Non Hodgkin's LymphomaPhase 1/2NCT06014073
TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-NHL
A Phase 1/2 study testing TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T), Fludarabine and Cyclophosphamide in people with Non Hodgkin's Lymphoma, run by Chinese PLA General Hospital at 3 sites in China.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non Hodgkin's Lymphoma
- What is being tested?
- TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T), Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesChina
- Study dates
- 6 Sep 2023to 1 Sep 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-70 (inclusive).
- 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);
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- 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.
- 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.
- 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.
- CD19 positive (detected by immunohistochemistry [IHC]).
- 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).
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- 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).
- 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.
- 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).
- Voluntarily participate in this clinical trial and sign an informed consent form.
Who cannot join
- 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:
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- 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.
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Recruiting
Biotherapeutic Department, Chinese PLA General Hospital
Beijing
Weidong Han, Ph.D, +86-010-55499341, hanwdrsw@sina.com
- Recruiting
EdiGene Inc
Beijing
Zixuan Pang, Ph.D, 010-80733899, zxpang@edigene.com
- Recruiting
School of Life Sciences, Peking University
Beijing
Wensheng Wei, Ph.D, 010-62757794, wswei@pku.edu.cn
About this study
Official title: 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
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.
Read the detailed description
Phase 1 (dose escalation)
In phase 1, 6-18 subjects will be enrolled. Subjects will receive 3 doses of ATHENA CAR-T cell therapy ( 1× 10^6 cells/kg、3× 10^6 cells/kg、1 × 10^7 cells/kg) increases from low dose to high dose according to the "3 + 3" principle:
Three (3) subjects are enrolled in a cohort corresponding to a dose level. If 1 subject in a cohort of 3 subjects experiences a dose-limiting toxicity (DLT), 3 additional subjects will be enrolled at the current dose level. For safety purposes, the administration of ATHENA CAR T will be staggered by 28 days between the first two subjects in each cohort. And for each of the remaining cohorts, the administration of ATHENA CAR-T will be staggered by 28 days before enter into the next cohort.
Phase 2 (expansion cohort)
In phase 2, 10 to 12 subjects will be enrolled and receive ATHENA CAR-T cell infusion at dose of recommended phase 2 dose (RP2D), which will be determined based on the maximum tolerated dose (MTD), occurrence of DLT, the obtained efficacy results, pharmacokinetics/pharmacodynamics and other data according to the phase 1.
Objectives
The primary objectives of the phase 1 were to evaluate the tolerability and safety of ATHENA CAR-T in patients with r/r B-cell NHL, and determine RP2D. The primary purpose of the phase 2 study was to evaluate the efficacy of ATHENA CAR-T in the above population.
- Conditions
- Non Hodgkin's Lymphoma
- Being tested
- TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T), Fludarabine, Cyclophosphamide
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T)Biological
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.
FludarabineDrug
Also called Fludarabine Phosphate for Injection
Intravenous fludarabine 30~50 mg/m^2/day on days -5, -4, and -3.
CyclophosphamideDrug
Also called Cyclophosphamide for Injection
Intravenous cyclophosphamide 500~1000 mg/m^2/day on days -5, -4, and -3.
| Study group | Role | What they receive |
|---|---|---|
| Patients with refractory or relapsed B-cell NHL | Experimental | A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, TRAC and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T. Receives: Biological: TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T); Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Incidence of adverse events (AE) defined as DLT
DLT is defined as any AE related to the investigational drug that occurs within 28 days after administration of the ATHENA CAR-T and meets any one of the criteria listed in the DLT criteria. The severity of AE will be assessed according to NCI-CTCAE v5.0. cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) will be evaluated according to the standards released by ASTCT in 2019. Graft-versus-host-disease(GvHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium.
- Grade 3 aGVHD that does not resolve to Grade 1 or 2 within 7 days, with the exception of isolated skin involvement aGVHD;
- Grade 4 CRS or grade 3 CRS that does not resolve to grade 2 or lower within 2 weeks;
- Grade 3 ICANS lasting for ≥7 days or Grade 4 ICANS;
- Any other Grade ≥4 and Grade 3 AE related to the ATHENA CAR-T that lasts for ≥14 days, except hematology toxicity.
Measured: First infusion date of CAR-T cells up to 28 days
Phase 1: RP2D
The RP2D was determined through phase 1 study.
Measured: 12 months
Phase 2: 3-month objective response rate (ORR)
ORR is defined as the proportion of patients who have achieved complete response (CR) and partial response (PR) assessed by investigators and based on the Lugano 2014 assessment criterion.
Measured: 3 months
Phase 2: CR rate
CR rate is defined as the proportion of patients who have achieved CR assessed by investigators and based on the Lugano 2014 assessment criterion.
