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

Myelodysplastic Syndrome Clinical Trial

Official title: An Open-Label Phase II Study of Nivolumab (BMS-936558) in Combination With 5-Azacytidine (Vidaza) or Nivolumab With Ipilimumab in Combination With 5-Azacytidine for the Treatment of Patients With Refractory/ Relapsed Acute Myeloid Leukemia and Newly Diagnosed Older AML (> 65 Years) Patients

Status Completed

Clinical Trial Summary

This phase II trial studies the side effects and best dose of nivolumab and azacitidine with or without ipilimumab when given together and to see how well they work in treating patients with acute myeloid leukemia that has not responded to previous treatment or has returned after a period of improvement or is newly diagnosed. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab, azacitidine and ipilimumab may kill more cancer cells.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Acute Bilineal Leukemia
• Acute Biphenotypic Leukemia
• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Chronic Myelomonocytic Leukemia
• Leukemia
• Leukemia, Biphenotypic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia
• Syndrome
• Therapy-Related Acute Myeloid Leukemia

• NCT number: NCT02397720
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 2
• Start date: April 7, 2015
• Completion date: October 9, 2023