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

• ClinicalTrials.gov Identifier: NCT03484520
• Recruitment Status: Terminated
• First Posted: March 30, 2018
• Last Update Posted: December 30, 2022
• Sponsor: AbbVie
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: March 26, 2018
• First Posted Date: March 30, 2018
• Last Update Posted Date: December 30, 2022
• Actual Study Start Date: July 23, 2018
• Actual Primary Completion Date: December 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 26, 2018)

• Tmax of Venetoclax [ Time Frame: Approximately 29 days after first dose of study drug ]
  Time to maximum plasma concentration (Tmax) of venetoclax.
• Recommended Phase 2 Dose (RPTD) of co-administered Dinaciclib and Venetoclax [ Time Frame: Minimum first cycle of dosing (21 days) ]
  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 [ Time Frame: Approximately 29 days after first dose of study drug ]
  Maximum observed plasma concentration (Cmax) for Venetoclax.
• AUCt of Venetoclax [ Time Frame: Approximately 29 days after first dose of study drug ]
  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 [ Time Frame: Approximately 29 days after first dose of study drug ]
  Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.
• Cmax of Dinaciclib [ Time Frame: Approximately 29 days after first dose of study drug ]
  Maximum plasma concentration (Cmax) of dinaciclib.
• Half-life (t1/2) of Dinaciclib [ Time Frame: Approximately 29 days after first dose of study drug ]
  Half-life (t1/2) of dinaciclib.
• AUCt Post-dose of Dinaciclib [ Time Frame: Approximately 29 days after first dose of study drug ]
  Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose dinaciclib.
• AUC0-∞ of Dinaciclib [ Time Frame: Approximately 29 days after first dose of study drug ]
  Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of dinaciclib.
• Clearance of Dinaciclib [ Time Frame: Approximately 29 days after first dose of study drug ]
  Clearance (CL) of dinaciclib.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 26, 2018)

• Complete Response (CR) Rate [ Time Frame: Up to approximately 18 months ]
  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) [ Time Frame: Up to approximately 18 months ]
  Composite is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.
• Objective Response Rate (ORR) [ Time Frame: Up to approximately 18 months ]
  ORR is defined as the proportion of participants with documented partial response (PR) or better (CR + CRi + partial response [PR]) based on IWG criteria.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer - Acute Myeloid Leukemia

Intervention

• Drug: Venetoclax
  tablet, oral
  Other Names:

  • ABT-199
  • GDC-0199
• Drug: Dinaciclib
  intravenous
  Other Names:

  • MK-7965
  • SCH-727965

Study Arms

Experimental: Venetoclax + Dinaciclib

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

Interventions:

• Drug: Venetoclax
• Drug: Dinaciclib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 26, 2018): 48
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 1, 2022
• Actual Primary Completion Date: December 1, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Spain, United States

Administrative Information

• NCT Number: NCT03484520
• Other Study ID Numbers: M16-183; 2017-003213-26 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: December 2022