- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03441555
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
Conditions
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
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Dresden, Germany, 01307
- Universitaetsklinikum Dresden /ID# 168636
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Hamburg, Germany, 20246
- Univ Klinik Eppendorf Hamburg /ID# 168633
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Cardiff, United Kingdom, CF14 4EN
- University Hospital of Wales /ID# 202302
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Dundee, United Kingdom, DD1 9SY
- Ninewells Hospital /ID# 202304
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Leeds, United Kingdom, LS9 7TF
- St. James University Hospital /ID# 202303
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California
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Los Angeles, California, United States, 90033
- USC Norris Cancer Center /ID# 170844
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Orange, California, United States, 92868
- UC Irvine /ID# 201093
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Sacramento, California, United States, 95817
- University of California, Davis Comprehensive Cancer Center /ID# 170799
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Florida
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Miami, Florida, United States, 33136-1002
- Sylvester Comprehensive Cancer /ID# 170761
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Indiana
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Indianapolis, Indiana, United States, 46237
- Indiana Blood & Marrow Transpl /ID# 170793
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New York
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New York, New York, United States, 10016-6402
- NYU Langone Medical Center /ID# 201559
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New York, New York, United States, 10021
- Weill Cornell Medical College /ID# 170800
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North Carolina
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Durham, North Carolina, United States, 27710-3000
- Duke University Medical Center /ID# 170842
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15261
- University of Pittsburgh Medic /ID# 170790
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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 |
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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.
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tablet, oral
Other Names:
Intravenous
Other Names:
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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
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Time to maximum plasma concentration (Tmax) of venetoclax
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Approximately 32 days after first dose of study drug
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Clearance of Alvocidib
Time Frame: Approximately 32 days after first dose of study drug
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Clearance (CL) of alvocidib
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Approximately 32 days after first dose of study drug
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AUC0-∞ of Alvocidib
Time Frame: Approximately 32 days after first dose of study drug
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Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of alvocidib
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Approximately 32 days after first dose of study drug
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Cmax of Venetoclax
Time Frame: Approximately 32 days after first dose of study drug
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Maximum plasma concentration (Cmax) of venetoclax
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Approximately 32 days after first dose of study drug
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Half-life (t1/2) of Alvocidib
Time Frame: Approximately 32 days after first dose of study drug
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Half-life (t1/2) of alvocidib
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Approximately 32 days after first dose of study drug
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AUC0-24 Post-dose of Venetoclax
Time Frame: Approximately 32 days after first dose of study drug
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Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.
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Approximately 32 days after first dose of study drug
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Cmax of Alvocidib
Time Frame: Approximately 32 days after first dose of study drug
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Maximum plasma concentration (Cmax) of alvocidib.
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Approximately 32 days after first dose of study drug
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AUCt Post-dose of Alvocidib
Time Frame: Approximately 32 days after first dose of study drug
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Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose alvocidib.
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Approximately 32 days after first dose of study drug
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Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib
Time Frame: Minimum first cycle of dosing (up to 28 days)
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RPTD will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.
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Minimum first cycle of dosing (up to 28 days)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete Response (CR) Rate
Time Frame: Up to approximately 8 months
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CR is defined as the proportion of participants with documented complete response (CR) based on International Working Group (IWG) criteria.
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Up to approximately 8 months
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Combined CR Rate
Time Frame: Up to approximately 8 months
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Combined CR rate is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.
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Up to approximately 8 months
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Objective Response Rate (ORR)
Time Frame: Up to approximately 18 months
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ORR is defined as the proportion of participants with documented partial response (PR) or better based on IWG criteria.
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Up to approximately 18 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
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.
Helpful Links
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
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- M16-186
- 2017-002531-42 (EudraCT Number)
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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