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
Intervention: therapeutic autologous dendritic cells; indinavir sulfate; peripheral blood stem cell transplantation
Intervention description: 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.
Intervention MeSH terms: Indinavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 5 Years
Maximum age: 35 Years
Healthy volunteers: No
Keywords: Rhabdomyosarcoma; Ewing's Sarcoma; Immunotherapy; Tumor Vaccine; Interleukin-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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Patients with fusion protein bearing, metastatic malignancies of the following histologic
        subtypes are eligible for evaluation for treatment on this protocol: alveolar
        rhabdomyosarcoma (AR), and Ewing's sarcoma family of tumors (ESFT) which includes
        classical, atypical and extraosseous Ewing's sarcoma, peripheral primitive neuroectodermal
        tumors, peripheral neuroepithelioma, primitive sarcoma of bone, and ectomesenchymoma.
        Eligibility will not be confirmed until the presence of a tumor-specific fusion protein is
        documented by reverse transcription polymerase chain reaction (RT-PCR) which corresponds to
        one of the tumor-specific peptides available for vaccination.

        Patients with Stage IV or metastatic disease are eligible to be enrolled on study at the
        time of initial presentation with tumor, prior to any cytoreductive therapy.

        Alternatively, patients who have recurrent disease, but who have been remotely treated
        (completed all antineoplastic therapy greater than or equal to one year prior to enrollment
        for patients who are greater than 5 years of age, or completed all antineoplastic therapy
        greater than 6 months prior to enrollment for patients who are less than or equal to 5
        years of age), are also eligible for enrollment prior to any subsequent cytoreductive
        therapy.

        Patients who have received cytoreductive therapy for Stage IV or metastatic disease may be
        enrolled at the time of completion of cytoreductive therapy if an apheresis specimen is
        available which was collected and processed prior to cytotoxic therapy according to the
        guidelines described in the protocol Section 3.2.2.

        Such products will have been obtained by apheresis at the Clinical Center, National
        Institutes of Health (NIH), with informed consent administered as per protocol 98-C-37,
        97-C-0050 or as described on standard government request form 2626 for invasive procedures.

        Patients must be less than or equal to 35 years at the time of initial diagnosis of
        alveolar rhabdomyosarcoma or ESFT, weight greater than 10 kg at the time of apheresis.
        Patients between 10-15 kg must be approved by the apheresis unit in the Department of
        Transfusion Medicine (DTM) prior to enrollment on the protocol.

        All patients or their legal guardians must give written informed consent indicating their
        understanding of the investigational nature and risks of the study.

        Patients must have adequate renal function (serum creatinine (Cr) less than 1.5 mg/dl or
        creatinine clearance (Cr Cl), greater than 60 ml/min./1.73 m^2 and liver function
        (transaminases less than 3 times normal, bilirubin less than 2.0 mg/dl). Patients will not
        be excluded based upon abnormal hepatic function which is related to hepatic involvement by
        tumor.

        For remotely treated patients, a CD4 count of greater than or equal to 400 cells/mm^3 is
        required.

        EXCLUSION CRITERIA:

        Women who are pregnant or lactating.

        Patients with human immunodeficiency virus infection due to confounding effects on immune
        function.

        Patients with hepatitis B or hepatitis C infection will be excluded due to the untoward
        risks to personnel working with blood specimens.

        Patients who require daily oral corticosteroid therapy for any underlying disease will be
        excluded.

        Topical or inhaled corticosteroids are permitted.

        Patients who are allergic to eggs, egg products, or thimerosal, or have a history of
        Guillain-Barre syndrome may be enrolled on study but are ineligible to receive the
        influenza vaccine.