CLIC-02: A Phase I Trial of CLIC-2201 for the Treatment of Relapsed/Refractory B Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 7
- 主要终点
- Proportion of participants who experienced any grade of CRS to define the safety of CLIC-2201
研究概览
简要总结
This is a phase I dose-finding trial of an autologous CD22 targeting chimeric antigen receptor (CAR)-T cell product, called CLIC-2201, for participants with relapsed/refractory B cell malignancies. In the proposed trial, eligible enrolled participants will undergo leukapheresis for autologous T cell collection to enable CLIC-2201 manufacturing, followed by lymphodepletion with cyclophosphamide and fludarabine, then intravenous infusion of the autologous CLIC-2201 product. The trial will use the 3+3 design to escalate or de-escalate the dose level of CLIC-2201 administered. Participants will be monitored for safety and tolerability up to day 365 following CLIC-2201 infusion.
The primary objective is to evaluate the safety and tolerability of CLIC-2201 and estimate the maximum tolerated dose (MTD) of CLIC-2201 in B-cell malignancies.
The secondary objectives are to evaluate the (i) feasibility; (ii) anti-tumour activity of CLIC-2201; (iii) and characterize the pharmacokinetic (PK) profile of CLIC-2201.
Exploratory objectives will include: i) characterizing the cellular and humoral immune responses against CLIC-2201 up to 1 year following infusion of CLIC-2201; (ii) characterizing the phenotype and gene expression profile of CLIC-2201 cells; (iii) evaluating immune and tumour cells at baseline and relapse for biomarkers of response or toxicity; (iv) evaluating serum cytokines, circulating tumour DNA (ctDNA) and B cell aplasia as biomarkers of clinical outcomes; and (v) assessing the quality of life.
详细描述
This is a Phase I, first-in-human, open-label multicenter trial of CLIC-2201 CAR-T cells for participants with relapsed/refractory B cell malignancies.
This trial will be conducted in two cohorts (cohort A, including 12 adult participants with B-NHL and cohort B, including 12 paediatric/young adult participants with B-ALL).
Consented participants will undergo a series of tests to confirm eligibility. Following eligibility confirmation, participants will undergo leukapheresis, which enables CLIC-2201 manufacturing. Leukapheresis is a procedure where white blood cells are collected from the blood. The collected cells will be shipped fresh to the Conconi Family Immunotherapy Laboratory (CFIL) in Victoria, BC, where manufacturing will take place.
At the CFIL lab, the autologous T cells will be selected, activated, and transduced with lentivirus to deliver the sdCD22 CAR transgene and then expanded over a period of 8 days in an automated, closed process on the CliniMACS Prodigy.
Participants will undergo lymphodepleting chemotherapy consisting of fludarabine (40 mg/m^2 daily x 3 days) and cyclophosphamide (500 mg/m^2 daily x 2 days) on trial days -4 and -3. The chemotherapy will deplete the exciting immune cells and give a chance to the infused CAR-T cells to expand and grow in the body.
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
- 1 Year 至 —（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
- •Any uncontrolled or serious active infection at the time of enrolment.
- •Active autoimmune disease requiring immunosuppressive therapy within 4 weeks of enrolment.
- •Live vaccine ≤6 weeks prior to enrolment
- •Active Graft Versus Host Disease (GVHD) requiring systemic immunosuppressive therapy within 4 weeks of enrolment.
- •Treatment with any of the following in the specified time period before leukapheresis:
- •Allogeneic HCT within 3 months,
- •Autologous HCT within 3 months,
- •CD19 CAR-T cell infusion within 3 months,
- •Donor lymphocyte infusion (DLI) within 3 months,
- •Bendamustine within the last 6 months,
- •Any investigational agent within 30 days or 5 half-lives (whichever is shorter),
- •Systemic administration of therapeutic dose corticosteroids (>20 mg/day prednisone or equivalent for adults and ≥ 12 mg/m2/day for paediatric participants) within 7 days prior to leukapheresis.
- •Immunosuppressive therapies (i.e., calcineurin inhibitors, methotrexate, mycophenolate, rapamycin) within 4 weeks.
- •Oral chemotherapy agents (i.e., venetoclax) within 5 half-lives. An exception to this is that bruton tyrosine kinase (BTK) inhibitors like ibrutinib can be continued in participants with mantle cell lymphoma throughout the trial period.
