Diffuse large B-cell lymphoma is the most commonly occurring subtype of non-Hodgkin lymphoma, but treatment is often not curative, with as many as 50% of patients with adverse risk factors developing relapsed/refractory disease. CAR T-cell therapy has revolutionized modern cancer therapy, with axicabtagene ciloleucel and lisocabtagene maraleucel (anti-CD19 CAR T-cell therapies) FDA approved for second- or later-line treatment of relapsed/refractory large B-cell lymphoma. IL-7 plays a crucial role in T-cell homeostasis by inducing thymic differentiation, peripheral expansion, and extrathymic differentiation. It is the main regulator of T-cell hemostasis, inducing T-cell growth and proliferation in lymphopenic patients. There is data that suggests that exposure of T-cells to IL-7 may expand T-cells, prevent T-cell exhaustion, and improve effector functions. NT-I7 is a long-acting human IL-7 cytokine which has been shown in nonclinical studies to increase peripheral T-cells, antitumor efficacy, and tumor infiltrating lymphocytes, either as a monotherapy or in combination with chemo/radiotherapy and/or immune checkpoint inhibitors and CAR T therapy. This study is testing the hypothesis that the administration of NT-I7 following standard of care (SOC) approved CD19 CAR T-cell therapies for subjects with relapsed/refractory large B-cell lymphoma (LBCL) will be safe and tolerable and may increase the expansion and persistence of CAR T-cells in vivo, which may result in increased tumor response rate and improved clinical outcomes.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Provided by NeoImmune Tech
Standard of care: Will be given on day 0 and will be either axicabtagene ciloleucel or lisocabtagene maraleucel .
Washington University School of Medicine
St Louis, Missouri, United States
RECRUITINGIncidence of adverse events
Measured per CTCAE v 5.0. CRS and ICANS will be graded per ASTCT guidelines
Time frame: From start of CAR T-cell infusion (day 0) through day 90 (post CAR T-cell infusion)
Maximum tolerated dose of NT-I7 (Dose Escalation only)
Determined by incidence and nature of dose-limiting toxicities (DLTs). DLTs are defined in the protocol.
Time frame: From first dose of NT-I7 until 14 days after the second dose NT-I7 dose (estimated to be 35 days)
Recommended phase 2 dose of NT-I7 (Dose Escalation only)
Determined by the potential correlation of dose levels with safety and efficacy parameters.
Time frame: Through 90 days after CAR T-cell infusion
Overall response rate (ORR)
Response will be assessed based on IWG response criteria for lymphoma
Time frame: Through completion of follow-up (estimated to be 1 year)
Partial response (PR) rate
Response will be assessed based on IWG response criteria for lymphoma
Time frame: Through completion of follow-up (estimated to be 1 year)
Complete response (CR) rate
Response will be assessed based on IWG response criteria for lymphoma
Time frame: Through completion of follow-up (estimated to be 1 year)
Duration of response (DoR)
For responders only: defined as the time from the first occurrence of a documented objective response (PR or CR) to the time of the first documented disease progression or death from any cause, whichever occurs first, per IWG. Response will be assessed based on IWG response criteria for lymphoma
Time frame: Through completion of follow-up (estimated to be 1 year)
Progression-free survival (PFS)
Defined as the time from the CAR T-cell infusion (Day 0) to the first occurrence of progression or death from any cause, whichever occurs first, per IWG.
Time frame: Through completion of follow-up (estimated to be 1 year)
Overall survival (OS)
Defined as the time from CAR T-cell infusion (Day 0) to death from any cause.
Time frame: Through completion of follow-up (estimated to be 1 year)
Effect of NT-I7 on CAR T-cell expansion as measured by quantitative DNA PCR and/or flow cytometry
Time frame: From day 0 to day 42 post CAR T-cell infusion
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