Cancer - Acute Myeloid Leukemia
Conditions
Keywords
Cancer, Acute Myeloid Leukemia (AML), venetoclax, dinaciclib, Relapsed/refractory AML, Pharmacokinetics, Venetoclax, Dinaciclib
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).
Interventions
DRUGVenetoclax
tablet, oral
DRUGDinaciclib
intravenous
Sponsors
Merck Sharp & Dohme LLC
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clearance of Dinaciclib | Approximately 29 days after first dose of study drug | Clearance (CL) 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. |
| Tmax of Venetoclax | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Australia, Spain, United States
Outcome results
None listed