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A Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Sponsor
AbbVie (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03484520
Collaborator
Merck Sharp & Dohme LLC (Industry)
48
Enrollment
13
Locations
1
Arm
50.3
Anticipated Duration (Months)
3.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

An open-label, dose-escalation study to assess safety, pharmacokinetics and efficacy as well as determine the recommended Phase 2 doses of co-administered therapy of dinaciclib and venetoclax for patients with relapsed or refractory Acute Myeloid Leukemia (R/R AML).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
48 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Actual Study Start Date :
Jul 23, 2018
Actual Primary Completion Date :
Jan 21, 2020
Anticipated Study Completion Date :
Sep 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Venetoclax + Dinaciclib

Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored.

Drug: Venetoclax
tablet, oral
Other Names:
  • ABT-199
  • GDC-0199

    • Drug: Dinaciclib
    intravenous
    Other Names:
  • MK-7965
  • SCH-727965

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Tmax of Venetoclax [Approximately 29 days after first dose of study drug]

      Time to maximum plasma concentration (Tmax) of venetoclax.

    2. Recommended Phase 2 Dose (RPTD) of co-administered Dinaciclib and Venetoclax [Minimum first cycle of dosing (21 days)]

      Tthe RPTD of co-administered venetoclax and dinaciclib will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.

    3. Cmax of Venetoclax [Approximately 29 days after first dose of study drug]

      Maximum observed plasma concentration (Cmax) for Venetoclax.

    4. AUCt of Venetoclax [Approximately 29 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)

    5. AUC0-24 Post-dose of Venetoclax [Approximately 29 days after first dose of study drug]

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

    6. Cmax of Dinaciclib [Approximately 29 days after first dose of study drug]

      Maximum plasma concentration (Cmax) of dinaciclib.

    7. Half-life (t1/2) of Dinaciclib [Approximately 29 days after first dose of study drug]

      Half-life (t1/2) of dinaciclib.

    8. AUCt Post-dose of Dinaciclib [Approximately 29 days after first dose of study drug]

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

    9. AUC0-∞ of Dinaciclib [Approximately 29 days after first dose of study drug]

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

    10. Clearance of Dinaciclib [Approximately 29 days after first dose of study drug]

      Clearance (CL) of dinaciclib.

    Secondary Outcome Measures

    1. Complete Response (CR) Rate [Up to approximately 18 months]

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

    2. Composite CR Rate (CR + CRi) [Up to approximately 18 months]

      Composite 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 (CR + CRi + partial response [PR]) 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:

    • Diagnosis of acute myeloid leukemia (AML) by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3.

    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

    • Participant must have adequate hematologic, renal, and liver function laboratory values as described in the protocol.

    Exclusion Criteria:

    • Known central nervous system leukemia

    • Severe chronic obstructive pulmonary disease (COPD) with hypoxemia

    • History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment.

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

    • History of clinically significant medical condition that, in the opinion of the investigator, would adversely affect participation in this study.

    • Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.

    • History of tumor lysis syndrome (TLS) due to previous exposure to venetoclax.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Arkansas /ID# 200016 Little Rock Arkansas United States 72205
    2 David Geffen School of Medicin /ID# 200015 Los Angeles California United States 90095
    3 The University ofChicago /ID# 200017 Chicago Illinois United States 60637
    4 Univ Maryland School Medicine /ID# 204015 Baltimore Maryland United States 21201-1544
    5 Wake Forest Baptist Medical Center /ID# 200288 Winston-Salem North Carolina United States 27157-0001
    6 The Ohio State University /ID# 200668 Columbus Ohio United States 43210
    7 University of Texas MD Anderson Cancer Center /ID# 205215 Houston Texas United States 77030
    8 Gold coast University Hospital /ID# 202759 SouthPort Queensland Australia 4215
    9 Royal Hobart Hospital /ID# 202763 Hobart Tasmania Australia 7000
    10 Monash Medical Centre /ID# 202762 Melbourne Victoria Australia 3168
    11 Hospital Universitario Ramon y Cajal /ID# 201729 Madrid Spain 28034
    12 Hospital Clinico Universitario de Salamanca /ID# 201728 Salamanca Spain 37007
    13 Hospital Universitario y Politecnico La Fe /ID# 202318 Valencia Spain 46026

    Sponsors and Collaborators

    • AbbVie
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: ABBVIE INC., AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT03484520
    Other Study ID Numbers:
    • M16-183
    • 2017-003213-26
    First Posted:
    Mar 30, 2018
    Last Update Posted:
    Jan 11, 2022
    Last Verified:
    Dec 1, 2021
    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), venetoclax, dinaciclib, Relapsed/refractory AML, Pharmacokinetics, Venetoclax, Dinaciclib
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Venetoclax

    Study Results

    No Results Posted as of Jan 11, 2022