Brain Stem Gliomas Treated With Adoptive Cellular Therapy During Focal Radiotherapy Recovery Alone or With Dose-intensified Temozolomide (Phase I) (BRAVO)

This is an interventional treatment trial for Diffuse Intrinsic Pontine Glioma (DIPG) focused on measuring Tumor mRNA-pulsed autologous Dendritic Cells (TTRNA-DCs), Tumor-specific autologous lymphocyte transfer (TTRNA-xALT), Autologous G-CSF mobilized HSCs, Temozolomide (TMZ), Cyclophosphamide (CTX), Fludarabine (Flu), Immunotherapy, Pediatric, Young Adult, Brain Tumor, CNS, Vaccine Therapy Read More

Inclusion Criteria:

Initial Screening

• Radiologically confirmed DIPG or other diffuse intrinsic brain stem glioma (Grade III or IV).
• Patient and/or parents/guardian willing to consent to biopsy for obtaining tumor material for confirmatory diagnosis and/or tumor RNA extraction and amplification.
• Biopsy confirmation of any grade of glioma (for patients with classic DIPG on neuroimaging or at least grade III glioma in case of other diffuse intrinsic brain stem gliomas)
• 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;
• ANC (absolute neutrophil count) ≥ 1000/µl (unsupported)
• Platelets ≥ 100,000/µl (unsupported)
• Hemoglobin > 8 g/dL (can be transfused)
• Renal;
• Serum creatinine ≤ upper limit of institutional normal
• Hepatic;
• Bilirubin ≤ 1.5 times upper limit of institutional normal for age
• SGPT (ALT) ≤ 3 times upper limit of institutional normal for age
• SGOT (AST) ≤ 3 times upper limit of institutional normal for age
• Patients of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control while being treated on this study.
• Signed informed consent according to institutional guidelines.

Post Biopsy

• Patients with post-surgical neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration;
• Pathologic diagnosis of glioma on tumor biopsy.

Exclusion Criteria:

• Patients with severe dysphagia, obtundation, or tetraplegia (poor risks for anesthesia and biopsy procedure);
• Absence of tumor on biopsy specimen;
• Pregnant or need to breast feed during the study period (Negative serum pregnancy test required)
• Known autoimmune or immunosuppressive disease or human immunodeficiency virus infection;
• Patients with significant renal, cardiac, pulmonary, hepatic or other organ dysfunction;
• Severe or unstable concurrent medical conditions;
• Patients who require corticosteroids above physiologic doses (>4 mg/day dexamethasone) after chemoradiotherapy;
• Patients scheduled to receive any other concurrent anticancer or investigational drug therapy;
• Prior allergic reaction to TMZ, GM-CSF, or Td;
• Patients who are unwilling or unable to receive treatment and undergo follow-up evaluations at University of Florida;
• Patient and/or parent/guardian demonstrating an inability to comply with the study and/or follow-up procedures.