This research study is for people who have relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) that has not responded to two or more lines of therapy. The purpose of this study is to identify the recommended dose of allogeneic NK cells in combination with IL-2, Tafasitamab and Rituximab for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma. NK cells are an investigational (experimental) treatment which means they are not approved by the Food and Drug Administration (FDA). NK cells are a type of lymphocyte that's part of the body's natural immune system, and they can kill cancer cells by creating pores in the cancer cell membranes and inducing apoptosis (programmed cell death). Participants in this study will receive lymphodepleting chemotherapy, as well as Allogeneic NK cells, Tafasitamab and Interleukin-2 (IL-2) by an intravenous (IV) infusion. Participants are expected to complete one cycle, and they may be eligible to complete a second cycle of the same regiment if they have stable disease, partial or complete remission at the end of the first cycle. Participants will be in this study for about 12 months.
More than 80,000 cases of non-Hodgkin lymphoma (NHL) are diagnosed each year in the United States (US), with nearly 20,000 people dying from this group of diseases annually. There are several subgroups of NHL, with the B cell lymphomas being much more common than T-cell lymphomas. B cell lymphomas include multiple different diseases, including some that are more aggressive (like diffuse large B cell lymphoma (DLBCL) and others), as well as those with a slower progression (i.e. indolent lymphomas like follicular lymphoma (FL)). Over the past 20 years, there have been advances in the treatment of most NHL subtypes. However, disease recurrence continues to be frequent and happens in more than a third of people with DLBCL and in most people with indolent lymphomas. A treatment called anti CD19 chimeric antigen receptor T-cell therapies (CAR T-cell) have helped to treat relapsed and primary refractory lymphomas. However, CAR-T cells therapies are limited by the cost and logistics of manufacture. Additionally, relapses are common (40-60%) in people treated with CAR-T cells, and people who experience these relapses have poor survival outcomes. While CAR-T cells still receive a lot of attention, there is a growing interest in using other strategies including NK cells combined with monoclonal antibodies or molecules developed to activate NK cells against tumors. NK cells are lymphocytes, a type of immune cell, that can naturally fight cancer cells. They are important in fighting cancer and can do so without needing to recognize specific cell markers. Allogeneic, non-HLA-matched NK cells have been found to be safe and not associated with the development of graft-versus-host disease. It is still important to improve the manufacture, application, and efficacy of NK cell therapy. Breakthroughs in ex vivo NK cell expansion have allowed for large doses to be made, which may address some of these limitations. This study uses a "universal donor" of ex vivo expanded NK cell product that is made at a lab at Case Western Reserve University. These NK cells are "experimental," meaning that they are not approved by the Food and Drug Administration (FDA). Participants in this study will receive these NK cells in addition to other standard cancer treatments for NHL.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Allogeneic NK cells are given intravenously (IV) weekly for 3 weeks on Days 0, 7, 14. Dose escalation will be conducted using a Bayesian optimal interval (BOIN) design starting at dose level 1 (500 x 106 cells) and proceeding to dose level 2 (1,000 x 106 cells) if criteria are met.
Rtx is dosed at 375mg/m2 and give once (on Day -5 for Cycle 1 and Day 0 for Cycle 2, if applicable).
Tafasitamab is dosed at 12 mg/kg and given intravenously (IV) weekly for 3 weeks on Days 0,7,14).
Interleukin-2 is dosed at 5 million IU and given weekly for 3 weeks on Days 0,7,14.
Fludarabine is dosed at 30 mg/m2/d with dose adjustment for renal function, and cyclophosphamide is dosed at 500 mg/m2/d. These are given on 3 days (Days -5 to -3).
Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center
Cleveland, Ohio, United States
Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute
Cleveland, Ohio, United States
Dose limiting toxicity (DLT)
Non hematologic AEs will be measured during cycle 1 (first 28 days) and hematologic AEs will be measured during the first 42 days for all dose levels. DLTs are graded for severity by the Common Terminology Criteria for Adverse Events v5.0 (CTCAEv5.0) criteria.
Time frame: Up to 42 days
Incidence of adverse events (AEs)
Time frame: Up to 12 months
Timing of adverse events (AEs)
Time frame: Up to 12 months
Severity of adverse events (AEs)
AE severity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0
Time frame: Up to 12 months
Complete response (CR) rate
CR is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy and measured according to the 2014 Lugano Response for Malignant Lymphoma criteria.
Time frame: Day 28
Complete response (CR) rate
CR is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy and measured according to the 2014 Lugano Response for Malignant Lymphoma criteria.
Time frame: Day 100
Overall response rate (ORR)
ORR is defined as the rate of participants who had CR and partial response (PR). CR is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy and measured according to the 2014 Lugano Response for Malignant Lymphoma criteria. PR is defined as not meeting criteria for CR but having an improvement in symptom criteria specified by the 2014 Lugano Response for Malignant Lymphoma criteria.
Time frame: Day 28
Overall response rate (ORR)
ORR is defined as the rate of participants who had CR and partial response (PR). CR is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy and measured according to the 2014 Lugano Response for Malignant Lymphoma criteria. PR is defined as not meeting criteria for CR but having an improvement in symptom criteria specified by the 2014 Lugano Response for Malignant Lymphoma criteria.
Time frame: Day 100
Overall survival (OS)
OS is defined as the time from infusion until death from any cause, or until last contact if alive
Time frame: Up to 12 months
Event-free survival (EFS)
EFS is defined as the time from infusion until the first occurrence of an event (relapse, progression, or death from any cause), or until last contact if no event occurs.
Time frame: Up to 12 months
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