Randomized Phase 3 Trial of Standard Care Plus AV-GBM-1 vs Autologous Monocytes as Adjunctive Therapy Following Primary Surgery Plus Concurrent Radiation-temozolomide in Patients With Newly Diagnosed Glioblastoma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 672
- 主要终点
- Overall survival from date of randomization
研究概览
简要总结
This is a multi-center, double-blind, 2:1 randomized phase III trial to determine whether the addition of AV-GBM-1, a therapeutic, patient-specific dendritic cell vaccine, to standard therapy increases OS of patients with a recent diagnosis of primary GBM.
The intent is to enroll approximately 726 patients for tumor collection to enroll 690 who are eligible for treatment at the time of randomization and who have granted consent for participation. Because of the lack of toxicity, there are no restrictions related to performance status or blood tests at the time of treatment. The key endpoint is OS from date of first injection after RT/TMZ; secondary endpoints are PFS from date of first injection, and OS and PFS from date of randomization prior to RT/TMZ. Date of PFS will be determined by the principal investigator at each site.
详细描述
This is a multi-center, double-blind, 2:1 randomized phase 3 trial to determine whether the addition of AV-GBM-1 to standard therapy increases OS of patients with a recent diagnosis of primary GBM.
Patients will sign two treatment-related consents, one for obtaining fresh tumor tissue at the time of craniotomy for the purpose of establishing a short-term tumor cell line and for awareness of subsequent leukapheresis procedure, and the other for randomization and participation in the randomized trial. As required for related medical procedures, patients will sign medical consents for craniotomy/tumor resection, and for leukapheresis to obtain monocytes for the MC control arm, or to manufacture DC.
Key eligibility criteria are (1) recovered from maximal safe surgical resection surgery from which a short-term cell culture has been established, (2) undergone leukapheresis prior to planned concurrent RT/TMZ, from which a sufficient number of MC have been derived, (3) screened, stratified and randomized prior to starting RT/TMZ. Patients will be stratified by age (70 years or greater or less than 70), KPS (90 or 100 vs 70 or 80), MGMT promotor-methylation (yes or no), and IDH-mutation status (mutated or wild-type), then randomized 2:1 (AV-GBM-1 vs MC control).
The final products will be manufactured while the patient is being treated with RT/TMZ. After recovery from RT/TMZ, one of the study agents, either the DC-ATA AV-GBM-1 or autologous MC control, will be administered weekly for three weeks just prior to starting adjuvant TMZ, and then every four weeks concurrently with, adjuvant TMZ or second-line therapy per managing physician. Both products are admixed with adjuvant 500 mcg of GM-CSF by a local pharmacist, just prior to each injection. The pharmacist, the patient, their health care givers and local research team will be masked as to whether the patient is receiving AV-GBM-1 or MC control, which are similar in appearance. Only the AIVITA manufacturing team will be aware of randomization so that the appropriate product can be manufactured per SOPs.
The first 3 weekly SC injections of study agent will be administered prior to beginning adjuvant or salvage temozolomide, temozolomide plus bevacizumab, or temozolomide plus tumor treating fields. Thereafter study agents will be injected about every 28 days for up to 18 additional vaccines (i.e. a total of 21 vaccines over 18 months from the start of investigational therapy. Depending on the number of study-agent doses available, additional leukaphereses and manufacturing of more study agent may be required if treatment is to continue up to 18 months from the start of therapy. In previous trials, 8 total injections were given over 6 months. In this trial up to 21 doses may be given over 18 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •For tumor collection: Age >18, Presumptive diagnosis of primary GBM with plans for surgical resection, Written informed consent to provide tumor and blood and intent to proceed with leukapheresis
- •For randomization: Confirmation of GBM histology, AIVITA Biomedical confirmation of established cancer cell line and sufficient monocytes derived from PBMC during leukapheresis collection, age 70 years or greater or less than 70, KPS 90 or 100 vs 70 or 80, MGMT promotor methylation classified as positive or negative, IDH mutation classified as mutated or wild-type, and planning to initiate RT/TMZ. Written informed consent for randomization and treatment per protocol
排除标准
- •For tumor collection: Prior history of astrocytoma or other glial tumor, Known autoimmune disease or immunodeficiency. Diagnosis of any other invasive cancer or disease process considered to be life-threatening within the next 5 years. Known allergy to GM-CSF
- •For randomization: Active infection or other active medical condition that could be life-threatening, Diagnosis of underlying cardiac disease that requires active medical treatment, Pregnant, Enrolled in another investigational trial to receive an investigational treatment, KPS < 70, Did not meet inclusion/exclusion criteria for tumor collection
结局指标
主要结局
Overall survival from date of randomization
时间窗: 2.0 years
Overall survival
次要结局
- PFS from date of first AV-GBM-1 injection(2.0 years)
- PFS from date of randomization(2.0 years)
- Determine and compare TEAE for both study arms(2.0 years)
- OS from date of first AV-GBM-1 injection(2.0 years)