Study for Subjects With Relapsed/Refractory Non- Hodgkin Lymphoma

NCT05618925 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: QUILT-3.092
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

Open-label, Phase 1 Study of CD19 t-haNK as a Single Agent and in Combination With an IL-15 Superagonist (N-803) and Rituximab in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma. Up to 20 subjects will be enrolled and randomized 1:1 to 1 of 2 cohorts, as outlined below. The initial 3 subjects will be sequentially enrolled in a staggered fashion, with a 7 day interval between each subject to enable the capture and monitoring of any acute and subacute toxicities.

Conditions

Non Hodgkin's Lymphoma Refractory/Relapsed

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measures

  Safety of CD19 t-haNK will be assessed by incidence and severity of TEAEs and SAEs, as well as incidence of clinically significant in safety laboratory tests and vital signs

  within 30 days after each cell infusion

Secondary Outcomes (1)

• Secondary Outcome measures

  Within 12 months after first cell infusion

Other Outcomes (3)

• Progression-free survival (PFS) after infusion in accordance with LYRIC

  Within 12 months after first cell infusion

• Duration of response (DoR) in accordance with LYRIC

  Within 12 months after first cell infusion

• Overall survival (OS) after infusion

  Within 12 months after first cell infusion

Study Arms (2)

Arm A

EXPERIMENTAL

Subjects in both cohorts will initially receive lymphodepleting chemotherapy followed by a single 4-week cycle of the CD19 t-haNK single-agent regimen. Following a 1-week rest period, subjects will then receive lymphodepleting chemotherapy followed by a single 4-week cycle of CD19 t-haNK in combination with rituximab

Biological: CD19t-haNK suspension; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

Arm B

EXPERIMENTAL

Subjects in both cohorts will initially receive lymphodepleting chemotherapy followed by a single 4-week cycle of the CD19 t-haNK single-agent regimen. Following a 1-week rest period, subjects will then receive lymphodepleting chemotherapy followed by a single 4-week cycle of CD19 t-haNK in combination with rituximab (cohort A) or in combination with rituximab and N-803 (cohort B).

Drug: N803; Biological: CD19t-haNK suspension; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

Interventions

CD19t-haNK suspension BIOLOGICAL

Derived 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).

Arm A; Arm B

Rituximab DRUG

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: Rituxan

Arm A; Arm B

N803 DRUG

nogapendekin alfa inbakicept (also known as ALT-803; recombinant human superagonist interleukin-15 (IL-15) complex \[also known as IL 15N72D:IL-15RαSu/IgG1 Fc complex\])

Also known as: Anktiva

Arm B

Cyclophosphamide DRUG

Cyclophosphamide is a synthetic antineoplastic drug chemically related to the nitrogen mustards. The chemical name for cyclophosphamide is 2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate and has the molecular formula C7H15Cl2N2O2P•H2O and a molecular weight of 279.1.

Also known as: Cytoxan

Arm A; Arm B

Fludarabine DRUG

Fludarabine phosphate is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-β-D-arabinofuranosyladenine (ara-A) that is relatively resistant to deamination by adenosine deaminase. The chemical name for fludarabine phosphate is 9H-Purin-6-amine, 2-fluoro-9-(5-0-phosphono β-D-arabino-furanosyl) (2-fluoro-ara-AMP). The molecular formula of fludarabine phosphate is C10H13FN5O7P and it has a molecular weight of 365.2.

Also known as: Fludara

Arm A; Arm B

Eligibility Criteria

• Age: 18 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 Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
• Histologically documented CD19- and CD20-positive B-cell NHL with the following specific criteria:
• Have active disease after ≥ 2 lines of cytotoxic chemotherapy.
• Have received rituximab or another anti-CD20 antibody.
• Have either failed autologous transplant or are ineligible to receive autologous transplant.
• 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 on most recent biopsy performed (a repeat biopsy is not mandatory for this study except as noted below). A minimum of 5% CD19 and CD20 positivity by immunohistochemistry or flow cytometry on prior or repeat biopsy is required.
• History of central nervous system (CNS) involvement with cerebral spinal fluid (CSF) analysis following magnetic resonance imaging (MRI) brain and lumbar puncture showing no evidence of CNS involvement by cytology and flow cytometry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Expected survival \> 12 weeks.
• Willing and able to have central line placed for study drug infusions.
• 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 subjects of child-bearing potential and nonsterile males. Female subjects of child-bearing 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 subjects 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) used with spermicide, intrauterine devices (IUDs), and abstinence.

You may not qualify if:

• Known hypersensitivity to any component of the study medication(s), including anaphylactic reaction to sulfur-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 subject 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) or allogeneic chimeric antigen receptor (CAR) T therapy within 6 months of day 1 or require ongoing systemic graft versus host disease (GvHD) therapy.
• Anti-CD19 or anti-CD20 antibody treatment within 4 weeks of cell infusion.
• Live vaccine \< 6 weeks prior to starting lymphodepleting chemotherapy.
• History of receiving allograft organ transplant requiring immunosuppression.
• Subjects post solid organ transplant who develop high grade lymphomas or leukemias.
• Known lymphomatous involvement of 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).
• 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 (2)

Hoag Memorial Hospital

Newport Beach, California, 92663, United States

RECRUITING

Texas Oncology

Tyler, Texas, 75702, United States

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

ALT-803; Cyclophosphamide; fludarabine; fludarabine phosphate; Rituximab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Mark Nelson

CONTACT

213 414 3566; mark.nelson@immunitybio.com

Atessa Kiani

CONTACT

9499038749; atessa.kiani@immunitybio.com

Study Design

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

Model Details: Subjects in both cohorts will initially receive lymphodepleting chemotherapy followed by a single 4 week cycle of the CD19 t haNK single-agent regimen. Following a 1-week rest period, subjects will then receive lymphodepleting chemotherapy followed by a single 4-week cycle of CD19 t-haNK in combination with rituximab (cohort A) or in combination with rituximab and N-803 (cohort B). Following a second 1-week rest period, subjects will receive up to 4 repeated 4 week cycles of CD19 t haNK in combination with rituximab (cohort A) or in combination with rituximab and N 803 (cohort B) without lymphodepleting chemotherapy.

Study Record Dates

• First Submitted: October 19, 2022
• First Posted: November 16, 2022
• Study Start: August 22, 2025
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): March 15, 2027
• Last Updated: April 1, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)