venetoclax
Antineoplastic Agents