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Investigator(s):
Crystal  Mackall, M.D. Principal Investigator Phone: 301-402-5940 mackallc@mail.nih.gov
Referral Contact(s):
Pediatric Oncology  Phone: 1-877-624-4878 (Toll free)

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Primary Eligibility:

• Diagnosis of one of the following:
  • Ewing’s sarcoma family of tumors
  • Rhabdomyosarcoma
  • Neuroblastoma
• Newly diagnosed metastatic (Stage IV) or recurrent disease:
  • Patients with newly diagnosed Stage IV or metastatic disease, enrolled prior to any cytoreductive therapy
  • Patients with late-recurrent disease must have completed all antineoplastic therapy including investigational therapy ≥ 1 year prior to recurrence (for patients > 5 years of age) or > 6 months prior to recurrence (for patients ≤ 5 years of age)
    • Multiple recurrences are allowable as long as these treatment-free intervals have been met. At least 4 weeks must have elapsed since last dose of non-cytotoxic therapies (e.g., Avastin, monoclonal antibodies such as anti-IgF1R and anti-TRAIL, and immunotherapies)
• Must have sufficient accessible tumor for biopsy to generate tumor lysate, meeting the following criteria:
  • Tumor must measure ≥ 2 cm in diameter
  • Bone marrow aspirates may be used as a source of tumor for tumor lysates in patients with bone marrow involvement
  • Patients who have already undergone surgery are eligible provided sufficient tumor tissue is available for production of tumor lysate
  • Patients for whom tumor biopsy would entail extensive surgery such as thoracotomy or laparotomy or whose tumor site places the patient at a substantial risk from the biopsy procedure are not eligible
• No condition related to the tumor that requires emergency treatment (e.g., airway compression or spinal cord compression)
• Patients with a history of central nervous system metastases are eligible provided it has been effectively treated and there is no evidence of active disease as evidenced by stable clinical and radiographic findings for a period of 6 weeks
• No prior allogeneic stem cell or bone marrow transplantation
• At least 3 weeks since prior cytotoxic therapy or radiotherapy and recovered
• Recovered from prior therapy
• Concurrent corticosteroids allowed during the apheresis/tumor biopsy portion of the trial provided they were initiated at time of tumor diagnosis or recurrence for treatment of nerve compression or other symptoms
  • No concurrent corticosteroids during the immunotherapy portion of the study except for a time-limited course of steroids for an unrelated medical condition (e.g., allergic reaction or poison ivy)
    • At least 2 weeks must elapse between completion of steroids and initiation of immunotherapy
  • Concurrent topical or inhaled corticosteroids allowed
• No concurrent cytoreductive radiotherapy or chemotherapy
• No other concurrent immunosuppressive therapy during the immunotherapy portion of the trial
• Age > 18 months and ≤ 35 years at the time of initial diagnosis
• Weight > 10 kg at the time of apheresis (patients between 10–15 kg must be approved by the apheresis unit prior to enrollment on protocol)
• Creatinine clearance > 60 mL/min OR serum creatinine normal for age
• AST and ALT < 2.5 x upper limit of normal (ULN)
• Bilirubin < 1.5 x ULN
• Platelet count > 75,000/µL*
• Hemoglobin > 9.0 g/dL*
• PT < 1.5 x ULN*
• Not pregnant or nursing; fertile patients must use effective contraception
• No HIV infection; no hepatitis B or C infection
• No clinically significant unrelated systemic illness that would preclude study participation
  
  *Patients may receive transfusions in order to meet these criteria

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Treatment Plan:

• Patients undergo tumor biopsy and/or bone marrow aspiration; tumor samples are used to generate tumor lysate
• Patients also undergo leukapheresis in order to obtain autologous lymphocytes; 8H9/αCD25-depleted lymphocytes and dendritic cells (DC) are obtained
• Patients then undergo standard therapy for their disease
• After recovery from standard therapy, patients with CD4-positive cell count ≥ 200/µL proceed to step 1; patients with CD4-positive cell count < 200/µL proceed to step 2



Step 1–Lymphodepletion:
• Patients receive one cycle of fludarabine phosphate intravenously (IV) over 30 minutes on Days 1–3, cyclophosphamide IV over 1 hour on Days 1 and 2, and pegfilgrastim on Day 4 or 5
• After blood counts recover, patients proceed to step 2



Step 2–Immunotherapy:
• DC are pulsed with tumor lysate and cultured in the presence of keyhole limpet hemocyanin (KLH)
• Patients receive tumor lysate/KLH pulsed DC vaccine intradermally or subcutaneously in Weeks 2, 4, 6, 8, 10, and 12
• Patients also receive 8H9/αCD25-depleted lymphocytes IV over 15–30 minutes on Day 1 of Week 2


• Treatment continues in the absence of disease progression requiring intervention (e.g., radiotherapy, surgery, or chemotherapy) during immunotherapy or unacceptable toxicity
• After completion of study therapy, patients are followed periodically for 5 years

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Additional Information:

• This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
• There is no charge for medical care received at NIH Clinical Center.
• PDQ (Physicians Data Query) - provides additional details about this study for health care providers.

Reviewed: 11/12/08
Updated: 11/26/08