U69-CART-Cells For R/R T-ALL

A Phase I, Single-Arm, Open-Label Clinical Study to Evaluate the Safety and Efficacy of U69 in Patients With Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL)

Overall Introduction This single-arm, open-label clinical trial aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of CXCR4-enabled CCR9 chimeric antigen receptor T-cell injection (CXCR4 CCR9 CAR-T) in patients with relapsed or refractory T-lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL). Additionally, the study seeks to preliminarily assess the efficacy of CXCR4 CCR9 CAR-T cells and explore the appropriate dosage and administration schedule for subsequent Phase II clinical trials. A dose escalation study following the 3+3 design was implemented across three dose cohorts, with each cohort planned to enroll 3 to 6 patients, totaling 9 to 18 participants. Following cell infusion, subjects underwent safety and efficacy follow-up, which continued until 2 years post-infusion, subject withdrawal, or study termination-whichever occurred first. For subjects with available follow-up information after study completion or early termination, long-term follow-up-including long-term safety monitoring-was conducted for up to 15 years.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory T-lymphoblastic Leukemia/Lymphoma
• Intervention / Treatment: Drug: CXCR4 CCR9 CAR-T

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sheng-Li Xue, M.D.; Phone Number: 008651267781139; Email: slxue@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Sheng-Li Xue, M.D.; Phone Number: +8651267781139; Email: slxue@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects must meet all of the following criteria to be eligible for the study:

  1. Informed Consent: Voluntary provision of written informed consent and anticipated ability to complete all required study procedures and follow-up assessments.
  2. Age: ≥15 and ≤75 years of age at the time of signing the informed consent form.For minors (age ≤ 18 years), informed consent must be provided by a legal guardian; minors with capacity to sign should co-sign the consent form alongside their guardian.

  3. Diagnosis and Disease Status: Histologically or cytologically confirmed diagnosis of relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) according to the 2022 WHO Classification of Haematolymphoid Tumours, for which standard curative treatments are no longer effective.

     3.1 For T-ALL: Presence of ≥5% blasts in bone marrow or peripheral blood at screening. Relapse: Defined as recurrence of blasts (≥5%) in peripheral blood or bone marrow or emergence of extramedullary disease after prior achievement of complete remission (CR/CRi). This includes early relapse (within 12 months of first remission), late relapse (≥12 months) failing to achieve remission after one multi-agent re-induction chemotherapy cycle, or relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT).

     Refractory: Defined as failure to achieve CR after at least two cycles of induction chemotherapy, or failure to achieve CR after one cycle of salvage therapy following relapse.

     3.2 For T-LBL: Presence of at least one measurable lesion at screening, defined as a nodal lesion with a long axis >15 mm or an extranodal lesion with a long axis >10 mm, as assessed by CT or MRI per the 2014 Lugano criteria.

     Relapsed/Refractory: Defined as relapse or disease progression after at least two prior lines of therapy; primary refractory disease (failure to achieve at least a partial response, PR, after first-line therapy); or relapse/progression after autologous or allogeneic HSCT (must be confirmed by tissue biopsy).

  4. Biomarker: Confirmed CCR9 positivity on tumor cells via flow cytometry of bone marrow samples and/or via immunohistochemistry of extramedullary lesion biopsies at screening.
  5. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  6. Life Expectancy: Estimated life expectancy of greater than 3 months.

  7. Bone Marrow Reserve: Adequate bone marrow reserve at screening, defined as:

     Absolute Neutrophil Count (ANC) ≥ 1.0 × 10⁹/L Absolute Lymphocyte Count (ALC) ≥ 0.3 × 10⁹/L Platelet Count (PLT) ≥ 20 × 10⁹/L (transfusion support is permitted).

  8. Organ Function: Adequate organ function defined as:

     Hepatic: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3 × Upper Limit of Normal (ULN); Total Bilirubin ≤ 2 × ULN.

     Renal: Serum Creatinine ≤ 1.5 × ULN, OR Creatinine Clearance ≥ 50 mL/min (calculated by the Cockcroft-Gault formula).

     Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 45%. Pulmonary: Oxygen saturation ≥ 92% on room air.

  9. Contraception: Female subjects of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective contraception for at least one year post-infusion. Male subjects with female partners of childbearing potential must agree to use barrier contraception and refrain from sperm donation for at least one year post-infusion.
  10. Leukapheresis: Must have adequate venous access for leukapheresis or venous blood draw and no other contraindications to leukapheresis.

