Therapy to Treat Ewing's Sarcoma, Rhabdomyosarcoma or Neuroblastoma
- 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.
-To determine whether immune therapy given after immune suppression can help the body fight the tumor and to determine the safety of the treatment.
-Patients with Ewing's sarcoma, rhabdomyosarcoma or neuroblastoma whose disease has recurred after treatment or spread beyond the original site
- 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. The vaccine is given at study weeks 2, 4, 6, 8, 10 and 12. Each vaccine is given as a total of six separate injections: three intradermal (like a 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.
Neuroectodermal Tumors, Primitive, Peripheral
Drug: Tumor Purged/CD25 Depleted Lymphocytes
Biological: Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine
Device: Miltenyi CliniMACS-System
Drug: Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine
Drug: MAB 8H9
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Tumor Vaccination and R-hIL-7 Following Standard Multimodality Therapy in Patients With High Risk Pediatric Solid Tumors|
- Immune response, feasibility, toxicity.
- Identify immunogenic tumor antigens, evaluate contamination after 8H9 purging, event-free and overall survival, evaluate diminished reconstitution, tumor-host immunobiology studies.
|Study Start Date:||August 2007|
|Estimated Study Completion Date:||July 2013|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Drug: Tumor Purged/CD25 Depleted Lymphocytes
- 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.
- To determine whether Alpha CD25 and 8H9 depleted autologous lymphocytes plus tumor lysate/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 CD4 plus CD25plus suppressor T cells plus or minus r-hIL (CYT107) to lymphopenic hosts.
- 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.
- 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 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.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Crystal L Mackall, M.D.||National Cancer Institute (NCI)|