Phase II Trial O6-benzylguanine(BG) and Temozolomide(TMZ) Therapy of Glioblastoma Multiforme (GBM) With Infusion of Autologous P140K MGMT+Hematopoietic Progenitors to Protect Hematopoiesis

Leland Metheny2 个研究点分布在 1 个国家目标入组 16 人开始时间: 2023年1月20日最近更新: 2026年9月10日

适应症

干预措施

试验速览

阶段: 2 期
状态: 招募中
发起方
入组人数: 16
试验地点: 2
主要终点: Overall Survival

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This phase II trial studies the effect of P140K MGMT hematopoietic stem cells, O6-benzylguanine, temozolomide, and carmustine in treating participants with supratentorial glioblastoma or gliosarcoma who have recently had surgery to remove most or all of the brain tumor (resected). Chemotherapy drugs, such as 6-benzylguanine, temozolomide, and carmustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing. Placing P140K MGMT, a gene that has been created in the laboratory into bone marrow making the bone more resistant to chemotherapy, allowing intra-patient dose escalation which kills more tumor cells while allowing bone marrow to survive.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Participants with histologically confirmed, newly diagnosed, supratentorial glioblastoma or gliosarcoma who have undergone tumor resection are eligible up to 35 days postoperatively. Participants with primarily infratentorial disease, or with multifocal, or leptomeningeal dissemination of disease will be excluded. In general, participants will not have > 1 cm residual measurable or evaluable disease after surgical tumor resection.
•Participant must have unmethylated MGMT
•Absence of IDH1 or IDH2 mutation on tumor tissue by a CLIA-approved immunohistochemistry or DNA sequencing test on local testing.
•Participants aged 18 years or older.
•ECOG performance status 0-1or Karnofsky ≥
•Life expectancy of at least 12 weeks.
•No plan for hypofractionated radiation therapy
•Adequate hematologic and hepatic function:
•CBC/differential obtained within 28 days prior to registration:
•Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 Note: the use of G-CSF or other intervention to achieve Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 is acceptable)
•Platelets ≥ 50,000 cells/mm3 (Note: the use of transfusion or other intervention to achieve Platelets ≥ 50,000 cells/mm3 is acceptable)
•Hemoglobin ≥ 9.0 g/dl (Note: the use of transfusion or other intervention to achieve Hgb ≥9.0 g/dl is acceptable)
•Adequate hepatic function within 28 days prior to registration:
•Bilirubin ≤ 3 ULN
•ALT and AST ≤ 3 x ULN
•Participants of child-bearing potential must agree to use single barrier contraception from time of trial entry to completion of the last cycle of chemotherapy.
•Must be willing and able to understand and provide informed consent.
•Participant must be considered to be clinically stable.
•The participant will be identified as a candidate for an autologous transplant via an evaluation by a transplant physician per standard of care.
•No evidence of active infection.
•Participant must have the ability to understand and willingness to sign an informed consent document.

排除标准

•Any known medical or hereditary condition associated with immunosuppression; or other medical illness, which may jeopardize participant safety.
•Pregnant or lactating women. There is data to indicate that BCNU and TMZ is teratogenic and carcinogenic. Thus, its use in pregnant women would confer unnecessary risk to the fetus.
•Participants with a corrected DLCO or FEV1 < 50% of predicted.
•Participants with known diagnosis heart failure or cardiac insufficiency and an LVEF of < 40%.
•Inability to undergo repeated MRI evaluation; or allergy or intolerance of Gadoliniumcontaining contrast agent.
•Active illicit drug use or diagnosis of active alcoholism.
•Prior diagnosis of any malignant disease with the exception of non-melanomatous skin cancer, or carcinoma in situ of the cervix, bladder, prostate, or breast, unless the participant has been disease-free/in remission for ≥2 years prior to date of study enrollment.
•Known human immunodeficiency virus infection or acquired immunodeficiency syndrome related illness.
•Serologic status reflecting active hepatitis B or C infection. Individuals that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive individuals will be excluded).