NIH Clinical Research Studies

Protocol Number: 97-C-0052

Active Accrual, Protocols Recruiting New Patients

Title:
A Pilot Study of Autologous T-Cell Transplantation with Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas
Number:
97-C-0052
Summary:
This is a single arm study.

The tumor specimen is analyzed for the presence of a fusion protein which corresponds to available peptides. Patients undergo T cell harvest 10 days after an initial priming peptide-pulsed antigen presenting cell (APC) vaccine is performed.

Fresh APCs are utilized for initial priming vaccination. All subsequent vaccinations will use cryopreserved APCs. Minimum number of APCs administered per vaccination is 100,000/kg and maximum is 100,000,000/kg.

Patients undergo cytoreductive therapy for the treatment of their particular malignancy. This therapy usually consists of multiagent chemotherapy in the context of a separate protocol.

Following chemotherapy, infusion of harvested T cells followed by infusion of peptide-pulsed APC vaccinations occurs every 6 weeks for a total of 3 post-priming vaccinations. Influenza vaccine is administered by intramuscular injection concurrent to peptide-pulsed APC vaccines.

IL-2 is administered as a continuous IV infusion for 4 days/week for 3 successive weeks starting on the same day as T cell /peptide-pulsed infusions.

Sponsoring Institute:
National Cancer Institute (NCI)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: Yes
Population Exclusion(s): None

Eligibility Criteria:
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 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, 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 procedures.

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 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 Cr less than 1.5 mg/dl or 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 required.

EXCLUSION CRITERIA:

Women who are pregnant or lactating.

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

Special Instructions:
Many protocols are potentially hazardous, are intended only for use by clinical oncologists in carefully structured settings, and may not prove to bemore effective than standard treatment. A responsible investigator associated with this protocol should be consulted before using this protocol. Dose and schedule modifications are required for patients who develop gastrointestinal, hematologic, neurologic, and biochemical (renal, hepatic, etc.) and/or other abnormalities after the administration of therapy. Additionally, Federal regulations for the protection of human subjects require approval of clinical trials by your local Institutional Review Board.
Keywords:
Rhabdomyosarcoma
Ewing's Sarcoma
Immunotherapy
Tumor Vaccine
Interleukin-2
Recruitment Keywords:
None
Conditions:
Ewing's Sarcoma
Rhabdomyosarcoma
Investigational Drug(s):
EF-1 Peptide
PXFK Peptide
E7 Peptide
IL-4
CD40 Ligand
Indinavir
Investigational Device(s):
None

Contacts:
CSSC
Clinical Studies Support Center/NCI
164 Rollins Avenue
2nd FLoor
Rockville, MD 20852
Phone: (888) 624-1937
Fax: (301) 881-8239
Electronic Address: ncicssc@mail.nih.gov

Citations:
A mutant p53 tumor suppressor protein is a target for peptide-induced CD8+ cytotoxic T cells

Thymic-independent T cell regeneration occurs via antigen driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing

Age, thymopoiesis and CD4+ T lymphocyte regeneration after intensive chemotherapy

Active Accrual, Protocols Recruiting New Patients

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