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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03625505
Recruitment Status : Recruiting
First Posted : August 10, 2018
Last Update Posted : August 18, 2020
Sponsor:
Collaborator:
Astellas Pharma Inc Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE August 8, 2018
First Posted Date  ICMJE August 10, 2018
Last Update Posted Date August 18, 2020
Actual Study Start Date  ICMJE October 18, 2018
Estimated Primary Completion Date October 14, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2020)
  • 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.
  • 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).
Original Primary Outcome Measures  ICMJE
 (submitted: August 8, 2018)
  • Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs [ Time Frame: Up to approximately 6 months after the last subject 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.
  • Composite Complete Remission (CRc) Rate [ Time Frame: Up to approximately 6 months after the last subject is enrolled ]
    CRc rate is defined as the proportion of participants with documented complete response (CR) + CR with incomplete platelet recovery (CRp) + CR with incomplete blood count recovery (CRi) based on guidelines adapted from the International Working Group (IWG) for Acute Myeloid Leukemia (AML).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2020)
  • Pharmacokinetics - Cmax of Venetoclax [ Time Frame: Approximately 16 days after first dose of study drug ]
    Maximum observed plasma concentration (Cmax) of study drug.
  • Pharmacokinetics - Cmax of Gilteritinib [ Time Frame: Approximately 16 days after first dose of study drug ]
    Maximum observed plasma concentration (Cmax) of study drug.
  • Pharmacokinetics - Tmax of Venetoclax [ Time Frame: Approximately 16 days after first dose of study drug ]
    Time to maximum plasma concentration (Tmax) of study drug.
  • Pharmacokinetics - Tmax of Gilteritinib [ Time Frame: Approximately 16 days after first dose of study drug ]
    Time to maximum plasma concentration (Tmax) of study drug.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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).
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2018)
  • Pharmacokinetics - Cmax [ Time Frame: Approximately 16 days after first dose of study drug ]
    Maximum observed plasma concentration (Cmax) of study drug.
  • Pharmacokinetics - Tmax [ Time Frame: Approximately 16 days after first dose of study drug ]
    Time to maximum plasma concentration (Tmax) of study drug.
  • Pharmacokinetics - AUCt [ 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.
  • Pharmacokinetics - AUC0-24 Post-dose of study drug [ 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Participants With Relapsed/Refractory Acute Myeloid Leukemia
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia (AML)
Intervention  ICMJE
  • Drug: Venetoclax
    tablet, oral
    Other Names:
    • ABT-199
    • GDC-0199
  • Drug: Gilteritinib
    tablet, oral
    Other Name: ASP-2215
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Venetoclax
    • Drug: Gilteritinib
  • Experimental: Dose Expansion Venetoclax + Gilteritinib
    Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion.
    Interventions:
    • Drug: Venetoclax
    • Drug: Gilteritinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 14, 2020)
64
Original Estimated Enrollment  ICMJE
 (submitted: August 8, 2018)
52
Estimated Study Completion Date  ICMJE October 14, 2021
Estimated Primary Completion Date October 14, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03625505
Other Study ID Numbers  ICMJE M16-802
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Astellas Pharma Inc Genentech, Inc.
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP