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
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
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
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
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
University of Minnesota, Masonic Cancer Center
Minneapolis, Minnesota, United States
Establish maximum tolerated dose (MTD)
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.
Time frame: 1 month
Number of participants experiencing adverse events
Number of participants experiencing adverse events related to E7777 to determine safety of the E7777
Time frame: 100 days Post E7777 infusion
Number of participants experiencing disease free survival (DFS)
Number of participants experiencing disease free survival (DFS) at 1 year
Time frame: 1 year Post E7777 infusion
Number of participants experiencing overall survival (OS)
Number of participants experiencing overall survival (DFS) at 1 year
Time frame: 1 year Post E7777 infusion
Number of non-relapse mortality incidents at day 100
Number of participants experiencing non-relapse mortality at day 100 post E7777 infusion
Time frame: 100 days Post E7777 infusion
Number of Grade 3 or 4 cytokine release syndrome (CRS) incidents
Number of participants experiencing Grade 3 or 4 cytokine release syndrome (CRS) after CAR-T cell therapy.
Time frame: 28 Days Post E7777 infusion
Number of Grade 3 or 4 immune effector cell associated neurotoxicity (ICAN) syndrome incidents
Number of participants experiencing Grade 3 or 4 immune effector cell associated neurotoxicity (ICAN) syndrome after CAR-T cell therapy.
Time frame: 28 Days Post E7777 infusion
Number of participants experiencing dose limiting toxicity events
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: * Grade 4 infusion related reaction (IRR) associated with E7777 * Grade 4 or Grade 3 capillary leak syndrome (CLS) * Grade 3 or 4 liver function test abnormality that do not resolve to \<Grade 2 within 5 days * Grade 3 or 4 non-hematologic toxicity event that occurs after the administration of E7777 and before lymphodepleting therapy * Any adverse event that results in a delay of lymphodepleting therapy for more than 72 hours and attributed to E7777 * Any Grade 5 adverse event
Time frame: 28 Days Post E7777 infusion
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