Donor-Derived CD5-Gene-Edited CAR-T Cells for Relapsed / Refractory T-ALL: A Phase 1 Trial With 100% Complete Remission β Published in Nature Medicine
NCT05032599 was a first-in-human Phase 1 trial of allogeneic, CD5-gene-edited CAR-T cells derived from haematopoietic stem cell transplant donors, tested in patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) β most of whom had previously failed CD7-directed CAR-T therapy. All 16 patients who received infusions achieved complete remission by day 30 (100% ORR). The trial registry was terminated due to institutional restructuring at Beijing Boren Hospital, not due to safety or efficacy concerns. Full results were published in Nature Medicine (January 2025). This page documents the published findings and connects patients to currently available options.
About This Clinical Trial
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive haematological malignancy arising from T-lymphocyte precursors. While modern chemotherapy achieves high initial remission rates, relapsed or refractory T-ALL carries a devastating prognosis β with median overall survival measured in months and fewer than 20% of adult patients surviving five years after relapse. Unlike B-cell ALL, where CD19-directed CAR-T therapies have been transformative, T-ALL poses a fundamentally harder target for CAR-T therapy: T-cell surface antigens (CD5, CD7, CD3) are shared between the malignant blasts and the healthy T cells used to manufacture CAR-T products β a problem called fratricide, where CAR-T cells kill each other during manufacturing.
Building on the group's landmark work with donor-derived CD7 CAR-T cells (Pan et al., JCO 2021), investigators at Beijing Boren Hospital led by Dr. Jing Pan initiated NCT05032599 β a Phase 1 first-in-human trial of donor-derived, CD5-gene-edited CAR-T cells targeting CD5 in patients with r/r T-ALL. The critical insight motivating CD5 as the next target was that a substantial proportion of T-ALL patients who initially responded to CD7-directed CAR-T therapy relapsed with CD7 antigen-negative disease β escaping the CD7-targeted therapy while retaining CD5 expression. CD5 is expressed on leukemic blasts in over 80% of T-ALL cases and is not expressed on haematopoietic stem cells, making it an attractive target with reduced off-tumour risk. To prevent fratricide, the donors' T cells had their CD5 gene deleted using CRISPR/Cas9 technology before CAR engineering β rendering the CAR-T cells resistant to self-destruction while preserving their cytotoxic function against CD5-positive tumour cells.
The trial enrolled 19 patients between September 2021 and the primary completion date of September 2023, meeting its planned minimum enrollment of at least 18 patients. Of 19 enrolled, 16 received JCXH-213 infusions β the remainder did not proceed for reasons including disease progression before treatment or inability to complete manufacturing. The registry was subsequently terminated due to departmental restructuring as Beijing Boren Hospital was integrated into Beijing GoBroad Boren Hospital within the GoBroad Healthcare Group β a logistical and organisational closure, not a signal of harm or failure.
Full results were published in Nature Medicine on October 1, 2024, with the corrected version appearing in the January 2025 print edition (Pan J et al. Nat Med. 2025;31(1):126β136. doi: 10.1038/s41591-024-03282-2). This represents the first published Phase 1 clinical data on donor-derived CD5-targeted CAR-T therapy for r/r T-ALL.
All 16 patients who received CD5 CAR-T infusions achieved complete remission or complete remission with incomplete blood count recovery by day 30. This 100% ORR in a heavily pre-treated r/r T-ALL population β most of whom had failed prior CD7 CAR-T therapy β is among the most striking efficacy signals reported in T-ALL cell therapy to date.
Trial at a Glance
Key registry details for NCT05032599. The trial is terminated but its science is published. Details are provided as scientific reference with published outcomes.
NCT05032599 is terminated. Full trial results are published: Pan et al., Nat Med 2025;31(1):126β136.
