Anti-BCMA Chimeric Antigen Receptor (CARTemis-1) T-lymphocyte Therapy in the Treatment of Patients With Multiple Myeloma in Relapse After Allogeneic Transplant: Endothelial Growth Factor Receptor Expression as a Control Mechanism of Treatment-derived Complications
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 10
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
Most patients with multiple myeloma (MM) die due to relapse resistant to current treatment, including treatment with anti-B cell maturation antigen (BCMA) CAR-T cells. To overcome some of the potential limitations of this therapy, a new and optimized Anti-BCMA CAR-T has been developed, with the aim of using it in patients with MM who relapse after Allogeneic Haematopoietic Haematopoietic Progenitor. This trial is a prospective phase I/II trial with a 3+3 design. Once Dose Limiting Toxicity is identified, Phase II will begin to assess the efficacy of the procedure.
详细描述
This trial is a prospective phase I/II trial with a 3+3 design. Once Dose Limiting Toxicity is identified (up to a maximum dose of 6x106 CAR-T/kg divided over 2 days), phase II of the trial will begin to assess the efficacy of the procedure.
A number of 25 patients will be included to evaluate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Patients > 18 years old with a diagnosis of post-allogeneic transplant relapse multiple myeloma.
- •Measurable disease at the time of screening
- •Previous treatment with ≥2 lines before and/or after allogeneic transplant.
- •Patients who are not receiving immunosuppressants at least 1 month before inclusion and who do not have active graft-versus-host disease.
- •Eastern Cooperative Oncology Group functional status from 0 to
- •Life expectancy greater than 3 months (at the time of screening)
- •Patients who give their consent by signing the Informed Consent document.
排除标准
- •Active systemic immunosuppressive treatment
- •Patients who have previously received treatment with CAR-T Anti-BCMA.
- •Absolute lymphocyte count <0.2x109/L
- •Previous neoplasm, except if it has been in complete remission >3 years, with the exception of skin carcinoma (non-melanoma)
- •Active infection requiring treatment.
- •Active HIV, hepatitis B virus or hepatitis C virus infection.
- •Uncontrolled medical illness.
- •Severe organic disease that meets any of the following criteria: left ventricular ejection fraction <40%, carbon monoxide diffusion test <40%, glomerular filtration rate <50 ml/min, bilirubin >3 normal value (except Gilbert syndrome).
- •Previous diagnosis of symptomatic amyloid light chain or primary amyloidosis or POEMS Syndrome.
- •Pregnant or lactating women.
- •Women of childbearing age, unable or unwilling to use highly effective contraceptive methods.
- •Men who cannot or do not wish to use highly effective contraceptive methods. The partner of the male participants, if they are women of childbearing age, must also use highly effective contraceptive methods during the study period.
- •Contraindication to receive lymphodepleting chemotherapy.
- •Patients with known hypersensitivity to the active ingredients or any of the excipients of the product to be infused.
结局指标
主要结局
Maximum tolerated dose
时间窗: Up to 30 days
To determine the maximum tolerated dose of CarTemis-1
Purity of CARTemis-1
时间窗: Immediately after infusion
Number of cases in which, after performing apheresis, the manufacturing process is completed and CARTemis-1 cells are infused
Suspected Unexpected Serious Adverse Reaction
时间窗: Up to 36 months after treatment administration
Describe the adverse event that occurs in a clinical trial subject, which is assessed by the sponsor and or study investigator as being unexpected, serious and as having a reasonable possibility of a causal relationship with the study drug.
Infusion reactions
时间窗: Immediately after intravenous administration of CARTemis-1
To appearance of any of the following symptoms after intravenous administration of CARTemis-1: cardiac events, chills, dyspnea, fatigue, sudden hypertension, hypotension, nausea, pain, fever, skin rash, and urticaria.
Tumor lysis syndrome
时间窗: Up to 30 days after treatment administration
To increase nucleic acids, potassium, and phosphate in the blood
Serious Adverse Event
时间窗: Up to 36 months after treatment administration
Type, incidence, severity (graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0), timing, intensity, and relatedness of adverse events).
次要结局
- Persistence of CARTemis-1(Peripheral blood:days 3,7,10,14,17 (only in cohort 3 and 4),21,30,56,90,128 and 156, and months 6,9,12,15,18,24 and relapse or month 36 post-infusion; Marrow: 1,3,6,12,18 and 24 months post-infusion and in the progression or month)
- Expression of B cell maturation antigen (BCMA)(Screening and at the time of follow up when a relapse occurs, an average after 1 year)
- CART cell quality(During the manufacturing process, at the time of infusion and at Month+1, Month+3, Month+6, Month+12, Month+18 and Month+24 post-infusion)
- Overall response rate(3, 6 and 12 months after CARTemis-1 infusion)
- Progression-free survival.(Up to 36 months after treatment administration)
- Number of Participants with cytopenias(During the first 90 days after administration of CARTemis-1)
- Overall survival(Up to 36 months after treatment administration)
- Time to best response(Up to 36 months after treatment administration)
- Negative Minimum Residual Disease Rate(3, 6 and 12 months after CARTemis-1 infusion)
- Response rate of extramedullary disease(3 months after CARTemis-1 infusion)
- B cell maturation antigen (BCMA) levels(Screening, Day -5, Day 0, +1, +3, +7 y +28 and months +3, +6, +12, +18 and +24)
- Number of Participants with prolonged cytopenias(Up to 12 months after treatment administration)
- Duration of clinical response(Screening, day -5, -4, -3, +28, +56, +100 and months +4, +5, 6, +7, +8, +9, +10, +11, +12, +15 , +18, +21, +27, +30, +33, +36 or progression)
- Time to complete remission(Up to 36 months after treatment administration)