Study of CD19 t-haNK and NAI With Rituximab in Participants With Indolent Non-Hodgkin Lymphoma

Official title

Open-Label, Phase 2 Chemotherapy-Free Study of CD19 t-haNK and NAI in Combination With Rituximab in Participants With Relapsed/Refractory B-Cell Indolent Non-Hodgkin Lymphoma

Overview

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.

Detailed description

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.

Interventions

• Biological CD19 t-haNK- IV Administration
  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.
• Drug N-803
  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.
• Drug rituximab
  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.

Primary outcome measures

• 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]

Secondary outcome measures (9)

• 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 [Time frame: Up to 37 weeks]
• Clinically important changes in laboratory tests - Chemistry [Time frame: Up to 37 weeks]
• Clinically important changes in laboratory tests - Urinalysis [Time frame: By end of screening]
• Clinically important changes in laboratory tests - Pregnancy Test [Time frame: Up to 37 weeks]
• Clinically important changes in vital signs - heart rate [Time frame: Up to 37 weeks]
• Clinically important changes in vital signs - blood pressure [Time frame: Up to 37 weeks]
• Clinically important changes in vital signs - respiratory rate [Time frame: Up to 37 weeks]
• Clinically important changes in vital signs - Oxygen saturation [Time frame: Up to 37 weeks]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 to ≤ 75 years old.
• Able to understand and provide a signed informed consent that fulfils the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
• Histologically or flow cytometry documented relapsed/refractory B-cell indolent NHL (iNHL) including but not limited to follicular lymphoma \[FL\]; lymphoplasmacytic lymphoma \[LPL\], also known as Waldenstrom macroglobulinemia \[WM\]; marginal zone lymphoma \[MZL\] with the following specific criteria:

• Have completed ≥ 2 lines of cytotoxic chemotherapy.
• Have received rituximab or another anti-CD20 antibody.
• Have measurable disease by Lugano classification documented within 8 weeks of the time of consent, defined as nodal lesions > 15 mm in the long axis or extranodal lesions > 10 mm in long and short axis, or bone marrow involvement that is biopsy proven.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Stated willingness to comply with study procedures.
• Able to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female participants of childbearing potential and nonsterile males. Female participants of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Female participants of childbearing potential must have a negative pregnancy test and adhere to using a highly effective method of contraception (eg, tubal ligation, approved hormonal contraceptive, or an intrauterine device \[IUD\]) prior to screening and agree to continue its use during the study or be surgically sterilized (eg, hysterectomy) while on study and for 12 months post last dose of study drug. Male participants must agree to use barrier methods of birth control while on study and for 12 months post last dose of study drug).

Exclusion criteria

• Histologically documented large B-cell lymphomas (eg, diffuse large B-cell lymphoma \[DLBCL\], anaplastic large cell lymphoma \[ALCL\], follicular large cell lymphoma, mantle cell lymphoma), primary central nervous system (CNS) lymphoma, chronic lymphocytic leukemia (CLL), Burkitt and Burkitt-like lymphoma.
• Known hypersensitivity or allergy to any component of the study medications, including sulfa containing study medication(s) (eg, albumin \[human\], dimethyl sulfoxide \[DMSO\]).
• Inadequate organ function, evidenced by the following laboratory results:

• ANC < 1000 cells/mm3.
• Platelet count < 100,000 cells/mm3.
• Total bilirubin ≥ 1.5 × the upper limit of normal (ULN; unless the participant has documented Gilbert's syndrome or indirect hyperbilirubinemia).
• Aspartate aminotransferase (AST /ALT ≥ 2.5 × ULN.
• Alkaline phosphatase (ALP) levels ≥ 2.5 × ULN (or ≥ 5 × ULN in participants with bone metastases).
• Serum creatinine ≥ 2 mg/dL. NOTE: Each study site should use its institutional ULN to determine eligibility
• Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the participant at high risk for treatment-related complications.
• History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon: such as systemic lupus erythematous, Wegner's glomerulonephritis, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura requiring steroid therapy defined as > 20 mg of prednisone or equivalent daily.
• History of allogeneic hematopoietic stem cell transplantation (HSCT) requiring ongoing systemic graft versus host disease (GvHD) therapy.
• Anti-CD20 antibody treatment less than 2 weeks prior to cell infusion.
• History of receiving allograft organ transplant requiring immunosuppression.
• Participants that underwent a solid organ transplant who develop high grade lymphomas or leukemias.
• Metastases to the CNS, including the parenchyma or leptomeninges.
• Nonmalignant CNS disease (eg, stroke, epilepsy, vasculitis, or neurodegenerative disease).
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association Class 2 or higher; or serious cardiac arrhythmia requiring medication.
• Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids as defined as > 20 mg of prednisone or equivalent daily, excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in participants who have known contrast allergies is allowed.
• Currently taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
• History of human immunodeficiency virus (HIV) with current CD4+ T-cell count < 350 cells/μL and/or a detectable HIV viral load.
• Known carriers of hepatitis B virus (HBV) infection that is currently hepatitis B surface antigen (HBsAg) positive.
• Concurrent active malignancy other than basal or squamous cell carcinomas of the skin.
• Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
• Women who are pregnant or breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07477366 · ResQ215B-BCELL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