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Autologous T-Cell Transplantation, Vaccine Therapy, and Indinavir in Treating Patients With Metastatic Pediatric Sarcomas
This study has been completed.
Study NCT00019266   Information provided by National Cancer Institute (NCI)
First Received: July 11, 2001   Last Updated: February 6, 2009   History of Changes

July 11, 2001
February 6, 2009
December 1997
 
 
 
Complete list of historical versions of study NCT00019266 on ClinicalTrials.gov Archive Site
 
 
 
Autologous T-Cell Transplantation, Vaccine Therapy, and Indinavir in Treating Patients With Metastatic Pediatric Sarcomas
Pilot Study of Autologous T Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Indinavir may stimulate a person's white blood cells to kill sarcoma cells. Combining vaccine therapy and indinavir with autologous T-cell transplantation may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with indinavir and autologous T-cell transplantation works in treating patients with metastatic or recurrent pediatric sarcomas.

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.

Phase II
Interventional
Treatment
Sarcoma
  • Biological: therapeutic autologous dendritic cells
  • Drug: indinavir sulfate
  • Procedure: peripheral blood stem cell transplantation
 
 

*   Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
 
Completed
 
 
 

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
Both
up to 35 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00019266
 
CDR0000065344, NCI-97-C-0052, NCI-T96-0038
National Cancer Institute (NCI)
 
Study Chair: Crystal Mackall, MD NCI - Pediatric Oncology Branch
National Cancer Institute (NCI)
February 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP