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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

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

A Phase 1/2 Single-center Study Evaluating the Safety and Efficacy of TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T Cell (ATHENA) Therapy in Adults With Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-NHL (NCT06014073) is a Phase 1 / Phase 2 interventional studying Non Hodgkin's Lymphoma, sponsored by Chinese PLA General Hospital. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Non Hodgkin's Lymphoma, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 30 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Age 18-70 (inclusive). 2. Subjects who meet the following requirements: 2.1 diagnosed by tissue sample (biopsy-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. 2.2 Relapsed disease is defined as disease progression (PD) after achieving disease remission (including CR and PR) with the latest standard regimen. 2.3 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. 2.4 Individuals who are intolerant to standard treatment can also be included in the study in the investigator's judgment. 3. Individuals must have received adequate prior therapy: 3.1 For MCL, prior therapy must have included: - Anthracycline or bendamustine-containing chemotherapy and ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. Age 18-70 (inclusive). 2. Subjects who meet the following requirements: 2.1 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. 2.2 Relapsed disease is defined as disease progression (PD) after achieving disease remission (including CR and PR) with the latest standard regimen. 2.3 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. 2.4 Individuals who are intolerant to standard treatment can also be included in the study in the investigator's judgment. 3. Individuals must have received adequate prior therapy: 3.1 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). 3.2 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. 3.3 For individual with transformed FL must have relapse or refractory disease after transformation to DLBCL. 4. At least 1 measurable lesion: lymph node site with a long axis \>1.5cm, extranodal site with a long axis \>1.0cm (according to Lugano2014). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. 5. CD19 positive (detected by immunohistochemistry \[IHC\]). 6. Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for hematological toxicities and clinically non-significant toxicities such as alopecia). 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 8. Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L, Platelet count ≥50 x 10\^9/L, hemoglobin (Hgb) ≥ 80g/L (hemocytopenia caused by lymphoma invasion of bone marrow is not subject to conditions above). 9. Adequate renal, hepatic, pulmonary and cardiac function defined as: 9.1 Serum creatinine≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min. 9.2 Serum alanine aminotransferase / aspartate aminotransferase (ALT/AST) ≤ 3 upper limit of normal (ULN); Total bilirubin ≤ 1.5 ULN, except in subjects with 3) Gilbert's syndrome. 9.3 Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings. 9.4 Coagulation Function: International Normalized Ratio (INR) ≤ 1.5 times the upper limit of normal (ULN), and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN. 9.5 Baseline oxygen saturation \>91% on room air. 10. Subjects of both genders who are willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential). 11. Voluntarily participate in this clinical trial and sign an informed consent form. Exclusion Criteria: 1. Expected survival time \< 3 months per Principal Investigator's opinion. 2. 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. 3. Autologous stem cell transplant with therapeutic intent within 3 months of planned ATHENA CAR-T infusion. 4. History of allogeneic stem cell transplantation. 5. Prior CD19 targeted therapy. 6. Patients who have used any of the following agents or treatments within a specific period of time: 6.1 Received any chemotherapy drugs or small molecule targeted drugs within 2 weeks prior to lymphodepletion; 6.2 Received any monoclonal antibodies, antibody drug conjugates (ADCs), or bispecific antibodies within 3 weeks prior to lymphodepletion; 6.3 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. 7. Prior CAR-T therapy or other genetically modified T cell therapy. 8. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma. 9. History of severe, immediate hypersensitivity reaction attributed to lymphodepletion drugs or any component of ATHENA CAR-T. 10. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. 11. 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. 12. 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. 13. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement. 14. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment. 15. Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome). 16. Primary immunodeficiency. 17. 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. 18. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months of enrollment. 19. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment. 20. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 21. Vaccine ≤ 6 weeks prior to planned start of conditioning regimen. 22. 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.

Treatments Being Tested

BIOLOGICAL

TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T)

Phase 1 dose escalation (3+3) : dose 1 (1 × 10\^6 cells/kg) , dose 2 (3 × 10\^6 cells/kg), dose 3 (1 × 10\^7 cells/kg); Phase 2 : dose of RP2D. No more than 2 × 10\^5 per kilogram of allogenic residual CD3+T cells harbouring in grafts can only be released for recipient infusion.

DRUG

Fludarabine

Intravenous fludarabine 30\~50 mg/m\^2/day on days -5, -4, and -3.

DRUG

Cyclophosphamide

Intravenous cyclophosphamide 500\~1000 mg/m\^2/day on days -5, -4, and -3.

Locations (3)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Biotherapeutic Department, Chinese PLA General Hospital
Beijing, China
EdiGene Inc
Beijing, China
School of Life Sciences, Peking University
Beijing, China

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06014073), the sponsor (Chinese PLA General Hospital), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06014073 clinical trial studying?

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… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06014073?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06014073?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06014073. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06014073. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.