Phase 1b Study of Pembrolizumab, Decitabine +/- Venetoclax Combination Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
City of Hope Medical Center
Summary
This phase Ib trial studies the side effects and best dose of pembrolizumab and how well it works in combination with decitabine with or without venetoclax in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly-diagnosed, has come back (recurrent), or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. 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. This trial may help doctors find the best dose of pembrolizumab that can be safely given in combination with decitabine with or without venetoclax, and to determine what side effects are seen with this treatment.
Description
PRIMARY OBJECTIVES: I. Assess the safety and tolerability of pembrolizumab combined with decitabine, with or without the addition of venetoclax (treatment cohorts 1 and 2), by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (ACUTE MYELOID LEUKEMIA \[AML\] ARM) II. Assess the safety and tolerability of pembrolizumab combined with decitabine, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (MYELODYSPLASTIC SYNDROME \[MDS\] ARM) III. Determine the maximum tolerated dose(s)/schedule (MTD…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Agreement to allow the use of archival blood samples and marrow from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval * Eastern Cooperative Oncology Group (ECOG) status =\< 1 * Histologically confirmed AML (not including acute promyelocytic leukemia) or MDS * Patients with the following diagnoses * Refractory/relapsed AML by World Health Organization (WHO) classification, who are not candidates for allogeneic ste…
Interventions
- DrugDecitabine
Given IV
- BiologicalPembrolizumab
Given IV
- DrugVenetoclax
Given PO
Location
- City of Hope Medical CenterDuarte, California