A Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia
- Conditions
- Cancer - Acute Myeloid Leukemia
- Interventions
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 48
- 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.
- 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)
David Geffen School of Medicin /ID# 200015
🇺🇸Los Angeles, California, United States
The Ohio State University /ID# 200668
🇺🇸Columbus, Ohio, United States
Gold coast University Hospital /ID# 202759
🇦🇺SouthPort, Queensland, Australia
University of Texas MD Anderson Cancer Center /ID# 205215
🇺🇸Houston, Texas, United States
Monash Medical Centre /ID# 202762
🇦🇺Melbourne, Victoria, Australia
University of Arkansas /ID# 200016
🇺🇸Little Rock, Arkansas, United States
The University ofChicago /ID# 200017
🇺🇸Chicago, Illinois, United States
Hospital Universitario de Salamanca /ID# 201728
🇪🇸Salamanca, Spain
Hospital Universitario Ramon y Cajal /ID# 201729
🇪🇸Madrid, Spain
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
Royal Hobart Hospital /ID# 202763
🇦🇺Hobart, Tasmania, Australia
Hospital Universitario y Politecnico La Fe /ID# 202318
🇪🇸Valencia, Spain