Pembrolizumab and Decitabine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome That Is Newly-Diagnosed, Recurrent, or Refractory

Summary

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Description

PRIMARY OBJECTIVES: I. Assess the safety and tolerability of pembrolizumab in combination with decitabine, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. II. Determine the maximum tolerated dose(s)/schedule (MTD) and phase 2 recommended dose(...

PRIMARY OBJECTIVES: I. Assess the safety and tolerability of pembrolizumab in combination with decitabine, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. II. Determine the maximum tolerated dose(s)/schedule (MTD) and phase 2 recommended dose(s)/ schedule (RP2D) of the combination for acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). III. Obtain preliminary estimate of complete remission (CR/CR with incomplete hematologic recovery [CRi]) rate. SECONDARY OBJECTIVES: I. Obtain estimates of remission duration and survival probabilities (overall and progression-free) at 2 years. II. Explore the possible association between pre-treatment PD-1, PD-L1, and PD-L2 and clinical response. III. Evaluate change in PD-1, PD-L1, PD-L2 levels as a result of the combination therapy. IV. Explore the possible association between specific T cell subsets (e.g. CD4 T regulatory cells, T naive, effector and memory cells), other immunological correlatives (e.g. T-cell receptor [TCR] repertoire analysis) including post-treatment changes, and clinical response to combination therapy. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT I: Patients with AML receive pembrolizumab intravenously (IV) over 30 minutes on days 1 and 22 and decitabine IV over 1 hour on days 1-10. Patients who achieve a CR receive decitabine on days 1-5. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity. COHORT II: Patients with MDS receive pembrolizumab IV over 30 minutes on days 1 and 22 and decitabine over 1 hour on days 1-5. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days, then every 3 and 6 months for up to 2 years.

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