A Phase 1/2 Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Allogeneic CRISPR-Cas9-Engineered T Cells (CTX110) in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 93
- 试验地点
- 33
- 主要终点
- Dose Escalation Phase 1: Number of Participants With Dose-limiting Toxicities (DLT) in NHL and B Cell ALL Population
研究概览
简要总结
This is an open-label, multicenter, Phase 1/2 study evaluating the safety and efficacy of CTX110 in subjects with relapsed or refractory B-cell malignancies.
详细描述
The study may enroll up to 227 subjects in total. CTX110 is a CD19-directed chimeric antigen receptor (CAR) T cell immunotherapy comprised of allogeneic T cells prepared for the treatment of B cell malignancies. The cells are from healthy adult volunteer donors that are genetically modified ex vivo using CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9) gene editing components (single guide RNA and Cas9 nuclease).
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
- •For NHL patients: Age ≥18 years. For B cell ALL patients: age ≥18 years to ≤70 years
- •Refractory or relapsed non-Hodgkin lymphoma, as evidenced by 2 or more lines of prior therapy, or histologically confirmed B cell ALL, refractory or relapsed.
- •Eastern Cooperative Oncology Group performance status 0 or
- •Adequate renal, liver, cardiac and pulmonary organ function
- •Female subjects of childbearing potential and male subjects must agree to use acceptable method(s) of contraception from enrollment through at least 12 months after CTX110 infusion.
排除标准
- •For NHL patients: prior allogeneic HSCT. For B cell ALL patients: prior allogeneic HSCT within 6 months, and/or any evidence of GvHD.
- •History of central nervous system (CNS) involvement by malignancy
- •History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
- •Presence of bacterial, viral, or fungal infection that is uncontrolled.
- •Positive for HIV, or active hepatitis B virus or hepatitis C virus infection.
- •Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥5 years.
- •For NHL patients: Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of CTX110 infusion. For B cell ALL patients: Use of systemic antitumor therapy within 7 days of CTX110 infusion.
- •Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
- •Women who are pregnant or breastfeeding.
研究组 & 干预措施
CTX110
Administered by IV infusion following lymphodepleting chemotherapy.
干预措施: CTX110 (Biological)
结局指标
主要结局
Dose Escalation Phase 1: Number of Participants With Dose-limiting Toxicities (DLT) in NHL and B Cell ALL Population
时间窗: Up to 28 days
A DLT is defined as any of the following events occurring during the DLT evaluation period that persisted beyond the specified duration from onset: Grade ≥2 graft-versus-host disease (GvHD) that was steroid-refractory (e.g., progressive disease after 3 days of steroid treatment \[e.g., 1 mg/kg/day\], stable disease after 7 days, or partial response after 14 days of treatment); death during the DLT period, unless due to disease progression; Grade 4 neurotoxicity of any duration that was related or possibly related to CTX110; or any CTX110-related grade 3 or 4 toxicity deemed clinically significant by the investigator that did not improve within 72 hours.
Dose Expansion Phase 1 and Phase 2: Percentage of Participants With Objective Response Rate in NHL Population
时间窗: Up to 5 years
The objective response rate (complete response + partial response) was analyzed as per Lugano Response Criteria for Malignant Lymphoma, as determined by independent central radiology review. For participants who received the second course of treatment, the response assessments before and after the second course are combined for the derivation of objective response. Percentages are calculated with the number of participants in the specific analysis set in each column as the denominator. Confidence intervals (CI) of percentage are calculated with Clopper-Pearson exact method.
次要结局
- Dose Escalation Phase 1: Percentage of Participants With Objective Response Rate in B Cell ALL Population(Up to 5 years)
- Dose Escalation and Expansion Phase 1: Duration of Response in NHL Population(Up to 5 years)
- Dose Escalation and Expansion Phase 1: Progression Free Survival (PFS) in NHL Population(Up to 5 years)
- Dose Escalation and Expansion Phase 1: Median Overall Survival (OS) in NHL Population(Up to 5 years)
- Dose Escalation and Expansion: Number of Participants With Treatment Emergent Adverse Events (TEAEs) in NHL and B Cell ALL Population(Up to 5 years)
- Dose Escalation and Expansion: Number of Participants With Clinically Significant Laboratory Abnormalities in NHL and B Cell ALL Population(Up to 5 years)
- Dose Escalation and Expansion: Mean Concentration of CTX110 in Blood Over Time Following the First CTX110 Infusion in NHL Population(Day 1 pre-infusion, Day 1 post-infusion, Day 2, Day 3, Day 5, Day 8, Day 10, Day 14, Day 21, Day 28, Month 2, Month 3, Month 6, Month 9, Month 12 and Month 24)
- Dose Escalation and Expansion Phase 1: Mean Concentration of CTX110 in Blood Over Time Following the First CTX110 Infusion in B Cell ALL Population(Day 1 pre-infusion, Day 1 post-infusion, Day 2, Day 3, Day 5, Day 8, Day 10, Day 14, Day 21, Day 28, and Month 2)
- Dose Escalation and Expansion: Number of Participants With Serious Adverse Events (SAEs) in NHL and B Cell ALL Population(Up to 5 years)