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

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ClinicalTrials.gov Identifier: NCT03441555
Recruitment Status : Recruiting
First Posted : February 21, 2018
Last Update Posted : April 22, 2019
Sponsor:
Collaborator:
Tolero Pharmaceuticals, Inc.
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE February 16, 2018
First Posted Date  ICMJE February 21, 2018
Last Update Posted Date April 22, 2019
Actual Study Start Date  ICMJE May 30, 2018
Estimated Primary Completion Date May 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2018)
  • Tmax of venetoclax [ Time Frame: Approximately 32 days after first dose of study drug ]
    Time to maximum plasma concentration (Tmax) of venetoclax
  • Clearance of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Clearance (CL) of alvocidib
  • AUC0-∞ of Alvocidib [ Time Frame: 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
  • Cmax of Venetoclax [ Time Frame: Approximately 32 days after first dose of study drug ]
    Maximum plasma concentration (Cmax) of venetoclax
  • Half-life (t1/2) of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Half-life (t1/2) of alvocidib
  • AUC0-24 Post-dose of Venetoclax [ Time Frame: 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.
  • Cmax of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Maximum plasma concentration (Cmax) of alvocidib.
  • AUCt Post-dose of Alvocidib [ Time Frame: 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.
  • Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 16, 2018)
  • Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib [ Time Frame: 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.
  • Tmax of venetoclax [ Time Frame: Approximately 32 days after first dose of study drug ]
    Time to maximum plasma concentration (Tmax) of venetoclax
  • Clearance of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Clearance (CL) of alvocidib
  • AUC0-∞ of Alvocidib [ Time Frame: 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
  • Cmax of Venetoclax [ Time Frame: Approximately 32 days after first dose of study drug ]
    Maximum plasma concentration (Cmax) of venetoclax
  • Half-life (t1/2) of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Half-life (t1/2) of alvocidib
  • AUC0-24 Post-dose of Venetoclax [ Time Frame: 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.
  • Cmax of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Maximum plasma concentration (Cmax) of alvocidib.
  • AUCt Post-dose of Alvocidib [ Time Frame: 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.
Change History Complete list of historical versions of study NCT03441555 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2018)
  • Complete Response (CR) Rate [ Time Frame: 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.
  • Combined CR Rate [ Time Frame: Up to approximately 8 months ]
    Combined CR rate is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 18 months ]
    ORR is defined as the proportion of participants with documented partial response (PR) or better based on IWG criteria.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Official Title  ICMJE Phase 1b Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia (AML)
Intervention  ICMJE
  • Drug: Venetoclax
    tablet, oral
    Other Name: ABT-199
  • Drug: Alvocidib
    Intravenous
    Other Name: Flavopiridol
Study Arms  ICMJE 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.
Interventions:
  • Drug: Venetoclax
  • Drug: Alvocidib
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: February 16, 2018)
44
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 28, 2021
Estimated Primary Completion Date May 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 2.
  • 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.
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 Germany,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03441555
Other Study ID Numbers  ICMJE M16-186
2017-002531-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
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 Tolero Pharmaceuticals, Inc.
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date April 2019

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