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A Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT03441555
Collaborator
Sumitomo Pharma Oncology, Inc. (Industry)
36
Enrollment
14
Locations
1
Arm
31.9
Actual Duration (Months)
2.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

An open-label, dose-escalation study to assess the safety and pharmacokinetics (PK), to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of alvocidib with venetoclax when co-administered in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
36 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Actual Study Start Date :
May 30, 2018
Actual Primary Completion Date :
Jan 25, 2021
Actual Study Completion Date :
Jan 25, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Venetoclax + Alvocidib

Venetoclax administered orally once daily (QD) and Alvocidib administered as an intravenous infusion on Days 1, 2, and 3 for all 28-day treatment cycles. Different combinations of dose levels for venetoclax and alvocidib may be explored.

Drug: Venetoclax
tablet, oral
Other Names:
  • ABT-199

    • Drug: Alvocidib
    Intravenous
    Other Names:
  • Flavopiridol

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Tmax of venetoclax [Approximately 32 days after first dose of study drug]

      Time to maximum plasma concentration (Tmax) of venetoclax

    2. Clearance of Alvocidib [Approximately 32 days after first dose of study drug]

      Clearance (CL) of alvocidib

    3. AUC0-∞ of Alvocidib [Approximately 32 days after first dose of study drug]

      Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of alvocidib

    4. Cmax of Venetoclax [Approximately 32 days after first dose of study drug]

      Maximum plasma concentration (Cmax) of venetoclax

    5. Half-life (t1/2) of Alvocidib [Approximately 32 days after first dose of study drug]

      Half-life (t1/2) of alvocidib

    6. AUC0-24 Post-dose of Venetoclax [Approximately 32 days after first dose of study drug]

      Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.

    7. Cmax of Alvocidib [Approximately 32 days after first dose of study drug]

      Maximum plasma concentration (Cmax) of alvocidib.

    8. AUCt Post-dose of Alvocidib [Approximately 32 days after first dose of study drug]

      Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose alvocidib.

    9. Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib [Minimum first cycle of dosing (up to 28 days)]

      RPTD will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.

    Secondary Outcome Measures

    1. Complete Response (CR) Rate [Up to approximately 8 months]

      CR is defined as the proportion of participants with documented complete response (CR) based on International Working Group (IWG) criteria.

    2. Combined CR Rate [Up to approximately 8 months]

      Combined CR rate is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.

    3. Objective Response Rate (ORR) [Up to approximately 18 months]

      ORR is defined as the proportion of participants with documented partial response (PR) or better based on IWG criteria.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Must have adequate coagulation, hematology, kidney, and liver function, per protocol.

    • Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML)

    • Meet the following disease activity criteria:

    • an established, confirmed diagnosis of AML by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3; and

    • an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to

    • If male participant is sexually active, he must agree from day 1 through 6 months after the last dose of alvocidib or 90 days after the last dose of venetoclax, whichever is longer, to practice the protocol-specified protection.
    Exclusion Criteria:

    • History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment such as non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostate cancer in situ.

    • Prior allogeneic stem cell transplant within 6 months of study drug administration and no requirement for graft versus host therapy.

    • History of previous enrollment in Studies NCT02993523 or NCT03069352.

    • History of exposure to alvocidib or any other cyclin-dependent kinase 9 (CDK9) inhibitor.

    • History of Tumor Lysis Syndrome (TLS) due to previous exposure to venetoclax.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 USC Norris Cancer Center /ID# 170844 Los Angeles California United States 90033
    2 UC Irvine /ID# 201093 Orange California United States 92868
    3 University of California, Davis Comprehensive Cancer Center /ID# 170799 Sacramento California United States 95817
    4 Sylvester Comprehensive Cancer /ID# 170761 Miami Florida United States 33136-1002
    5 Indiana Blood & Marrow Transpl /ID# 170793 Indianapolis Indiana United States 46237
    6 NYU Langone Medical Center /ID# 201559 New York New York United States 10016-6402
    7 Weill Cornell Medical College /ID# 170800 New York New York United States 10021
    8 Duke University Medical Center /ID# 170842 Durham North Carolina United States 27710-3000
    9 University of Pittsburgh Medic /ID# 170790 Pittsburgh Pennsylvania United States 15261
    10 Universitaetsklinikum Dresden /ID# 168636 Dresden Germany 01307
    11 Univ Klinik Eppendorf Hamburg /ID# 168633 Hamburg Germany 20246
    12 University Hospital of Wales /ID# 202302 Cardiff United Kingdom CF14 4EN
    13 Ninewells Hospital /ID# 202304 Dundee United Kingdom DD1 9SY
    14 St. James University Hospital /ID# 202303 Leeds United Kingdom LS9 7TF

    Sponsors and Collaborators

    • AbbVie
    • Sumitomo Pharma Oncology, Inc.

    Investigators

    • Study Director: AbbVie Inc., AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT03441555
    Other Study ID Numbers:
    • M16-186
    • 2017-002531-42
    First Posted:
    Feb 22, 2018
    Last Update Posted:
    Feb 1, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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 Acute Myeloid Leukemia
    refractory Acute Myeloid Leukemia
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Venetoclax
    Alvocidib

    Study Results

    No Results Posted as of Feb 1, 2022