Trial record 1 of 1 for:    NCT01834248
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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

April 12, 2013
July 14, 2014
July 2013
February 2016   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01834248 on ClinicalTrials.gov Archive Site
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
Not Provided
Not Provided
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DEC-205/NY-ESO-1 Fusion Protein CDX-1401and Decitabine in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
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

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
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.
Interventions:
  • Biological: DEC-205/NY-ESO-1 fusion protein CDX-1401
  • Drug: poly ICLC
  • Drug: decitabine
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
15
Not Provided
February 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States
 
NCT01834248
I 227712, NCI-2013-00565, I 227712, P30CA016056
No
Roswell Park Cancer Institute
Roswell Park Cancer Institute
  • National Cancer Institute (NCI)
  • Celldex Therapeutics
Principal Investigator: Elizabeth Griffiths Roswell Park Cancer Institute
Roswell Park Cancer Institute
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP