Protocol Summary

Protocol No.: OCR13166

Sponsor Protocol No.: W81XWH-10-1-0089

Study Title
Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor Adoptive T Cell Therapy During Recovery from Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation

Principal Investigator(s)
Mitchell, Duane

Objective
Immunotherapy is a specific approach to treating cancer that has shown promise in adult patients for the treatment of melanoma, malignant brain tumors, and other cancers. The study investigators will use the experience they have gained from these studies to try to improve the outcome for children affected by a recurrent brain tumor.

Description
This study will have two phases:

During Phase I, approximately 9 patients will be treated with increasing doses of tumor-specific immune cells to determine the safety of this treatment. Phase I patients will also receive dendritic cell vaccines to help boost the function of these immune cells and maintain their growth.

During Phase II, approximately 35 patients will be treated with tumor-specific immune cells and dendritic cell vaccines to see what impact they have on the tumor.

Phase: Phase II

Age Group: Both

Scope: National

Treatment
All participants will receive:

1. Total tumor RNA Autologous Lymphocyte Transfer (TTRNA-xALT) - 3 x 10^7/kg by intravenous injection once, and

2. Total tumor RNA Dendritic Cells (TTRNA-DCs) - 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses.

Detailed Eligibility
Inclusion Criteria:
1. Age 30 years of age and younger.
2. Patients must have histologically confirmed recurrent MB/PNET and received definitive radiotherapy (craniospinal + focal boost) prior to first relapse or who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (ie. Gorlin's syndrome or NF1 mutation).
3. Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
4. Karnofsky Performance Status of >= 50% or Lansky Performance Score of >= 50.
5. Absolute Neutrophil Count (ANC) >= 1000/µl (unsupported).
6. Platelets >= 100,000/µl (unsupported).
7. Hemoglobin > 8 g/dL (may be supported).
8. Serum creatinine =9. Bilirubin =10. Serum Glutamic Oxaloacetic Transaminase (ALT) =11. Serum Glutamic Oxaloacetic Transaminase (AST) =12. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
13. Patient or patient guardian consent to peripheral blood stem cell (PBSC) and/or bone marrow harvest following registration if PBSC or bone marrow (CD34 count of at least 2x10^6/kg) has not been previously stored and available for use.
14. Signed informed consent according to institutional guidelines must be obtained prior to registration.

Exclusion Criteria:
1. Pregnant or need to breast feed during the study period.
2. Active infection requiring treatment or an unexplained febrile (> 101.5o F) illness.
3. Known immunosuppressive disease, human immunodeficiency virus infection, or carriers of Hepatitis B or Hepatitis C virus.
4. Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or pulmonary disease.
5. Patients receiving concomitant immunosuppressive agents for medical condition.
6. Patients who need definitive radiotherapy for treatment of recurrent MB/PNET. Focal boost radiotherapy may be delivered prior to immunotherapy if required for local control.
7. Patients receiving any other concurrent anticancer or investigational drug therapy.
8. Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
9. Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

Applicable Disease Sites

Brain and Nervous System
Pediatric (Childhood) Cancer

Therapies Involved
Autologous Stem Cell Transplant
Reduced-Intensity Conditioning

Drugs Involved
Carboplatin
Cyclophosphamide
Cytoxan (Cyclophosphamide)
Etoposide
Filgrastim
Fludarabine
G-CSF (Filgrastim)
Mesna
Neupogen (Filgrastim)
Temodar (Temozolomide)
Temozolomide
Thiotepa
Urotimexan (Mesna)
VP-16 (Etoposide)
Vepesid (Etoposide)

Participating Institutions
Children's Hospital Los Angeles
Children's National Medical Center
UF Gainesville : Marcia Hodik

Contact
Marcia Hodik
Phone: +1 352-273-6971
Email: marcia.hodik@neurosurgery.ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT01326104