DIPG-23. PHASE I STUDY OF ADOPTIVE CELLULAR THERAPY (X-ALT) PLUS TOTAL TUMOR RNA-DENDRITIC CELL VACCINE (TTRNA-DC) + HEMATOPOIETIC STEM CELLS (HSC) DURING RECOVERY FROM IRRADIATION(RT) WITH (GROUP A) OR WITHOUT (GROUP B) DOSE-INTENSIFIED TEMOZOLOMIDE (DI-TMZ) IN PATIENT (PTS) WITH NEWLY DIAGNOSED DIFFUSE BRAIN STEM GLIOMAS (DIPG) (BRAVO TRIAL)

摘要

Children with DIPG have a dismal prognosis and novel therapies are needed to improve survival. Based on lab studies demonstrating efficacy of x-ALT + ttRNA-DC vaccine +HSC following DI chemotherapy in DIPG models, we plan to conduct a study of this strategy in newly diagnosed pts with DIPG evaluating toxicity, preliminary evidence of efficacy, and usefulness of DI-TMZ in augmenting immune responses. Eligible pts (age 3- 21 years) will undergo tumor biopsy and a PBMC apheresis to obtain DCs for vaccine preparation. All pts will receive focal XRT (+/-TMZ). Four weeks following RT, group A pts will receive 3 bi-weekly tt-RNA DC (vaccines #1–3) followed by 2 monthly vaccines (vaccines # 4 and 5) during recovery from monthly DI-TMZ (85–100 mg/m2/day for 21 days) (cycles 1–3). Further apheresis (for lymphocytes and HSC) will be obtained following vaccine #3. Subsequently, pts will receive two additional monthly vaccines (# 6 and 7) with chemotherapy (cycle 4–5) followed by vaccine # 8 + x-ALT + HSC after cycle 6. Group B pts will receive a similar vaccine schedule (#1–7) and lymphocytes + HSC collection as Group A but without DI-TMZ and vaccine #8 +x-ALT + HSC following lymphodepletive conditioning with i.v cyclophosphamide +Fludarabine. Both groups will receive two additional vaccines (#9 and 10). Td boosts will be given to all pts at specific intervals. DC vaccine dose will be 1 x 10⁷ cells. The starting dose of x-ALT will be 3 x 10⁷/kg. Dose escalation of x-ALT will be based on phase I 3+3 design. Correlative studies include routine MRI imaging, profiling T-cell receptor repertoire and cytokines before and during treatment, and Gliosequencing plus immune transcriptome analysis of tumor tissue. The trial is expected to begin enrollment at our institution shortly following FDA and IRB approval with an accrual goal of 12–15 pts.