Guadecitabine and Atezolizumab in Treating Patients With Advanced Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia That Is Refractory or Relapsed
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|ClinicalTrials.gov Identifier: NCT02935361|
Recruitment Status : Active, not recruiting
First Posted : October 17, 2016
Last Update Posted : April 6, 2021
|Condition or disease||Intervention/treatment||Phase|
|Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes||Drug: Atezolizumab Drug: Guadecitabine||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||November 2, 2016|
|Estimated Primary Completion Date :||November 30, 2022|
|Estimated Study Completion Date :||November 30, 2023|
Experimental: Treatment (guadecitabine, atezolizumab)
Patients receive guadecitabine SC on days 1-5 and atezolizumab 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.
- Incidence of dose-limiting toxicities evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) [ Time Frame: Up to 56 days ]Descriptive summaries and analyses of CTCAE 4.0 toxicities that occur will be produced, both by patient and by cycle.
- Overall response (complete response [CR] + partial response + marrow CR + hematological improvement) (Phase II) [ Time Frame: Up to 168 days ]
- Incidence of grade 3 or higher adverse events and grade 2 toxicities that do not resolve after 3 weeks assessed by CTCAE 4.0 [ Time Frame: Up to 8 weeks ]Descriptive summaries of toxicities that occur will be produced, both by patient and by course.
- Overall response rate (Phase II) [ Time Frame: Up to 4 years ]
- Overall survival [ Time Frame: From start of treatment to death from any cause, assessed up to 4 years ]Will be analyzed using survival analysis methods.
- Percentage of patients who were transfusion-dependent on study entry who become transfusion-independent [ Time Frame: Up to 4 years ]
- Progression free survival [ Time Frame: From start of treatment to the first disease progression or recurrence, assessed up to 4 years ]Will be analyzed using survival analysis methods.
- Time to best response [ Time Frame: Up to 4 years ]Will be analyzed using survival analysis methods.
- Degree of PD-L1 expression assessed in bone marrow, T cells, and malignant cells by immunohistochemistry or flow cytometry [ Time Frame: Up to 4 years ]
- PD-1 expression by T cells and malignant cells [ Time Frame: Up to 4 years ]Relationship of PD-1/PD-L1 expression to efficacy endpoints will be explored.
- Percentage of T cells expressing PD-1/methylation levels [ Time Frame: Up to 4 years ]
- T-cell antigen recognition in MDS blood and bone marrow [ Time Frame: Up to 4 years ]Relationship of T-cell antigen recognition to efficacy endpoints will be explored.
- T-cell subset combinations in MDS blood and bone marrow [ Time Frame: Up to 4 years ]Relationship of T-cell subset combination to efficacy endpoints will be explored.
- Tumor antigen expression on MDS blasts [ Time Frame: Up to 4 years ]Relationship of tumor expression to efficacy endpoints will be explored.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02935361
|United States, California|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|United States, Maryland|
|University of Maryland Medical Center|
|Baltimore, Maryland, United States, 21201|
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111|
|Temple University Hospital|
|Philadelphia, Pennsylvania, United States, 19140|
|Principal Investigator:||Casey O'Connell||University of Southern California|