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CDX-1401 and Poly-ICLC Vaccine Therapy With or Without CDX-301 in Treating Patients With Stage IIB-IV Melanoma

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ClinicalTrials.gov Identifier: NCT02129075
Recruitment Status : Suspended (Drug supply issues)
First Posted : May 2, 2014
Last Update Posted : March 13, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized phase II trial studies how well DEC-205/NY-ESO-1 fusion protein CDX-1401 (CDX-1401) and neoantigen-based melanoma-poly-ICLC vaccine (poly-ICLC) vaccine therapy work when given with or without recombinant flt3 ligand (CDX-301) in treating patients with stage IIB-IV melanoma. The cancer vaccine CDX-1401 attaches to a protein that is made in tumor cells. The vaccine helps the body recognize the tumor to fight the cancer. The CDX-301 vaccine may help the body make more of the tumor fighting cells, known as dendritic cells. The poly-ICLC vaccine stimulates the immune system and may help these dendritic cells mature so that they can recognize the tumor. It is not yet known whether CDX-1401 and poly-ICLC will work better with or without CDX-301 in treating melanoma.

Condition or disease Intervention/treatment Phase
Cutaneous Melanoma Mucosal Melanoma NY-ESO-1 Positive Tumor Cells Present Ocular Melanoma Stage IIB Cutaneous Melanoma AJCC v6 and v7 Stage IIC Cutaneous Melanoma AJCC v6 and v7 Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401 Other: Laboratory Biomarker Analysis Biological: Neoantigen-based Melanoma-Poly-ICLC Vaccine Other: Pharmacological Study Biological: Recombinant Flt3 Ligand Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether the immune response to cancer/testis antigen 1B (NY-ESO-1) elicited by vaccination with CDX-1401 (anti-DEC205-NY-ESO-1 fusion protein vaccine) plus polyinosinic-polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (poly-ICLC) is substantially increased by prior expansion in the number of circulating dendritic cells (DC) by therapy with CDX-301 (fms-related tyrosine kinase 3 ligand [Flt3L]) (recombinant flt3 ligand).

II. To determine whether the proportion of responders to NY-ESO-1 is > 50% when T cell responses are elicited by vaccination with CDX-1401 plus poly-ICLC in combination with CDX-301 (Flt3L) 75 mcg/kg/day administered prior to vaccination for 5 days in both of the first two vaccine cycles; and for 5 days in the first vaccine cycle only.

SECONDARY OBJECTIVES:

I. To assess the effect of the vaccine regimen on immune responses to other ongoing and nascent antitumor response antigens associated with melanoma (e.g., PRAME, MAGE-A3, p53, and gp100) as well as memory viral responses (influenza A) and chronic viral responses (cytomegalovirus [CMV], Epstein-Barr virus [EBV]).

II. To assess the effect of the vaccine regimen on the frequency and phenotypic character of peripheral blood mononuclear cell (PBMC) subsets including DCs, monocyte populations, T cells, and natural killer (NK) cells.

III. To assess the safety, tolerability, and clinical efficacy of the vaccine regimens.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive recombinant flt3 ligand subcutaneously (SC) on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or intradermally (ID) on day 1; and poly-ICLC SC on days 1 and 2. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive recombinant flt3 ligand SC on days -7 to -3 and 22-26 of course 1 only and DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM IV: Patients receive recombinant flt3 ligand SC on days -7 to -3 of course 1 only, and DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 and 12 weeks and then annually thereafter.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-Label, Multicenter, Randomized Study of CDX-1401, a Dendritic Cell Targeting NY-ESO-1 Vaccine, in Patients With Malignant Melanoma Pre-treated With Recombinant CDX-301, a Recombinant Human Flt3 Ligand
Actual Study Start Date : April 9, 2014
Estimated Primary Completion Date : February 2, 2020


