Brain Stem Gliomas Treated With Adoptive Cellular Therapy During Focal Radiotherapy Recovery Alone or With Dose-intensified Temozolomide (Phase I) (BRAVO)
Diffuse Intrinsic Pontine Glioma (DIPG), Brain Stem Glioma
About this trial
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
Eligibility Criteria
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.
Sites / Locations
- UF Health Shands Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Group A
Group B
TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) during cycles of Dose-intensified TMZ
TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) with Cyclophosphamide + Fludarabine Lymphodepletive Conditioning