Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor (Re-MATCH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by University of Florida
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01326104
First received: July 22, 2010
Last updated: February 5, 2015
Last verified: February 2015
  Purpose

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 Intervention Phase
Medulloblastoma
Neuroectodermal Tumor
Biological: TTRNA-xALT
Biological: TTRNA-DCs
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 50
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)
Arms Assigned Interventions
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.
Biological: TTRNA-xALT
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.

Detailed Description:

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.

  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 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).
  • Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
  • Karnofsky Performance Status of ≥ 50% or Lansky Performance Score of ≥ 50.
  • Absolute Neutrophil Count (ANC) ≥ 1000/µl (unsupported).
  • Platelets ≥ 100,000/µl (unsupported).
  • Hemoglobin > 8 g/dL (may be supported).
  • Serum creatinine ≤ upper limit of institutional normal
  • Bilirubin ≤ 1.5 times upper limit of normal for age.
  • Serum Glutamic Oxaloacetic Transaminase (ALT) ≤ 3 times institutional upper limit of normal for age.
  • Serum Glutamic Oxaloacetic Transaminase (AST) ≤ 3 times institutional upper limit of normal for age.
  • 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 if PBSC or bone marrow (CD34 count of at least 2x10^6/kg) has not been previously stored and available for use.
  • 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.
  • Active infection requiring treatment or an unexplained febrile (> 101.5o F) illness.
  • Known immunosuppressive disease, human immunodeficiency virus infection, or carriers of Hepatitis B or Hepatitis C virus.
  • 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 recurrent MB/PNET. Focal boost radiotherapy may be delivered prior to immunotherapy if required for local control.
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Marcia Hodik, RN 352-273-6971 marcia.hodik@neurosurgery.ufl.edu

Locations
United States, California
Children's Hospital Los Angeles Not yet recruiting
Los Angeles, California, United States, 90027
Contact: Olalekan Olaifa    323-361-7319    oolaifa@chla.usc.edu   
Principal Investigator: Girish Dhall, MD         
Stanford University Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Prianka Kumar    650-724-3866    priankak@stanford.edu   
Principal Investigator: Gerald Grant, MD         
United States, District of Columbia
Children's National Medical Center Not yet recruiting
Washington, District of Columbia, United States, 20010
Contact: Swapna Pamu, MS    202-476-6493    SPamu@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    marcia.hodik@neurosurgery.ufl.edu   
Principal Investigator: Duane Mitchell         
United States, North Carolina
Duke University Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Jennifer King, RN    919-668-5364    Jennifer.f.king@duke.edu   
Principal Investigator: Sridharan Gururangan, MRCP         
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Duane Mitchell, MD, PhD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01326104     History of Changes
Other Study ID Numbers: Re-MATCH, W81XWH-10-1-0089, CDMRP-PRO93877
Study First Received: July 22, 2010
Last Updated: February 5, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by University of Florida:
Medulloblastoma
Primitive Neuroectodermal Tumor

Additional relevant MeSH terms:
Medulloblastoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial

ClinicalTrials.gov processed this record on May 26, 2015