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

Phase 1

Terminated

• Conditions: Cancer - Acute Myeloid Leukemia
• Interventions: Drug: Venetoclax; Drug: Dinaciclib

• Registration Number: NCT03484520
• Lead Sponsor: AbbVie

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 available

Study Timeline

• Study First Submitted: 2018-03-26
• Study First Submitted QC: 2018-03-26
• Study First Posted: 2018-03-30
• Study Start: 2018-07-23
• Status Verified: 2022-12
• Primary Completion: 2022-12-01
• Study Completion: 2022-12-01
• Last Update Submitted: 2022-12-28
• Last Update Posted: 2022-12-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 48

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Venetoclax + Dinaciclib	Venetoclax	Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored.
Venetoclax + Dinaciclib	Dinaciclib	Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored.

Primary Outcome Measures

Name	Time	Method
Recommended Phase 2 Dose (RPTD) of co-administered Dinaciclib and Venetoclax	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.
Tmax of Venetoclax	Approximately 29 days after first dose of study drug	Time to maximum plasma concentration (Tmax) of venetoclax.
Cmax of Venetoclax	Approximately 29 days after first dose of study drug	Maximum observed plasma concentration (Cmax) for Venetoclax.
AUCt of Venetoclax	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	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	Approximately 29 days after first dose of study drug	Maximum plasma concentration (Cmax) of dinaciclib.
Half-life (t1/2) of Dinaciclib	Approximately 29 days after first dose of study drug	Half-life (t1/2) of dinaciclib.
AUCt Post-dose of Dinaciclib	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	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	Approximately 29 days after first dose of study drug	Clearance (CL) of dinaciclib.

Secondary Outcome Measures

Name	Time	Method
Complete Response (CR) Rate	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)	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)	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.

Trial Locations

Locations (13)

University of Arkansas /ID# 200016; 🇺🇸 Little Rock, Arkansas, United States

David Geffen School of Medicin /ID# 200015; 🇺🇸 Los Angeles, California, United States

The University ofChicago /ID# 200017; 🇺🇸 Chicago, Illinois, United States

University of Maryland School of Medicine /ID# 204015; 🇺🇸 Baltimore, Maryland, United States

Wake Forest Baptist Medical Center /ID# 200288; 🇺🇸 Winston-Salem, North Carolina, United States

The Ohio State University /ID# 200668; 🇺🇸 Columbus, Ohio, United States

University of Texas MD Anderson Cancer Center /ID# 205215; 🇺🇸 Houston, Texas, United States

Gold coast University Hospital /ID# 202759; 🇦🇺 SouthPort, Queensland, Australia

Royal Hobart Hospital /ID# 202763; 🇦🇺 Hobart, Tasmania, Australia

Monash Medical Centre /ID# 202762; 🇦🇺 Melbourne, Victoria, Australia

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