Therapy to Treat Ewing's Sarcoma, Rhabdomyosarcoma or Neuroblastoma
Condition: Neuroblastoma; Sarcoma; Rhabdomyosarcoma-Embryonal; Rhabdomyosarcoma- Alveolar; Neuroectodermal Tumors, Primitive, Peripheral
MeSH terms: Sarcoma; Neuroblastoma; Rhabdomyosarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral
Study type: Interventional
Phase: Phase 1/Phase 2

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 suppress immunity if needed) patients
           receive immune therapy in Cohorts A and B. rhIL-7 is given 48 hours before the vaccine,
           as an injection under the skin in an extremity that will not be used for the vaccine in
           patients in Cohort B only. You will be watched closely for 6 hours after the rhIL-7 for
           any signs of reaction. rhIL-7 will be given before vaccine doses #1, #2, #3, and #4. The
           vaccine is given at study weeks 2, 4, 6, 8, 10 and 12. Each vaccine is given as a total
           of six separate rhIL-7 followed by injections: three intradermal (like a (tuberculosis)
           TB test) on one arm or leg and three subcutaneous (like those for insulin injections for
           diabetes). on the other arm or leg. An anesthetic cream may be used to minimize the
           discomfort of injections.

        -  Patients' white cells are returned to them by infusion through a vein on the first day
           of immune therapy.

        -  Imaging studies and immune studies are done at weeks 1, 8 and 20 to determine the
           response to treatment on the tumor and on the immune system.
    

Detailed description: 
      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
           between the time points.

      Design:

        -  Immunotherapy consists of one autologous lymphocyte infusion depleted of CD25plus
           suppressive T cells and depleted of contaminating tumor cells plus 6 sequential tumor
           lysate/KLH pulsed dendritic cell vaccines. No cytokine is administered on Arm A and
           r-hIL7 (CYT107) is administered on Arm B.

        -  Patients will be evaluated for immune responses to tumor lysates using ex vivo assays
           and delayed type hypersensitivity (DTH).

        -  The trial uses a one-stage design targeting a response rate of 50 percent. Up to 47
           patients will be treated.

        -  Stopping rules will take effect if excessive toxicity is observed.
    

Intervention name(s): Tumor Purged/CD25 Depleted Lymphocytes; Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine; rhIL-7; Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine
Intervention type(s): Drug; Biological; Drug; Biological
Intervention description(s): Tumor lysate/KLH pulsed dendritic cells (minimum of 1 X 10e6 cells/kg) on Day2.; rhIL-7 (20 mcg/kg/dose SQ) approx. 48 hours prior to vaccine) Day 0, Day 14, Day 28 and Day 42; Tumor lysate/KLH Pulsed dendritic cell vaccine (1-5 X 10e7 cells/injection site, given in 3 sites intradermal) on Day 2, Day 16, Day 30, Day 44, Day 56, Day 70.
Intervention MeSH terms: Vaccines
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Vaccine; Immunotherapy; Cancer; Chemotherapy; Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine; Neuroblastoma; Autologous Lymphocyte Infusion; Ewing's Sarcoma; Rhabdomyosarcoma