Clinical Trial: Therapy to Treat Ewing's Sarcoma, Rhabdomyosarcoma or Neuroblastoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Pilot Study of Tumor Vaccination and R-hIL-7 Following Standard Multimodality Therapy in Patients With High Risk Pediatric Solid Tumors

Brief Summary:

Background:

• Pediatric solid tumors (Ewing's sarcoma, rhabdomyosarcoma, and neuroblastoma) are often difficult to cure with standard treatment.
• Immune therapy using an experimental vaccine made from proteins from the patient's tumor cells may boost the body's immune response against the tumor.
• The effects of chemotherapy on the immune system can potentially make immunotherapy more effective if administered soon after completion of chemotherapy. The addition of recombinant human IL-7 (interleukin 7) (rhIL-7 (recombinant human interleukin 7)) may make the immunotherapy more effective.

Objectives:

-To determine whether immune therapy given after immune suppression can help the body fight the tumor and to determine the safety of the treatment.

Eligibility:

-Patients with solid tumors, i.e., Ewing's sarcoma, rhabdomyosarcoma or neuroblastoma whose disease has recurred after treatment or spread beyond the original site

Design:

• Patients undergo tumor biopsy (removal of a piece of tumor tissue) to collect tumor cells for making a vaccine from proteins in the patient's tumor and apheresis (removal of a quantity of white blood cells) to collect white cells for re-building the immune system after immune therapy. Apheresis is repeated three times during immunotherapy (weeks 8, 14 and 20).
• After receiving standard chemotherapy for their tumor (and an additional course of fludarabine and cyclophosphamide to further supp
  

  Detailed Summary:

  Background:

  • Patients with recurrent or metastatic pediatric solid tumors experience low survival rates, but using current standard therapies, many patients with these diseases are rendered into a state of minimal residual disease associated with lymphopenia.
  • Lymphopenic hosts show augmented immune reactivity, which may be favorable for inducing antitumor immune responses.

  Objectives:

  • To determine whether Alpha cluster of differentiation 25 (CD25) and 8H9 depleted autologous lymphocytes plus tumor lysate/keyhole limpet hemocyanin (KLH) pulsed dendritic cell vaccines plus or minus r-hIL7 (CYT107) can induce immune responses to tumor lysate in this patient population rendered lymphopenic by cytotoxic therapy.
  • To assess the safety of administering lymphocytes depleted of cluster of differentiation 4 (CD4) plus CD25plus suppressor T cells plus or minus r-hIL (CYT107 (interleukin 7)) to lymphopenic hosts.

  Eligibility:

  • Patients with metastatic or recurrent pediatric solid tumors of the following histologies: Ewing's sarcoma family of tumors, rhabdomyosarcoma or neuroblastoma, synovial cell sarcoma, desmoplastic small round cell tumor, undifferentiated sarcoma, embryonal sarcoma.
  • Patients must have sufficient accessible tumor for biopsy to generate tumor lysate.
  • Patients must meet eligibility criteria upon enrollment and upon completion of standard therapy prior to administration of immunotherapy as significant time will have elapsed betw
    Sponsor: National Cancer Institute (NCI)
    

    Current Primary Outcome:

    • Number of Participants With a Positive Immune Response as Evidenced by the Delayed Type of Hypersensitivity (DTH) Reaction Assay [ Time Frame: Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (± 7 days) (Arm B) ]

      A positive response to the tumor vaccine requires a positive reaction in at least one of the two assays below (immune responses to tumor lysates using ex vivo and delayed type of hypersensitivity (DTH).

      The presence of a positive delayed type of hypersensitivity (DTH) reaction to the tumor lysate in a patient who did not show a positive DTH reaction prior to immunotherapy. A positive reaction is induration of at least 0.5 cm.

      Immunotherapy administered to patients with recurrent or metastatic pediatric solid tumors such as Ewing's sarcoma, rhabdomyosarcoma, or neuroblastoma. Each vaccine is given as 6 separate injections. Three intradermal on one arm or leg and three subcutaneous on the other arm or leg.

    • Toxicity [ Time Frame: 49.5 months ]
      Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
    • Overall Survival [ Time Frame: At time of patients death ]
      Overall survival is defined as the time between the first day of treatment to the day of death.
    
    
    

    Original Primary Outcome: Immune response, feasibility, toxicity.
    
    

    Current Secondary Outcome:
    
    

    Original Secondary Outcome: Identify immunogenic tumor antigens, evaluate contamination after 8H9 purging, event-free and overall survival, evaluate diminished reconstitution, tumor-host immunobiology studies.
    
    Information By: National Institutes of Health Clinical Center (CC)
    

    Dates:
    Date Received: June 17, 2009
    Date Started: August 2007
    Date Completion: July 2017
    Last Updated: August 24, 2016
    Last Verified: August 2016