A Phase 2, Open-Label, Multicenter, Basket Study Evaluating the Safety and Efficacy of Brexucabtagene Autoleucel in Adults with Rare B-cell Malignancies (ZUMA 25) – Substudy B – Relapsed/Refractory Richter Transformation (RT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 17
- 主要终点
- The primary endpoint of ZUMA-25 as per the master protocol is response rates by central assessment as defined in each substudy. The primary end point of Substudy B (RT) is ORR, defined as the proportion of subjects who achieve a best response of either complete response (CR) or partial response (PR).
研究概览
简要总结
The primary objective of ZUMA-25 is to evaluate the efficacy of brexucabtagene autoleucel in subjects with rare B-cell malignancies, by determining the Response Rates as defined within the substudies by central assessment. The primary objective of ZUMA-25 substudy B (RT) is to evaluate the efficacy of brexucabtagene autoleucel on diffuse large B cell lymphoma (DLBCL)-RT in subjects with RT, by determining the objective response rate (ORR) by central assessment.
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
- •Male or female 18 years of age or older at the time of signing the informed consent
- •At least 1 measurable lesion based on the Lugano Classification {Cheson 2014}. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- •Presence of toxicities due to prior therapy must be stable and recovered to Grade 1 or lower
- •ECOG performance status score of 0 or
- •Adequate hematologic and end-organ function.
- •Participants of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception
- •Confirmed diagnosis of CLL based on IWCLL 2018 criteria Hallek et al 2018 (Substudy protocol section 12.3.2), with histologically confirmed RT to a DLBCL subtype
- •Relapsed or refractory disease after 1 line of therapy, defined as at least 1 of the following:
- •a) Refractory disease, defined as progressive disease or stable disease as best response to first-line therapy
- •b) Relapsed disease, defined as complete remission to first-line therapy followed by biopsy proven disease relapse
排除标准
- •Prior CAR therapy or treatment with any anti-CD19 therapy
- •HIV-positive patients, unless taking appropriate anti-HIV medications, having an undetectable viral load by quantitative polymerase chain reaction (qPCR) and a CD4 count > 200 cells/uL.
- •History or presence of detectable cerebrospinal fluid malignant cells or brain metastases, with the exception of prior CNS disease in WM
- •History of autoimmune disease (eg, Crohn’s disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
- •Diagnosis of RT not of DLBCL subtype (including, but not limited to, Hodgkin lymphoma and prolymphocytic leukemia)
- •Prior allogeneic stem cell transplant < 3 months prior to screening and/or <4 months prior to planned infusion of brexucabtagene autoleucel.
- •Presence of active graft-versus-host disease following prior allogeneic stem cell transplant.
研究组 & 干预措施
-
Participants receiving -
干预措施: - (Drug)
结局指标
主要结局
The primary endpoint of ZUMA-25 as per the master protocol is response rates by central assessment as defined in each substudy. The primary end point of Substudy B (RT) is ORR, defined as the proportion of subjects who achieve a best response of either complete response (CR) or partial response (PR).
The primary endpoint of ZUMA-25 as per the master protocol is response rates by central assessment as defined in each substudy. The primary end point of Substudy B (RT) is ORR, defined as the proportion of subjects who achieve a best response of either complete response (CR) or partial response (PR).
Response will be determined by central assessment per the Lugano Classification (Cheson et al 2014).
Response will be determined by central assessment per the Lugano Classification (Cheson et al 2014).
次要结局
- The secondary endpoints of ZUMA-25 as per the master protocol are: • CR rate by central assessment as defined in each substudy
- • Duration of Response
- • Overall Survival
- • Progression-free survival
- • Time to next treatment defined as the time from enrollment (for Full Analysis Set [FAS]) or brexucabtagene autoleucel infusion (for modified intention to treat [mITT]) to the initiation of subsequent anticancer therapy/treatment
- • Time to first response from brexucabtagene autoleucel infusion to the first response as defined in the substudy
- Substudy B (RT) specific secondary endpoints are:
- •ORR, defined as the proportion of subjects who achieve a best response of either CR or PR. Response will be determined by investigator assessment per the Lugano Classification
- •ORR, defined as the proportion of subjects who achieve a best response of either CR or PR by central assessment per the Lugano Classification, in subgroups by clonal relationship to the underlying CLL. Clonality will be assessed by central assessment
- •ORR, defined as the proportion of subjects who achieve a best response of either CR, CR with incomplete marrow recovery (CRi), or PR per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria.
研究者
EU Clinical Trials Support
Scientific
Kite Pharma Inc.