Phase I/II study of BCMA directed humanised CAR-T cell therapy (hBCMA) in patients with relapsed/refractory Multiple myeloma
试验速览
- 阶段
- 1/2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 57
- 试验地点
- 5
- 主要终点
- Phase I
研究概览
简要总结
Multiple Myeloma is difficult to treat disease. It is incurable with current available treatment options. Also, most of these options are beyond the reach of our population due to their availability and affordability. Anti-BCMA CAR-T cell therapy is a proven effective option which is not available in India. The treatment cost of the approved CART therapies in USA is exorbitant and ranges from $419,500 to $465,000. Thus, there is an urgent need to develop an indigenous, cost-effective CAR T-cell therapy for Myeloma in India. This is a phase I/II study BCMA-directed humanized CAR-T cell therapy in patients with relapsed/refractory Multiple myeloma. The primary aim of the Phase I part of the study is to assess the safety of hBCMA and the Phase II study will assess the efficacy of hBCMA. In Phase I a 3 + 3 dose escalation model will be utilized to establish safety. In Phase II a total of 39 patients will be enrolled at the dose level that has already been established, to assess the efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •18 years and above
- •Subjects with diagnosis of multiple myeloma who have received at least two lines of therapy or double refractory to immunomodulatory drug (IMiD) and proteasome inhibitor (PI) combination or refractory to last line of treatment.
- •Measurable Disease defined by at least one of the criteria a. Serum M-protein greater or equal to 1.0 g/dL b. Urine M-protein greater or equal to 200 mg/24 h c. Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal d. A biopsy-proven evaluable plasmacytoma e. Bone marrow plasma cells ≥ 10% of total bone marrow cells
- •All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study.
- •Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy.
- •Ability and willingness to adhere to the study visit schedule and all protocol requirements.
- •Written informed consent.
排除标准
- •1 Subjects who received the following treatments will be excluded a.
- •Any therapy that is targeted to B-cell maturation antigen (BCMA) b.
- •Ongoing treatment with chronic immunosuppressants since 2 weeks (eg cyclosporine or systemic steroids at any dose) c.
- •Previous history of an allogeneic bone marrow transplantation or treatment with any gene therapy-based therapeutic for cancer Any prior systemic therapy for MM within 14 days prior to scheduled protocol required leukapheresis
- •LVEF less than 50 percent
- •Subjects with a history of class III or IV congestive heart failure (CHF) or severe non ischemic cardiomyopathy, history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months
- •Subjects with known active, or prior history of central nervous system (CNS) involvement
- •Subjects with plasma cell leukaemia
- •Subjects with solitary plasmacytomas without other evidence of measurable disease
- •Subjects with second malignancies in addition to myeloma if the second malignancy has required therapy in the last 3 years or is not in complete remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or incidental histologic finding of prostate cancer (T1a or T1b using the TNM tumour, nodes, metastasis clinical staging system) or prostate cancer that is curative
- •Inadequate hepatic function defined by AST and ALT greater than 5 times the upper limit of normal (ULN) and direct bilirubin greater than 2 times ULN
- •Inadequate renal function defined by CrCl less than or equal to 30 ml/min using Cockcroft-Gault equation
- •International ratio (INR) or partial thromboplastin time (PTT) greater than three times ULN, unless on a stable dose of anticoagulant for a thromboembolic event, or history of grade 2 or more hemorrhage within 30 days
- •Evidence of human immunodeficiency virus (HIV) infection
- •Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV)
- •Seropositive for and with active viral infection with hepatitis C virus (HCV)
- •Pregnant or lactating women
- •Significant comorbidities or disease which in the judgement of the Investigator would place the subject at undue risk or interfere with the study
- •Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis
- •Patient with history of auto-immune disorders to be excluded.
结局指标
主要结局
Phase I
时间窗: Phase I | Safety | DLT will be assessed within 21 days post administration | of hBCMA CAR | Phase II | Overall Response Rate: 3 Months
Safety
时间窗: Phase I | Safety | DLT will be assessed within 21 days post administration | of hBCMA CAR | Phase II | Overall Response Rate: 3 Months
The MTD is the highest dose that causes DLTs in greater than or equal to 2 of 6 subjects. For a dose level to be declared the MTD at least 5 evaluable subject must be enrolled with no DLTs reported or 6 evaluable subjects if 1 subject experiences a DLT.
时间窗: Phase I | Safety | DLT will be assessed within 21 days post administration | of hBCMA CAR | Phase II | Overall Response Rate: 3 Months
Phase II
时间窗: Phase I | Safety | DLT will be assessed within 21 days post administration | of hBCMA CAR | Phase II | Overall Response Rate: 3 Months
Overall Response Rate
时间窗: Phase I | Safety | DLT will be assessed within 21 days post administration | of hBCMA CAR | Phase II | Overall Response Rate: 3 Months
Percentage of subjects who achieved a PR or better
时间窗: Phase I | Safety | DLT will be assessed within 21 days post administration | of hBCMA CAR | Phase II | Overall Response Rate: 3 Months
according to IMWG Uniform Response Criteria for Multiple Myeloma.
时间窗: Phase I | Safety | DLT will be assessed within 21 days post administration | of hBCMA CAR | Phase II | Overall Response Rate: 3 Months
次要结局
- Phase I(hBCMA persistence and quantification)
- Phase I & II: Overall Survival(5 years : (Time from the first infusion to time of death due to any cause))
- Phase I & II: Progression Free Survival(5 years (Time from the first infusion to first documentation of)
- Phase I: Overall Response Rate(Month 3)
- Phase I & II: Duration of Response(5 year Follow up period:(Time from first documentation of response of PR or better to first documentation of response to disease progression or death from any cause, whichever occurs first))
研究者
Dr Manju Sengar
Tata Memorial Centre