Arm Intervention/treatment
Experimental: Arm I (CDX-301, CDX-1401, and poly-ICLC)
Patients receive recombinant flt3 ligand SC on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or ID on days 1 and 2; and poly-ICLC SC on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401
Given SC or ID
Other Name: CDX-1401
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Neoantigen-based Melanoma-Poly-ICLC Vaccine
Given SC
Other Name: NeoVax Melanoma Vaccine
Other: Pharmacological Study
Correlative studies
Biological: Recombinant Flt3 Ligand
Given SC
Other Names:
  • CDX-301
  • FLT 3 Ligand
  • FLT3 Ligand
  • Flt3-Ligand
  • Flt3L
  • Mobist
  • Mobista
  • rhuFlt3L
Active Comparator: Arm II (CDX-1401 and poly-ICLC)
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401
Given SC or ID
Other Name: CDX-1401
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Neoantigen-based Melanoma-Poly-ICLC Vaccine
Given SC
Other Name: NeoVax Melanoma Vaccine
Other: Pharmacological Study
Correlative studies
Experimental: Arm III (CDX-301, CDX-1401, and poly-ICLC)
Patients receive recombinant flt3 ligand SC on days -7 to -3 and 22-26 of course 1 only and DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401
Given SC or ID
Other Name: CDX-1401
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Neoantigen-based Melanoma-Poly-ICLC Vaccine
Given SC
Other Name: NeoVax Melanoma Vaccine
Other: Pharmacological Study
Correlative studies
Biological: Recombinant Flt3 Ligand
Given SC
Other Names:
  • CDX-301
  • FLT 3 Ligand
  • FLT3 Ligand
  • Flt3-Ligand
  • Flt3L
  • Mobist
  • Mobista
  • rhuFlt3L
Experimental: Arm IV (CDX-301, CDX-1401, and poly-ICLC)
Patients receive recombinant flt3 ligand SC on days -7 to -3 of course 1 only, and DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401
Given SC or ID
Other Name: CDX-1401
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Neoantigen-based Melanoma-Poly-ICLC Vaccine
Given SC
Other Name: NeoVax Melanoma Vaccine
Other: Pharmacological Study
Correlative studies
Biological: Recombinant Flt3 Ligand
Given SC
Other Names:
  • CDX-301
  • FLT 3 Ligand
  • FLT3 Ligand
  • Flt3-Ligand
  • Flt3L
  • Mobist
  • Mobista
  • rhuFlt3L



Primary Outcome Measures :
  1. Immune T-cell response to NY-ESO-1 [ Time Frame: At 4 weeks after final vaccination ]
    Will be compared between cohorts 3 and 4. One-sided binomial exact test with significance level of 0.1 will be performed, assuming the proportion of responders of 50% as the null hypothesis. One-sided 90% confidence interval estimate will be calculated for the proportion of responders.

  2. Immune T-cell response to NY-ESO-1 [ Time Frame: At 12 weeks after final vaccination ]
    Response rates will be analyzed by tabulating the frequency of positive response for each assay by antigen and treatment arm at each time point for which an assessment is performed. Response rates will be presented with their corresponding 95% confidence interval estimates calculated using the score test method. Fisher's exact tests will be used to compare cohort 1 and cohort 2 at the peak time point, with a significant difference declared if the 1-sided P value is =< 0.10.


Secondary Outcome Measures :
  1. T cell responses to other ongoing and nascent antitumor response antigens associated with melanoma (e.g. PRAME, MAGE-A3, p53, and gp1000) as well as memory and chronic viral responses (CMV, EBV) [ Time Frame: Up to 12 weeks after final vaccination ]
    Will be considered between each pair of randomized cohorts.

  2. Frequency and phenotypic character of PBMC subsets including DCs, monocyte populations, T cells, and NK cells [ Time Frame: Up to 12 weeks after final vaccination ]
    Graphical and tabular summaries of the assay data will be made. Linear mixed effects model and possibly weighted generalized estimating equation methods will be considered for a supportive analysis of the longitudinal data over time.

  3. Incidence of adverse events, graded and reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 12 weeks after final vaccination ]
    Will be presented in tabular form.

  4. Dose limiting toxicities graded and reported using the NCI CTCAE version 4.0 [ Time Frame: Up to 12 weeks after final vaccination ]
    Will be presented in tabular form.

  5. Time to tumor recurrence [ Time Frame: Up to 12 weeks after final vaccination ]
    Summarized by treatment arms using Kaplan-Meier estimates.

  6. Overall survival [ Time Frame: Up to 1 year after patient's 12 week visit ]
    Summarized by treatment arms using Kaplan-Meier estimates.

  7. Change in T cell receptor sequencing in blood (Cohorts 3 and 4) [ Time Frame: Baseline up to 12 weeks after final vaccination ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with fully resected stage IIb through IV melanoma, with melanoma validated by histology or cytology, who have NOT received prior therapy

    • Patients may have had primary cutaneous, mucosal, or ocular melanoma or metastasis from an unknown primary site
    • Tissue should be submitted for evaluation of NY-ESO-1 expression and T-cell infiltrates; however, availability of tissue and/or positivity for NY-ESO-1 is not mandatory
  • Prior therapy requirements:

