Acute Myeloid Leukemia (AML)
Conditions
Keywords
Cancer, Acute Myeloid Leukemia (AML), relapsed Acute Myeloid Leukemia, refractory Acute Myeloid Leukemia
Brief summary
An open-label, dose-escalation study to assess the safety and pharmacokinetics (PK), to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of alvocidib with venetoclax when co-administered in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML).
Interventions
DRUGVenetoclax
tablet, oral
DRUGAlvocidib
Intravenous
Sponsors
Sumitomo Pharma America, Inc.
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have adequate coagulation, hematology, kidney, and liver function, per protocol. * Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML) * Meet the following disease activity criteria: * an established, confirmed diagnosis of AML by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3; and * an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. * If male participant is sexually active, he must agree from day 1 through 6 months after the last dose of alvocidib or 90 days after the last dose of venetoclax, whichever is longer, to practice the protocol-specified protection.
Exclusion criteria
* History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment such as non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostate cancer in situ. * Prior allogeneic stem cell transplant within 6 months of study drug administration and no requirement for graft versus host therapy. * History of previous enrollment in Studies NCT02993523 or NCT03069352. * History of exposure to alvocidib or any other cyclin-dependent kinase 9 (CDK9) inhibitor. * History of Tumor Lysis Syndrome (TLS) due to previous exposure to venetoclax.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib | Minimum first cycle of dosing (up to 28 days) | RPTD will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase. |
| AUC0-24 Post-dose of Venetoclax | Approximately 32 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 Alvocidib | Approximately 32 days after first dose of study drug | Maximum plasma concentration (Cmax) of alvocidib. |
| AUCt Post-dose of Alvocidib | Approximately 32 days after first dose of study drug | Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose alvocidib. |
| Tmax of venetoclax | Approximately 32 days after first dose of study drug | Time to maximum plasma concentration (Tmax) of venetoclax |
| Clearance of Alvocidib | Approximately 32 days after first dose of study drug | Clearance (CL) of alvocidib |
| AUC0-∞ of Alvocidib | Approximately 32 days after first dose of study drug | Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of alvocidib |
| Cmax of Venetoclax | Approximately 32 days after first dose of study drug | Maximum plasma concentration (Cmax) of venetoclax |
| Half-life (t1/2) of Alvocidib | Approximately 32 days after first dose of study drug | Half-life (t1/2) of alvocidib |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combined CR Rate | Up to approximately 8 months | Combined CR rate 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 based on IWG criteria. |
| Complete Response (CR) Rate | Up to approximately 8 months | CR is defined as the proportion of participants with documented complete response (CR) based on International Working Group (IWG) criteria. |
Countries
Germany, United Kingdom, United States
Outcome results
None listed