Trial record 2 of 2 for:    celldex act IV

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborators:
Celldex Therapeutics
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01834248
First received: April 12, 2013
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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, 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.


Condition Intervention Phase
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Chronic Myelomonocytic Leukemia
de Novo Myelodysplastic Syndromes
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Myeloid Leukemia
Refractory Anemia With Excess Blasts in Transformation
Untreated Adult Acute Myeloid Leukemia
Biological: DEC-205/NY-ESO-1 fusion protein CDX-1401
Drug: poly ICLC
Drug: decitabine
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of DEC205mAb-NY ESO 1 Fusion Protein (CDX-1401) Given With Adjuvant polyICLC in Conjunction With 5-Aza-2'Deoxycytidine (Decitabine) in Patients With MDS or Low Blast Count AML

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Grade 3+ adverse event and serious adverse event (SAE) rate, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 30 days after last dose of study treatment ] [ Designated as safety issue: Yes ]
    Toxicity rates will be described using upper one-sided 95% Clopper Pearson binomial confidence intervals.


Secondary Outcome Measures:
  • Immune and molecular epigenetic response [ Time Frame: At baseline and during treatment ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 15
Study Start Date: July 2013
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (CDX-1401, decitabine)
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 SC and ID and poly-ICLC SC on day -14 and day 15 of courses 1-4. 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-1401
Drug: poly ICLC
Given SC
Other Names:
  • Hiltonol
  • poly I:poly C with poly-1-lysine stabilizer
  • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
  • stabilized polyriboinosinic/polyribocytidylic acid
Drug: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Other: laboratory biomarker analysis
Correlative studies

Detailed 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 day -14 and day 15 of courses 1-4. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with a confirmed diagnosis of:

    • International Prognostic Scoring System (IPSS) intermediate-I, intermediate-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 and for the duration of study participation; 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

Exclusion Criteria:

  • 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(I 6;16); t(8;21) or t(1 5;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 extra-medullary 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 (eg. 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
  • Subjects previously treated with an allogeneic stem cell transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01834248

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    ASKRPCI@roswellpark.org   
Principal Investigator: Elizabeth A. Griffiths         
Sponsors and Collaborators
Roswell Park Cancer Institute
Celldex Therapeutics
Investigators
Principal Investigator: Elizabeth Griffiths Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01834248     History of Changes
Other Study ID Numbers: I 227712, NCI-2013-00565, I 227712, P30CA016056
Study First Received: April 12, 2013
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Anemia, Refractory
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Anemia, Refractory, with Excess of Blasts
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Disease
Pathologic Processes
Anemia
Myelodysplastic-Myeloproliferative Diseases
Poly ICLC
Poly I-C
Decitabine
Carboxymethylcellulose Sodium
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014