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

January 24, 2022 updated by: AbbVie

Phase 1b Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia

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).

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
tablet, oral
Other Names:
  • ABT-199
Intravenous
Other Names:
  • Flavopiridol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tmax of venetoclax
Time Frame: Approximately 32 days after first dose of study drug
Time to maximum plasma concentration (Tmax) of venetoclax
Approximately 32 days after first dose of study drug
Clearance of Alvocidib
Time Frame: Approximately 32 days after first dose of study drug
Clearance (CL) of alvocidib
Approximately 32 days after first dose of study drug
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
Approximately 32 days after first dose of study drug
Cmax of Venetoclax
Time Frame: Approximately 32 days after first dose of study drug
Maximum plasma concentration (Cmax) of venetoclax
Approximately 32 days after first dose of study drug
Half-life (t1/2) of Alvocidib
Time Frame: Approximately 32 days after first dose of study drug
Half-life (t1/2) of alvocidib
Approximately 32 days after first dose of study drug
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.
Approximately 32 days after first dose of study drug
Cmax of Alvocidib
Time Frame: Approximately 32 days after first dose of study drug
Maximum plasma concentration (Cmax) of alvocidib.
Approximately 32 days after first dose of study drug
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.
Approximately 32 days after first dose of study drug
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.
Minimum first cycle of dosing (up to 28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to approximately 8 months
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.
Up to approximately 8 months
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.
Up to approximately 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 30, 2018

Primary Completion (Actual)

January 25, 2021

Study Completion (Actual)

January 25, 2021

Study Registration Dates

First Submitted

February 16, 2018

First Submitted That Met QC Criteria

February 16, 2018

First Posted (Actual)

February 22, 2018

Study Record Updates

Last Update Posted (Actual)

February 1, 2022

Last Update Submitted That Met QC Criteria

January 24, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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