Avelumab and Azacitidine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia

Refractory Acute Myeloid Leukemia Clinical Trial

Official title: An Open-Label Phase Ib/II Study of Avelumab in Combination With 5-Azacytidine (Vidaza) for the Treatment of Patients With Refractory/Relapsed Acute Myeloid Leukemia

Status Terminated

Clinical Trial Summary

This phase Ib/II trial studies the best dose and side effects of avelumab when given together with azacitidine and to see how well they work in treating patients with acute myeloid leukemia that is not responding to treatment or has come back. Monoclonal antibodies, such as avelumab, may interfere with the ability of cancer cells to grow and spread. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving avelumab and azacitidine may work better in treating patients with acute myeloid leukemia.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of avelumab in combination with azacitidine (5-azacytidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Phase IB)

II. To determine the overall response rate (ORR) defined as complete remission (CR)/complete remission with incomplete platelet recovery (CRp)/complete remission with incomplete count recovery (CRi)/partial remission (PR)/hematologic improvement (HI)/morphologic leukemia free state (MLFS) of avelumab in combination with 5-azacytidine in patients with refractory/relapsed AML. (Phase II

SECONDARY OBJECTIVES:

I. To determine the number of patients achieve > 50% reduction in blasts on therapy with this combination.

II. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination

TERTIARY OBJECTIVES:

I. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to include quantify immune ligand expression by the AML blasts and AML stromal components (myeloid-derived suppressor cells [MDSCs] and mesenchymal stem cells [MSCs]) including 4-1BBL, ICOSL, PD-L1, PD-L2, OX-40L, CD137L.

II. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to determine the quantitative expression of positive and negative co-stimulatory molecules on individual T-lymphocyte subsets including 4-1BB, CTLA-4, ICOS, PD-1, OX40, LAG-3 and TIM-3.

III. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to identify the immunophenotype of tumor-infiltrating T-lymphocytes (TILs) pre- and post-therapy with the combination: CD8+, CD4+ effector, or CD4+ regulatory.

IV. To develop a micro-array based gene expression profile (GEP) predictor of response to anti-PDL1 and epigenetic therapy in AML.

V. To determine the correlation of responses to the combination with baseline cytogenetic and molecular abnormalities

OUTLINE: This is a phase Ib, dose-escalation study of avelumab followed by a phase II study

Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

After completion of study treatment, patients are followed up every 3-6 months for up to 5 years. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

• NCT number: NCT02953561
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 20, 2017
• Completion date: September 30, 2019