Phase I/II Trial Using E7777 to Enhance Regulatory T-Cell Depletion Prior to CAR-T Therapy for Relapsed/Refractory Large B-Cell Lymphomas
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
• 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.