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

Primary Purpose

Acute Myeloid Leukemia (AML)

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Venetoclax
Alvocidib
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Cancer, Acute Myeloid Leukemia (AML), relapsed Acute Myeloid Leukemia, refractory Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • USC Norris Cancer Center /ID# 170844
  • UC Irvine /ID# 201093
  • University of California, Davis Comprehensive Cancer Center /ID# 170799
  • Sylvester Comprehensive Cancer /ID# 170761
  • Indiana Blood & Marrow Transpl /ID# 170793
  • NYU Langone Medical Center /ID# 201559
  • Weill Cornell Medical College /ID# 170800
  • Duke University Medical Center /ID# 170842
  • University of Pittsburgh Medic /ID# 170790
  • Universitaetsklinikum Dresden /ID# 168636
  • Univ Klinik Eppendorf Hamburg /ID# 168633
  • University Hospital of Wales /ID# 202302
  • Ninewells Hospital /ID# 202304
  • St. James University Hospital /ID# 202303

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Venetoclax + Alvocidib

Arm Description

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.

Outcomes

Primary Outcome Measures

Tmax of venetoclax
Time to maximum plasma concentration (Tmax) of venetoclax
Clearance of Alvocidib
Clearance (CL) of alvocidib
AUC0-∞ of Alvocidib
Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of alvocidib
Cmax of Venetoclax
Maximum plasma concentration (Cmax) of venetoclax
Half-life (t1/2) of Alvocidib
Half-life (t1/2) of alvocidib
AUC0-24 Post-dose of Venetoclax
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.
Cmax of Alvocidib
Maximum plasma concentration (Cmax) of alvocidib.
AUCt Post-dose of Alvocidib
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
RPTD will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.

Secondary Outcome Measures

Complete Response (CR) Rate
CR is defined as the proportion of participants with documented complete response (CR) based on International Working Group (IWG) criteria.
Combined CR Rate
Combined CR rate is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.
Objective Response Rate (ORR)
ORR is defined as the proportion of participants with documented partial response (PR) or better based on IWG criteria.

Full Information

First Posted
February 16, 2018
Last Updated
January 24, 2022
Sponsor
AbbVie
Collaborators
Sumitomo Pharma America, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03441555
Brief Title
A Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Official Title
Phase 1b Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
May 30, 2018 (Actual)
Primary Completion Date
January 25, 2021 (Actual)
Study Completion Date
January 25, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Sumitomo Pharma America, Inc.

4. Oversight

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
Data Monitoring Committee
Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
Keywords
Cancer, Acute Myeloid Leukemia (AML), relapsed Acute Myeloid Leukemia, refractory Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Venetoclax + Alvocidib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199
Intervention Description
tablet, oral
Intervention Type
Drug
Intervention Name(s)
Alvocidib
Other Intervention Name(s)
Flavopiridol
Intervention Description
Intravenous
Primary Outcome Measure Information:
Title
Tmax of venetoclax
Description
Time to maximum plasma concentration (Tmax) of venetoclax
Time Frame
Approximately 32 days after first dose of study drug
Title
Clearance of Alvocidib
Description
Clearance (CL) of alvocidib
Time Frame
Approximately 32 days after first dose of study drug
Title
AUC0-∞ of Alvocidib
Description
Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of alvocidib
Time Frame
Approximately 32 days after first dose of study drug
Title
Cmax of Venetoclax
Description
Maximum plasma concentration (Cmax) of venetoclax
Time Frame
Approximately 32 days after first dose of study drug
Title
Half-life (t1/2) of Alvocidib
Description
Half-life (t1/2) of alvocidib
Time Frame
Approximately 32 days after first dose of study drug
Title
AUC0-24 Post-dose of Venetoclax
Description
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.
Time Frame
Approximately 32 days after first dose of study drug
Title
Cmax of Alvocidib
Description
Maximum plasma concentration (Cmax) of alvocidib.
Time Frame
Approximately 32 days after first dose of study drug
Title
AUCt Post-dose of Alvocidib
Description
Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose alvocidib.
Time Frame
Approximately 32 days after first dose of study drug
Title
Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib
Description
RPTD will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.
Time Frame
Minimum first cycle of dosing (up to 28 days)
Secondary Outcome Measure Information:
Title
Complete Response (CR) Rate
Description
CR is defined as the proportion of participants with documented complete response (CR) based on International Working Group (IWG) criteria.
Time Frame
Up to approximately 8 months
Title
Combined CR Rate
Description
Combined CR rate is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.
Time Frame
Up to approximately 8 months
Title
Objective Response Rate (ORR)
Description
ORR is defined as the proportion of participants with documented partial response (PR) or better based on IWG criteria.
Time Frame
Up to approximately 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
USC Norris Cancer Center /ID# 170844
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UC Irvine /ID# 201093
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California, Davis Comprehensive Cancer Center /ID# 170799
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Sylvester Comprehensive Cancer /ID# 170761
City
Miami
State/Province
Florida
ZIP/Postal Code
33136-1002
Country
United States
Facility Name
Indiana Blood & Marrow Transpl /ID# 170793
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
NYU Langone Medical Center /ID# 201559
City
New York
State/Province
New York
ZIP/Postal Code
10016-6402
Country
United States
Facility Name
Weill Cornell Medical College /ID# 170800
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Duke University Medical Center /ID# 170842
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710-3000
Country
United States
Facility Name
University of Pittsburgh Medic /ID# 170790
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
Universitaetsklinikum Dresden /ID# 168636
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Univ Klinik Eppendorf Hamburg /ID# 168633
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
University Hospital of Wales /ID# 202302
City
Cardiff
ZIP/Postal Code
CF14 4EN
Country
United Kingdom
Facility Name
Ninewells Hospital /ID# 202304
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Facility Name
St. James University Hospital /ID# 202303
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.abbvieclinicaltrials.com/search-results/?SearchTerm=NCT03441555&Latitude=&Longitude=&LocationName=&conditions=&Status=&phases=&AgeRanges=&gender=&GenderDescriptions=&StudyTypes=&AttachmentTypes=&MileRadius=100&PageIndex=0&hasResults=&isHighValue=&SortField=&SortOrder=
Description
clinical study report synopsis

Learn more about this trial

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

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