Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor (PNET) - Full Text View

Sponsor:	Duke University
Information provided by (Responsible Party):	Duke University
ClinicalTrials.gov Identifier:	NCT01326104

Purpose

This study will have two phases. During Phase I, the investigators will treat patients with increasing doses of the tumor-specific immune cells that the investigators have expanded in the investigators clinical laboratory to establish the safety of this treatment regimen. These patients will also receive dendritic cell vaccines to help boost the function of these immune cells and maintain their growth after being returned to the patient. The investigators expect to treat approximately 9 patients during the Phase I component to establish that this treatment seems safe. In the Phase II component, once the treatment has been shown to be safe, the investigators will treat a larger number of patients (approximately 35) with expanded tumor-specific immune cells and dendritic cell vaccines and evaluate the impact on tumor growth in these patients. This will allow us to determine whether tumor growth is prevented or delayed compared to patients that have received similar treatment without immunotherapy. This type of comparison to previously treated patients (called historical control comparison) will allow us to determine whether this treatment regimen looks promising enough to evaluate in larger clinical trials to definitively establish the effectiveness of this approach.

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, and the investigators hope to use the experience the investigators have gained in the immunologic treatment of adult patients with malignant brain tumors at the investigators center to improve the clinical outcome for children affected by this disease. This study has significant potential to impact the families of civilians and military dependents, as the brain is the most frequent site of crippling injuries in humans and unfortunately, brain cancer is currently the leading cause of cancer deaths in children in the United States.

Condition	Intervention	Phase
Medulloblastoma Neuroectodermal Tumors	Biological: TTRNA-xALT with TTRNA-DCs	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor Adoptive T Cell Therapy During Recover From Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Establishing the safety and DLT of DC + xALT therapy in this patient population with TTRNA-xALT and TTRNA-DCs will be the primary goal in the Phase I portion of the trial. [ Time Frame: 44 months ] [ Designated as safety issue: Yes ]
A 3+3 Phase I study design with 3 lymphocyte (xALT) dose levels will be used to assess the safety of DC + xALT therapy, and to determine the maximum tolerated dose (MTD) for DC + xALT. An escalating total dose of TTRNA-xALT (3 x 10^6/Kg, 3 x 10^7/Kg, and 3 x 10^8/Kg) with TTRNA-DCs (2 x 10^7) will be evaluated in separate cohorts of 3 to 6 patients each for the purpose of establishing a MTD and a DLT in this patient population.
For the Phase II portion of the trial, the primary efficacy endpoint will be 12-month progression-free survival (PFS-12) rate after treatment with DC + xALT therapy as a surrogate for overall survival. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
The Phase II portion of this study will assess the clinical impact of DC + xALT therapy among pediatric patients with reMB/PNETs. The basis for making this assessment will be the proportion of patients who survive 12 months without disease progression (PFS-12) as a surrogate clinical marker for OS in this patient population. Progression-free survival will be measured from the initiation of HDC for comparison to our historical experience of HDC + PBSCT (Group A) or NMA salvage chemotherapy (Group B) in this patient population.

Estimated Enrollment:	64
Study Start Date:	April 2010
Estimated Study Completion Date:	March 2015
Estimated Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TTRNA-xALT with TTRNA-DC An escalating total dose of TTRNA-xALT (3 x 10^6/Kg, 3 x 10^7/Kg, and 3 x 10^8/Kg) with TTRNA-DCs (2 x 10^7) will be evaluated in separate cohorts of 3 to 6 patients each for the purpose of establishing a maximally tolerated dose (MTD) and a dose-limiting toxicity (DLT) in this patient population.	Biological: TTRNA-xALT with TTRNA-DCs An escalating total dose of TTRNA-xALT (3 x 106/Kg, 3 x 107/Kg, and 3 x 108/Kg) with TTRNA-DCs (2 x 107) will be evaluated in separate cohorts of 3 to 6 patients each for the purpose of establishing a maximally tolerated dose (MTD) and a dose-limiting toxicity (DLT) in this patient population.

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Eligibility

Ages Eligible for Study:	up to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age ≤ 30 years of age.
Patients must have histologically confirmed reMB/PNET and received definitive radiotherapy (craniospinal + focal boost) prior to relapse.
Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
Karnofsky Performance Status (KPS) of > 50% (KPS for > 16 years of age) or Lansky performance Score (LPS) of ≥ 50 (LPS for ≤ 16 years of age) assessed within 2 weeks prior to registration.
Bone Marrow:
- ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported).
- Platelets ≥ 100,000/µl (unsupported).
- Hemoglobin > 8 g/dL (may be supported).
Renal:
- Serum creatinine ≤ upper limit of institutional normal
- GFR of at least 70 ml/min/1.73m2.
Hepatic:
- Bilirubin ≤ 1.5 times upper limit of normal for age.
- SGPT (Serum Glutamic Oxaloacetic Transaminase)(ALT) ≤ 3 times institutional upper limit of normal for age.
- SGOT (AST) ≤ 3 times institutional upper limit of normal for age.
Cardiac:
- ECHO cardiogram with a shortening fraction of > 45%.
- EKG without clinically significant arrhythmias.
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.
Patient or patient guardian consent to PBSC and/or bone marrow harvest following registration.
Signed informed consent according to institutional guidelines must be obtained prior to registration.

Exclusion Criteria:

Pregnant or need to breast feed during the study period (Negative serum pregnancy test required).
Active infection requiring treatment or an unexplained febrile (> 101.5o F) illness.
Known immunosuppressive disease or human immunodeficiency virus infection.
Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or pulmonary disease.
Patients receiving concomitant immunosuppressive agents for medical condition
Patients who need definitive radiotherapy for treatment of reMB/PNET.
Patients receiving any other concurrent anticancer or investigational drug therapy.
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction),
Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326104

Contacts

Contact: Jennifer F King, RN

919-668-5364

jennifer.f.king@duke.edu

Locations

United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27710
Contact: Denise Lally-Goss 919-684-3862
Principal Investigator: Duane Mitchell

Sponsors and Collaborators

Duke University

More Information

Additional Information:

Duke Brain Tumor Immunotherapy Program This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Duke University
ClinicalTrials.gov Identifier:	NCT01326104 History of Changes
Other Study ID Numbers:	Pro00018020
Study First Received:	July 22, 2010
Last Updated:	September 8, 2011
Health Authority:	United States: Food and Drug Administration United States: Department of Defense

Keywords provided by Duke University:

Recurrent Medulloblastoma and Primitive Neuroectodermal Tumors

Additional relevant MeSH terms:

Medulloblastoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Glioma
Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on May 23, 2012