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

  • Interventional
  • Not Recruiting
  • NCT02129075
Eligibility Details Visit Clinicaltrials.gov

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

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.

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.

Gender
All

Age Group
18 Years and up

Accepting Healthy Volunteers?
No

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

At a Glance

National Government IDNCT02129075

IRB#IRB14-1520

Lead SponsorNational Cancer Institute (NCI)

Lead PhysicianThomas F. Gajewski

Collaborator(s)N/A

EligibilityAll
18 Years and up
Not Recruiting