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

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03441555
• Other study ID #: M16-186
• Secondary ID: 2017-002531-42
• Status: Completed
• Phase: Phase 1
• Start date: May 30, 2018
• Est. completion date: January 25, 2021

Study information

• Verified date: January 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 25, 2021
• Est. primary completion date: January 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Venetoclax
tablet, oral
• Alvocidib
Intravenous

Locations

Country	Name	City	State
Germany	Universitaetsklinikum Dresden /ID# 168636	Dresden
Germany	Univ Klinik Eppendorf Hamburg /ID# 168633	Hamburg
United Kingdom	University Hospital of Wales /ID# 202302	Cardiff
United Kingdom	Ninewells Hospital /ID# 202304	Dundee
United Kingdom	St. James University Hospital /ID# 202303	Leeds
United States	Duke University Medical Center /ID# 170842	Durham	North Carolina
United States	Indiana Blood & Marrow Transpl /ID# 170793	Indianapolis	Indiana
United States	USC Norris Cancer Center /ID# 170844	Los Angeles	California
United States	Sylvester Comprehensive Cancer /ID# 170761	Miami	Florida
United States	NYU Langone Medical Center /ID# 201559	New York	New York
United States	Weill Cornell Medical College /ID# 170800	New York	New York
United States	UC Irvine /ID# 201093	Orange	California
United States	University of Pittsburgh Medic /ID# 170790	Pittsburgh	Pennsylvania
United States	University of California, Davis Comprehensive Cancer Center /ID# 170799	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Sumitomo Dainippon Pharma Oncology, Inc

Countries where clinical trial is conducted

United States,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tmax of venetoclax	Time to maximum plasma concentration (Tmax) of venetoclax	Approximately 32 days after first dose of study drug
Primary	Clearance of Alvocidib	Clearance (CL) of alvocidib	Approximately 32 days after first dose of study drug
Primary	AUC0-8 of Alvocidib	Area under the plasma concentration-time curve from 0 to infinity (AUC0-8) post-dose of alvocidib	Approximately 32 days after first dose of study drug
Primary	Cmax of Venetoclax	Maximum plasma concentration (Cmax) of venetoclax	Approximately 32 days after first dose of study drug
Primary	Half-life (t1/2) of Alvocidib	Half-life (t1/2) of alvocidib	Approximately 32 days after first dose of study drug
Primary	AUC0-24 Post-dose of Venetoclax	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
Primary	Cmax of Alvocidib	Maximum plasma concentration (Cmax) of alvocidib.	Approximately 32 days after first dose of study drug
Primary	AUCt Post-dose of Alvocidib	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
Primary	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.	Minimum first cycle of dosing (up to 28 days)
Secondary	Complete Response (CR) Rate	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
Secondary	Combined CR Rate	Combined CR rate is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.	Up to approximately 8 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of participants with documented partial response (PR) or better based on IWG criteria.	Up to approximately 18 months

External Links

•   clinical study report synopsis