Exclusion Criteria:

• Subjects will be excluded from the study if they meet any of the following criteria:

  1. Diagnosis of any other malignancy within 3 years prior to screening, except for those who have completed curative therapy and achieved over 3 years of disease-free survival with a low risk of recurrence as determined by the investigator (e.g., carcinoma in situ of the lung, basal cell carcinoma of the skin).
  2. History or presence of central nervous system (CNS) disorders unrelated to the disease under study at screening or previously, such as seizure, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the CNS.
  3. Prior receipt of cell therapies targeting CCR9, including but not limited to CAR-T or CAR-γδT cells.
  4. Significant or active parenchymal CNS or cranial nerve lesions where, in the investigator's judgment, the risks outweigh the benefits.
  5. Systemic corticosteroid use discontinued ≤72 hours prior to apheresis, except for physiological replacement doses (e.g., prednisone <10 mg/day or equivalent).
  6. Donor lymphocyte infusion (DLI) within 6 weeks prior to apheresis.
  7. Treatment with any anti-T-cell antibody therapy within 4 weeks prior to apheresis.
  8. Presence of any of the following: positive hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) with HBV-DNA above the lower limit of quantification; positive hepatitis C antibody (HCV-Ab) with HCV-RNA above the lower limit of quantification; positive treponema pallidum antibody (TP-Ab); positive human immunodeficiency virus (HIV) antibody test; or EBV-DNA or CMV-DNA levels above the lower limit of quantification by quantitative PCR.
  9. Active or uncontrolled infection requiring systemic therapy at the time of screening (excluding mild genitourinary or upper respiratory tract infections), as assessed by the investigator.
  10. Coronary angioplasty or stent placement within 12 months prior to informed consent; congestive heart failure of New York Heart Association (NYHA) Class III-IV; myocardial infarction, unstable angina, or other clinically significant cardiac conditions within 6 months deemed ineligible by the investigator; QTc interval >480 ms (calculated using Fridericia's formula) at screening; or uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg) or pulmonary hypertension despite standard treatment.
  11. Unstable systemic diseases per investigator judgment, including but not limited to severe hepatic, renal, or metabolic diseases requiring pharmacological intervention.
  12. Active or uncontrolled autoimmune disease, or primary/secondary immunodeficiency.
  13. History of severe immediate hypersensitivity to any drug used in the study.
  14. Administration of any live vaccine within 6 weeks prior to screening.
  15. Pregnant or lactating individuals.
  16. History of autoimmune disease requiring systemic immunosuppressive or disease-modifying medication within the past 2 years (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).
  17. Allogeneic hematopoietic stem cell transplantation within 12 weeks prior to apheresis; presence of acute or moderate-to-severe chronic GVHD within 4 weeks prior to screening; or any systemic GVHD treatment within 4 weeks prior to cell infusion, including those requiring concomitant corticosteroid use.
  18. Participation in any other interventional clinical trial within 4 weeks prior to screening.
  19. Inability to comply with study procedures, or any other condition considered by the investigator to render the subject unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose group; The investigational product is the CXCR4-enhanced CCR9 Chimeric Antigen Receptor T-Cell Injection (CXCR4/CCR9 CAR-T, U69). The planned doses per cohort are: Low Dose Cohort: 1 × 10⁶ CAR-positive T cells per kg of body weight. The product is administered as a single intravenous infusion. The actual administered dose is acceptable within a range of 70% to 130% of the target dose. The required cell number will be calculated based on the subject's body weight at the time of apheresis. The Investigator may adjust the final cell dose based on the subject's specific clinical condition.	Drug: CXCR4 CCR9 CAR-T; CXCR4-enabled CCR9 chimeric antigen receptor T-cell injection solution
Experimental: Medium dose group; The investigational product is the CXCR4-enhanced CCR9 Chimeric Antigen Receptor T-Cell Injection (CXCR4/CCR9 CAR-T, U69). The planned doses per cohort are: Medium Dose Cohort: 3 × 10⁶ CAR-positive T cells per kg of body weight. The product is administered as a single intravenous infusion. The actual administered dose is acceptable within a range of 70% to 130% of the target dose. The required cell number will be calculated based on the subject's body weight at the time of apheresis. The Investigator may adjust the final cell dose based on the subject's specific clinical condition.	Drug: CXCR4 CCR9 CAR-T; CXCR4-enabled CCR9 chimeric antigen receptor T-cell injection solution
Experimental: High dose group; The investigational product is the CXCR4-enhanced CCR9 Chimeric Antigen Receptor T-Cell Injection (CXCR4/CCR9 CAR-T, U69). The planned doses per cohort are: High Dose Cohort: 6 × 10⁶ CAR-positive T cells per kg of body weight. The product is administered as a single intravenous infusion. The actual administered dose is acceptable within a range of 70% to 130% of the target dose. The required cell number will be calculated based on the subject's body weight at the time of apheresis. The Investigator may adjust the final cell dose based on the subject's specific clinical condition.	Drug: CXCR4 CCR9 CAR-T; CXCR4-enabled CCR9 chimeric antigen receptor T-cell injection solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	DLT refers to any of the following conditions occurring within 28 days after cell reinfusion that are related to cell infusion: ① Hematologic DLT: Grade 4 toxicity (excluding lymphopenia) not caused by the underlying disease and taking more than 30 days to resolve to ≤ Grade 2. ② Non-hematologic DLT: Any toxicity ≥ Grade 4 that is possibly related to CAR-T therapy, or Grade 3 toxicity that requires ≥7 days to resolve to ≤ Grade 2 or to return to baseline.	Within 28 days after CXCR4 CCR9 CAR-T cell infusion
Adverse Event (AE）	Record the types, occurrence frequency and severity of adverse events (AEs) related to CAR-T, with specific definitions determined according to CTCAE v5.0.The CRS and ICANS ratings do not use CTCAE but adopt the evaluation criteria in the ASTCT standards.	2 years
The Recommended Phase II Dose（RP2D）	The dose recommended for use in phase 2 studies on the basis of dose limiting toxicities observed in phase 1 studies.	Within 28 days after CXCR4 CCR9 CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Defined as the proportion of subjects achieving an objective response (complete or partial response). All subjects not meeting the objective response criteria as of the data cutoff date will be considered non-responders. ①For T-ALL patients: Treatment response is defined as the achievement of either Complete Remission (CR) or Complete Remission with Incomplete Hematologic Recovery (CRi); ②For T-LBL patients: Treatment response is defined as the achievement of either Complete Response (CR) or Partial Response (PR);	28 days and within 3 months after infusion of CXCR4 CCR9 CAR-T cells
MRD-negative rate (for T-ALL)	The proportion of T-ALL patients with negative MRD in the bone marrow when the therapeutic effect reaches remission. T-ALL patients have residual leukemia cells in the bone marrow detected by flow cytometry below 10-⁴ and/or negative qualitative or quantitative detection of bone marrow fusion genes (if any).	28 days and within 3 months after infusion of CXCR4 CCR9 CAR-T cells
Duration of Response (DOR)	It refers to the period from the time when the subject first achieves remission to the time of disease progression or death due to the disease. Subjects who have not experienced disease progression or death by the time of the final data collection will be censored at the time of their last valid tumor assessment. Common reasons for censoring include, but are not limited to: Loss to follow-up; ②Withdrawal from the study; ③Initiation of a new anticancer therapy.	2 years
Progression-Free Survival (PFS)	Defined as the time from the date of cell infusion to the date of first documented disease progression or death from any cause, whichever occurs first. Subjects who have not experienced disease progression or death by the data cutoff date will be censored at the time of their last tumor assessment.	2 years
Event-Free Survival (EFS)	Defined as the time from the date of cell infusion to the occurrence of any of the following events (whichever comes first): Death from any cause after achieving remission ②Disease relapse or progression ③Treatment failure, defined as either lack of efficacy or discontinuation of the clinical trial due to:DeathAdverse eventsLack of efficacy or disease progressionInitiation of new antitumor therapy	2 years
Overall Survival (OS)	Defined as the time from the date of cell infusion to the date of death from any cause. For subjects who are still alive at the time of analysis, OS will be censored on the date of last known contact. It is specifically noted that subsequent allogeneic hematopoietic stem cell transplantation or receipt of any new antitumor therapy will not constitute a censoring event for OS analysis.	2 years
Pharmacokinetics-AUC(0-28)	The area under the curve from 0 to 28 days for the reinfusion.	2 years
Pharmacokinetics-Cmax	The peak concentration of the drug in the peripheral blood sample.	2 years
Pharmacokinetics-Tmax	The time at which the peak concentration of the drug is reached in the peripheral blood sample.	2 years
IL-6	Changes in the levels of IL-6.	Within 28 days after CXCR4 CCR9 CAR-T cell infusion
IFNγ	Changes in the levels of IFNγ.	Within 28 days after CXCR4 CCR9 CAR-T cell infusion
Ferritin	Changes in the levels of Ferritin.	Within 28 days after CXCR4 CCR9 CAR-T cell infusion
C-reactive protein(CRP)	Changes in the levels of CRP.	Within 28 days after CXCR4 CCR9 CAR-T cell infusion

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Publications and helpful links

General Publications

• Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
• Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
• Li YR, Zhu Y, Chen Y, Yang L. The clinical landscape of CAR-engineered unconventional T cells. Trends Cancer. 2025 Jun;11(6):520-539. doi: 10.1016/j.trecan.2025.03.001. Epub 2025 Mar 27.

Study record dates

Study Major Dates

• Study Start (Estimated): June 25, 2026
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): July 15, 2028

Study Registration Dates

• First Submitted: December 23, 2025
• First Submitted That Met QC Criteria: January 12, 2026
• First Posted (Actual): January 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Recurrence
• Other Study ID Numbers: SZRTALL02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Baseline characteristics of patients, outcomes
• IPD Sharing Time Frame: one year after the study termination
• IPD Sharing Access Criteria: Clinical researchers worldwide can access the IPD and supporting information after author authorization. They can get IPD details by visiting the ResMan system.
• IPD Sharing Supporting Information Type: SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No