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A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas

Phase 2
5 Years
35 Years
Not Enrolling
Ewing's Sarcoma, Rhabdomyosarcoma

Thank you

Trial Information

A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas

Eradication of low tumor burdens can occur in vivo when T-cell mediated responses are
generated against specific tumor antigens. The Ewing's sarcoma family of tumors (ESFT) and
alveolar rhabdomyosarcoma (AR) display several features which make them candidate diseases
for trials of such immunotherapy. First, intensive cytotoxic chemotherapy is generally able
to eradicate bulk disease in patients with metastatic disease, but tumor relapse eventually
occurs in nearly all patients. Second, tumor-specific chromosomal translocations resulting
in the production of novel fusion proteins have been identified in the great majority of
these tumors. Peptides derived from these fusion proteins have been shown to function as
tumor antigens for cytolytic T cells in animal studies. Third, studies of immune
reconstitution after intensive cytotoxic therapy have provided evidence that
antigen-specific T cells can be generated in vivo when the adoptive transfer of peripheral T
cells and antigen are provided during the period of T cell regeneration. This process can
be augmented in murine models by the use of human immunodeficiency virus (HIV) active
protease inhibitor, indinavir, potentially through inhibition of programmed cell death in
expanding T cells. Merging these concepts, this protocol will attempt to eradicate minimal
residual disease in pediatric patients with metastatic ESFT and AR via vaccination with
tumor-specific peptides undertaken concomitant with autologous T cell transplantation and

Inclusion Criteria


Patients with fusion protein bearing, metastatic malignancies of the following histologic
subtypes are eligible for evaluation for treatment on this protocol: alveolar
rhabdomyosarcoma (AR), and Ewing's sarcoma family of tumors (ESFT) which includes
classical, atypical and extraosseous Ewing's sarcoma, peripheral primitive neuroectodermal
tumors, peripheral neuroepithelioma, primitive sarcoma of bone, and ectomesenchymoma.
Eligibility will not be confirmed until the presence of a tumor-specific fusion protein is
documented by reverse transcription polymerase chain reaction (RT-PCR) which corresponds
to one of the tumor-specific peptides available for vaccination.

Patients with Stage IV or metastatic disease are eligible to be enrolled on study at the
time of initial presentation with tumor, prior to any cytoreductive therapy.

Alternatively, patients who have recurrent disease, but who have been remotely treated
(completed all antineoplastic therapy greater than or equal to one year prior to
enrollment for patients who are greater than 5 years of age, or completed all
antineoplastic therapy greater than 6 months prior to enrollment for patients who are less
than or equal to 5 years of age), are also eligible for enrollment prior to any subsequent
cytoreductive therapy.

Patients who have received cytoreductive therapy for Stage IV or metastatic disease may be
enrolled at the time of completion of cytoreductive therapy if an apheresis specimen is
available which was collected and processed prior to cytotoxic therapy according to the
guidelines described in the protocol Section 3.2.2.

Such products will have been obtained by apheresis at the Clinical Center, National
Institutes of Health (NIH), with informed consent administered as per protocol 98-C-37,
97-C-0050 or as described on standard government request form 2626 for invasive

Patients must be less than or equal to 35 years at the time of initial diagnosis of
alveolar rhabdomyosarcoma or ESFT, weight greater than 10 kg at the time of apheresis.
Patients between 10-15 kg must be approved by the apheresis unit in the Department of
Transfusion Medicine (DTM) prior to enrollment on the protocol.

All patients or their legal guardians must give written informed consent indicating their
understanding of the investigational nature and risks of the study.

Patients must have adequate renal function (serum creatinine (Cr) less than 1.5 mg/dl or
creatinine clearance (Cr Cl), greater than 60 ml/min./1.73 m^2 and liver function
(transaminases less than 3 times normal, bilirubin less than 2.0 mg/dl). Patients will not
be excluded based upon abnormal hepatic function which is related to hepatic involvement
by tumor.

For remotely treated patients, a CD4 count of greater than or equal to 400 cells/mm^3 is


Women who are pregnant or lactating.

Patients with human immunodeficiency virus infection due to confounding effects on immune

Patients with hepatitis B or hepatitis C infection will be excluded due to the untoward
risks to personnel working with blood specimens.

Patients who require daily oral corticosteroid therapy for any underlying disease will be

Topical or inhaled corticosteroids are permitted.

Patients who are allergic to eggs, egg products, or thimerosal, or have a history of
Guillain-Barre syndrome may be enrolled on study but are ineligible to receive the
influenza vaccine.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With an Immune Response to Tumor-specific and Non-tumor Specific Peptides During a Period of Immune Reconstitution

Outcome Description:

Immune response was defined as a percent specific lysis of >10% following challenge with peptide pulsed targets, or interferon gamma production following challenge with peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0. Tumor specific peptides: Ewings sarcoma Type 1: EF-1 (EWS/FLI-1)*SSSYGQQN/PSYDSVRRGA,Ewing's Sarcoma Type 2: EF-2 (EWS/FLI-2)* SSSYGQ/QSSLLAYNT, Alveolar rhabdomyosarcoma: PXFK (PAX3/FKHR)† TIGNGLSPQ/NSIRHNLSL. Non-tumor specific peptide:HPV16E7 MLDLQPETT-MET-9-THR. See protocol link module for additional information re: peptides.

Outcome Time Frame:

20 weeks post vaccination

Safety Issue:


Principal Investigator

Crystal Mackall, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health


United States: Federal Government

Study ID:




Start Date:

December 1996

Completion Date:

September 2008

Related Keywords:

  • Ewing's Sarcoma
  • Rhabdomyosarcoma
  • Rhabdomyosarcoma
  • Ewing's Sarcoma
  • Immunotherapy
  • Tumor Vaccine
  • Interleukin-2
  • Rhabdomyosarcoma
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma



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