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

Phase 1b Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

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).

Study Overview

• Status: Terminated
• Conditions: Cancer - Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax; Drug: Dinaciclib

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • SouthPort, Queensland, Australia, 4215
      • Gold coast University Hospital /ID# 202759
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital /ID# 202763
  • Victoria
    • Melbourne, Victoria, Australia, 3168
      • Monash Medical Centre /ID# 202762
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal /ID# 201729
  • Salamanca, Spain, 37711
    • Hospital Universitario de Salamanca /ID# 201728
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe /ID# 202318
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas /ID# 200016
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicin /ID# 200015
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University ofChicago /ID# 200017
  • Maryland
    • Baltimore, Maryland, United States, 21201-1544
      • University of Maryland School of Medicine /ID# 204015
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-0001
      • Wake Forest Baptist Medical Center /ID# 200288
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University /ID# 200668
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center /ID# 205215

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venetoclax + Dinaciclib; Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored.	Drug: Venetoclax; tablet, oral; Other Names: ABT-199; GDC-0199; Drug: Dinaciclib; intravenous; Other Names: MK-7965; SCH-727965

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax of Venetoclax	Time to maximum plasma concentration (Tmax) of venetoclax.	Approximately 29 days after first dose of study drug
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.	Minimum first cycle of dosing (21 days)
Cmax of Venetoclax	Maximum observed plasma concentration (Cmax) for Venetoclax.	Approximately 29 days after first dose of study drug
AUCt of Venetoclax	Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt)	Approximately 29 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 29 days after first dose of study drug
Cmax of Dinaciclib	Maximum plasma concentration (Cmax) of dinaciclib.	Approximately 29 days after first dose of study drug
Half-life (t1/2) of Dinaciclib	Half-life (t1/2) of dinaciclib.	Approximately 29 days after first dose of study drug
AUCt Post-dose of Dinaciclib	Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose dinaciclib.	Approximately 29 days after first dose of study drug
AUC0-∞ of Dinaciclib	Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of dinaciclib.	Approximately 29 days after first dose of study drug
Clearance of Dinaciclib	Clearance (CL) of dinaciclib.	Approximately 29 days after first dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 18 months
Composite CR Rate (CR + CRi)	Composite is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.	Up to approximately 18 months
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.	Up to approximately 18 months

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2018
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: March 26, 2018
• First Posted (Actual): March 30, 2018

Study Record Updates

• Last Update Posted (Actual): December 30, 2022
• Last Update Submitted That Met QC Criteria: December 28, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Cancer, Acute Myeloid Leukemia (AML), venetoclax, dinaciclib, Relapsed/refractory AML, Pharmacokinetics, Venetoclax, Dinaciclib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: M16-183; 2017-003213-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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