NCT02935361

Guadecitabine and Atezolizumab in Treating Patients With Advanced Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia That Is Refractory or Relapsed

A Phase I/II Multicenter Study Combining Guadecitabine, a DNA Methyltransferase Inhibitor, With Atezolizumab, an Immune Checkpoint Inhibitor, in Patients With Intermediate or High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: University of Southern California · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of guadecitabine when given together with atezolizumab and to see how well they work in treating patients with myelodysplastic syndrome or chronic myelomonocytic leukemia that has spread to other places in the body and has come back or does not respond to treatment. Guadecitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of cancer cells to grow and spread. Giving guadecitabine and atezolizumab may work better in treating patients with myelodysplastic syndrome or chronic myelomonocytic leukemia.

Detailed 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 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.

Conditions

• Chronic Myelomonocytic Leukemia
• Myelodysplastic Syndrome
• Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes

Interventions

Type	Name	Description
DRUG	Atezolizumab	Given IV
DRUG	Guadecitabine	Given SC

Timeline

• Start date: 2016-11-02
• Primary completion: 2026-12-31
• Completion: 2027-12-31
• First posted: 2016-10-17
• Last updated: 2026-01-29

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study