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

NCT01834248 | Completed Phase 1 DMC

• 2 other identifiers: I 227712NCI-2013-00565
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts in Transformation

Outcome Measures

Primary Outcomes (1)

• Incidence of toxicity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Toxicity rates will be described using upper one-sided 95% Clopper Pearson binomial confidence intervals.

  Up to 30 days after last dose of study treatment

Secondary Outcomes (1)

• Change in immune and molecular epigenetic response

  Baseline to up to 16 weeks

Study Arms (1)

Treatment (CDX-1401, Poly ICLC, decitabine)

EXPERIMENTAL

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; Drug: Decitabine; Other: Laboratory Biomarker Analysis; Drug: Poly ICLC

Interventions

DEC-205/NY-ESO-1 Fusion Protein CDX-1401 BIOLOGICAL

Given SC and ID

Also known as: CDX-1401

Treatment (CDX-1401, Poly ICLC, decitabine)

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (CDX-1401, Poly ICLC, decitabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (CDX-1401, Poly ICLC, decitabine)

Poly ICLC DRUG

Given SC

Also known as: Hiltonol, Poly I:Poly C with Poly-L-Lysine Stabilizer, poly-ICLC, PolyI:PolyC with Poly-L-Lysine Stabilizer, Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose, Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose, Stabilized Polyriboinosinic/Polyribocytidylic Acid

Treatment (CDX-1401, Poly ICLC, decitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with a confirmed diagnosis of:
• International Prognostic Scoring System (IPSS) intermediate-I, interrnediate-2 or high-risk MDS including chronic myelomonocytic leukemia (CMML) or
• Low blast count AML with =\< 30% blasts previously classified as refractory anemia with excess blasts in transformation who have not been previously treated with a hypomethylating agent
• Patients with IPSS intermediate-1 disease with an isolated deletion of chromosome 5q must have previously failed treatment with lenalidomide
• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Total bilirubin =\< 2 x upper limit of normal (ULN)
• Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine transaminase (ALT/serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN
• Serum creatinine =\< 1.5 x ULN
• Any human leukocyte antigen (HLA) type
• Subjects of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after the last treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

You may not qualify if:

• Subjects with life-threatening illnesses other than MDS, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study outcomes at risk
• AML associated with inv(16); t(16;16); t(8;21) or t(15;17)
• Subjects with uncontrolled or symptomatic arrhythmias, or any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification
• Subjects with symptomatic central nervous system (CNS) disease which is not adequately controlled
• Subjects who have received prior radiation therapy for extramedullary disease within 2 weeks of first dose
• Subjects with human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Subjects who are being treated with systemic corticosteroids
• Subjects who have hypersensitivity to decitabine
• History of auto-immune disease (e.g. thyroiditis, lupus) except vitiligo
• Pregnant or nursing female subjects
• Unwilling or unable to follow protocol requirements
• Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug
• Received an investigational agent within 30 days prior to enrollment
• Active malignancy with the exception of basal cell carcinoma, non-melanoma skin cancer, cervical carcinoma-in-situ; other prior malignancies in remission for less than 1 year

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

Decitabine; Injections; poly ICLC

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Elizabeth Griffiths

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2013
• First Posted: April 17, 2013
• Study Start: July 30, 2013
• Primary Completion: June 9, 2015
• Study Completion: March 21, 2016
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

US (1)