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T Cells Expressing HER2-specific Chimeric Antigen Receptors(CAR) for Patients With HER2-Positive CNS Tumors
Bu Faz 1 (Phase 1) çalışma, beyin tümörü olan hastalarda antikor ve T hücresi yaklaşımlarını birleştirerek HER2'ye (Human Epidermal Growth Factor Receptor 2) özgü kimerik antijen reseptörü taşıyan T hücrelerini üç farklı doz şemasıyla incelemektedir. Anti-HER2 antikorunun tanıdığı HER2 proteini birçok tümör hücresinin yüzeyinde bulunmakta ve bu sayede genetik olarak değiştirilmiş T hücrelerinin tümörü hedeflemesi amaçlanmaktadır. Katılım için yineleyen ya da tedaviye dirençli HER2-pozitif primer merkezi sinir sistemi (central nervous system, CNS) tümörü veya merkezi sinir sistemine yayılmış HER2-pozitif tümör bulunması gerekmekte; tıbben uygun olan hastalarda hücre toplama sonrası tümör cerrahisi yapılabilmektedir.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion criteria at the time of procurement. * Recurrent or refractory HER2 positive primary central nervous system (CNS) tumor or HER2 positive tumor metastatic to the CNS. Patients in whom tumor resection (gross total or subtotal resection) is medically feasible can undergo surgery after procurement and prior to treatment. * Karnofsky/Lansky score of greater than or equal to 60 * Informed consent explained to, understood by and signed by subject/guardian. Subject/guardian given copy of informed consent Exclusion Criteria at the time of procurement: * Diagnosis of DIPG * Bulky tumors causing midline shift and/or symptoms/signs due to impending herniation * Known HIV positivity Treatment Inclusion criteria: * Recurrent or refractory HER2-positive\* primary CNS tumor or HER2-positive solid tumor metastatic to the CNS \* Immunohistochemistry (IHC) or RT-PCR will be used to determine HER2 positivity. Results will be compared to standard controls. HER2 expression in tumors on IHC should be greater than or equal to grade 1 and greater than or equal to 1+ intensity score. Wherein grades are defined as: Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-75% and Grade 4: 76-100% of cell staining for HER2 and intensity scores are: negative; 1+; 2+ and 3+ using breast cancer standard arrays as a guide for intensity. * Intracranial catheter (such as Rickham or Ommaya) in place * Age ≥ 3 years * Life expectancy ≥ 6 weeks * Karnofsky/Lansky score ≥ 60 * Bilirubin less than or equal to 3x upper limit of normal, AST less than or equal to 5x upper limit of normal, ALT less than or equal to 5x upper limit of normal, serum creatinine less than or equal to 2x upper limit of normal for age, and Hgb greater than or equal to 7.0 g/dL * Pulse oximetry of greater than or equal to 90% on room air * Sexually active subjects must be willing to utilize one of the more effective birth control methods for 6 months after the T cell infusion. The male partner should use a condom * Available autologous transduced T lymphocytes with greater than or equal to 15% expression of HER2 CAR determined by flow-cytometry and killing of HER2-positive targets greater than or equal to 20% in cytotoxicity assay * Patients who have undergone tumor resection should have recovered from the surgery. Patients with neurological deficits should have deficits that are stable for minimum of 1 week prior to treatment. * Subjects should have been off other investigational antineoplastic therapy for two weeks prior to CAR T cell infusion. Temozolomide will be allowed up to 48 hours pre-infusion. Dexamethasone up to a total dose of 2 mg per day will be allowed if medically indicated * Informed consent explained to, understood by and signed by research subjects/guardian. Subject/guardian given copy of informed consent. Treatment Exclusion Criteria: * Severe intercurrent infection * Known HIV positivity * Pregnant or lactating * History of hypersensitivity reactions to murine protein-containing products. * Diagnosis of DIPG * Steroid dose of dexamethasone greater than 2 mg per day (or equivalent)