Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Autologous T-Cell Transplantation, Vaccine Therapy, and Indinavir in Treating Patients With Metastatic Pediatric Sarcomas

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 35 and under at initial diagnosis NCI NCI-97-C-0052 NCI-T96-0038, T96-0038, NCT00019266

Objectives

1. 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.
2. 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.
3. 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.
4. Determine the event-free and overall survival rate of patients treated with this regimen.
5. Determine the feasibility and toxicity of this regimen in these patients after intensive chemotherapy.

Entry Criteria

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/mm³

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

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/mm³
  • Absolute neutrophil count greater than 1,000/mm³

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]

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

Crystal Mackall, MD, Protocol chair		Ph: 301-402-5940

Registry Information
Official Title		Pilot Study of Autologous T Cell Transplantation with Vaccine Driven Expansion of Anti-tumor Effectors after Cytoreductive Therapy in Metastatic Pediatric Sarcomas
Trial Start Date		1997-12-02
Registered in ClinicalTrials.gov		NCT00019266
Date Submitted to PDQ		1996-12-24
Information Last Verified		2007-02-06