Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor (Re-MATCH)
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|ClinicalTrials.gov Identifier: NCT01326104|
Recruitment Status : Active, not recruiting
First Posted : March 30, 2011
Last Update Posted : March 19, 2019
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.
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.
|Condition or disease||Intervention/treatment||Phase|
|Medulloblastoma Neuroectodermal Tumor||Biological: TTRNA-xALT Biological: TTRNA-DCs||Phase 1 Phase 2|
Malignant brain tumors now represent the most frequent cause of cancer death in children. Despite aggressive and highly toxic multi-modality therapy including surgery, craniospinal radiation, and high-dose chemotherapy coupled with peripheral blood stem cell transplantation, almost half the children diagnosed with the most common malignant brain tumors, medulloblastoma (MB) and primitive neuroectodermal tumors (PNET), will still die from recurrent disease. Furthermore, survivors are often left with severe and lifelong treatment-associated cognitive and motor deficits. The development of more effective and tumor-specific therapies that will not add further toxicity to existing treatments is paramount in improving clinical outcomes for children affected by MB/PNETs. Immunotherapy targeting tumor-specific antigens expressed within brain tumors is a modality potentially capable of meeting this clear and urgent need.
Despite considerable advancements and promising clinical results observed in immunotherapy trials directed against adult malignant brain tumors, efforts in the immunologic treatment of pediatric brain tumors have been limited to relatively few notable studies. This is due, at least in part, to the often limited viable tumor tissue available for tumor cell-based vaccine preparations, and the lack of identification of consistently expressed tumor-specific antigens within these cancers.
The use of total tumor RNA (TTRNA)-loaded dendritic cells (DCs) was pioneered at Duke University, as a novel platform for inducing potent immunologic responses against the variety of uncharacterized and patient-specific antigens present within malignant tumor cells. Duke demonstrated that sufficient RNA for clinical vaccine preparations can be amplified with high fidelity using existing molecular technologies from as few as 500 isolated pediatric and adult brain tumor cells, thus allowing vaccine preparation from surgical biopsies and even microdissected archival tumor specimens. In this study, the investigators will treat recurrent MB/PNETs during hematopoietic recovery from chemotherapy.
Immunotherapy administered during recovery from chemotherapy may have tremendous advantages, as adoptive cellular therapy following lymphodepletive conditioning regimens has emerged as the most effective treatment strategy for advanced and refractory melanoma. Our hypothesis is that DC + ex vivo expanded Autologous Lymphocyte Transfer (xALT) therapy targeting recurrent MB/PNETs during recovery from myeloablative chemotherapy will be safe and will prolong survival in children and young adults with recurrent MB/PNETs.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor Adoptive T Cell Therapy During Recover From Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation|
|Study Start Date :||April 2010|
|Estimated Primary Completion Date :||September 2019|
|Estimated Study Completion Date :||September 2020|
Experimental: TTRNA-xALT & TTRNA-DCs
TTRNA-xALT 3 x 10^7/kg by intravenous injection once. TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses.
TTRNA-xALT 3 x 10^7/kg by intravenous injection once.
TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses.
- Evaluate safety of TTRNA-DCs and TTRNA-xALT [ Time Frame: 28 Days ]
- Determine progression-free survival [ Time Frame: 12 Months ]
- Determine Objective Radiographic Response Rate [ Time Frame: 24 Months ]
- Correlate magnitude and persistence of anti-tumor humoral or cellular immunity with clinical outcome [ Time Frame: 12 Months ]
- Evaluate changes in cytokine profile and Toll-Like Receptor activation status [ Time Frame: 12 Months ]
- Characterize the immunologic phenotype of lymphocyte subsets (naïve, effector, memory, regulatory) and natural killer cells [ Time Frame: 12 Months ]
- Identify potential tumor specific antigens as vaccine candidates [ Time Frame: 12 Months ]
- Determine the progression-free survival and overall survival rate [ Time Frame: 36 Months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01326104
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32610|
|Principal Investigator:||Duane Mitchell, MD, PhD||University of Florida|