Measured: 24 months
Phase 2: Duration of Response (DOR)
DOR is defined as the date of their first CR or PR (which is subsequently confirmed) to PD assessed by investigators and based on the Lugano 2014 assessment criterion for r/r B-cell NHL, or death regardless of cause.
Measured: 24 months
Phase 2: Overall Survival (OS)
OS is defined as the time from CAR-T cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Measured: 24 months
Phase 2: Progression Free Survival (PFS)
PFS is defined as the time from the CAR-T cells infusion date to the date of disease progression assessed by investigators and based on the Lugano 2014 assessment criterion, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Measured: 24 months
Secondary outcomes (6)
Phase 1 and phase 2: Pharmacokinetics: Levels of ATHENA CAR-positive T cells circulating in blood over time
Number and copy number of ATHENA CAR-T cells were assessed by number in peripheral blood. Blood samples were collected before and one year after cell infusion (until CAR-T cells were not detected for two consecutive times) to detect the number and copy number of CAR-T cells, and to evaluate the pharmacokinetics of CAR-T.
Measured: 12 months
Phase 1 and phase 2: Pharmacodynamics: Levels of CD19+ cells and serum cytokines in peripheral blood
The cytokines mainly include interleukin-2 (IL-2 ), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C reactive protein (CRP), ferritin.
Measured: Up to 28 days after infusion
Phase 1: 3-month ORR
ORR is defined as the proportion of patients who have achieved CR and PR assessed by investigators and based on the Lugano 2014 assessment criterion.
Measured: 3 months
Phase 1: OS
The definition of OS has already been mentioned above
Measured: 24 months
Phase 1: PFS
The definition of PFS has already been mentioned above
Measured: 24 months
Phase 2: Incidence of AE and clinical significant changes in safety lab values
AE is defined as any adverse medical event from the date of enrollment to 24 months after CAR-T cells infusion.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2023
- Study start6 Sep 2023
- Primary completion1 Sep 2025 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University, EdiGene Inc.
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
- Investigators
- Weidong Han, Ph.D, Principal investigator, Biotherapeutic Department, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06014073
- Sponsor's protocol ID
- CHN-PLAGH-BT-082
- Status last verified
- May 2025
- First submitted
- 23 Aug 2023
- Last updated
- 25 May 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wu Z, Shi J, Lamao Q, Qiu Y, Yang J, Liu Y, Liang F, Sun X, Tang W, Chen C, Yang Q, Wang C, Li Z, Zhang H, Yang Z, Zhang Y, Yi Y, Zheng X, Sun Y, Ma K, Yu L, Yang H, Wang Z, Zheng W, Yang L, Zhang Z, Zhang Y, Wu Z, Wang Y, Wong CCL, Jin M, Yuan P, Han W, Wei W. Glycan shielding enables TCR-sufficient allogeneic CAR-T therapy. Cell. 2025 Oct 30;188(22):6317-6334.e21. doi: 10.1016/j.cell.2025.07.046. Epub 2025 Aug 21.
PubMed 40845838
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06014073
- Acronym / sponsor ID
- CHN-PLAGH-BT-082
- Conditions
- Non Hodgkin's Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Collaborators
- Peking University, EdiGene Inc.
- Study start
- 6 Sep 2023 (actual)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 28 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Phase 1 (dose escalation)
In phase 1, 6-18 subjects will be enrolled. Subjects will receive 3 doses of ATHENA CAR-T cell therapy ( 1× 10^6 cells/kg、3× 10^6 cells/kg、1 × 10^7 cells/kg) increases from low dose to high dose according to the "3 + 3" principle:
Three (3) subjects are enrolled in a cohort corresponding to a dose level. If 1 subject in a cohort of 3 subjects experiences a dose-limiting toxicity (DLT), 3 additional subjects will be enrolled at the current dose level. For safety purposes, the administration of ATHENA CAR T will be staggered by 28 days between the first two subjects in each cohort. And for each of the remaining cohorts, the administration of ATHENA CAR-T will be staggered by 28 days before enter into the next cohort.
Phase 2 (expansion cohort)
In phase 2, 10 to 12 subjects will be enrolled and receive ATHENA CAR-T cell infusion at dose of recommended phase 2 dose (RP2D), which will be determined based on the maximum tolerated dose (MTD), occurrence of DLT, the obtained efficacy results, pharmacokinetics/pharmacodynamics and other data according to the phase 1.
Objectives
The primary objectives of the phase 1 were to evaluate the tolerability and safety of ATHENA CAR-T in patients with r/r B-cell NHL, and determine RP2D. The primary purpose of the phase 2 study was to evaluate the efficacy of ATHENA CAR-T in the above population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with refractory or relapsed B-cell NHL | Experimental | Biological: TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T), Drug: Fludarabine, Drug: CyclophosphamideA conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, TRAC and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (39 listed)
- Age 18-70 (inclusive).
