DEC-205/NY-ESO-1 Fusion Protein CDX-1401and Decitabine in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

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

Status Completed

Clinical Trial Summary

This phase I trial studies the side effects and immune response to DEC-205/NY-ESO-1 fusion protein CDX-1401 and decitabine in patients with myelodysplastic syndrome or acute myeloid leukemia. DEC-205-NY-ESO-1 fusion protein, called CDX-1401, is a full length NY-ESO-1 protein sequence fused to a monoclonal antibody against DEC-205, a surface marker present on many immune stimulatory cells. This drug is given with another substance called PolyICLC, which acts to provoke any immune stimulatory cells which encounter the NY-ESO-1-DEC-205 fusion protein to produce an immune response signal against NY-ESO-1. Immune cells which have thus been primed to react against NY-ESO-1 may then attack myelodysplastic or leukemic cells which express NY-ESO-1 after exposure to the drug decitabine. The chemotherapy drug decitabine is thought to act in several different ways, first, it may directly kill cancer cells, and secondly, the drug can cause cancer cells to re-express genes that are turned off by the cancer, including the gene for NY-ESO-1. Giving DEC-205/NY-ESO-1 fusion protein (CDX-1401) and polyICLC together with decitabine may allow the immune system to more effectively recognize cancer cells and kill them.

Clinical Trial Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.

OUTLINE:

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. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Alkylating Agent-Related Acute Myeloid Leukemia
• Anemia, Refractory, with Excess of Blasts
• Chronic Myelomonocytic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Refractory Anemia With Excess Blasts in Transformation
• Syndrome

• NCT number: NCT01834248
• Study type: Interventional
• Source: Roswell Park Cancer Institute
• Status: Completed
• Phase: Phase 1
• Start date: July 30, 2013
• Completion date: March 21, 2016