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

NCT03358719 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: I 49217NCI-2017-02012
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects of DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, decitabine, and nivolumab in treating patients with myelodysplastic syndrome or acute myeloid leukemia. DEC-205/NY-ESO-1 fusion protein CDX-1401 is a vaccine that may help the immune system specifically target and kill cancer cells. Poly ICLC may help stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as nivolumab, may interfere with the ability of cancer cells to grow and spread. Giving DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, decitabine, and nivolumab may work better in treating patients with myelodysplastic syndrome or acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia; Blasts 30 Percent or Less of Bone Marrow Nucleated Cells; Chronic Myelomonocytic Leukemia; High Risk Myelodysplastic Syndrome; Myelodysplastic Syndrome; Refractory Anemia

Outcome Measures

Primary Outcomes (1)

• Proportion or Participants Experiencing a Dose-limiting Toxicity

  Will evaluate the proportion of n=8 evaluable patients in the expansion cohort experiencing a dose-limiting toxicity. Toxicity rates will be described using upper 1-sided 95% Jeffreys binomial confidence intervals.

  Up to 180 days

Secondary Outcomes (2)

• Immune Cell Profile

  Up to 180 days

• Peripheral Blood and Bone Marrow Cells Responses

  Cycle 1- 4 weekly to EOT (up to 180 days from baseline)

Other Outcomes (3)

• Complete Response Rate

  Up to 180 days

• Partial Response Rate

  Up to 180 days

• Hematologic Improvement

  Up to 180 days

Study Arms (1)

Treatment (CDX-1401, poly ICLC, decitabine, nivolumab)

EXPERIMENTAL

Patients receive 1mg/1.8mg DEC-205/NY-ESO-1 fusion protein CDX-1401 intracutaneously and poly ICLC SC on day -14, on day 15 of courses 1-4, and then on day 1 of every 4 courses thereafter. Patients also receive 3mg/kg nivolumab IV over 30 minutes on days 1 and 15 and 20 mg/m2 decitabine IV over 1 hour on days 1-5. Courses with nivolumab and decitabine repeat every 4 weeks in the absence of disease progression or unaccepted toxicity.

Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Drug: Decitabine; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Drug: Poly ICLC

Interventions

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

Given intracutaneously

Also known as: CDX-1401

Treatment (CDX-1401, poly ICLC, decitabine, nivolumab)

Decitabine DRUG

Given IV

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

Treatment (CDX-1401, poly ICLC, decitabine, nivolumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (CDX-1401, poly ICLC, decitabine, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (CDX-1401, poly ICLC, decitabine, nivolumab)

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, nivolumab)

Eligibility Criteria

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

You may qualify if:

• Have a confirmed diagnosis of:
• International Prognostic Scoring System (IPSS) intermediate-1, 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
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Hepatic:
• Total bilirubin =\< 3 X upper limit of normal (ULN) (except subjects with Gilbert syndrome, who can have total bilirubin up to 3.5 X ULN)
• Aspartate aminotransferase (aspartate transaminase \[AST\]/serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (alanine transaminase \[ALT\]/serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 X ULN
• Serum creatinine =\< 2.5 X ULN
• Troponin-I =\< ULN
• Creatine kinase (CK)-MB =\< ULN
• Left ventricular ejection fraction (LVEF) \>= ULN (institutional limit)
• Participants 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; 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
• Participant 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
• No prior exposure to Nivolumab
• No prior investigational therapy within 2 weeks prior to study enrollment

You may not qualify if:

• We will exclude patients who are eligible for an allogeneic bone marrow transplant at the time of study enrollment; if an enrolled patient subsequently becomes eligible for transplant, they will not be prevented from proceeding to the appropriate clinical treatment indicated
• 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)
• Previously untreated MDS with isolated del5q (for which lenalidomide is approved as approved therapy) and chronic myelomonocytic leukemia (CMML) with rearrangements of the PDGF receptor (for which imatinib is approved therapy) unless they have previously failed these approaches
• 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
• Has known immunosuppressive disease (e.g. human immunodeficiency virus \[HIV\], acquired immunodeficiency syndrome \[AIDS\] or other immune depressing disease); testing is not required, only to be done for a possible diagnosis which is not confirmed
• 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; in addition, subjects will be excluded for any of the following:
• Myocardial infarction or arterial or venous thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) class III or IV disease
• Active congestive heart failure (New York Heart Association functional classification III or IV)
• Documented history of cardiomyopathy with EF \< 30%
• Uncontrolled hypertension (systolic blood pressure \[SBP\] \> 160/diastolic blood pressure \[DBP\] \> 100 despite medical intervention)
• History of myocarditis of any etiology
• Subjects who have hypersensitivity to decitabine, CDX-1401, poly-ICLC or nivolumab
• History of auto-immune disease (e.g., thyroiditis, lupus), except vitiligo

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Celldex Therapeutics: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Related Publications (1)

• Griffiths EA, Srivastava P, Gomez EC, Matsuzaki J, Odunsi K, Dillon LW, Mukherjee D, Hourigan CS, Peng J, Bandyopadhyay S, Tan K, Attwood KM, Kuechle JB, Singh PK, Wang J, Nemeth MJ. Checkpoint immunotherapy is associated with preferential activation of tumor antigen-specific CD4+ T cells in MDS. Blood Neoplasia. 2025 Apr 25;2(3):100106. doi: 10.1016/j.bneo.2025.100106. eCollection 2025 Aug.

  PMID: 40809194 DERIVED

MeSH Terms

Conditions

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

Interventions

Decitabine; Injections; Nivolumab; 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; Anemia

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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Comprehensive Cancer Center

Elizabeth.Griffiths@RoswellPark.org

716-845-2300

Study Officials

• Elizabeth Griffiths

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: November 13, 2017
• First Posted: December 2, 2017
• Study Start: March 27, 2018
• Primary Completion: February 27, 2020
• Study Completion: August 25, 2021
• Last Updated: February 27, 2026
• Results First Posted: February 27, 2026

Record last verified: 2026-02

Locations

US (1)