Study for Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma

NCT06334991 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: QUILT-106
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

Open Label, Phase 1 study of CD19 t-haNK as a single agent and combination with rituximab in subjects with selected CD19+ and CD20+ R/R B-cell non-Hodgkin Lymphoma( NHL).

Conditions

Non-Hodgkin Lymphoma Refractory/ Relapsed

Outcome Measures

Primary Outcomes (2)

• Overall safety evaluation in combining CD19 t haNK as a single agent with rituximab

  Safety will be assessed for all participants and will include vital signs, physical examinations, clinical labs (hematology, chemistry panel, pregnancy tests), cytokine levels, electrocardiograms, neurological assessments, and the incidence and severity of adverse events (AEs) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. All participants will receive follow-up phone calls 6 hours (± 1 hour) and 24 hours (± 2 hours) post infusion for AE collection during Cycle 1

  30 days

• Incidence of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) graded using the National Cancer Institute (NCI) CTCAE Version 5.0.Clinically important changes in safety laboratory tests and vital signs.

  The incidence of TEAEs and SAEs will be presented by System Organ Class and Medical Dictionary for Regulatory Activities (MedDRA) preferred term. All AEs will be graded using CTCAE Version 5.0 except for CRS and ICANS, which will be graded using ICE score. The incidence of clinically important changes in safety laboratory tests and vital signs will also be presented.

  12 months

Secondary Outcomes (1)

• Best tumor response in accordance with Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).

  12 Months

Study Arms (1)

CD19 t-haNK with Rituximab

EXPERIMENTAL

Participants will initially receive a single 3-week cycle of the CD19 thaNK as a single-agent regimen. Following a 1-week safety pause, participants will then receive a single 3-week cycle of CD19 t-haNK in combination with rituximab. Participants will then undergo the first tumor assessment. Participants with no evidence of progressive disease (PD) will be eligible to receive up to 2 additional 3-week cycles of CD19 t-haNK combination with rituximab.

Biological: CD19 t-haNK

Interventions

CD19 t-haNK BIOLOGICAL

CD19t-haNK erived from the parental NK-92 (aNK) cell line, CD19 t-haNK is a human, allogeneic, NK cell line that has been engineered to express a CAR targeting CD19. Similar to the haNK cell line, CD19 t haNK has also been engineered to produce endoplasmic reticulum-retained IL 2 and the high-affinity (158V) variant of the Fcγ receptor (FcγRIIIa/CD16a), and thereby has enhanced CD16-targeted ADCC capabilities. CD19 t-haNK is similar to PD L1 t-haNK, differing only in the CAR that is expressed (CD19 vs PD-L1). 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.

Also known as: Rituximab

CD19 t-haNK with Rituximab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant Human Research Ethics Committee (HREC) or Independent Ethics Committee (IEC) guidelines.
• Histologically documented CD19- and CD20-positive B-cell NHL (excluding primary CNS lymphoma, 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.
• Have CD19- and CD20-positive disease confirmed on the diagnostic or repeat biopsy specimen. A minimum of 5% CD19 and CD20 positivity by immunohistochemistry or flow cytometry is required.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Expected survival \> 16 weeks.
• Stated willingness to comply with study procedures.
• Able to attend required study visits and return for adequate followup, as required by this protocol.
• 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 5 months after the last dose of study drug. Nonsterile male participants must agree to use a condom while on study and for up to 5 months after the last dose of study drug. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm), and intrauterine devices (IUDs).

You may not qualify if:

• Histologically documented primary CNS lymphoma, CLL, Burkitt, or Burkitt-like lymphoma.
• Known hypersensitivity to sulfa-containing study medication(s), including anaphylactic reaction to sulfa-containing medications.
• Known allergy to albumin (human) or dimethyl sulfoxide (DMSO).
• 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 post solid organ transplant who develop high grade lymphomas or leukemias.
• CD19- and CD20-positive metastases to the CNS, including the parenchyma
• Nonmalignant CNS disease (eg, stroke, epilepsy, vasculitis, or neurodegenerative disease).
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Inadequate organ function, evidenced by the following laboratory results:
• ANC \< 1000 cells/mm3.
• Platelet count \< 100,000 cells/mm3.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (3)

FARMOVS

Bloemfontein, Free State, 9301, South Africa

RECRUITING

Dr. Jackie Thomson Inc.

Johannesburg, Gauteng, 2193, South Africa

RECRUITING

Albert Cellular Therapy

Pretoria, Gauteng, 0044, South Africa

RECRUITING

MeSH Terms

Interventions

Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Kayleigh Russell

CONTACT

424-539-2412; kayleigh.russell@immunitybio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is open label, for Refractory/ Relapsed Non-Hodgkin Lymphoma. Up to 10 subjects will receive at least 1 dose of study drug. The initial 3 subjects will receive study drug in a staggered fashion, with a 7 day interval between each subject to evaluate any toxicities.

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 28, 2024
• Study Start: August 23, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (3)