Phase I/II, Open Label, Multicenter Study of Rapcabtagene Autoleucel in Adult Patients With CLL/SLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 217
- 试验地点
- 48
- 主要终点
- Phase 1: Dose recommendation: Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only)
研究概览
简要总结
This is a phase I/II study to evaluate the feasibility, safety and preliminary antitumor efficacy of rapcabtagene autoleucel (also known as YTB323). Rapcabtagene autoleucel will be investigated in combination with ibrutinib in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and as single agent in diffuse large B-cell lymphoma (3L+ DLBCL), adult acute lymphoblastic leukemia (ALL) and 1st Line High Risk Large B-Cell Lymphoma (1L HR LBCL).
详细描述
This clinical trial is phase I/II open label, multi-center study of rapcabtagene autoleucel.
The Phase I part of the study comprises three independent treatment arms:
- Rapcabtagene autoleucel in combination with ibrutinib in adult CLL/SLL participants with SD or PR after at least 6 months of second or subsequent line ibrutinib therapy. As of 05-May-2021, this arm had completed enrollment.
- Rapcabtagene autoleucel single agent in adult DLBCL participants having failed two or more lines of chemotherapy and either having progressed (or relapsed) after autologous HSCT or being ineligible for or not consenting to the procedure.
- Rapcabtagene autoleucel single agent in adult relapsed/refractory ALL participants
The Phase II part of the study comprises two independent cohorts:
- Rapcabtagene autoleucel single agent in adult 3L + DLBCL participants having failed two or more lines of chemoimmunotherapy and either having progressed (or relapsed) after autologous HSCT or being ineligible for or not consenting to the procedure. This is an extension of the Phase I r/r DLBCL treatment arm to support Phase II objectives
- Rapcabtagene autoleucel single agent in newly diagnosed, adult 1L HR LBCL participants defined as IPI 3-5 and/or DH/TH disease who have completed 2 cycles of CIT and have a response of PR/SD (with a Deauville score of 4-5).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ECOG performance status 0-1 for ALL and DLBCL
- •ECOG performance status 0-2 for 1L HR LBCL at screening
- •CLL or SLL diagnosis according to iwCLL criteria
- •CLL/SLL in SD or PR after at least 6 months of ibrutinib, either as second or subsequent line of therapy
- •DLBCL diagnosis by local histopathology
- •DLBCL relapsed or refractory after 2 or more lines of therapy, including autologous hematopoietic stem cell transplantation (HSCT)
- •Refractory or relapsed CD19-positive ALL
- •ALL with morphologic disease in the bone marrow
- •1L HR LBCL - Considered to be high-risk based on at least 1 of the following at diagnosis:
- •IPI score of 3, 4 or 5
- •MYC and BCL2 and/or BCL6 rearrangement (DH/TH lymphoma)
- •Participants must have received 2 cycles of frontline therapy for LBCL with R-CHOP or Pola-R-CHP or DA-EPOCH-R. Participants with DH/TH lymphoma must have received at least one cycle (the most recent) DA-EPOCH-R.
- •Participants must have a positive PET per Lugano classification (Deauville PET score of 4 or 5 and an overall response of PR/SD) after 2 cycles of frontline CIT. Note: Patient's with Deauville PET score of 5 and overall response of PD, or with Deauville PET score of 1, 2, or 3 and overall response of CR, are not eligible for this trial.
排除标准
- •Prior CD19-directed therapy
- •Prior administration of a genetically engineered cellular product
- •Prior allogeneic HSCT
- •Richter's transformation
- •For 1L HR LBCL: Richter's transformation, Burkitt lymphoma, primary DLBCL of CNS, DLBCL associated with chronic inflammation, intravascular large B-cell lymphoma, ALK- positive large B-cell lymphoma, HHV8 positive LBCL, DLBCL leg type or EBV positive DLBCL, NOS.
- •Active CNS lymphoma
- •For 1L HR LBCL: Active or prior history CNS involvement by malignancy
- •Targeted small molecule or kinase inhibitor within 2 weeks from leukapheresis
- •Other protocol-defined inclusion/exclusion may apply.
