Immune Consolidation With Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) After Peripheral Blood Stem Cell Transplant for High Risk CD20+ Non-Hodgkin's Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- To perform a dose escalation trial of ATC armed with CD20Bi immunotherapy after PBSCT to determine the maximum tolerated dose (MTD) of ATC armed with CD20BI.
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, and melphalan work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving white blood cells, that have been treated in the laboratory with antibodies, may make the transplant work better. Giving combination chemotherapy followed by an autologous stem cell transplant, and white blood cell infusions may be an effective treatment for non-Hodgkin's lymphoma.
PURPOSE: This phase I trial is studying the side effects and best dose of white blood cell infusions when given together with combination chemotherapy, and autologous stem cell transplant in treating patients with non-Hodgkin's lymphoma that has relapsed, is refractory, or is in remission.
详细描述
OBJECTIVES:
- Determine the toxicity of high-dose combination chemotherapy comprising cyclophosphamide, thiotepa, and carboplatin followed by autologous peripheral blood stem cell transplantation and immunotherapy consolidation therapy comprising anti-CD3 x anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC) in patients with non-Hodgkin's lymphoma.
- Determine the maximum tolerated dose of CD20Bi-ATC in patients treated with this regimen.
- Determine whether ATC traffic to tumor sites in select patients treated with this regimen.
- Assess the immune reconstitution of B cells and incidence of infection in patients treated with this regimen.
- Compare relapse rates and overall survival of patients treated with this regimen with historical controls.
OUTLINE: This is a dose-escalation study of activated T cells.
- Peripheral blood stem cell (PBSC) mobilization and collection: Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily for 5 days. They then undergo leukaphereses to collect peripheral blood stem cells (PBSC). Some of the lymphocytes are treated in the laboratory to produce anti-CD3 x anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC).
- High-dose chemotherapy and PBSC transplantation: Patients receive carmustine IV on day -7, etoposide IV twice daily and cytarabine IV twice daily on days -6, -5, -4, and -3, and melphalan IV on day -2. Autologous PBSC are reinfused on day 0.
- Immunotherapy consolidation: Patients receive immunotherapy consolidation comprising CD20Bi-ATC IV over 15-30 minutes starting on day 4, once a week for 4 weeks for a total of four infusions.
Cohorts of 3-6 patients receive escalating doses of CD20Bi-ATC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
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
- 15 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT
- minus Day 8 ADMIT for Hydration
- minus Day 7 Carmustine 300 mg/m2 x 1 dose
- minus Day 6 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 5 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 4 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 3 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 2 Melphalan 140 mg/m2 x 1 dose
- minus Day 1 Day of Rest
- Day 0 Transplant
干预措施: therapeutic autologous lymphocytes (Biological)
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT
- minus Day 8 ADMIT for Hydration
- minus Day 7 Carmustine 300 mg/m2 x 1 dose
- minus Day 6 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 5 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 4 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 3 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 2 Melphalan 140 mg/m2 x 1 dose
- minus Day 1 Day of Rest
- Day 0 Transplant
干预措施: carmustine (Drug)
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT
- minus Day 8 ADMIT for Hydration
- minus Day 7 Carmustine 300 mg/m2 x 1 dose
- minus Day 6 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 5 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 4 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 3 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 2 Melphalan 140 mg/m2 x 1 dose
- minus Day 1 Day of Rest
- Day 0 Transplant
干预措施: cytarabine (Drug)
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT
- minus Day 8 ADMIT for Hydration
- minus Day 7 Carmustine 300 mg/m2 x 1 dose
- minus Day 6 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 5 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 4 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 3 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 2 Melphalan 140 mg/m2 x 1 dose
- minus Day 1 Day of Rest
- Day 0 Transplant
干预措施: etoposide (Drug)
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT
- minus Day 8 ADMIT for Hydration
- minus Day 7 Carmustine 300 mg/m2 x 1 dose
- minus Day 6 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 5 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 4 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 3 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 2 Melphalan 140 mg/m2 x 1 dose
- minus Day 1 Day of Rest
- Day 0 Transplant
干预措施: melphalan (Drug)
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCT
- minus Day 8 ADMIT for Hydration
- minus Day 7 Carmustine 300 mg/m2 x 1 dose
- minus Day 6 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 5 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 4 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 3 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr
- minus Day 2 Melphalan 140 mg/m2 x 1 dose
- minus Day 1 Day of Rest
- Day 0 Transplant
干预措施: peripheral blood stem cell transplantation (PBSCT) (Procedure)
结局指标
主要结局
To perform a dose escalation trial of ATC armed with CD20Bi immunotherapy after PBSCT to determine the maximum tolerated dose (MTD) of ATC armed with CD20BI.
时间窗: When two patienst at any dose levet have their infusion stopped due to side effects.
This will be the called the maximum tolerated dose. The maximum tolerated dose (MTD) is defined as the dose level below the one at which the side effects are serious enough to prevent an increase in the dose or level of the treatment.
次要结局
- Evaluate immune B-cell recovery after ATC infusion(2 weeks (+/- 7 days), 1, 2, 3, 6 months (+/- 7 days) and 12, and 24 months (+/- one month) after Peripheral Blood Stem Cell Transplants (PBSCT))
- Evaluate response rates of infusions and compare relapse rates and overall survival to historical controls(1, 2, 4, 8, 16 and/or 24, 48 and 72 hours post infusion)
- Evaluate the toxicities of ATC infusions armed with CD20Bi(2 weeks (+/- 7 days), 1, 2, 3, 6 months (+/- 7 days) and 12, and 24 months (+/- one month) after Peripheral Blood Stem Cell Transplants (PBSCT))
研究者
Lawrence Lum
Principal Investigator
Barbara Ann Karmanos Cancer Institute