TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-NHL

Recruiting now · Phase 1/Phase 2

Conditions studied: Non Hodgkin's Lymphoma

In brief

ATHENA chimeric antigen receptor (CAR)-T, a CD19-directed CAR-T cell immunotherapy comprised of allogeneic T cells prepared for the treatment of relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL). The cells are from healthy adult volunteer donors that are knocked out of TRAC and Power3 (SPPL3) genes ex vivo using CRISPR-Cas9 gene editing components. In this study, a second-generation anti-CD19 CAR prototype was constructed, bearing murine FMC63 single-chain variant fragment (scFv) together with intracellular CD28 co-stimulatory and CD3ζ signaling domains linked by a CD28 sequence comprising the hinge and transmembrane domains. This is a single center, prospective, open-label, single-arm, phase 1/2 study. A total of around 30 patients with r/r B-cell NHL will be enrolled in the study and receive allogeneic CD19-CAR-T cell infusion. Phase 1 (n=6 to 18) is a dose escalation part, and phase 2 (n=10 to 12) is a expansion cohort part. The primary objective of this study was to evaluate the safety and efficacy of ATHENA CAR-T cell therapy in patients with r/r B-cell NHL.

Key facts

Study ID

NCT06014073

Run by

Chinese PLA General Hospital

People needed

30

Starts

2023-09-06

Expected to finish

2026-09-01

Last updated by the study team

2025-05-25

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age 18-70 (inclusive).
• Subjects who meet the following requirements:
• 1 Histologically confirmed refractory/relapsed B cell NHL, including the following types defined by WHO 2016:
• Diffuse large B-cell lymphoma (DLBCL) not otherwise specified;
• Primary mediastinal (thymic) large B-cell lymphoma (PMBCL);
• Transformed follicular lymphoma (TFL);
• High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBCL);
• Follicular lymphoma (FL);
• Mantle cell lymphoma (MCL) (pathologically confirmed, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1);
• Marginal zone lymphoma (MZL), including nodal or splenic marginal zone B-cell lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma.
• 2 Relapsed disease is defined as disease progression (PD) after achieving disease remission (including CR and PR) with the latest standard regimen.
• 3 Refractory disease is defined as no CR to first-line therapy:
• Evaluation of PD (never reached response or SD) after standard first-line treatment, or
• SD as best response after at least 4 cycles of first-line therapy (eg,4 cycles of R-CHOP), or
• PR as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 6 months of therapy, or
• Refractory post-autologous stem cell transplant (ASCT) i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy.
• 4 Individuals who are intolerant to standard treatment can also be included in the study in the investigator's judgment.
• Individuals must have received adequate prior therapy:
• 1 For MCL, prior therapy must have included:
• Anthracycline or bendamustine-containing chemotherapy and
• Anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative) and
• Bruton's tyrosine kinase inhibitor (BTKi).
• 2 For other types, prior therapy must have included:
• Anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative) and
• Anthracycline containing chemotherapy regimen.

You may not qualify if…

• Expected survival time < 3 months per Principal Investigator's opinion.
• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years.
• Autologous stem cell transplant with therapeutic intent within 3 months of planned ATHENA CAR-T infusion.
• History of allogeneic stem cell transplantation.
• Prior CD19 targeted therapy.
• Patients who have used any of the following agents or treatments within a specific period of time:
• 1 Received any chemotherapy drugs or small molecule targeted drugs within 2 weeks prior to lymphodepletion;
• 2 Received any monoclonal antibodies, antibody drug conjugates (ADCs), or bispecific antibodies within 3 weeks prior to lymphodepletion;
• 3 Received radiotherapy within 6 weeks prior to lymphodepletion. However, if disease progressed at the site of radiotherapy, or if there are positive lesions detected by PET-CT at non-radiotherapy sites, enrollment is allowed.
• Prior CAR-T therapy or other genetically modified T cell therapy.
• Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma.
• History of severe, immediate hypersensitivity reaction attributed to lymphodepletion drugs or any component of ATHENA CAR-T.
• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
• Uncontrolled or active infectious diseases, such as human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B or C, epstein-barr virus (EBV), and cytomegalovirus (CMV) infection.
• History or presence of central nervous system (CNS) disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Subjects with cardiac atrial or cardiac ventricular lymphoma involvement.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome).
• Primary immunodeficiency.
• History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
• History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months of enrollment.
• Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Vaccine ≤ 6 weeks prior to planned start of conditioning regimen.
• In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

Where it is running

• Biotherapeutic Department, Chinese PLA General Hospital — Beijing, China (enrolling)
• EdiGene Inc — Beijing, China (enrolling)
• School of Life Sciences, Peking University — Beijing, China (enrolling)

Full record on ClinicalTrials.gov

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