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

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.


Condition Intervention Phase
Sarcoma
Biological: therapeutic autologous dendritic cells
Drug: indinavir sulfate
Procedure: peripheral blood stem cell transplantation
Phase II

Study Type: Interventional
Study Design: Treatment
Official Title: Pilot Study of Autologous T Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: December 1997
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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/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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00019266

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Crystal Mackall, MD NCI - Pediatric Oncology Branch
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000065344, NCI-97-C-0052, NCI-T96-0038
Study First Received: July 11, 2001
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00019266     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood rhabdomyosarcoma
alveolar childhood rhabdomyosarcoma
metastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma
previously untreated childhood rhabdomyosarcoma
previously treated childhood rhabdomyosarcoma
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
childhood malignant mesenchymoma

Additional relevant MeSH terms:
Anti-Infective Agents
HIV Protease Inhibitors
Anti-HIV Agents
Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Indinavir
Neoplasms, Nerve Tissue
Enzyme Inhibitors
Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Neuroectodermal Tumors
Neoplasms, Connective and Soft Tissue
Neoplasms
Anti-Retroviral Agents
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Sarcoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 09, 2009