A Phase 1 Study of Nivolumab in Combination With ASTX727 in B-cell Lymphoma (NHL or HL) With an Expansion Cohort in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and Hodgkin Lymphoma (HL)
National Cancer Institute (NCI)
Summary
This phase I trial tests the safety, side effects, and best dose of nivolumab in combination with ASTX727 in treating B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. ASTX727 consists of the combination of decitabine and cedazuridine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. 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. Giving nivolumab in combination with ASTX727 may shrink and stabilize cancer.
Description
PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of the combination of oral deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibition and checkpoint inhibition in relapsed or refractory B cell lymphoma (dose escalation) and diffuse large B-cell lymphoma (DLBCL) (dose expansion) or Hodgkin lymphoma (dose expansion). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the response rate (overall response \[ORR\], complete response \[CR\], and partial response \[PR\]), and the progression free survival (PFS) and overall survival (OS) in patient…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Dose Escalation: Histologically confirmed relapsed or refractory B cell lymphoma (non-Hodgkin lymphoma \[NHL\] or Hodgkin lymphoma \[HL\]) * Dose Expansion: Patients must have histologically confirmed relapsed or refractory DLBCL or HL * Patients with DLBCL must have failed at least first line chemotherapy and must be transplant ineligible (either secondary to performance status or lack of adequate disease control or patient preference). Patients may be relapsed after autologous or allogeneic stem cell transplant (SCT), or after chimeric antigen receptor (CAR)-T cell the…
Interventions
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- ProcedureComputed Tomography
Undergo PET/CT
- DrugDecitabine and Cedazuridine
Given PO
- BiologicalNivolumab
Given IV
- ProcedurePositron Emission Tomography
Undergo PET/CT
Locations (9)
- University of Alabama at Birmingham Cancer CenterBirmingham, Alabama
- City of Hope Comprehensive Cancer CenterDuarte, California
- University of California Davis Comprehensive Cancer CenterSacramento, California
- Yale UniversityNew Haven, Connecticut
- University of Chicago Comprehensive Cancer CenterChicago, Illinois
- UC Comprehensive Cancer Center at Silver CrossNew Lenox, Illinois