DEC-205/NY-ESO-1 Fusion Protein CDX-1401and Decitabine in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
|Acute Myeloid Leukemia Alkylating Agent-Related Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome Refractory Anemia With Excess Blasts in Transformation||Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401 Drug: Decitabine Other: Laboratory Biomarker Analysis Drug: Poly ICLC||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Study of DEC205mAb-NY-ESO-1 Fusion Protein (CDX-1401) Given With Adjuvant PoIylCLC in Conjunction With 5-Aza-2'Deoxycytidine (Decitabine) in Patients With MDS or Low Blast Count AML|
- Incidence of toxicity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days after last dose of study treatment ]Toxicity rates will be described using upper one-sided 95% Clopper Pearson binomial confidence intervals.
- Change in immune and molecular epigenetic response [ Time Frame: Baseline to up to 16 weeks ]Summarized by descriptive statistics (means, medians, quartiles, etc.) Confidence intervals will be constructed for the median and the mean. Exploratory graphical analysis will be used to discover associations among variables. The statistical significance of the change in marker values resulting from treatment will be assessed using the (paired sample) Wilcoxon Signed Rank test.
|Actual Study Start Date:||July 30, 2013|
|Study Completion Date:||March 21, 2016|
|Primary Completion Date:||June 9, 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (CDX-1401, Poly ICLC, decitabine)
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 SC and ID and poly-ICLC SC on days -14 and 15 of course 1 and on day 15 for courses 2-4. Patients also receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401
Given SC and ID
Other Name: CDX-1401Drug: Decitabine
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Poly ICLC
I. Evaluate the safety of Anti-DEC-205-NY-ESOI (CDX-1401) fusion protein (DEC-205/NY-ESO-1 fusion protein CDX-1401) given in combination with decitabine 20 mg/m^2 intravenously.
I. To evaluate NY-ESO-1 specific cellular and humoral immunity by determination of NY-ESO-1 specific antibody, and T-cell clones following standard treatment with 5-aza-2'-deoxycytidine (decitabine) in conjunction with immune sensitization with Anti-DEC 205-NY-ESO-I fusion protein (CDX-1401).
II. To determine the impact of decitabine treatment on peripheral blood cells from patients treated in this manner on NY-ESO-1 target gene expression, NY-ESO protein expression, NY-ESO-1 promoter methylation, and global deoxyribonucleic acid (DNA) methylation.
I. To record the response rate (complete response, partial response and hematological improvement) in myelodysplastic syndrome (MDS) or low blast count acute myeloid leukemia (AML) patients treated with the combination in order to provide descriptive characteristics.
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 subcutaneously (SC) and intradermally (ID) and poly-ICLC subcutaneously (SC) on days -14 and 15 of course 1 and on day 15 for courses 2-4. Patients also receive decitabine intravenously (IV) over 1 hour on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30, 60, 90, and 180 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01834248
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Elizabeth Griffiths||Roswell Park Cancer Institute|