Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor (PNET) (REMATCH)
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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: | Endpoint Classification: Safety Study Intervention Model: Single Group 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 |
- Establishing the safety of DC + xALT therapy in this patient population with total tumor RNA (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 ]Number of participants with adverse events as a measure of safety and tolerability.
| 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.
Other Names:
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Show Detailed Description Eligibility| Ages Eligible for Study: | up to 30 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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:
- Absolute Neutrophil Count (ANC) ≥ 1000/µl (unsupported).
- Platelets ≥ 100,000/µl (unsupported).
- Hemoglobin > 8 g/dL (may be supported).
Renal:
- Serum creatinine ≤ upper limit of institutional normal
- Glomerular Filtration Rate (GFR) of at least 70 ml/min/1.73m2.
Hepatic:
- Bilirubin ≤ 1.5 times upper limit of normal for age.
- Serum Glutamic Oxaloacetic Transaminase (SGPT)(ALT) ≤ 3 times institutional upper limit of normal for age.
- Serum Glutamic Oxaloacetic Transaminase (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 peripheral blood stem cell (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| Contact: Jennifer F King, RN | 919-668-5364 | jennifer.f.king@duke.edu |
| 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 | |
| Principal Investigator: | Duane A Mitchell, M.D., Ph.D. | Duke University |
More Information
Additional Information:
No publications provided
| Responsible Party: | Duane Mitchell, Assistant Professor, Duke University Medical Center |
| ClinicalTrials.gov Identifier: | NCT01326104 History of Changes |
| Other Study ID Numbers: | Pro00018020 |
| Study First Received: | July 22, 2010 |
| Last Updated: | April 6, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
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 16, 2013