Clinical trial NCT03441555: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Keywords: Cancer
Acute Myeloid Leukemia (AML)
relapsed Acute Myeloid Leukemia
refractory Acute Myeloid Leukemia
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Sumitomo Pharma America, Inc.
First posted: 2018-02-22
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Tmax of venetoclax
timeFrame: Approximately 32 days after first dose of study drug
measure: Clearance of Alvocidib
timeFrame: Approximately 32 days after first dose of study drug
measure: AUC0-∞ of Alvocidib
timeFrame: Approximately 32 days after first dose of study drug
measure: Cmax of Venetoclax
timeFrame: Approximately 32 days after first dose of study drug
measure: Half-life (t1/2) of Alvocidib
timeFrame: Approximately 32 days after first dose of study drug
measure: AUC0-24 Post-dose of Venetoclax
timeFrame: Approximately 32 days after first dose of study drug
measure: Cmax of Alvocidib
timeFrame: Approximately 32 days after first dose of study drug
measure: AUCt Post-dose of Alvocidib
timeFrame: Approximately 32 days after first dose of study drug
measure: Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib
timeFrame: Minimum first cycle of dosing (up to 28 days)
Secondary outcomes:
measure: Complete Response (CR) Rate
timeFrame: Up to approximately 8 months
measure: Combined CR Rate
timeFrame: Up to approximately 8 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 18 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Cancer Center /ID# 170844
state: California
city: Orange
country: United States
facility: UC Irvine /ID# 201093
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center /ID# 170799
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer /ID# 170761
state: Florida
city: Indianapolis
country: United States
facility: Indiana Blood & Marrow Transpl /ID# 170793
state: Indiana
city: New York
country: United States
facility: NYU Langone Medical Center /ID# 201559
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College /ID# 170800
state: New York
city: Durham
country: United States
facility: Duke University Medical Center /ID# 170842
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medic /ID# 170790
state: Pennsylvania
city: Dresden
country: Germany
facility: Universitaetsklinikum Dresden /ID# 168636
city: Hamburg
country: Germany
facility: Univ Klinik Eppendorf Hamburg /ID# 168633
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales /ID# 202302
city: Dundee
country: United Kingdom
facility: Ninewells Hospital /ID# 202304
city: Leeds
country: United Kingdom
facility: St. James University Hospital /ID# 202303
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: