NCT03441555

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started May 2018

Typical duration for phase_1

Geographic Reach
3 countries

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 16, 2018

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 22, 2018

Completed
3 months until next milestone

Study Start

First participant enrolled

May 30, 2018

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 25, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 25, 2021

Completed
Last Updated

February 1, 2022

Status Verified

January 1, 2022

Enrollment Period

2.7 years

First QC Date

February 16, 2018

Last Update Submit

January 24, 2022

Conditions

Acute Myeloid Leukemia (AML)

Keywords

CancerAcute Myeloid Leukemia (AML)relapsed Acute Myeloid Leukemiarefractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (9)

  • Tmax of venetoclax

    Time to maximum plasma concentration (Tmax) of venetoclax

    Approximately 32 days after first dose of study drug

  • Clearance of Alvocidib

    Clearance (CL) of alvocidib

    Approximately 32 days after first dose of study drug

  • AUC0-∞ of Alvocidib

    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

    Maximum plasma concentration (Cmax) of venetoclax

    Approximately 32 days after first dose of study drug

  • Half-life (t1/2) of Alvocidib

    Half-life (t1/2) of alvocidib

    Approximately 32 days after first dose of study drug

  • 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

  • Cmax of Alvocidib

    Maximum plasma concentration (Cmax) of alvocidib.

    Approximately 32 days after first dose of study drug

  • 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

  • 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 Outcomes (3)

  • Complete Response (CR) Rate

    Up to approximately 8 months

  • Combined CR Rate

    Up to approximately 8 months

  • Objective Response Rate (ORR)

    Up to approximately 18 months

Study Arms (1)

Venetoclax + Alvocidib

EXPERIMENTAL

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.

Drug: VenetoclaxDrug: Alvocidib

Interventions

VenetoclaxDRUG

tablet, oral

Also known as: ABT-199
Venetoclax + Alvocidib
AlvocidibDRUG

Intravenous

Also known as: Flavopiridol
Venetoclax + Alvocidib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

USC Norris Cancer Center /ID# 170844

Los Angeles, California, 90033, United States

Location

UC Irvine /ID# 201093

Orange, California, 92868, United States

Location

University of California, Davis Comprehensive Cancer Center /ID# 170799

Sacramento, California, 95817, United States

Location

Sylvester Comprehensive Cancer /ID# 170761

Miami, Florida, 33136-1002, United States

Location

Indiana Blood & Marrow Transpl /ID# 170793

Indianapolis, Indiana, 46237, United States

Location

NYU Langone Medical Center /ID# 201559

New York, New York, 10016-6402, United States

Location

Weill Cornell Medical College /ID# 170800

New York, New York, 10021, United States

Location

Duke University Medical Center /ID# 170842

Durham, North Carolina, 27710-3000, United States

Location

University of Pittsburgh Medic /ID# 170790

Pittsburgh, Pennsylvania, 15261, United States

Location

Universitaetsklinikum Dresden /ID# 168636

Dresden, 01307, Germany

Location

Univ Klinik Eppendorf Hamburg /ID# 168633

Hamburg, 20246, Germany

Location

University Hospital of Wales /ID# 202302

Cardiff, CF14 4EN, United Kingdom

Location

Ninewells Hospital /ID# 202304

Dundee, DD1 9SY, United Kingdom

Location

St. James University Hospital /ID# 202303

Leeds, LS9 7TF, United Kingdom

Location

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteNeoplasms

Interventions

venetoclaxalvocidib

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeHematologic DiseasesHemic and Lymphatic Diseases

Study Officials

  • AbbVie Inc.

    AbbVie

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 16, 2018

First Posted

February 22, 2018

Study Start

May 30, 2018

Primary Completion

January 25, 2021

Study Completion

January 25, 2021

Last Updated

February 1, 2022

Record last verified: 2022-01

Data Sharing

IPD Sharing
Will not share

Locations

DE(2)US(9)GB(3)