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.
Histologically confirmed relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high grade B-cell lymphoma, DLBCL arising from an indolent lymphoma, grade 3B follicular lymphoma and primary mediastinal large B-cell lymphoma.
Measurable disease by IWG response criteria for lymphoma.
Baseline FDG-PET/CT scan must show FDG-avid lesions compatible with CT-defined anatomical tumor sites.
A previously irradiated lesion can be considered a target lesion if it is well defined, measurable, and has clearly progressed following radiation.
Previous receipt of an allogeneic solid organ transplant or bone marrow transplant.
Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
Chemotherapy or biologic or hormonal therapy for prior or concurrent cancer treatment, within 14 days prior to the first NT-I7 injection.
NOTE: Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable.
Sequential
NT-I7
DrugProvided by NeoImmune Tech
CAR T-cell therapy
Biological/VaccineStandard of care: Will be given on day 0 and will be either axicabtagene ciloleucel or lisocabtagene maraleucel .
Incidence of adverse events
Measured per CTCAE v 5.0. CRS and ICANS will be graded per ASTCT guidelines
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.
Recommended phase 2 dose of NT-I7 (Dose Escalation only)
Determined by the potential correlation of dose levels with safety and efficacy parameters.
Overall response rate (ORR)
Response will be assessed based on IWG response criteria for lymphoma
Partial response (PR) rate
Response will be assessed based on IWG response criteria for lymphoma
Complete response (CR) rate
Response will be assessed based on IWG response criteria for lymphoma
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
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Washington University School of Medicine
Lead sponsor
NeoImmuneTech
Collaborator
The Foundation for Barnes-Jewish Hospital
Collaborator
Daniel E Corbin Lymphoma Research Fund
Collaborator
National Cancer Institute (NCI)
Collaborator
