This phase I trial tests the safety, side effects, and best dose of a new 8-chloroadenosine in combination with venetoclax in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). 8-Chloroadenosine may help block the formation of growths that may become cancer. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving 8-chloroadenosine in combination with venetoclax may help prevent the disease from coming back in patients with acute myeloid leukemia.
Documented informed consent of the participant and/or legally authorized representative.
Age: >= 18 years.
Eastern Cooperative Oncology Group (ECOG) =< 2.
Life expectancy > 3 months.
Hydroxyurea which may be continued through cycle 1.
Expected to undergo HCT within 120 days of enrollment.
Current or planned use of agents that prolong or suspected to prolong QTc.
Received strong or moderate CYP3A inducers or St. John's Wort within 7 days prior to day 1 of protocol therapy.
Single group
8-Chloroadenosine
DrugGiven IV
Venetoclax
DrugGiven PO
Incidence of adverse events (AEs)
Toxicities will be graded using the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0.
Dose limiting toxicity (DLT)
Toxicities will be graded using the NCI-Common Terminology Criteria for Adverse Events version 5.0. DLT will be assessed after cycle one.
Time to response
Defined by European LeukemiaNet (ELN) criteria 2017 in response-evaluable participants that achieve a best response of either complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or partial response (PR) at the end of study therapy. Will be estimated using the product-limit method of Kaplan and Meier.
Duration of response (DOR)
Patients will be considered evaluable for response if they are eligible, have baseline disease assessments, and receive 2 cycles of protocol treatment, or achieve a CR/CRi after 1 cycle of protocol treatment, or progressed. Patients will have their response classified according to the European Leukemia Network (ELN) 2017 criteria. Will be estimated using the product-limit method of Kaplan and Meier.
Overall survival (OS)
Patients will be considered evaluable for response if they are eligible, have baseline disease assessments, and receive 2 cycles of protocol treatment, or achieve a CR/CRi after 1 cycle of protocol treatment, or progressed. Patients will have their response classified according to the European Leukemia Network (ELN) 2017 criteria. Will be estimated using the product-limit method of Kaplan and Meier.
Event-free survival (EFS)
Patients will be considered evaluable for response if they are eligible, have baseline disease assessments, and receive 2 cycles of protocol treatment, or achieve a CR/CRi after 1 cycle of protocol treatment, or progressed. Patients will have their response classified according to the European Leukemia Network (ELN) 2017 criteria. Will be estimated using the product-limit method of Kaplan and Meier.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