Treatment Being Studied
The central challenge in designing CAR-T therapy for T-cell malignancies is fratricide β when CAR-T cells attack each other during manufacturing and after infusion, because the target antigen (CD5 or CD7) is expressed on both the malignant T cells and the healthy donor T cells being engineered into CAR-T cells. Without solving fratricide, it is impossible to manufacture sufficient numbers of functional CAR-T cells.
The Beijing Boren team addressed fratricide for CD5 targeting using CRISPR/Cas9 gene editing β deleting the CD5 gene from donor T cells before engineering them with the anti-CD5 CAR. CD5-knockout CAR-T cells cannot be killed by each other during manufacturing because they no longer express the CD5 protein that the CAR recognises. They can be expanded to therapeutic numbers and remain fully cytotoxic against CD5-positive T-ALL cells after infusion.
How the therapy works (in simple terms)
How it is given
In T-ALL, manufacturing autologous CAR-T cells from the patient's own blood is extremely difficult: the patient's T cells are often contaminated with malignant blasts, depleted by prior chemotherapy, or functionally exhausted. Using cells from a previous stem cell transplant donor (Cohort A) or a newly HLA-matched donor (Cohort B) allows reliable manufacturing from healthy T cells β while also providing a graft-versus-leukemia effect that may contribute to durable remission.
Who This Trial May Be For
These eligibility criteria defined the patient population for NCT05032599. They are provided for scientific reference only β this trial is terminated.
Patients must have had CD5-positive (by flow cytometry or IHC) relapsed or refractory T-ALL who had progressed on all standard therapies or were intolerant of standard care, with no available curative treatment options (no viable SCT or chemotherapy path).
The trial accepted both paediatric (from age 1) and adult patients (up to 70) β reflecting the population affected by T-ALL across life stages. Consent procedures were appropriately stratified by age (child assent with guardian consent for ages 1β18).
ECOG 0β2; no significant cardiovascular, respiratory, hepatic, or renal dysfunction; no uncontrolled infections, diabetes, or severe mental disorders; life expectancy β₯ 60 days.
CD5 expression was rigorously defined: (1) Positive: >80% of tumour cells express CD5 at normal T-cell MFI; (2) Dim: >80% express CD5 at reduced MFI (at least 1 log below normal); (3) Partial positive: 20β80% of tumour cells express CD5. By IHC in tissue: β₯30% of tumour cells CD5-positive. Patients needed to meet at least one of these criteria.
Patients must have had a suitable and available allogeneic HSCT donor for PBMC collection (the source of CAR-T cells), and must have been willing to proceed to stem cell transplantation if complete remission was achieved. This is the unique dual-purpose donor requirement: the same donor provides both the CAR-T cells and the subsequent graft.
Eligibility Criteria
Taken directly from the ClinicalTrials.gov registry for NCT05032599. For scientific reference only β this trial is terminated.
check_circleInclusion Criteria β May Be Eligible
- βRelapsed or refractory CD5+ T-cell ALL, having progressed after all standard therapies or intolerant of standard care, with limited prognosis and no available curative treatment options (SCT or chemotherapy)
- βAge 1 to 70 years
- βNo serious allergic constitution
- βECOG performance status 0β2
- βLife expectancy of at least 60 days per investigator assessment
- βCD5-positive confirmed by flow cytometry (positive, dim, or partial positive as defined) OR IHC showing β₯30% tumour cells CD5-positive
- βSigned informed consent (age-stratified consent procedures for children aged 1β18)
- βAvailable suitable allogeneic HSCT donor for PBMC collection
- βWillingness to proceed to SCT if complete remission achieved
cancelExclusion Criteria β May Not Be Eligible
- ΓIntracranial hypertension or disorder of consciousness
- ΓSymptomatic heart failure or severe arrhythmia
- ΓSymptoms of severe respiratory failure
- ΓCo-existent other malignant tumours
- ΓDiffuse intravascular coagulation (DIC)
- ΓSerum creatinine and/or blood urea nitrogen β₯ 1.5Γ upper limit of normal
- ΓSepticaemia or other uncontrollable infections
- ΓUncontrollable diabetes
- ΓSevere mental disorders
- ΓActive intracranial lesions on cranial MRI
- ΓPrior organ transplantation (excluding bone marrow transplant)
- ΓReproductive-age female with positive serum HCG
- ΓPositive hepatitis B, hepatitis C, HIV, or syphilis serology
- ΓPost-CAR SCT not feasible for patients planning to receive new-donor derived CD5 CAR-T cells
- ΓNo applicable donor for PBMC collection and no frozen donor PBMC available for manufacturing
NCT05032599 is terminated. These criteria are documented for scientific and educational reference. For currently active T-ALL CAR-T trials, contact CancerFax.