    • Prior radiation, chemotherapy or biologics NOT allowed
  • Not currently receiving any anticancer therapy
  • Eastern Cooperative Oncology Group (ECOG) performance score of 0-1
  • Life expectancy of at least 6 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 75,000/mcL
  • Hemoglobin > 9 g/dL
  • Total bilirubin < 1.5 x institutional upper limit of normal (bilirubin < 3 x institutional upper limit of normal for Gilbert's syndrome)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine < 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • The first six patients enrolled in the Flt3L arm of the study cannot be human immunodeficiency virus (HIV)-positive; after the evaluation of safety in the first 6 patients, HIV-positive patients with adequate immune function as evidenced by stable cluster of differentiation (CD)4 counts >= 350/mm^3 are allowed to participate if the following criteria are met:

    • Maintained on stable antiretroviral therapy with no significant drug interactions, and
    • No recent history of acquired immune deficiency syndrome (AIDS) indicator conditions (> 2 years from enrolling in trial), and
    • Physician providing patient's care for HIV must also approve of patient entering the study
  • Both men and women of all races and ethnic groups are eligible for this trial
  • Females of childbearing potential must have a negative pregnancy test within 7 days before the initiation of protocol therapy

    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) before 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; men treated or enrolled on this protocol must also agree to use adequate contraception before the study, for the duration of study participation, and 4 months after completion of CDX-1401 or CDX-301 administration
    • NOTE: Subjects are considered not of child bearing potential if they are surgically sterile, they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or they are postmenopausal; menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential; by a practical definition, it assumes menopause after 1 year without menses with an appropriate clinical profile at the appropriate age
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had cytotoxic chemotherapy, radiotherapy, interferon (IFN), or ipilimumab before entering the study
  • Immunosuppressive therapy within 30 days prior to initiation of protocol therapy
  • Steroid therapy, or steroid therapy with more than 7 consecutive days of steroids within the prior 4 weeks

    • The use of prednisone or equivalent < 0.125 mg/kg/day (absolute maximum of 10 mg/day) as replacement therapy is permitted
    • Inhaled or topical corticosteroids are permitted
  • Patients who are receiving any other investigational agents
  • Current or history of systemic autoimmune disease requiring systemic therapy

    • NOTE: The following will not be exclusionary:

      • The presence of laboratory evidence of autoimmune disease (e.g., positive ANA titer) without associated symptoms
      • Clinical evidence of vitiligo
      • Other forms of depigmenting illness
  • Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
  • Cirrhosis or chronic hepatitis C virus positivity or chronic hepatitis B infection

    • NOTE: A positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antibody [HBsAb]-positive and hepatitis B core antibody [HBcAb]-negative), or a fully resolved acute hepatitis B virus infection is not an exclusion criterion
  • Known history of immunodeficiency disorder other than HIV-positive status
  • Extensive active brain disease including symptomatic brain metastases or presence of leptomeningeal disease

    • NOTE: Patients with brain metastasis, after definitive therapy with surgery or stereotactic radiation and stable off steroids for >= 4 weeks, are eligible
  • Other invasive cancers that are clinically active
  • Pregnancy or nursing or unwilling to take adequate birth control during therapy

    • NOTE: Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with CDX-1401 or CDX-301 and poly-ICLC
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-1401 or CDX-301 or poly-ICLC
  • Prior organ allograft or allogeneic transplantation, if the transplanted tissue is still in place
  • 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
  • Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
  • History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second [FEV1] < 60% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with prolonged smoking history or symptoms of respiratory dysfunction
  • Vaccinations other than those given as part of this research study (with the exception of influenza vaccine) are prohibited throughout the duration of study participation

    • NOTE: Influenza vaccination (inactivated) is permitted during the flu season; the preferred time is 7 to 14 days after CDX-1401 administration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02129075


Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
United States, New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States, 10016
Mount Sinai Hospital
New York, New York, United States, 10029
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Nina Bhardwaj Cancer Immunotherapy Trials Network

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02129075     History of Changes
Other Study ID Numbers: NCI-2014-00898
NCI-2014-00898 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
s14-01284
CITN-07-FLT3L
CITN-07-FLT3L ( Other Identifier: Cancer Immunotherapy Trials Network )
CITN-07-FLT3L ( Other Identifier: CTEP )
P30CA015704 ( U.S. NIH Grant/Contract )
U01CA154967 ( U.S. NIH Grant/Contract )
First Posted: May 2, 2014    Key Record Dates
Last Update Posted: March 13, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Vaccines
Poly ICLC
Poly I-C
Flt3 ligand protein
Carboxymethylcellulose Sodium
Immunologic Factors
Physiological Effects of Drugs
Interferon Inducers
Laxatives
Gastrointestinal Agents
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Radiation-Protective Agents
Protective Agents