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A Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Primary Purpose

Cancer - Acute Myeloid Leukemia

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

About this trial

This is an interventional treatment trial for Cancer - Acute Myeloid Leukemia focused on measuring Cancer, Acute Myeloid Leukemia (AML), venetoclax, dinaciclib, Relapsed/refractory AML, Pharmacokinetics, Venetoclax, Dinaciclib

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosis of acute myeloid leukemia (AML) by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Participant must have adequate hematologic, renal, and liver function laboratory values as described in the protocol.

Exclusion Criteria:

  • Known central nervous system leukemia
  • Severe chronic obstructive pulmonary disease (COPD) with hypoxemia
  • History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment.
  • Prior allogeneic stem cell transplant within 6 months of study drug administration and no requirement for graft versus host therapy.
  • History of clinically significant medical condition that, in the opinion of the investigator, would adversely affect participation in this study.
  • Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
  • History of tumor lysis syndrome (TLS) due to previous exposure to venetoclax.

Sites / Locations

  • University of Arkansas /ID# 200016
  • David Geffen School of Medicin /ID# 200015
  • The University ofChicago /ID# 200017
  • University of Maryland School of Medicine /ID# 204015
  • Wake Forest Baptist Medical Center /ID# 200288
  • The Ohio State University /ID# 200668
  • University of Texas MD Anderson Cancer Center /ID# 205215
  • Gold coast University Hospital /ID# 202759
  • Royal Hobart Hospital /ID# 202763
  • Monash Medical Centre /ID# 202762
  • Hospital Universitario Ramon y Cajal /ID# 201729
  • Hospital Universitario de Salamanca /ID# 201728
  • Hospital Universitario y Politecnico La Fe /ID# 202318

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Venetoclax + Dinaciclib

Arm Description

Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored.

Outcomes

Primary Outcome Measures

Tmax of Venetoclax
Time to maximum plasma concentration (Tmax) of venetoclax.
Recommended Phase 2 Dose (RPTD) of co-administered Dinaciclib and Venetoclax
Tthe RPTD of co-administered venetoclax and dinaciclib will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.
Cmax of Venetoclax
Maximum observed plasma concentration (Cmax) for Venetoclax.
AUCt of Venetoclax
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt)
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 Dinaciclib
Maximum plasma concentration (Cmax) of dinaciclib.
Half-life (t1/2) of Dinaciclib
Half-life (t1/2) of dinaciclib.
AUCt Post-dose of Dinaciclib
Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose dinaciclib.
AUC0-∞ of Dinaciclib
Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of dinaciclib.
Clearance of Dinaciclib
Clearance (CL) of dinaciclib.

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.
Composite CR Rate (CR + CRi)
Composite 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 (CR + CRi + partial response [PR]) based on IWG criteria.

Full Information

First Posted
March 26, 2018
Last Updated
December 28, 2022
Sponsor
AbbVie
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03484520
Brief Title
A Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Official Title
Phase 1b Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Terminated
Why Stopped
Strategic considerations
Study Start Date
July 23, 2018 (Actual)
Primary Completion Date
December 1, 2022 (Actual)
Study Completion Date
December 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Merck Sharp & Dohme LLC

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
No

5. Study Description

Brief Summary
An open-label, dose-escalation study to assess safety, pharmacokinetics and efficacy as well as determine the recommended Phase 2 doses of co-administered therapy of dinaciclib and venetoclax for patients with relapsed or refractory Acute Myeloid Leukemia (R/R AML).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer - Acute Myeloid Leukemia
Keywords
Cancer, Acute Myeloid Leukemia (AML), venetoclax, dinaciclib, Relapsed/refractory AML, Pharmacokinetics, Venetoclax, Dinaciclib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Venetoclax + Dinaciclib
Arm Type
Experimental
Arm Description
Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199, GDC-0199
Intervention Description
tablet, oral
Intervention Type
Drug
Intervention Name(s)
Dinaciclib
Other Intervention Name(s)
MK-7965, SCH-727965
Intervention Description
intravenous
Primary Outcome Measure Information:
Title
Tmax of Venetoclax
Description
Time to maximum plasma concentration (Tmax) of venetoclax.
Time Frame
Approximately 29 days after first dose of study drug
Title
Recommended Phase 2 Dose (RPTD) of co-administered Dinaciclib and Venetoclax
Description
Tthe RPTD of co-administered venetoclax and dinaciclib will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.
Time Frame
Minimum first cycle of dosing (21 days)
Title
Cmax of Venetoclax
Description
Maximum observed plasma concentration (Cmax) for Venetoclax.
Time Frame
Approximately 29 days after first dose of study drug
Title
AUCt of Venetoclax
Description
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt)
Time Frame
Approximately 29 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 29 days after first dose of study drug
Title
Cmax of Dinaciclib
Description
Maximum plasma concentration (Cmax) of dinaciclib.
Time Frame
Approximately 29 days after first dose of study drug
Title
Half-life (t1/2) of Dinaciclib
Description
Half-life (t1/2) of dinaciclib.
Time Frame
Approximately 29 days after first dose of study drug
Title
AUCt Post-dose of Dinaciclib
Description
Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose dinaciclib.
Time Frame
Approximately 29 days after first dose of study drug
Title
AUC0-∞ of Dinaciclib
Description
Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of dinaciclib.
Time Frame
Approximately 29 days after first dose of study drug
Title
Clearance of Dinaciclib
Description
Clearance (CL) of dinaciclib.
Time Frame
Approximately 29 days after first dose of study drug
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 18 months
Title
Composite CR Rate (CR + CRi)
Description
Composite is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.
Time Frame
Up to approximately 18 months
Title
Objective Response Rate (ORR)
Description
ORR is defined as the proportion of participants with documented partial response (PR) or better (CR + CRi + partial response [PR]) 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: Diagnosis of acute myeloid leukemia (AML) by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Participant must have adequate hematologic, renal, and liver function laboratory values as described in the protocol. Exclusion Criteria: Known central nervous system leukemia Severe chronic obstructive pulmonary disease (COPD) with hypoxemia History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment. Prior allogeneic stem cell transplant within 6 months of study drug administration and no requirement for graft versus host therapy. History of clinically significant medical condition that, in the opinion of the investigator, would adversely affect participation in this study. Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. 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
University of Arkansas /ID# 200016
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
David Geffen School of Medicin /ID# 200015
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
The University ofChicago /ID# 200017
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Maryland School of Medicine /ID# 204015
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201-1544
Country
United States
Facility Name
Wake Forest Baptist Medical Center /ID# 200288
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-0001
Country
United States
Facility Name
The Ohio State University /ID# 200668
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center /ID# 205215
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Gold coast University Hospital /ID# 202759
City
SouthPort
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Facility Name
Royal Hobart Hospital /ID# 202763
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Monash Medical Centre /ID# 202762
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Hospital Universitario Ramon y Cajal /ID# 201729
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario de Salamanca /ID# 201728
City
Salamanca
ZIP/Postal Code
37711
Country
Spain
Facility Name
Hospital Universitario y Politecnico La Fe /ID# 202318
City
Valencia
ZIP/Postal Code
46026
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

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