Clinical Trials /

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

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: I 49217
  • SECONDARY ID: NCI-2017-02012
  • SECONDARY ID: I 49217
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT03358719

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

Interventions

DrugSynonymsArms
DEC-205/NY-ESO-1 Fusion Protein CDX-1401CDX-1401Treatment (CDX-1401, poly ICLC, decitabine, nivolumab)
Decitabine5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, DezocitidineTreatment (CDX-1401, poly ICLC, decitabine, nivolumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (CDX-1401, poly ICLC, decitabine, nivolumab)
Poly ICLCHiltonol, 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 AcidTreatment (CDX-1401, poly ICLC, decitabine, nivolumab)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      I. 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:

      I. 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 60 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (CDX-1401, poly ICLC, decitabine, nivolumab)ExperimentalPatients receive 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 nivolumab IV over 60 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.
  • Decitabine
  • Poly ICLC

Eligibility Criteria

        Inclusion Criteria:

          -  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 and, who have not been previously treated
                  with a hypomethylating agent

          -  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

          -  Brain natriuretic peptide (BNP) =< 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 treatment with a hypomethylating agent, or previous exposure to CDX-1401

          -  No prior investigational therapy within 2 weeks prior to study enrollment

        Exclusion Criteria:

          -  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

               -  History of documented congestive heart failure (New York Heart Association
                  functional classification III or IV)

               -  Documented history of cardiomyopathy

               -  Uncontrolled hypertension (systolic blood pressure [SBP] > 160/diastolic blood
                  pressure [DBP] > 100 despite medical intervention)

               -  History of myocarditis of any etiology

               -  History of cardiac surgery

               -  History of ventricular arrhythmias

          -  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 (> 15 mg prednisone
             equivalents), azathioprine, tacrolimus, cyclosporine, etc; use is not permitted within
             4 weeks before recruitment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 180 days
Safety Issue:
Description:Will evaluate the proportion of n=12 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.

Secondary Outcome Measures

Measure:Immune cell profile
Time Frame:Up to 180 days
Safety Issue:
Description:Descriptive statistics will be used to evaluate the Immune cell profile in the peripheral blood and bone marrow following combination therapy using mass cytometry.
Measure:Peripheral blood and bone marrow cells responses
Time Frame:Up to 180 days
Safety Issue:
Description:Will determine the impact of combination treatment on peripheral blood and bone marrow cells from patients treated in this manner on NY-ESO-1 target gene expression, NY-ESO-1 protein expression, NY-ESO-1 promoter methylation, and global deoxyribonucleic acid (DNA) methylation. The statistical significance of the change in marker values resulting from treatment will be assessed using the (paired sample) Wilcoxon Signed Rank test.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

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