A Phase I Clinical Trial of T-Cells Targeting B-Cell Maturation Antigen for Previously Treated Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
Background:
- T cells are white blood cells that fight several cancers. One cancer therapy involves removing a persons' T cells, changing them in a lab, and then returning them to the person. Researchers want to see if this helps people with multiple myeloma.
Objective:
- To test the safety of giving anti-B-Cell Maturation Antigen T cells to people with multiple myeloma.
Eligibility:
- Adults ages 18-70 with multiple myeloma that has not responded to standard therapies.
Design:
- Participants may be screened with:
- Medical history
- Physical exam
- Blood and urine tests
- Heart tests
- Bone marrow sample
- Multiple scans and X-rays
- Participants will have apheresis. Blood is removed through a needle in an arm. T cells are removed. The rest of the blood is returned through a needle in the other arm.
- The cells will be changed in a laboratory.
- Participants will get 2 chemotherapy drugs over 3 days.
- Two days later, participants will check into the hospital. They will get an intravenous (IV) catheter in an arm or chest vein. They will get the T cells through the IV in 1 infusion.
- After this, participants will stay in the hospital for at least 9 days and stay nearby for 2 weeks. Then they will have blood tests and see a doctor.
- Participants will visit the clinic 1, 2, 3, 4, 6, and 12 months after the infusion, then every 6 months. A bone marrow sample will be taken at the 2-month visit.
- Participants blood will be collected for several years. Participants will have an annual physical at National Institutes of Health (NIH) for 5 years after the infusion. Then for 10 years they will answer health questionnaires.
详细描述
BACKGROUND:
- Multiple myeloma (MM) is a malignancy of plasma cells.
- MM is nearly always incurable.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens.
- Autologous T cells genetically modified to express CARs targeting the B-cell antigen cluster of differentiation 19 (CD19) have caused complete remissions in a small number of patients with leukemia or lymphoma. These results demonstrate that CAR-expressing T cells have anti-malignancy activity in humans.
- B-cell maturation antigen (BCMA) is a protein expressed by normal plasma cells and the malignant plasma cells of multiple myeloma.
- BCMA is not expressed by normal cells except for plasma cells and some mature B cells.
- We have constructed an anti-BCMA CAR that can specifically recognize BCMA-expressing target cells in vitro and eradicate BCMA-expressing tumors in mice.
- Anti-BCMA-CAR-expressing T cells have not been previously tested in humans.
- We hypothesize that anti-BCMA-CAR-expressing T cells will specifically eliminate
BCMA-expressing MM cells in patients
-Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of normal plasma cells and unknown toxicities are also possible.
OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 73 Years（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
Multiple Myeloma
Dose Escalation with 5 dose levels based on the patients actual bodyweight
干预措施: Cyclophosphamide (Drug)
Multiple Myeloma
Dose Escalation with 5 dose levels based on the patients actual bodyweight
干预措施: Fludarabine (Drug)
Multiple Myeloma
Dose Escalation with 5 dose levels based on the patients actual bodyweight
干预措施: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells (Biological)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities
时间窗: After the start of treatment and up to 60 days
Dose limiting toxicities are defined as follows: Grade 3 toxicities possibly or probably related to either the anti-BCMA CAR T cells or the fludarabine and cyclophosphamide chemotherapy and lasting more than 7 days. Grade 4 toxicities possibly or probably related to the study interventions.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
时间窗: Date treatment consent signed to date off study, approx. 3 mos and 7 days for DL 0.3 x 10^6 CAR + T cells, 4 mos and 4 days for 1.0 x 10^6 CAR + T cells, 9 mos and 13 days for 3.0 x 10^6 CAR + T cells, and 48 mos and 12 days for 9.0 x 10^6 CAR + T cells.
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
次要结局
- Number of Participants With Best Response(From start of treatment up to 84 weeks)
研究者
James Kochenderfer, M.D.
Principal Investigator
National Cancer Institute (NCI)