Acute Myeloid LeukemiaPhase 1NCT03358719
DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, Decitabine, and Nivolumab in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
A Phase 1 study testing DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Decitabine and Laboratory Biomarker Analysis in people with Acute Myeloid Leukemia and Blasts 30 Percent or Less of Bone Marrow Nucleated Cells, run by Roswell Park Cancer Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Blasts 30 Percent or Less of Bone Marrow Nucleated Cells, Chronic Myelomonocytic Leukemia
- What is being tested?
- DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Decitabine and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Mar 2018to 25 Aug 2021
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
- Pregnant or nursing female subjects
- Unwilling or unable to follow protocol requirements
- Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
- Regular use of immunosuppressant drugs such as steroids (> 20 mg prednisone equivalents), azathioprine, tacrolimus, cyclosporine, etc>. Use is not permitted within 4 weeks before recruitment
Trial locations and contacts
1 site in 1 country.
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
Official title: A Phase 1 Study of DEC205mAb-NY ESO 1 Fusion Protein (CDX-1401) Given With Adjuvant Poly-ICLC in Conjunction With 5-Aza-2'Deoxycytidine (Decitabine) and Nivolumab in Patients With MDS or Low Blast Count AML
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.
Read the detailed description
PRIMARY OBJECTIVES:
- Evaluate the safety of NY-ESO-1 vaccination (Anti-DEC-205-NY-ESO-1 fusion protein + poly-ICLC) given in combination with decitabine 20 mg/m^2 intravenously and nivolumab 3 mg/kg in patients with myelodysplastic syndrome (MDS) or low blast count acute myeloid leukemia (AML).
SECONDRY OBJECTIVES:
- Assess immune and molecular epigenetic responses following combination therapy with nivolumab, decitabine and NY-ESO-1 fusion protein CDX-1401 (NY-ESO-1) vaccination.
TERTIARY OBJECTIVES:
- To record the response rate (complete response, partial response and hematological improvement) in MDS or low blast count AML patients treated with the combination in order to provide descriptive characteristics.
II. To record the overall survival (OS), progression free survival (PFS) and time to AML transformation (TTT) (for patients with MDS at diagnosis) enrolled on the study.
OUTLINE:
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 intracutaneously and poly ICLC subcutaneously (SC) on day -14, on day 15 of courses 1-4, and then on day 1 of every 4 courses thereafter. Patients also receive nivolumab intravenously (IV) over 30 minutes on days 1 and 15 and 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.
After completion of study treatment, patients are followed up at 30, 60, 90, and 180 days.
- 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
- Being tested
- DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Decitabine, Laboratory Biomarker Analysis, Nivolumab, Poly ICLC
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes, Anemia, Refractory
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DEC-205/NY-ESO-1 Fusion Protein CDX-1401Biological
Also called CDX-1401
Given intracutaneously
DecitabineDrug
Also called 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
Given IV
Poly ICLCDrug
Also called Hiltonol, Poly I:Poly C with Poly-L-Lysine Stabilizer, poly-ICLC, PolyI:PolyC with Poly-L-Lysine Stabilizer
Given SC
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Drug: Decitabine; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Drug: Poly ICLC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 180 days
Secondary outcomes (2)
Immune Cell Profile
Descriptive statistics will be used to evaluate the Immune cell profile in the peripheral blood and bone marrow following combination therapy using mass cytometry.
Measured: Up to 180 days
Peripheral Blood and Bone Marrow Cells Responses
The degree of DNA methylation at CpG sites within the promoter of the tumor antigen NY-ESO-1 was quantified. Results are reported as the percentage of methylated cytosines relative to the total cytosines at the analyzed CpG sites.
Measured: Cycle 1- 4 weekly to EOT (up to 180 days from baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2017
- Study start27 Mar 2018
- Primary completion27 Feb 2020
- Study completion25 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Celldex Therapeutics
- Responsible party
- Sponsor
- Investigators
- Elizabeth Griffiths, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03358719
- Sponsor's protocol ID
- I 49217
- Other IDs
- NCI-2017-02012, I 49217
- Status last verified
- Feb 2026
- First submitted
- 13 Nov 2017
- Last updated
- 27 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40809194