- Subjects who meet the following requirements:
- 2.1 Histologically confirmed refractory/relapsed B cell NHL, including the following types defined by WHO 2016:
- 2.2 Relapsed disease is defined as disease progression (PD) after achieving disease remission (including CR and PR) with the latest standard regimen.
- 2.4 Individuals who are intolerant to standard treatment can also be included in the study in the investigator's judgment.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Biological | Patients with refractory or relapsed B-cell NHL |
| FludarabineAlso: Fludarabine Phosphate for InjectionIntravenous fludarabine 30~50 mg/m^2/day on days -5, -4, and -3. | Drug | Patients with refractory or relapsed B-cell NHL |
| CyclophosphamideAlso: Cyclophosphamide for InjectionIntravenous cyclophosphamide 500~1000 mg/m^2/day on days -5, -4, and -3. | Drug | Patients with refractory or relapsed B-cell NHL |
Primary outcome
Phase 1: Incidence of adverse events (AE) defined as DLT
Time frame: First infusion date of CAR-T cells up to 28 days
DLT is defined as any AE related to the investigational drug that occurs within 28 days after administration of the ATHENA CAR-T and meets any one of the criteria listed in the DLT criteria. The severity of AE will be assessed according to NCI-CTCAE v5.0. cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) will be evaluated according to the standards released by ASTCT in 2019. Graft-versus-host-disease(GvHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. * Grade 3 aGVHD that does not resolve to Grade 1 or 2 within 7 days, with the exception of isolated skin involvement aGVHD; * Grade 4 CRS or grade 3 CRS that does not resolve to grade 2 or lower within 2 weeks; * Grade 3 ICANS lasting for ≥7 days or Grade 4 ICANS; * Any other Grade ≥4 and Grade 3 AE related to the ATHENA CAR-T that lasts for ≥14 days, except hematology toxicity.
Phase 1: RP2D
Time frame: 12 months
The RP2D was determined through phase 1 study.
Phase 2: 3-month objective response rate (ORR)
Time frame: 3 months
ORR is defined as the proportion of patients who have achieved complete response (CR) and partial response (PR) assessed by investigators and based on the Lugano 2014 assessment criterion.
Phase 2: CR rate
Time frame: 24 months
CR rate is defined as the proportion of patients who have achieved CR assessed by investigators and based on the Lugano 2014 assessment criterion.
Phase 2: Duration of Response (DOR)
Time frame: 24 months
DOR is defined as the date of their first CR or PR (which is subsequently confirmed) to PD assessed by investigators and based on the Lugano 2014 assessment criterion for r/r B-cell NHL, or death regardless of cause.
Phase 2: Overall Survival (OS)
Time frame: 24 months
OS is defined as the time from CAR-T cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Phase 2: Progression Free Survival (PFS)
Time frame: 24 months
PFS is defined as the time from the CAR-T cells infusion date to the date of disease progression assessed by investigators and based on the Lugano 2014 assessment criterion, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
6 secondary outcomes
Phase 1 and phase 2: Pharmacokinetics: Levels of ATHENA CAR-positive T cells circulating in blood over time
Time frame: 12 months
Phase 1 and phase 2: Pharmacodynamics: Levels of CD19+ cells and serum cytokines in peripheral blood
Time frame: Up to 28 days after infusion
Phase 1: 3-month ORR
Time frame: 3 months
Phase 1: OS
Time frame: 24 months
Phase 1: PFS
Time frame: 24 months
Phase 2: Incidence of AE and clinical significant changes in safety lab values
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Derived from this study: PubMed 40845838Wu Z, Shi J, Lamao Q, Qiu Y, Yang J, Liu Y, Liang F, Sun X, Tang W, Chen C, Yang Q, Wang C, Li Z, Zhang H, Yang Z, Zhang Y, Yi Y, Zheng X, Sun Y, Ma K, Yu L, Yang H, Wang Z, Zheng W, Yang L, Zhang Z, Zhang Y, Wu Z, Wang Y, Wong CCL, Jin M, Yuan P, Han W, Wei W. Glycan shielding enables TCR-sufficient allogeneic CAR-T therapy. Cell. 2025 Oct 30;188(22):6317-6334.e21. doi: 10.1016/j.cell.2025.07.046. Epub 2025 Aug 21.
- Individual participant dataSharing planned: No
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Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Active, not recruitingPhase 2
A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy
B Cell ALL, B-Cell Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Weidong Han, Ph.D principal investigator
Biotherapeutic Department, Chinese PLA General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T cell (ATHENA CAR-T), Fludarabine and Cyclophosphamide in people with Non Hodgkin's Lymphoma, run by Chinese PLA General Hospital at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 39 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Weidong Han, Ph.D (+86-010-55499341, hanwdrsw@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Incidence of adverse events (AE) defined as DLT (time frame: First infusion date of CAR-T cells up to 28 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06014073, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.