Guadecitabine and Atezolizumab in Treating Patients With Advanced Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia That Is Refractory or Relapsed
Last updated on July 2021Recruitment
- Recruitment Status
- Active, not recruiting
- Estimated Enrollment
- 72
Summary
- Conditions
- Chronic Myelomonocytic Leukemia
- Myelodysplastic Syndrome
- Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes
- Type
- Interventional
- Phase
- Phase 1Phase 2
- Design
- Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
Description
PRIMARY OBJECTIVES: I. To identify a safe dose of guadecitabine in combination with atezolizumab and to assess the safety and tolerability of the combination in patients with myelodysplastic syndrome (MDS) who are refractory to or have lost their confirmed response to one or more hypomethylating age...
PRIMARY OBJECTIVES: I. To identify a safe dose of guadecitabine in combination with atezolizumab and to assess the safety and tolerability of the combination in patients with myelodysplastic syndrome (MDS) who are refractory to or have lost their confirmed response to one or more hypomethylating agents (HMAs) and in patients with newly diagnosed MDS. II. To evaluate the efficacy of guadecitabine in combination with atezolizumab for the treatment of patients with MDS who are refractory to or have lost their confirmed response to one or more HMAs. III. To evaluate the efficacy of guadecitabine in combination with atezolizumab for the treatment of patients with newly diagnosis MDS. SECONDARY OBJECTIVES: I. To measure the impact of the combination of guadecitabine and atezolizumab on overall survival among patients with relapsed/refractory MDS. II. To measure the impact of the combination of guadecitabine and atezolizumab on overall survival among patients with treatment-naive MDS. III. To evaluate the impact of the combination of guadecitabine and atezolizumab on the duration of response in patients with relapsed/refractory MDS and treatment-naive MDS. IV. To evaluate the impact of the combination of guadecitabine and atezolizumab on transfusion-dependence among patients with relapsed/refractory and treatment-naive MDS. TERTIARY OBJECTIVES: I. To determine the baseline expression/methylation of programmed cell death protein 1 (PD-1) in T cells among patients with relapsed, refractory and treatment-naive MDS. II. To quantify the impact of combination therapy with guadecitabine and atezolizumab on PD-1 expression/methylation in T cells. III. To correlate response with expression/methylation of PD-1 by T cells and with expression of programmed cell death-ligand 1 (PD-L1) in the bone marrow of patients with MDS treated with guadecitabine and atezolizumab. IV. To investigate the expression of tumor antigens on MDS blasts during combination therapy with guadecitabine and atezolizumab V. To investigate the specific T-cell subsets in MDS blood and bone marrow during combination therapy with guadecitabine and atezolizumab. VI. To investigate the specific antigens (epitopes) which are recognized by T-cells in MDS blood and bone marrow during combination therapy with guadecitabine and atezolizumab. OUTLINE: This is a phase I, dose-escalation study of guadecitabine followed by a phase II study. Patients receive guadecitabine subcutaneously (SC) on days 1-5 and atezolizumab intravenously (IV) over 30-60 minutes on days 8 and 22. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 or 90 days and every 6 months thereafter.
Tracking Information
- NCT #
- NCT02935361
- Collaborators
- National Cancer Institute (NCI)
- Van Andel Research Institute
- Investigators
- Principal Investigator: Casey O'Connell University of Southern California