A Phase II Study Evaluating Efficacy of B7-H3-CAR T Cells Administered at the End of Upfront Map Chemotherapy in Patients With Newly Diagnosed High-Risk Osteosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Event-free survival (EFS), defined as time from SJCARB7H3-41BBL infusion to disease relapse, progressive disease, new systemic therapy, secondary malignancy or death
研究概览
简要总结
The purpose of this study is to assess the safety, feasibility, and effectiveness of a consolidative B7-H3 CAR T cell therapy in patients with newly diagnosed high-risk osteosarcoma who have undergone upfront standard chemotherapy.
Primary Objectives:
- To evaluate 1-year RFS from the time of SJCARB7H3-41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy.
Secondary Objectives:
- To evaluate the OS from time of SJCARB7H3-41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy.
- To evaluate the feasibility of delivering SJCARB7H3-41BBL at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma.
- To describe the safety of autologous SJCARB7H3-41BBL therapy when delivered at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma.
详细描述
This is a phase 2 study of SJCARB7H3-41BBL for participants with newly diagnosed high-risk metastatic osteosarcoma who received standard chemotherapy.
All participants will receive standard chemotherapy (for example methotrexate, anthracycline, platinum), local control surgery, and pulmonary metastasectomy if applicable, and this is not considered part of protocol therapy. Participants will undergo apheresis prior to standard local control surgery (about 12 weeks after diagnosis) for SJCARB7H3-41BBL manufacture and then resume standard consolidation therapy. A safety run will initiate with Regimen A. For Regimen A, eligible participants with available SJCARB7H3-41BB product will receive lymphodepletion chemotherapy 14-28 days after the completion of standard chemotherapy (31 weeks after diagnosis), followed by SJCARB7H3-41BB infusion. If Regimen A is not cleared, then Regimen B will be evaluated, where lymphodepletion and SJCARB7H3-41BB infusion occur post pulmonary metastasectomy. Following successful clearance of either regimen A or, if necessary, regimen B, then the efficacy cohort will be initiated. Participants will be followed with serial disease evaluations for 2 years from SJCARB7H3-41BB infusion prior to transfer to our institutional long-term follow-up (LTFU) protocol. The total duration from completion of standard therapy, including experimental therapy and follow-up on 3CAR4OS, is approximately 2 years.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant and/or legally authorized representative has signed the Informed Consent Form for this study
- •Prior cancer therapy:
- •Regimen A only: Completed all planned cycles of consolidation therapy between 14-28 days prior.
- •Regimen B only: has completed all planned cycles of consolidation chemotherapy at least 14 days prior and if clinically indicated, participant has undergone pulmonary metastasectomy. They must have recovered from any surgical complications with no ongoing sequelae of category 2 or higher by the Clavien-Dindo classification system and less than 6 weeks must have passed from time of pulmonary metastasectomy.
- •No evidence of progressive disease since enrolled on study
- •Lansky performance status score of ≥ 50 for participants <16 years of age or Karnofsky score ≥ 50 for participants ≥ 16 years. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status
- •Adequate organ function as indicated by:
- •Renal: Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) based on enrollment eligibility table.
- •Hepatic: Total bilirubin ≤ 3 times ULN for age OR conjugated bilirubin ≤ 2 mg/dL AND ALT (SGPT) ≤ 5 times ULN
- •Cardiac: Shortening fraction ≥ 28% OR ejection fraction ≥ 50% as measured by echocardiogram
- •Respiratory: Oxygen saturation ≥ 90% on room air without supplemental oxygen or mechanical ventilation
- •Laboratory values meet the following criteria:
- •Absolute Neutrophil Count (ANC) ≥ 750 cells/uL
- •Platelet Count of ≥ 75,000 (can be transfused)
- •Hemoglobin ≥ 7 g/dL (can be transfused)
- •Participant is ≥ 7 days from receiving supra-physiologic dosing of systemic (IV or PO) corticosteroids. Glucocorticosteroid physiologic replacement therapy for management of adrenal insufficiency is allowed.
- •Participant and/or legally authorized representative has signed the Informed Consent Form for the treatment phase of this study.
排除标准
- •Major surgical adverse event related to the primary tumor local control defined as Clavien-Dindo category 3 requiring ongoing wound care.
- •Evidence of clinically significant encephalopathy/new focal neurologic deficits.
- •Presence of active severe infection, defined as:
- •positive blood culture within 48 hours of enrollment, OR
- •fever above 38.2° C, AND clinical signs of infection within 48 hours of enrollment
- •Participant has received prior disease-directed therapy other than 1st line therapy with methotrexate, an anthracycline, and a platinum and local control surgery
- •Regimen B only - okay to have undergone initial pulmonary metastasectomy
- •Pregnant or breastfeeding
- •Presence of any condition that, in the opinion of the investigator, would prohibit the participant from undergoing treatment under this protocol
研究组 & 干预措施
3CAR4OS Treatment
All patients will receive standard of care chemotherapy, which is not considered part of protocol therapy. Eligible patients will undergo apheresis prior to standard local control surgery for CAR T cell manufacture and then resume standard therapy. In the absence of progressive disease, eligible patients with available SJCARB7H3-41BBL product will receive lymphodepletion chemotherapy (fludarabine/cyclophosphamide) after the completion of standard chemotherapy, followed by SJCARB7H3-41BBL infusion. Pulmonary metastasectomy will be performed as indicated according to the standard of care and will be timed after (Regimen A) or before (Regimen B) lymphodepletion and SJCARB7H3-41BBL infusion. Following successful clearance of either regimen A or, if necessary, regimen B, the efficacy cohort will be initiated.
