E7777 在 Kymriah 之前用于 R/R DLBCL 的研究
在 Tisagenlecleucel (Kymriah) 治疗复发/难治性弥漫性大 B 细胞淋巴瘤 (DLBCL) 之前，使用 E7777 增强调节性 T 细胞耗竭的 I/II 期试验
This is a multicenter Phase I study to determine the maximum tolerated dose (MTD) of E7777 when given prior to cyclophosphamide/fludarabine (CY/Flu) lymphodepletion (LD) chemotherapy and an FDAapproved CAR-T product Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma grade 3 who are at a higher risk for failure of CAR-T therapy
研究概览
地位
详细说明
E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin. This trial is designed to augment lymphodepletion prior to CAR-T cells by administration of a targeted immunotoxin against CD25-expressing T-cells. CD25 is expressed at high levels on Tregs but also on activated effector T cells. The use of the CAR-T cell product and associated apheresis and LD chemotherapy is considered standard of care (SOC).
研究类型
注册 (估计的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
-
-
Minnesota
-
Minneapolis、Minnesota、美国、55455
- University of Minnesota, Masonic Cancer Center
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
-
Diagnosis of a relapse or refractory (r/r) B cell lymphoma, for which treatment with tisagenleucel (Kymriah), Axicabtagene (Yescarta) or Lisocabtagene Maraleucel (Breyanzi) is planned, including :
-
diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
-
high grade B-cell lymphoma
-
DLBCL arising from follicular lymphoma
-
Primary mediastinal B cell lymphoma
-
Follicular lymphoma grade 3B
-
And considered at high risk for progression after CAR-T therapy by meeting one or more of the following factors:
-
refractory to last line of therapy/remission of less than 12 months
-
myc over expression >40% in any prior biopsy or bcl2/bcl6 and c-myc re-arrangement (double/triple hit)
- 2 sites of extranodal disease
-
IPI ≥ 3
-
Elevated LDH at the time of relapse
-
Has secured coverage for Kymriah, Yescarta,Breyanzi administration
-
Age 18 years or older at the time of signing the consent
-
ECOG Performance status of 0, 1, or 2
-
Adequate bone marrow reserve (may be transfusion dependent)
-
Adequate organ function at enrollment and within 14 days of planned E7777 treatment as defined in Section 4.1.7
-
Hemodynamically stable and LVEF ≥ 50% confirmed by echocardiogram or MUGA
- Grade 1 dyspnea (CTCAE v5) and SpO2 > 91% on room air
-
Sexually active females of child-bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy
-
Provides voluntary written consent prior to the performance of any research related activities.
Exclusion Criteria:
- Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
- Known bone marrow involvement, if history of bone marrow involvement must have a BM biopsy to rule-out current involvement
- Prior allogeneic transplant
- Ocular disease or complaints visual acuity impairment, color or shape distortion, or blurred vision - potential participants are required to have an ophthalmological examine as part of screening
- Active CNS involvement by malignancy (history of CNS disease with negative CSF by flow cytometry and/or stable findings on brain MRI are acceptable)
- Uncontrolled active hepatitis B or hepatitis C
- Active or inactive HIV infection
- Untreated active bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to enrollment)
- History of heart failure or pulmonary edema, evidence of pleural effusion or active lower extremity edema
- Uncontrolled unstable angina and/or myocardial infarction within 3 months of enrollment
- Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：顺序分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Dose level 1 : E7777 at 5 mcg/kg
Single dose of E7777 given on Day -7 two days prior to the start of lymphodepleting chemotherapy |
E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin. E7777 is preferentially bound to and internalized by cells expressing the high affinity form (CD25+) of the IL-2 receptor. Fludarabine 25 mg/m2 IV daily for 3 days. Days -5, -4 and -3. Taken in combination with Cyclophosphamide Cyclophosphamide 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine. Days -5, -4 and -3. Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
|
|
实验性的：Dose level 1 : E7777 at 7 mcg/kg
Single dose of E7777 given on Day -7 two days prior to the start of lymphodepleting chemotherapy |
