Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor (Re-MATCH)
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.
|Study Design:||Endpoint Classification: Safety/Efficacy 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|
- Evaluate safety of TTRNA-DCs and TTRNA-xALT [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]
- Determine progression-free survival [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
- Determine Objective Radiographic Response Rate [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
- Correlate magnitude and persistence of anti-tumor humoral or cellular immunity with clinical outcome [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
- Evaluate changes in cytokine profile and Toll-Like Receptor activation status [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
- Characterize the immunologic phenotype of lymphocyte subsets (naïve, effector, memory, regulatory) and natural killer cells [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
- Identify potential tumor specific antigens as vaccine candidates [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
- Determine the progression-free survival and overall survival rate [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
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.Biological: TTRNA-DCs
TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01326104
|Contact: Marcia Hodik, RNemail@example.com|
|United States, California|
|Children's Hospital Los Angeles||Not yet recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Olalekan Olaifa 323-361-7319 firstname.lastname@example.org|
|Principal Investigator: Girish Dhall, MD|
|Stanford University||Not yet recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Prianka Kumar 650-724-3866 email@example.com|
|Principal Investigator: Sonia Partap, MD|
|United States, District of Columbia|
|Children's National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Sabrina Malik 202-476-4304 SaMalik@childrensnational.org|
|Principal Investigator: Eugene Hwang, MD|
|United States, Florida|
|University of Florida||Recruiting|
|Gainesville, Florida, United States, 32610|
|Contact: Marcia Hodik, RN 352-273-6971 firstname.lastname@example.org|
|Principal Investigator: Duane Mitchell, MD, PhD|
|United States, North Carolina|
|Duke University||Not yet recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Charlene Flahiff, MS 919-613-4527 email@example.com|
|Principal Investigator: Sridharan Gururangan, MRCP|
|Principal Investigator:||Duane Mitchell, MD, PhD||University of Florida|