OBJECTIVES:

• Determine whether immune responses to tumor-specific and non-tumor-specific peptides can be generated in patients with metastatic pediatric sarcoma by vaccine-driven expansion of antigen-specific T-cell populations during a period of immune reconstitution after intensive chemotherapy.
• Determine the percentage of patients with CD4 recovery (within 6 months of completion of chemotherapy) after treatment with peptide-pulsed antigen-presenting dendritic cell vaccination, autologous T-cell transplantation, and indinavir.
• Determine whether the breakpoint regions of tumor-specific fusion proteins found in Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (AR) function as tumor antigens in vivo as evidenced by the existence of peripheral T cells from patients with metastatic ESFT and AR at presentation that have been primed to such proteins.
• Determine the event-free and overall survival rate of patients treated with this regimen.
• Determine the feasibility and toxicity of this regimen in these patients after intensive chemotherapy.

OUTLINE:

• Part I: The tumor specimen is analyzed for the presence of a fusion protein which corresponds to available peptides. Patients undergo autologous T-cell harvest prior to cytoreductive therapy. Patients undergo cytoreductive therapy for the treatment of their particular malignancy. This therapy usually comprises chemotherapy in the context of a separate protocol.
• Part II: Beginning approximately 6 weeks after completion of cytoreductive therapy, patients receive immunotherapy comprising an infusion of harvested T cells over 15-30 minutes followed by peptide-pulsed antigen-presenting dendritic cell (APDC) vaccinations every 2 weeks for a total of 6 vaccinations (3 subcutaneously and 3 intradermally). Patients also receive influenza vaccine intramuscularly on the same day as peptide-pulsed APDC vaccine doses 1, 3, and 5.

Beginning the same day as peptide-pulsed APDC vaccination, patients receive oral indinavir 3 times daily for 16 weeks. Treatment continues in the absence of unacceptable toxicity or disease progression.

Patients are followed every 6 weeks for 6 months, every 3 months for 6 months, every 6 months for 1 year, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 34-45 patients will be accrued for this study within 1-3 years.

DISEASE CHARACTERISTICS:

• Diagnosis of previously untreated, fusion protein bearing, metastatic malignancies of the following histologic subtypes:

  • Alveolar rhabdomyosarcoma

  • Ewing's sarcoma family of tumors including:

    • Classical, atypical, and extraosseous Ewing's sarcoma
    • Peripheral primitive neuroectodermal tumor
    • Peripheral neuroepithelioma
    • Primitive sarcoma of bone
    • Ectomesenchymoma OR

• Recurrent disease at least 1 year after completion of prior antineoplastic therapy for children over age 5 (more than 6 months for age 5 and under)

  • Same histologies as above
  • Tumor-specific fusion protein documentation from primary or recurrent tumor
  • CD4 count at least 400/mm^3

PATIENT CHARACTERISTICS:

Age:

• Parts I and II:

  • 35 and under at initial diagnosis

Performance status:

• Part II:

  • ECOG 0-2

Life expectancy:

• Part II:

  • At least 8 weeks

Hematopoietic:

• Part I:

  • Hemoglobin greater than 9.0 g/dL before large-volume apheresis

• Part II:

  • Hemoglobin greater than 8.0 g/dL
  • Platelet count greater than 50,000/mm^3
  • Absolute neutrophil count greater than 1,000/mm^3

Hepatic:

• Part I:

  • No hepatitis B or C infections

• Parts I and II:

  • Transaminases less than 3 times normal*
  • Bilirubin less than 2.0 mg/dL*

• Part II:

  • PT less than 1.5 times normal NOTE: *Unless due to tumor involvement

Renal:

• Parts I and II:

  • Creatinine less than 1.5 mg/dL OR
  • Creatinine clearance greater than 60 mL/min

Cardiovascular:

• Part II:

  • Cardiac ejection fraction greater than 40% by MUGA scan OR
  • Shortening fraction greater than 27% by echocardiogram

Pulmonary:

• Part I:

  • No airway impairment

Other:

• Part I and II:

  • Not pregnant or nursing
  • Fertile patients must use effective nonhormonal contraception

• Part I:

  • Weight more than 10 kg at the time of apheresis (weight between 10-15 kg must be approved by the Department of Transfusion Medicine prior to enrollment in protocol)

• Part II:

  • No peripheral neurologic compression resulting in motor deficits
  • HIV negative
  • No allergy to eggs, egg products, or thimerosal*
  • No history of Guillain-Barre syndrome*
  • No active infection NOTE: *Eligible for study but may not receive influenza vaccine

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Part II:

  • No concurrent cytoreductive therapy for at least 2 weeks prior to the first immunotherapy course
  • Recovered from all acute toxic effects related to part I cytoreductive therapy

Endocrine therapy:

• Part II:

  • No concurrent corticosteroid therapy for at least 2 weeks prior to first immunotherapy course
  • No concurrent estrogen therapy, including birth control pills, during immunotherapy portion of protocol
  • No concurrent required daily oral corticosteroid therapy for any underlying disease
  • Concurrent topical or inhaled corticosteroids allowed

Radiotherapy:

• Part I:

  • No concurrent radiotherapy during the priming phase of protocol

• Part II:

  • No concurrent radiotherapy during immunotherapy

Surgery:

• Part I:

  • No concurrent surgical therapy during the priming phase of protocol

• Part II:

  • No concurrent surgical therapy during immunotherapy

Other:

• Part II:

  • No concurrent ketoconazole, rifampin, triazolam, Hypericum perforatum (St. John's wort), or midazolam during indinavir administration