Nivolumab and Azacitidine With or Without Ipilimumab in Treating Patients With Refractory/Relapsed or Newly Diagnosed Acute Myeloid Leukemia

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PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of nivolumab in combination with azacitidine (5-azacytidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Lead-in phase) II. To determine the maximum tolerated dose (MTD) and ...

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of nivolumab in combination with azacitidine (5-azacytidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Lead-in phase) II. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of nivolumab with ipilimumab in combination with 5-azacytidine in patients with refractory/relapsed acute myeloid leukemia (AML). (Lead-in phase) III. To determine the overall response rate (ORR) of nivolumab in combination with 5-azacytidine in patients with refractory/ relapsed AML. (Phase II) IV. To determine the overall response rate (ORR) of nivolumab in combination with 5-azacytidine in older patients (> 65 years) with newly diagnosed AML. (Phase II) V. To determine the overall response rate (ORR) of nivolumab with ipilimumab in combination with 5-azacytidine in patients with refractory/relapsed AML. (Phase II) VI. To determine the overall response rate (ORR) of nivolumab with ipilimumab in combination with 5- azacytidine in older patients (65 years) with newly diagnosed AML. (Phase II) SECONDARY OBJECTIVES: I. To determine the number of patients who achieve a > 50% reduction in blasts on therapy with either vidaza+nivolumab or vidaza+nivolumab+ipilimumab. II. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with either vidaza+nivolumab or vidaza+nivolumab+ipilimumab. III. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) in older patients with newly diagnosed AML treated with this combination with either vidaza+nivolumab or vidaza+nivolumab+ipilimumab. TERTIARY OBJECTIVES: I. To study immunological and molecular changes in the peripheral blood and bone marrow in response to nivolumab and 5-azacytidine therapy or nivolumab with ipilimumab and 5-azacytidine therapy. II. To determine induction of hypomethylation and deoxyribonucleic acid (DNA) damage during therapy with this combination and its correlation with response. OUTLINE: This is a lead-in phase, dose-escalation study followed by a phase II study. Patients are assigned to 1 of 2 arms. ARM I: Patients receive azacitidine intravenously (IV) over 1 hour or subcutaneously (SC) on days 1-7 or days 1-4 and 7-9. Patients also receive nivolumab IV over 60 minutes on days 1 and 14 (courses 1-4) or on day 1 (course 5 and all subsequent courses). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive azacitidine and nivolumab as Arm I. Patients also receive ipilimumab IV over 90 minutes on day 1 and then every 6 or 12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 5 years.

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