研究组 & 干预措施
CLL/SLL
Dose escalation of rapcabtagene autoleucel in combination with ibrutinib
干预措施: Rapcabtagene autoleucel single agent (Biological)
3L+ DLBCL
Dose escalation and expansion of rapcabtagene autoleucel single agent in 3L+ DLBCL
干预措施: Rapcabtagene autoleucel single agent (Biological)
CLL/SLL
Dose escalation of rapcabtagene autoleucel in combination with ibrutinib
干预措施: Ibrutinib (Drug)
Adult ALL
Dose escalation of rapcabtagene autoleucel single agent in adult ALL
干预措施: Rapcabtagene autoleucel single agent (Biological)
1L HR LBCL
Rapcabtagene autoleucel single agent in 1L HR LBCL
干预措施: Rapcabtagene autoleucel single agent (Biological)
结局指标
主要结局
Phase 1: Dose recommendation: Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only)
时间窗: 28 days
Phase 1: Safety: Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs
时间窗: 24 months
Phase 1: Tolerability: Ibrutinib dose modifications in the CLL/SLL arm
时间窗: 24 months
Phase 1: Manufacture success: Number of patients infused with planned target dose
时间窗: 24 months
Phase 2: Complete Response Rate (CRR) as assessed by local Investigator
时间窗: 24 months
CRR defined as best overall response (BOR) of CR after rapcabtagene autoleucel infusion as per Lugano criteria for 3L+ Diffuse Large B-Cell Lymphoma (DLBCL) and 1L High Risk Large B-Cell (HR LBCL)
次要结局
- Phase 1: Overall survival in adult ALL(24 months)
- Phase 1: Quality of life in adult ALL patients enrolled in the expansion part by use of Electronic Patient Reported Outcomes (ePRO) as per EORTC QLQ-C30 questionnaire(24 months)
- Phase 1: BOR of CR/PR per Lugano criteria in 3L+ DLBCL(24 months)
- Phase 1: Quality of life in adult ALL patients enrolled in the expansion part by use of Electronic Patient Reported Outcomes (ePRO) as per EQ-5D-3 questionnaire(24 months)
- Phase 1: EFS in ALL as assessed by an Independent Review Committee(24 months)
- Phase 1: MRD negative status by flow cytometry in adult ALL(24 months)
- Phase 2: Complete Response Rate (CRR)(months 6, 12)
- Phase 2: Event-free survival (EFS)(24 months)
- Phase 2: Overall survival (OS) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH(24 months)
- Phase 1: Complete Response (CR)/Partial Response (CR) in CLL/SLL(24 months)
- Phase 1/2: Cellular kinetics(24 months)
- Phase 1/2: Immunogenicity(24 months)
- Phase 2: Overall response rate (ORR)(24 months)
- Phase 2: Progression-free survival (PFS)(24 months)
- Phase 2: Overall response rate (ORR) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH(24 months)
- Phase 2: Progression-free survival (PFS) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH(24 months)
- Phase 1: Duration of response (DOR) in CLL/SLL and 3L+ DLBCL(24 months)
- Phase 1: BOR in ALL as assessed by an Independent Review Committee (IRC)(month 3)
- Phase 1: DOR in ALL as assessed by an Independent Review Committee(24 months)
- Phase 1: BOR in ALL as assessed by local Investigator(24 months)
- Phase 1: DOR in ALL as assessed by local Investigator(24 months)
- Phase 1: EFS in ALL as assessed by local Investigator(24 months)
- Phase 2: Overall survival (OS)(24 months)
- Phase 2: Complete Response Rate (CRR) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH(months 6, 12)
- Phase 2: Manufacturing vein to door time(24 months)
- Phase 2: Duration of response (DOR)(24 months)
- Phase 2: Duration of response (DOR) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH(24 months)
- Phase 2: Event-free survival (EFS) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH(24 months)
- Phase 2: Complete Response Rate (CRR)(months 3, 6)