干预措施: Apheresis (Procedure)
3CAR4OS Treatment
All patients will receive standard of care chemotherapy, which is not considered part of protocol therapy. Eligible patients will undergo apheresis prior to standard local control surgery for CAR T cell manufacture and then resume standard therapy. In the absence of progressive disease, eligible patients with available SJCARB7H3-41BBL product will receive lymphodepletion chemotherapy (fludarabine/cyclophosphamide) after the completion of standard chemotherapy, followed by SJCARB7H3-41BBL infusion. Pulmonary metastasectomy will be performed as indicated according to the standard of care and will be timed after (Regimen A) or before (Regimen B) lymphodepletion and SJCARB7H3-41BBL infusion. Following successful clearance of either regimen A or, if necessary, regimen B, the efficacy cohort will be initiated.
干预措施: SJCARB7H3_41BBL infusion (Procedure)
3CAR4OS Treatment
All patients will receive standard of care chemotherapy, which is not considered part of protocol therapy. Eligible patients will undergo apheresis prior to standard local control surgery for CAR T cell manufacture and then resume standard therapy. In the absence of progressive disease, eligible patients with available SJCARB7H3-41BBL product will receive lymphodepletion chemotherapy (fludarabine/cyclophosphamide) after the completion of standard chemotherapy, followed by SJCARB7H3-41BBL infusion. Pulmonary metastasectomy will be performed as indicated according to the standard of care and will be timed after (Regimen A) or before (Regimen B) lymphodepletion and SJCARB7H3-41BBL infusion. Following successful clearance of either regimen A or, if necessary, regimen B, the efficacy cohort will be initiated.
干预措施: Fludarabine (Drug)
3CAR4OS Treatment
All patients will receive standard of care chemotherapy, which is not considered part of protocol therapy. Eligible patients will undergo apheresis prior to standard local control surgery for CAR T cell manufacture and then resume standard therapy. In the absence of progressive disease, eligible patients with available SJCARB7H3-41BBL product will receive lymphodepletion chemotherapy (fludarabine/cyclophosphamide) after the completion of standard chemotherapy, followed by SJCARB7H3-41BBL infusion. Pulmonary metastasectomy will be performed as indicated according to the standard of care and will be timed after (Regimen A) or before (Regimen B) lymphodepletion and SJCARB7H3-41BBL infusion. Following successful clearance of either regimen A or, if necessary, regimen B, the efficacy cohort will be initiated.
干预措施: Cyclophosphamide (Drug)
3CAR4OS Treatment
All patients will receive standard of care chemotherapy, which is not considered part of protocol therapy. Eligible patients will undergo apheresis prior to standard local control surgery for CAR T cell manufacture and then resume standard therapy. In the absence of progressive disease, eligible patients with available SJCARB7H3-41BBL product will receive lymphodepletion chemotherapy (fludarabine/cyclophosphamide) after the completion of standard chemotherapy, followed by SJCARB7H3-41BBL infusion. Pulmonary metastasectomy will be performed as indicated according to the standard of care and will be timed after (Regimen A) or before (Regimen B) lymphodepletion and SJCARB7H3-41BBL infusion. Following successful clearance of either regimen A or, if necessary, regimen B, the efficacy cohort will be initiated.
干预措施: Mesna (Drug)
结局指标
主要结局
Event-free survival (EFS), defined as time from SJCARB7H3-41BBL infusion to disease relapse, progressive disease, new systemic therapy, secondary malignancy or death
时间窗: Time from SJCARB7H3-41BBL infusion to time of first event, followed up to 24-months post-infusion
Event-free participants will be censored at the time of last follow-up. This analysis will report the Kaplan-Meier (KM) curve, along with the 12-month EFS estimate and its 80% confidence interval using the arcsine-square root transformation. Evaluable participants are those who complete standard chemotherapy, receive SJCARB7H3-41BBL and are treated on the regimen used for the Efficacy phase.
Event-free survival (EFS), defined as time from SJCARB7H3_41BBL infusion to disease relapse, progressive disease, new systemic therapy, secondary malignancy or death
时间窗: Time from SJCARB7H3_41BBL infusion to time of first event, followed up to 24-months post-infusion
Event-free participants will be censored at the time of last follow-up. This analysis will report the Kaplan-Meier (KM) curve, along with the 12-month EFS estimate and its 80% confidence interval using the arcsine-square root transformation. Evaluable participants are those who complete standard chemotherapy, receive SJCARB7H3\_41BBL and are treated on the regimen used for the Efficacy phase.
次要结局
- Overall survival (OS), defined as time from SJCARB7H3_41BBL cell infusion to all-cause mortality.(Time from SJCARB7H3_41BBL infusion to time of death from any cause, followed up to 24-months post-infusion)
- Overall survival (OS), defined as time from SJCARB7H3-41BBL cell infusion to all-cause mortality.(Time from SJCARB7H3-41BBL infusion to time of death from any cause, followed up to 24-months post-infusion)
- Number of participants experiencing protocol-specified regimen-related toxicities.(Time from SJCARB7H3-41BBL infusion up to 28 days post-infusion.)
- Number of participants with successful manufacture of SJCARB7H3-41BBL cells of sufficient dose and planned product administration(Time of SJCARB7H3-41BBL infusion)
- Number of participants experiencing protocol-specified regimen-related toxicities.(Time from SJCARB7H3_41BBL infusion up to 28 days post-infusion.)
- Number of participants with successful manufacture of SJCARB7H3_41BBL cells of sufficient dose and planned product administration(Time of SJCARB7H3_41BBL infusion)