Trial record 3 of 158 for:    1401

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02129075
First received: April 30, 2014
Last updated: July 17, 2015
Last verified: July 2015
  Purpose

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 Intervention Phase
Carcinoma of Unknown Primary Origin
Iris Melanoma
Medium/Large Size Posterior Uveal Melanoma
Mucosal Melanoma
Ocular Melanoma With Extraocular Extension
Small Size Posterior Uveal Melanoma
Stage IIB Skin Melanoma
Stage IIB Uveal Melanoma
Stage IIC Skin Melanoma
Stage IIIA Skin Melanoma
Stage IIIA Uveal Melanoma
Stage IIIB Skin Melanoma
Stage IIIB Uveal Melanoma
Stage IIIC Skin Melanoma
Stage IIIC Uveal Melanoma
Stage IV Skin Melanoma
Stage IV Uveal Melanoma
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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Immune T-cell response to NY-ESO-1 [ Time Frame: Up to 12 weeks after final vaccination ] [ Designated as safety issue: No ]
    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 the response rates of the 2 treatments, with a significant difference declared if the 1-sided P value is =< 0.10.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Immune responses to other ongoing and nascent antitumor response antigens as well as memory and chronic viral responses [ Time Frame: Up to 12 weeks after final vaccination ] [ Designated as safety issue: No ]
  • Immunological response [ Time Frame: Up to 12 weeks after final vaccination ] [ Designated as safety issue: No ]
  • Incidence of adverse events, graded and reported using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 weeks after final vaccination ] [ Designated as safety issue: Yes ]
  • Survival [ Time Frame: Up to 1 year after patient's 12 week visit ] [ Designated as safety issue: No ]
  • Time to tumor recurrence [ Time Frame: Up to 12 weeks after final vaccination ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • CDX-301 serum level pharmacokinetic assessments [ Time Frame: Baseline (day -7) and days 1 and 8 of courses 1 and 2 ] [ Designated as safety issue: No ]
  • T cell infiltrates and NY-ESO-1 expression in pre-treatment tissue using immunohistochemistry [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: April 2014
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 day 1; 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

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).

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., preferentially expressed antigen in melanoma [PRAME], melanoma antigen family A, 3 [MAGE-A3], tumor protein p53 [p53], and premelanosome protein [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 2 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 day 1.

ARM II: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I.

In both arms, 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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: 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02129075

Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Jason J. Luke    773-834-7424      
Principal Investigator: Jason J. Luke         
United States, New Hampshire
Dartmouth Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Marc S. Ernstoff    603-650-5534    marc.s.ernstoff@hitchcock.org   
Principal Investigator: Marc S. Ernstoff         
United States, New York
Laura and Issac Perlmutter Cancer Center at NYU Langone Recruiting
New York, New York, United States, 10016
Contact: Anna C. Pavlick    212-263-4434    prmc.coordinator@nyumc.org   
Principal Investigator: Anna C. Pavlick         
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Paul B. Chapman    646-888-4162    chapmanp@mskcc.org   
Principal Investigator: Paul B. Chapman         
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Nina Bhardwaj    212-824-7320    jenny.figueroa@mssm.edu   
Principal Investigator: Nina Bhardwaj         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Brent A. Hanks    888-275-3853      
Principal Investigator: Brent A. Hanks         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Marc S. Ernstoff    866-223-8100      
Principal Investigator: Marc S. Ernstoff         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Brendan D. Curti    503-215-6412      
Principal Investigator: Brendan D. Curti         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Mark R. Albertini    877-405-6866      
Principal Investigator: Mark R. Albertini         
Sponsors and Collaborators
Investigators
Principal Investigator: Nina Bhardwaj Cancer Immunotherapy Trials Network
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02129075     History of Changes
Other Study ID Numbers: NCI-2014-00898, NCI-2014-00898, CITN-07-FLT3L, CITN-07-FLT3L, U01CA154967
Study First Received: April 30, 2014
Last Updated: July 17, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Melanoma
Neoplasms, Unknown Primary
Uveal Neoplasms
Eye Diseases
Eye Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplastic Processes
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Pathologic Processes
Uveal Diseases
Flt3 ligand protein
Poly ICLC
Adjuvants, Immunologic
Immunologic Factors
Interferon Inducers
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Protective Agents

ClinicalTrials.gov processed this record on September 01, 2015