E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin. E7777 is preferentially bound to and internalized by cells expressing the high affinity form (CD25+) of the IL-2 receptor. Fludarabine 25 mg/m2 IV daily for 3 days. Days -5, -4 and -3. Taken in combination with Cyclophosphamide Cyclophosphamide 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine. Days -5, -4 and -3. Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
|
|
实验性的：Dose level 1 : E7777 at 9 mcg/kg
Single dose of E7777 given on Day -7 two days prior to the start of lymphodepleting chemotherapy |
E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin. E7777 is preferentially bound to and internalized by cells expressing the high affinity form (CD25+) of the IL-2 receptor. Fludarabine 25 mg/m2 IV daily for 3 days. Days -5, -4 and -3. Taken in combination with Cyclophosphamide Cyclophosphamide 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine. Days -5, -4 and -3. Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
|
|
实验性的：MTD from phase 1
Single dose of E7777 (Maximum tolerated dose level identified in phase 1) given on Day -7 two days prior to the start of lymphodepleting chemotherapy |
E7777 is a recombinant fusion toxin consisting of full-length human IL-2 fused to the catalytic domains of diphtheria toxin. E7777 is preferentially bound to and internalized by cells expressing the high affinity form (CD25+) of the IL-2 receptor. Fludarabine 25 mg/m2 IV daily for 3 days. Days -5, -4 and -3. Taken in combination with Cyclophosphamide Cyclophosphamide 250 mg/m2 IV daily for 3 days starting with the first dose of fludarabine. Days -5, -4 and -3. Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
Patient will receive one FDA approved CAR-T product - Tisagenlecleucel/Kymriah, Axicabtagene Ciloleucel/Yescarta, or lisocabtagene maraleucel/Breyanzi) for the treatment of relapsed/refractory diffuse large B-cell lymphoma
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Establish maximum tolerated dose (MTD)
大体时间：1 month
|
The primary objective of this Phase I study is to establish a maximum tolerated dose (MTD) of E7777 when given prior to standard of care CAR-T therapy product for the treatment of relapsed/refractory B-cell lymphoma who are at a higher risk for failure of CAR-T therapy. |
1 month
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of participants experiencing adverse events
大体时间：100 days Post E7777 infusion
|
Number of participants experiencing adverse events related to E7777 to determine safety of the E7777 |
100 days Post E7777 infusion
|
|
Number of participants experiencing disease free survival (DFS)
大体时间：1 year Post E7777 infusion
|
Number of participants experiencing disease free survival (DFS) at 1 year |
1 year Post E7777 infusion
|
|
Number of participants experiencing overall survival (OS)
大体时间：1 year Post E7777 infusion
|
Number of participants experiencing overall survival (DFS) at 1 year |
1 year Post E7777 infusion
|
|
Number of non-relapse mortality incidents at day 100
大体时间：100 days Post E7777 infusion
|
Number of participants experiencing non-relapse mortality at day 100 post E7777 infusion |
100 days Post E7777 infusion
|
|
Number of Grade 3 or 4 cytokine release syndrome (CRS) incidents
大体时间：28 Days Post E7777 infusion
|
Number of participants experiencing Grade 3 or 4 cytokine release syndrome (CRS) after CAR-T cell therapy. |
28 Days Post E7777 infusion
|
|
Number of Grade 3 or 4 immune effector cell associated neurotoxicity (ICAN) syndrome incidents
大体时间：28 Days Post E7777 infusion
|
Number of participants experiencing Grade 3 or 4 immune effector cell associated neurotoxicity (ICAN) syndrome after CAR-T cell therapy. |
28 Days Post E7777 infusion
|
|
Number of participants experiencing dose limiting toxicity events
大体时间：28 Days Post E7777 infusion
|
Dose Limiting Toxicity (DLT) is defined as any of the following events based on CTCAE v5 from the 1st infusion of E7777 through 21 days after the administration of CAR-T:
|
28 Days Post E7777 infusion
|
合作者和调查者
调查人员
- 首席研究员：Veronika Bachanova, MD、Masonic Cancer Center, University of Minnesota
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 2020LS100
- MT2020-27 (其他标识符：University of Minnesota Masonic Cancer Center)
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.