- •Other concurrent malignancy or a prior malignancy treated within the past 2 years, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.
- •Concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure or immunodeficiency syndrome.
- •Active (confirmed by PCR) hepatitis B or hepatitis C at time of screening confirmed by PCR.
- •Any Human Immunodeficiency Virus (HIV) infection at time of screening.
- •Hypersensitivity to fludarabine or cyclophosphamide.
- •Any allergy to gentamycin or its derivatives
- •Pregnant or nursing participants.
研究组 & 干预措施
CLIC-2201
A single Intravenous infusion of CLIC-2201 will be given.
干预措施: CLIC-2201 (Biological)
结局指标
主要结局
Proportion of participants who experienced any grade of CRS to define the safety of CLIC-2201
时间窗: Within the first 28 days of CAR-T infusion
The safety will be measured by the proportion of participants who experienced any grade of CRS, ICANS, IEC-HS, any adverse events, and any severe adverse events.
Proportion of participants who experienced any SAEs to define the safety of CLIC-2201
时间窗: Within the first 28 days of CAR-T infusion
The safety will be measured by the proportion of participants who experienced any grade of CRS, any grade of ICANS, any adverse events, and any severe adverse events.
Proportion of participants who experienced any grade of ICANs to define the safety of CLIC-2201
时间窗: Within the first 28 days of CAR-T infusion
The safety will be measured by the proportion of participants who experienced any grade of CRS, any grade of ICANS, any adverse events, and any severe adverse events.
Proportion of participants who experienced any grade of IEC-HS to define the safety of CLIC-2201
时间窗: Within the first 28 days of CAR-T infusion
The safety will be measured by the proportion of participants who experienced any grade of CRS, any grade of ICANS, any adverse events, and any severe adverse events.
Defining the maximum tolerated dose (MTD) of CLIC-2201
时间窗: Within the first 28 days of CAR-T infusion
The MTD will be measured by monitoring and recording the AEs experienced by the participant within the first 28 days after the infusion, including the treatment-related death as deemed by the investigator, grade 3 Cytokine Release Syndrome (CRS), Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS), and Immune Effector Cell-Associated Hemophagocytic Lymphocytosis-Like Syndrome (IEC-HS) lasting for more than seven days; grade 4 CRS, ICANS, and IEC-HS; grade 4 non-hematologic toxicity that is not deemed related to CRS, ICANS, IEC-HS (except for Grade 4 transaminases and isolated, asymptomatic laboratory electrolyte abnormalities for seven days or more).
Proportion of participants who experienced any grade of AEs to define the safety of CLIC-2201
时间窗: Within the first 28 days of CAR-T infusion
The safety will be measured by the proportion of participants who experienced any grade of CRS, any grade of ICANS, any adverse events, and any severe adverse events.
次要结局
- Proportion of participants achieving achieving and/or maintaining Complete response (CR) or complete response with incomplete count recovery (CRi).(Within 365 days of CAR-T infusion)
- The average number of CAR transgene copies per cell(Up to day 365)
- Proportion of B-ALL participants with B with minimal residual disease (MRD) negative status by next-generation sequencing and/or high-resolution flow cytometry.(Within 365 days of CAR-T infusion)
- Overall survival rate(Up to 15 years of CAR-T infusion)
- Progression free survival rate(Up to 15 years of CAR-T infusion)
- Proportion of participants who fail enrollment that were successfully screened(Enrollment)
- Proportion of participants for whom CLIC-2201 manufacturing was unsuccessful that completed leukapheresis(Through manufacturing, an average of 8 days)
- Proportion of participants for whom leukapheresis failed that successfully completed trial enrollment(From date of enrollment until the date of leukapheresis, assessed up to 4 weeks)
- Median time from enrollment to CLIC-2201 infusion(From date of enrollment until the date of infusion, assessed up to 6 weeks)
- Median time from enrollment to disease progression that prevents CLIC-2201 infusion.(From date of enrollment until the date of infusion, assessed up to 6 weeks)
- Proportion of participants who fail to receive CLIC-2201 infusion for whom a CLIC-2201 was successfully manufactured(Day of CLIC-2201 infusion)
- Median time from enrollment to leukapheresis(From date of enrollment until the date of leukapheresis, assessed up to 4 weeks)
- Proportion of participants with an overall response [achieving a CR or partial remission (PR)](Within 365 days of CAR-T infusion)