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
- 2 期
- 状态
- 招募中
- 入组人数
- 142
- 试验地点
- 21
- 主要终点
- Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Incidence and nature of Dose Limiting Toxicities during the first 28 days after rapcabtagene autoleucel infusion (Dose Escalation part only) Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs after rapcabtagene autoleucel infusion.
研究概览
简要总结
Phase I: The primary objective of the Phase I part of this study is to identify the Recommended Dose of rapcabtagene autoleucel and to characterize safety of rapcabtagene autoleucel as single agent in r/r DLBCL and r/r adult ALL, and to characterize the safety of rapcabtagene autoleucel in combination with ibrutinib in CLL/SLL. Another primary objective is to evaluate the feasibility of rapcabtagene autoleucel manufacturing process. Phase II: 3L+ DLBCL: The primary objective is to demonstrate the antitumor activity of rapcabtagene autoleucel on complete disease response as assessed by local Investigator. 1L HR LBCL: The primary objective is to assess the antitumor activity of rapcabtagene autoleucel on complete disease response as assessed by local Investigator.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •3L+ DLBCL: Relapsed or refractory disease having received 2 or more lines of therapy, including anti-CD20 and anthracycline-based chemotherapy, and either having progressed (or relapsed) after autologous HSCT or being ineligible/not consenting to the procedure. Measurable disease at time of enrollment.
- •ALL: r/r CD19-positive ALL with morphologic disease in the bone marrow (≥ 5% blasts) and including at least 1 of the following: • After allogeneic HSCT • After 2 or more lines of treatment • Primary refractory disease • First relapse occurring within 12 months from first remission • Patients with Philadelphia chromosome-positive ALL must have failed at least 2 different tyrosine kinase inhibitors.
- •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).
- •1L HR LBCL: - 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 DA-EPOCH-R.
- •1L HR LBCL: - 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
- •ALL: allogeneic HSCT within 12 weeks prior to screening
- •Prior CD19-directed therapy with the exception of blinatumomab for patients with ALL
- •Prior administration of a genetically modified cellular product
- •3L+ DLBCL with primary CNS lymphoma
- •3L+ DLBCL: prior allogeneic HSCT
结局指标
主要结局
Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Incidence and nature of Dose Limiting Toxicities during the first 28 days after rapcabtagene autoleucel infusion (Dose Escalation part only) Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs after rapcabtagene autoleucel infusion.
Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Incidence and nature of Dose Limiting Toxicities during the first 28 days after rapcabtagene autoleucel infusion (Dose Escalation part only) Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs after rapcabtagene autoleucel infusion.
Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Ibrutinib dose modifications following rapcabtagene autoleucel infusion.
Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Ibrutinib dose modifications following rapcabtagene autoleucel infusion.
Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Manufacture success rate (defined as number of participants with product that meets release specifications and at or above the planned target dose divided by total number of patients enrolled).
Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Manufacture success rate (defined as number of participants with product that meets release specifications and at or above the planned target dose divided by total number of patients enrolled).
Phase II part – 3L+ DLBCL: - CRR defined as BOR of CR after rapcabtagene autoleucel infusion as per Lugano criteria.
Phase II part – 3L+ DLBCL: - CRR defined as BOR of CR after rapcabtagene autoleucel infusion as per Lugano criteria.
Phase II part – 1L HR LBCL: - CRR defined as BOR of CR after rapcabtagene autoleucel infusion as per Lugano criteria.
Phase II part – 1L HR LBCL: - CRR defined as BOR of CR after rapcabtagene autoleucel infusion as per Lugano criteria.
次要结局
- Phase I part - CLL/SLL, 3L+ DLBCL and ALL: - qPCR-detected rapcabtagene autoleucel transgene concentrations over time in peripheral blood and relevant tissues.
- Phase I part - CLL/SLL, 3L+ DLBCL, ALL: - Pre-existing and treatment induced immunogenicity (cellular and humoral) of rapcabtagene autoleucel.
- Phase I part - CLL/SLL: - BOR of CR/PR per iwCLL response criteria Duration of response (DOR), i.e., time from first achievement of CR/PR after rapcabtagene autoleucel infusion until first documented disease progression or death due to any cause.
- Phase I part - 3L+ DLBCL: - BOR of CR/PR as per Lugano criteria. Complete response rate (CRR) at months 3 and 6 DOR.
- Phase I part - ALL: - BOR of CR/Cri. Disease response (CR/Cri) at month 3 and 6. DOR, defined as the time from achievement of CR or Cri to relapse or death due to any cause. EFS, defined as the date from rapcabtagene autoleucel infusion to the earliest date of relapse after CR/Cri, treatment failure (defined as failure to achieve CR/Cri within 12 weeks of infusion), or death due to any cause.
- Phase I part – ALL: - MRD negative status by flow cytometry.
- Phase II part – 3L+ DLBCL: - Overall response rate (ORR) defined as BOR of CR/PR as per Lugano criteria.
- Phase II part – 3L+ DLBCL: - CRR at months 3 and 6.
- Phase II part – 3L+ DLBCL: - Duration of response (DOR), defined as time from first CR/PR to first documented progression or death due to any cause.
- Phase II part – 3L+ DLBCL: - Progression-free survival (PFS) defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause.
- Phase II part – 3L+ DLBCL: - Overall survival (OS), defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause.
- Phase II part – 3L+ DLBCL: - Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs after rapcabtagene autoleucel infusion.
- Phase II part – 3L+ DLBCL: - qPCR-detected rapcabtagene autoleucel transgene concentrations over time in peripheral blood and relevant tissues.
- Phase II part – 3L+ DLBCL: - Pre-existing and treatment induced immunogenicity (cellular and humoral) of rapcabtagene autoleucel.
- Phase II part – 3L+ DLBCL: - Time from apheresis completion until return of rapcabtagene autoleucel product to the clinic or hospital.
- Phase II part – 1L HR LBCL: - Overall response rate (ORR) defined as BOR of CR/PR as per Lugano criteria.
- Phase II part – 1L HR LBCL: - CRR at months 6 and 12.
- Phase II part – 1L HR LBCL: - Duration of response (DOR). Defined as time from first CR/PR to first documented progression or death due to any cause.
- Phase II part – 1L HR LBCL: - Progression-free survival (PFS) defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause.
- Phase II part – 1L HR LBCL: - Event-free survival (EFS) defined as time from rapcabtagene autoleucel infusion to first documented progression, start of new anti-lymphoma therapy, biopsy-proven residual disease on or after month 6, or death due to any cause.
- Phase II part – 1L HR LBCL: - Overall survival (OS), defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause.
- Phase II part – 1L HR LBCL: - Within each subgroup: CRR, ORR CRR at months 6 and 12 DOR, PFS, EFS, OS
- Phase II part – 1L HR LBCL: - Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs after rapcabtagene autoleucel infusion.
- Phase II part – 1L HR LBCL: - qPCR-detected rapcabtagene autoleucel transgene concentrations over time in peripheral blood and relevant tissues.
- Phase II part – 1L HR LBCL: - Pre-existing and treatment induced immunogenicity (cellular and humoral) of rapcabtagene autoleucel.
- Phase II part – 1L HR LBCL: - Time from apheresis completion until return of rapcabtagene autoleucel product to the clinic or hospital.
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG