A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas
Condition: Ewing's Sarcoma; Rhabdomyosarcoma
MeSH terms: Sarcoma; Rhabdomyosarcoma; Sarcoma, Ewing
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a single arm study.

      The tumor specimen is analyzed for the presence of a fusion protein which corresponds to
      available peptides. Patients undergo T cell harvest 10 days after an initial priming
      peptide-pulsed antigen presenting cell (APC) vaccine is performed.

      Fresh APCs are utilized for initial priming vaccination. All subsequent vaccinations will use
      cryopreserved APCs. Minimum number of APCs administered per vaccination is 100,000/kg and
      maximum is 100,000,000/kg.

      Patients undergo cytoreductive therapy for the treatment of their particular malignancy. This
      therapy usually consists of multiagent chemotherapy in the context of a separate protocol.

      Following chemotherapy, infusion of harvested T cells followed by infusion of peptide-pulsed
      APC vaccinations occurs every 6 weeks for a total of 3 post-priming vaccinations. Influenza
      vaccine is administered by intramuscular injection concurrent to peptide-pulsed APC vaccines.

      Interleukin -2 (IL-2) is administered as a continuous intravenous (IV) infusion for 4
      days/week for 3 successive weeks starting on the same day as T cell /peptide-pulsed
      infusions.
    

Detailed description: 
      Eradication of low tumor burdens can occur in vivo when T-cell mediated responses are
      generated against specific tumor antigens. The Ewing's sarcoma family of tumors (ESFT) and
      alveolar rhabdomyosarcoma (AR) display several features which make them candidate diseases
      for trials of such immunotherapy. First, intensive cytotoxic chemotherapy is generally able
      to eradicate bulk disease in patients with metastatic disease, but tumor relapse eventually
      occurs in nearly all patients. Second, tumor-specific chromosomal translocations resulting in
      the production of novel fusion proteins have been identified in the great majority of these
      tumors. Peptides derived from these fusion proteins have been shown to function as tumor
      antigens for cytolytic T cells in animal studies. Third, studies of immune reconstitution
      after intensive cytotoxic therapy have provided evidence that antigen-specific T cells can be
      generated in vivo when the adoptive transfer of peripheral T cells and antigen are provided
      during the period of T cell regeneration. This process can be augmented in murine models by
      the use of human immunodeficiency virus (HIV) active protease inhibitor, indinavir,
      potentially through inhibition of programmed cell death in expanding T cells. Merging these
      concepts, this protocol will attempt to eradicate minimal residual disease in pediatric
      patients with metastatic ESFT and AR via vaccination with tumor-specific peptides undertaken
      concomitant with autologous T cell transplantation and indinavir.
    

Intervention name(s): therapeutic autologous dendritic cells; indinavir sulfate; peripheral blood stem cell transplantation
Intervention type(s): Biological; Drug; Procedure
Intervention description(s): 3 syringes containing 1 x 10^6peptide pulsed dendritic cells; Oral dose, 350 mg/m^2 administered every 8 hours. Maximum dose is 800 mg every 8 hours.; Harvested autologous T cells, minimum dose 1 x 10^6/kg will be thawed rapidly in 37 degree water bath and infused sequentially over 5-15 minutes.
Other intervention name(s): Crixivan
Intervention MeSH terms: Indinavir
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Rhabdomyosarcoma; Ewing's Sarcoma; Immunotherapy; Tumor Vaccine; Interleukin-2