This phase 2 clinical trial will test the safety and tolerability of a nivolumab(Opdivo) and 5-azacytidine (Vidaza) combination with or without ipilimumab(Yervoy) in treating relapsed or refractory (unresponsive to treatment) acute myeloid leukemia (AML). The primary outcome will be measured by the maximum tolerated dose. This trial is being conducted at the University of Texas MD Anderson Cancer Center in Houston, Texas.
The details
5-azacytidine is a treatment that can stop cancer cells from dividing, or can signal for cancer cell death. Nivolumab and ipilimumab are immunotherapies. They use the body’s own immune system to identify and kill cancer cells throughout the body. Both drugs work by inhibiting proteins on immune cells that normally dampen immune responses.
This study will examine whether the combination of these treatments is effective in AML patients whose cancer has spread or has not responded to treatment. The study will determine the maximum tolerated dose (due to negative side effects) for 28 days. The overall response will also be observed for 3 months.
Who are they looking for?
This trial is recruiting 182 patients AML who have relapsed after prior therapy or failed a salvage therapy. Patients should not have previously received nivolumaband/or ipilimumabin combination with5-azacytidine. Patients should not have central nervous system involvement with leukemia, HIV, organ transplants, or select autoimmune diseases including inflammatory bowel diseases, rheumatoid arthritis, and lupus erythematosus. Patients should not have any active infections. Both male and female participants must agree to use contraception for up to 3 months after the last treatment.
How will it work
Patients will be divided into two groups. Group 1 will receive 5-azacitidine and nivolumab, and group 2 will receive 5-azacitidine, nivolumab, and ipilimumab. The trial will also be divided into parts A and B. During part A, a select number of patients (from each group) will receive an increasing dose of treatment until a maximum dose is determined. Patients enrolled in part B will receive the previously determined maximum dose.
All patients will receive 5-azacitidine intravenously (through IV directly into a vein) or as an injection under the skin on days 1-7 of each cycle, or on days 1-5, 8 and 9 of each 28-day cycle. Both groups will also receive nivolumabby IV on days 1 and 14 of cycles 1-4 and then on day 1 only of the following cycles. Those enrolled in group 2 will be given ipilimumabby IV starting on day 1 and every 6 weeks after that.
There will be a physical exam and possible biopsy within 2 weeks of the last treatment. Patients will then be followed regularly by phone.
