Study of E7777 Prior to Kymriah for R/R DLBCL

  • STATUS
    Recruiting
  • End date
    Dec 21, 2024
  • participants needed
    30
  • sponsor
    Masonic Cancer Center, University of Minnesota
Updated on 21 July 2021

Summary

This is a single institution Phase I study to determine the maximum tolerated dose (MTD) of E7777 when given prior to cyclophosphamide/fludarabine (CY/Flu) lymphodepletion (LD) chemotherapy and Kymriah, a commercial tisagenlecleucel product, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are at a higher risk for failure of CAR-T therapy.

Description

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).

Details
Condition Diffuse Large B-Cell Lymphoma, diffuse large cell lymphoma, diffuse large b cell lymphoma, High-grade B-cell Lymphoma, DLBCL Arising From Follicular Lymphoma, High-grade B-cell Lymphoma
Treatment E7777
Clinical Study IdentifierNCT04855253
SponsorMasonic Cancer Center, University of Minnesota
Last Modified on21 July 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosis of a relapse or refractory (r/r) large B cell lymphoma, for which treatment with Kymriah is planned, including
diffuse large B-cell lymphoma (DLBCL) not otherwise specified
high grade B-cell lymphoma
DLBCL arising from follicular lymphoma
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
myc over expression >40% in any prior biopsy
sites of extranodal disease
Received two or more lines of systemic therapy
Has secured insurance coverage for Kymriah administration either in the outpatient or inpatient setting
Age 18 years or older at the time of signing consent
ECOG performance status of 0, 1, or 2
Adequate bone marrow reserve defined as
Absolute neutrophil count (ANC) > 1,000/mm^3
Platelets 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided) Bone marrow involvement at disease assessment is an exclusion as these patients are at an increased risk of severe CRS and/or neurotoxicity
Adequate organ function at enrollment and within 14 days of planned E7777 treatment
including
renal function: eGFR 50 mL/min/1.73 m^2
liver function: ALT 3 times the upper limit of normal (ULN) for age, AST 3 times the ULN, total bilirubin 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is 3.0 x ULN and direct bilirubin 1.5 x ULN (if liver is involved by lymphoma, the exception are allowed upon approval of PI)
albumin 3.0 g/dl
Must have a minimum level of pulmonary reserve defined as Grade 1 dyspnea (CTCAE v5) and pulse oxygenation SpO2 > 91% on room air. Pulmonary function tests within 28 days of enrollment: >50% corrected DLCO and FEV1
Hemodynamically stable and LVEF 50% confirmed by echocardiogram or MUGA
Life expectancy 12 weeks in the opinion of the enrolling investigator as documented in the medical record
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use birth control for at least 30 days after study treatment or at least at least 4 months after the final dose of CY, whichever is longer Female participants: Two forms of birth control, one of which must be a barrier method, for example: use of intrauterine device (IUD) or oral contraceptives, plus a barrier method such as a condom, diaphragm or cervical cap Male participants: If possible to father a child (unless a successful vasectomy with confirmed azoospermia) participant and female partner, must use adequate contraception
Written voluntary consent prior to the performance of any research related tests or procedures

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
Known CNS involvement by malignancy - if clinically suspicious, must be ruled-out by examination of cerebrospinal fluid (CSF) by flow cytometry
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
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