Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor

NCT01326104 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB201500502W81XWH-10-1-0089CDMRP-PRO93877OCR13166
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

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. Approximately 35 patients with first recurrence of medulloblastoma (reMB)/supratentorial primitive neuroectodermal tumors (PNETs) will be treated with tumor-specific immune cells and dendritic cell vaccines to see what impact they have on the tumor.

Conditions

Medulloblastoma; Neuroectodermal Tumor

Keywords

Medulloblastoma; Primitive Neuroectodermal Tumor

Outcome Measures

Primary Outcomes (1)

• 12 Month Progression-free Survival (PFS-12)

  PFS is defined as time interval from date of first DC vaccine to date of progression (death is also treated as progression) or censoring, whichever happens first.

  up to 12 months

Secondary Outcomes (5)

• Objective Radiographic Response Rate

  best overall radiographic response through duration on study (up to 60 months)

• Correlate Magnitude and Persistence of Anti-tumor Humoral or Cellular Immunity With Clinical Outcome

  baseline compared to 6 weeks post vaccine #1 and longitudinal measures through overall survival (up to 60 months)

• Evaluate Changes in Cytokine Profile and Toll-Like Receptor Activation Status

  baseline compared to 6 weeks post vaccine #1 and longitudinal measures through overall survival (up to 60 months)

• Characterize Immunologic Phenotype of Lymphocyte Subsets and NK Cells

  baseline compared to 6 weeks post vaccine #1 and longitudinal measures through overall survival (up to 60 months)

• Determine of Overall Survival Rate

  up to 60 months

Study Arms (2)

Group A

EXPERIMENTAL

High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs.

Biological: TTRNA-xALT; Biological: TTRNA-DCs

Group B

EXPERIMENTAL

NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs.

Biological: TTRNA-xALT; Biological: TTRNA-DCs

Interventions

TTRNA-xALT BIOLOGICAL

TTRNA-xALT 3 x 10\^7/kg by intravenous injection once.

Group A; Group B

TTRNA-DCs BIOLOGICAL

TTRNA-DCs 1 x 10\^7 by intradermal injection every 2 weeks for 3 total doses.

Group A; Group B

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Screening:
• Age ≤ 30 years of age.
• Suspected first recurrence/progression of MB/PNET since completion of definitive focal +/- craniospinal irradiation. Disease progression prior to receiving definitive focal +/- craniospinal irradiation will not disqualify patients from enrollment if they have subsequently failed definitive radiotherapy and are at first recurrence/progression at time of enrollment. Patients who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (i.e. Gorlin's syndrome or NF1 mutation) are eligible for enrollment at first disease recurrence/progression.
• Re-MATCH Protocol:
• Patients must have histologically confirmed recurrent MB/PNET that is a first relapse/progression after completion of definitive radiotherapy +/- craniospinal irradiation. Patients with a first relapse/progression 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) are eligible for enrollment.
• 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.

You may not qualify if:

• Pregnant or need to breast feed during the study period.
• Active infection requiring treatment or an unexplained febrile (\> 101.5F) 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.

Sponsors & Collaborators

• University of Florida: lead
• United States Department of Defense: collaborator

Study Sites (3)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Medulloblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Given that number evaluable subjects was below targeted enrollment, this study was underpowered for the desired statistical comparison. Due to COVID we anticipate that the immunologic secondary endpoints will be completed in 6-12 months or change to exploratory.

Results Point of Contact

• Title: Kristine Wynne
• Organization: University of Florida

kristine.wynne@neurosurgery.ufl.edu

352-273-9727

Study Officials

• Duane Mitchell, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: March 30, 2011
• Study Start: September 7, 2010
• Primary Completion: March 28, 2020
• Study Completion: March 28, 2025
• Last Updated: April 27, 2025
• Results First Posted: February 7, 2022

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)