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

Study Overview
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Brief Summary
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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).

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

Conditions
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Cancer - Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Venetoclax
* Drug: Dinaciclib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Venetoclax + Dinaciclib<br>Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored. | Drug: Venetoclax<br>* tablet, oral<br>* Other names: GDC-0199;Drug: Dinaciclib<br>* intravenous<br>* Other names: SCH-727965;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Acute Myeloid Leukemia (AML), venetoclax, dinaciclib, Relapsed/refractory AML, Pharmacokinetics, Venetoclax, Dinaciclib