CD19 t-haNK and N-803 plus rituximab for relapsed or refractory B-cell non-Hodgkin lymphoma

Open Label, Phase 2 Study of CD19 t-haNK and N-803 in Combination With Rituximab in Participants With Relapsed/ Refractory B-cell Non- Hodgkin Lymphoma

This treatment tests whether giving lab-grown CD19-directed natural killer cells (t-haNK) together with N-803 and rituximab can help adults whose B-cell non-Hodgkin lymphoma has come back or not responded to prior therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: ImmunityBio, Inc. (Industry-sponsored)
• Drugs / interventions: rituximab, chemotherapy, prednisone, cyclophosphamide, Fludarabine
• Locations: 2 sites (Johannesburg and 1 other locations)
• Trial ID: NCT07125872 on ClinicalTrials.gov

What this trial studies

This open-label phase 2 trial will screen up to 40 people to enroll 20 adults with relapsed or refractory B‑cell non‑Hodgkin lymphoma. Participants receive three days of lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by IV CD19 t‑haNK cells with N‑803 and rituximab every three weeks for up to six induction cycles, with responders eligible for maintenance through cycle 12 (maximum 36 weeks of treatment). Each cycle includes treatments on days 1 and 8, routine labs, physical exams, and close safety monitoring including phone checks during the first cycle. After treatment participants are followed every 12 weeks to collect survival, disease status, and any posttreatment therapies.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically or flow-confirmed relapsed/refractory B‑cell non‑Hodgkin lymphoma (excluding primary CNS lymphoma, CLL, and Burkitt lymphoma) who have had at least two prior lines of cytotoxic chemotherapy, prior anti‑CD20 therapy, measurable disease, and ECOG performance status 0–1 are the intended candidates.

Not a fit: Patients with primary CNS lymphoma, CLL, or Burkitt lymphoma, those with ECOG >1, or those who cannot tolerate lymphodepleting chemotherapy or meet other safety exclusions are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this approach could produce deeper or longer-lasting remissions by adding an off-the-shelf NK cell therapy plus cytokine support to standard anti‑CD20 therapy.

How similar studies have performed: Early-phase work combining NK-cell platforms and the IL‑15 agonist N‑803 with monoclonal antibodies has shown encouraging safety and activity signals, but the specific CD19 t‑haNK plus N‑803/rituximab combination lacks large-scale proof of benefit.

Eligibility criteria

Inclusion Criteria:

* 1- Age\>18 years old 2- Able to understand and provide a signed informed consent that fulfills the relevant Human Research Ethics Committee( HRECC) or independent Ethics Committee( IEC) guidelines 3. Histologically or flow cytometry documented B-cell NHL, (excluding primary central nervous system \[CNS\] lymphoma, chronic lymphocytic leukemia \[CLL\], and Burkitt lymphoma) 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.

    4\. Eastern Cooperative Oncology Group (ECOG) performance status (Appendix 5) of 0 to 1.

    5\. Stated willingness to comply with study procedures. 6. Able to attend required study visits and return for adequate follow-up, as required by this protocol.

    7\. Agreement to practice effective contraception for female participants of childbearing potential and nonsterile males. Female participants of childbearing potential must agree to use effective contraception while on study and for at least 30 days after the last dose of study drug. Nonsterile male participants must agree to use a condom while on study and for up to 30 days after the last dose of study drug. Effective contraception includes orals, injectables, surgical sterilization (e.g., vasectomy, tubal ligation), two forms of barrier methods (e.g., condom, diaphragm) and implants such as intrauterine devices (IUDs).

Exclusion Criteria:

* Participants with ANY of the following criteria are excluded from participation in the study:

  1. Histologically documented primary CNS lymphoma, CLL, Burkitt, Burkitt-like lymphoma.
  2. Known hypersensitivity or allergy to any component of the study medications, including sulfa-containing study medication(s) (e.g., albumin \[human\], dimethyl sulfoxide \[DMSO\]).
  3. Inadequate organ function, evidenced by the following laboratory results:

     1. ANC \< 1000 cells/mm3.
     2. Platelet count \< 100,000 cells/mm3.
     3. Total bilirubin ≥ 1.5 × the upper limit of normal (ULN; unless the participant has documented Gilbert's syndrome or indirect hyperbilirubinemia).
     4. Aspartate aminotransferase (AST \[SGOT\])/ALT (SGPT) ≥ 2.5 × ULN.
     5. Alkaline phosphatase (ALP) levels ≥ 2.5 × ULN (or ≥ 5 × ULN in participants with bone metastases).
     6. Serum creatinine ≥ 160 µmol/L. NOTE: Each study site should use its institutional ULN to determine eligibility.
  4. 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.
  5. 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.
  6. History of allogeneic hematopoietic stem-cell transplantation (HSCT) requiring ongoing systemic graft versus host disease (GvHD) therapy.
  7. Anti-CD20 antibody treatment less than 2 weeks prior to cell infusion.
  8. History of receiving allograft organ transplant requiring immunosuppression.
  9. Participants post solid organ transplants who develop high grade lymphomas or leukemias.
  10. Metastases to the CNS, including parenchyma or leptomeninges.
  11. Nonmalignant CNS disease (e.g., stroke, epilepsy, vasculitis, or neurodegenerative disease).
  12. History of active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  13. Uncontrolled hypertension (systolic \> 160 mm Hg and/or diastolic \> 110 mm Hg) or clinically significant (i.e., 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 (Appendix 6) Class 2 or higher; or serious cardiac arrhythmia requiring medication.
  14. Current chronic daily treatment (continuous for \>3 months) with systemiccorticosteroids 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.
  15. Currently taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
  16. Tested positive for tuberculosis (TB) utilizing the QuantiFERON Gold TB test.
  17. History of human immunodeficiency virus (HIV) with current CD4+ T-cell count \< 350 cells/μL and a detectable HIV viral load.
  18. Known carriers of hepatitis B virus (HBV) infection that is currently hepatitis B surface antigen (HBsAg) positive.
  19. Concurrent active malignancy other than basal or squamous cell carcinomas of the skin.
  20. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  21. Women who are pregnant or breastfeeding.

Where this trial is running

Johannesburg and 1 other locations

• Dr. Jackie Thomson Inc — Johannesburg, South Africa (Recruiting)
• Albert Cellular Therapy — Pretoria, South Africa (Recruiting)

Study contacts

• Study coordinator: Atessa Kiani, MD

Conditions Relapsed B-Cell Non Hodgkin Lymphoma