Open-Label, Phase 2 Chemotherapy-Free Study ofCD19 t-haNK and NAI in Combination With Rituximab in Participants With Relapsed/Refractory B-Cell Indolent Non-Hodgkin Lymphoma. 40 Participant will be screened for 20 subjects enrollment.
Participants will receive treatment for a maximum of 12 cycles( 36 weeks) or until they have PD, unacceptable toxicity, withdrawal consent, or if the investigator feels it is no longer their best interest to continue treatment. Subjects first receive CD19t-haNK, N-803 and Rituximab for a 4-week induction cycle. If subjects respond to treatment they will receive maintenance therapy from cycle 2 to 12 (repeated 3 week cycles). All participants should be followed for collection of survival statis, disease status, and posttreatment therapies every 12 weeks (+/- 2 weeks). The follow up visits may occur in-person or via phone contact. The cycles have visits on the following days: Cycle 1 (Day 1, 8, and 15), Cycles 2-6 (Day 1, 8) and Cycles 7-12 (Day 1). On each of these days, the following will be conducted: Concomitant Medication, Physical Exam, Vitals, ECOG and Labs.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
CD19-Directed Therapies: CD19-targeted therapies, are biologic agents specifically designed to recognize and eliminate CD19-expressing B-cell malignancies. These therapies differ from traditional chemotherapy or small molecule inhibitors by leveraging the patient's immune system to achieve targeted cytotoxicity. Their mechanism of action involves direct binding to the CD19 antigen on malignant B cells, leading to immune-mediated cell death.
N-803 Subcutaneous (SQ): N-803 is a novel IL-15 superagonist immunotherapy administered subcutaneously. It is designed to enhance the proliferation and activation of natural killer (NK) cells and CD8+ T cells without stimulating regulatory T cells. N-803 SQ differs from other cytokine therapies due to its improved pharmacokinetic profile, enhanced in vivo activity, and reduced toxicity.
ORR in accordance with Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC)
Time frame: Up to 9 months
OS (time from study treatment initiation to death)
Time frame: Up to 89 weeks
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) graded using the National Cancer Institute (NCI) CTCAE Version 6.0
Time frame: Up to 37 weeks
Clinically important changes in laboratory tests - Hematology
Laboratory tests include hematology and will be assessed/measured per the site-specific normal lab ranges
Time frame: Up to 37 weeks
Clinically important changes in laboratory tests - Chemistry
Laboratory tests include chemistry and will be assessed/measured per the site-specific normal lab ranges
Time frame: Up to 37 weeks
Clinically important changes in laboratory tests - Urinalysis
Laboratory tests include urinalysis and will be assessed/measured per the site-specific normal lab ranges
Time frame: By end of screening
Clinically important changes in laboratory tests - Pregnancy Test
Laboratory tests include pregnancy test and will be assessed/measured per the site-specific normal lab ranges
Time frame: Up to 37 weeks
Clinically important changes in vital signs - heart rate
Vital signs include heart rate measured by how many heart beats per minute
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Rituximab is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen. Rituximab has an approximate molecular weight of 145 kD and has a binding affinity for the CD20 antigen of approximately 8.0 nM.
Time frame: Up to 37 weeks
Clinically important changes in vital signs - blood pressure
Vital signs include blood pressure reported as systolic/diastolic - measured in mm Hg
Time frame: Up to 37 weeks
Clinically important changes in vital signs - respiratory rate
Vital signs include respiratory rate measured in how many breaths per minute
Time frame: Up to 37 weeks
Clinically important changes in vital signs - Oxygen saturation
Vital signs include oxygen saturation measured by percentage of hemoglobin saturated with oxygen in the blood
Time frame: Up to 37 weeks