Trial Location and Hospital Information
NCT05032599 was conducted at Beijing Boren Hospital, Fengtai District, Beijing (zip: 100070) β the predecessor institution to Beijing GoBroad Boren Hospital, now operating as part of GoBroad Healthcare Group. The State Key Laboratory of Experimental Hematology and the Boren Clinical Translational Center at this site are among China's most prolific CAR-T research and clinical units, publishing landmark trials in CAR-T for T-ALL in multiple high-impact journals including JCO and Nature Medicine.
How CancerFax Can Help Patients With Relapsed / Refractory T-ALL
CancerFax is a global cancer navigation platform. For patients with r/r T-ALL β a disease with very few options β we provide expert-led navigation toward the most promising available cell therapy approaches.
Our medical team reviews bone marrow pathology, flow cytometry (CD5 and CD7 expression), prior treatment history (including any prior CAR-T), and performance status to map your case to the most appropriate currently active T-ALL CAR-T trial or treatment access pathway.
Based on the published results of NCT05032599, new CD5 CAR-T trials are actively recruiting. CancerFax can identify which trials accept patients with your specific CD5 expression status, prior treatment history, and donor availability β and coordinate your application to those programmes.
Beijing GoBroad Boren Hospital continues to operate CD7 CAR-T programmes for T-ALL. For patients whose disease is CD7-positive and who have not yet received CD7-directed therapy, CancerFax can explore access to currently active CD7 CAR-T programmes at GoBroad and affiliated centres.
The key lesson from NCT05032599 is that consolidative allogeneic SCT after CAR-T-induced remission dramatically improves late outcomes. CancerFax can help patients and families understand this recommendation, identify suitable donor evaluation pathways, and connect with HSCT programmes capable of supporting the post-CAR-T transplant sequence.
Beijing GoBroad Boren Hospital accepts international patients for CAR-T therapy for haematological malignancies with dedicated English-speaking coordinator support. CancerFax provides medical visa guidance, accommodation near the Fengtai District campus, interpreter services, and full logistics support for families travelling from outside China.
If CAR-T is not appropriate (no donor, CD5/CD7-negative disease, performance status concerns), CancerFax can identify alternative r/r T-ALL options including blinatumomab programmes, nelarabine-based salvage, and other investigational trials in China and internationally.
CancerFax does not guarantee access to any treatment or clinical trial. Our role is to navigate, not enroll.
Frequently Asked Questions
Looking for CD5 or CD7 CAR-T Options for T-ALL?
NCT05032599 is closed β but its 100% complete remission results have directly informed new CD5 CAR-T trials and treatment programmes now active at Beijing GoBroad Boren Hospital and internationally. Submit your case for review and CancerFax will identify what is currently appropriate for your situation.
The information on this page is for educational and patient-navigation purposes only. It does not replace medical advice, diagnosis, or treatment from a qualified physician. Clinical trial eligibility, enrollment, treatment decisions, and costs are determined only by the trial investigators, hospital, sponsor, and applicable regulations. CancerFax helps patients and families understand options and coordinate case review where appropriate, but does not guarantee trial acceptance, treatment response, or clinical outcome. All clinical decisions must be made in consultation with a qualified, licensed physician with access to the patient's complete medical information.
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