A Multicenter, Open-Label, Non-Randomized, Single-Arm Clinical Study of Nanobody CD5-CAR T Cell Therapy for Refractory/Relapsed T Lymphocyte Malignancies

NCT07070323 | Recruiting Phase 1 DMC

• 1 other identifier: BJGBYY-IIT-LCYJ-2025-049
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multi-center, open-label, non-randomized, phase 1/2 study of anti-CD5 CAR-T cell therapy in patients with CD5+ relapsed or refractory T-cell malignancies. A bayesian optimal interval (BOIN) 12 design will be used to explore the optimal biological dose (OBD) from starting dose level 1: 1×10\^6 (±20%) to dose level 2: 2×10\^6 (±20%) in three cohorts (autologous, previous-transplant-donor or newly matched donor-derived CD5 CAR T cells). If the manufactured cells are not sufficient to meet the preassigned standard dose criteria, patients will be given infusion at a low dose level of 5×10\^5 (±20%) /kg. The primary objective is to evaluate the safety and tolerability of CD5 CAR T cell therapy in subjects, determine the OBD and recommend phase 2 dose (RP2D) in phase 1, and evaluate the efficacy of CD5 CAR T cell therapy in phase 2. The primary endpoint is the type and incidence of dose-limiting toxicity (DLT) within 28 days, and the incidence and severity of adverse events (AEs) within 30 days after CD5 CAR T-cell infusion in phase 1, the best overall response (BOR) at 3 months (± 1 week) after CD5 CAR T-cell infusion in phase 2. A total number of 54 subjects will be enrolled.

Conditions

T-Cell Acute Lymphocytic Leukemia; Acute Lymphoblastic Leukemia, in Relapse; Refractory Acute Lymphoblastic Leukemia; T-cell Malignancies

Outcome Measures

Primary Outcomes (3)

• Phase 1-The incidence and type of dose-limiting toxicity (DLT)

  The number of patients experiencing dose-limiting toxicity (DLT) will be evaluated and the type of DLT will be recorded.

  28 days after CD5 CAR T cell infusion

• Phase 1-The incidence and severity of adverse events (AEs)

  The number of patients experiencing adverse events (AEs) and the severity of AEs will be evaluated.

  30 days after CD5 CAR T cell infusion

• Phase 2-Antitumor effect

  Assessment of best overall response (BOR) rate. BOR rate is the percentage of patients with the best overall response in complete response (CR), complete response with incomplete hematological recovery (CRi) or partial response (PR) based on the National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia.

  3 months (± 1 week) after CD5 CAR T infusion

Secondary Outcomes (8)

• Phase 1-Objective response rate (ORR)

  30 days after CD5 CAR T cell infusion

• Phase 1-Pharmacokinetics of CD5 CAR T cells

  Up to 2 years after CD5 CAR T cell infusion

• Phase 1-The incidence and severity of adverse events (AEs).

  From 30 days to 2 years after CD5 CAR T cell infusion

• Phase 1-Best overall response (BOR) rate.

  3 months (± 1 week) after CD5 CAR T cell infusion

• Phase 2-Objective response rate (ORR)

  1 months and 3 months after CD5 CAR T cell infusion

Study Arms (3)

Autologous CD5 CAR T-cells

EXPERIMENTAL

After a lymphodepleting regimen, the patients will receive autologous CD5 CAR T-cell infusion.

Drug: Autologous CD5 CAR T-cells

Prior stem-cell transplantation (SCT) donor-derived CD5 CAR T-cells

EXPERIMENTAL

After a lymphodepleting regimen, the patients will receive prior SCT donor-derived CD5 CAR T-cell infusion.

Drug: Previous stem-cell transplantation (SCT) donor-derived CD5 CAR T-cells

Newly matched donor-derived CD5 CAR T-cells

EXPERIMENTAL

After a lymphodepleting regimen, the patients will receive newly matched donor-derived CD5 CAR T-cell infusion

Drug: Newly matched donor-derived CD5 CAR T-cells

Interventions

Autologous CD5 CAR T-cells DRUG

Peripheral blood mononuclear cells for the production of CD5 CAR T-cells from patients.

Autologous CD5 CAR T-cells

Previous stem-cell transplantation (SCT) donor-derived CD5 CAR T-cells DRUG

Peripheral blood mononuclear cells for the production of CD5 CAR T cells are collected from previous SCT donors.

Prior stem-cell transplantation (SCT) donor-derived CD5 CAR T-cells

Newly matched donor-derived CD5 CAR T-cells DRUG

Peripheral blood mononuclear cells for the production of CD5 CAR T cells are collected from newly matched donors.

Newly matched donor-derived CD5 CAR T-cells

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Only patients who meet all the following criteria can be included:
• \. Candidates with relapse or refractory CD5+ T-cell malignancies, who have progressed after treatment with all standard therapies or been intolerant of standard care, have limited prognosis with currently available therapies and have no available curative treatment options (such as stem-cell transplantation (SCT) or chemotherapy); 2. For subjects who received autologous CD5 CAR T cells, the tumor burden in peripheral blood is less than 20%, and suspending anti-neoplastic treatment for more than 2 weeks; 3. Aged 1-70 years; 4. No severe allergy; 5. Eastern Cooperative Oncology Group (ECOG) performance status 1 score 0 to 2; 6. Patients are expected to live for at least 60 days; 7. CD5+ on blasts in bone marrow (BM) or cerebrospinal fluid (CSF) and tumor tissues by flow cytometry and immunohistochemistry, respectively. (Positive rate \>80% by flow cytometry with less than one log difference in mean fluorescence intensity from normal T cells, or positive rate \>30% positive by immunohistochemistry); 8. Provide a signed informed consent before any screening procedure. Subjects who voluntarily participate in the study should have the ability to understand and sign the informed consent form and be willing to follow the study visit schedule and relevant study procedure, as specified in the protocol. Candidates aged 19-70 years need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form. Children candidates of 8-18 years old need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form and their legal guardian or patient advocate has also need to sign the treatment consent form and voluntary consent form, respectively. Children candidates of 1-7 can be recruited after the legal guardian or patient advocate has signed the treatment consent form and voluntary consent form; 9. Have available allogeneic hematopoietic stem cell transplantation donor for the subject who received newly matched donor-derived CD5 CAR T cells, and is willing to perform SCT when CR is achieved.

You may not qualify if:

• Patients with at least one of the following conditions are excluded:
• \. Impaired consciousness or intracranial hypertension; 2. Symptomatic congestive heart failure or severe cardiac arrhythmia; 3. Manifestations of severe respiratory system failure; 4. Co-existence with other malignancies; 5. Disseminated intravascular coagulation; 6. Serum creatinine and/or blood urea nitrogen (BUN) ≥ 1.5-fold upper limit; 7. Sepsis or other uncontrollable infections; 8. Uncontrollable diabetes; 9. Serious mental illness; 10. Apparent and active intracranial lesions on cranial magnetic resonance imaging (MRI); 11. Underwent organ transplantation, excepting SCT; 12. Pregnant females; 13. Positive test for infectious hepatitis, acquired immune deficiency syndrome (AIDS) or syphilis; 14. Post-CAR SCT is not feasible in patients who plan to receive newly matched donor-derived CD5 CAR T cells; 15. Inability to collect peripheral blood mononuclear cells (PBMC) or no frozen PBMC available for CAR T cell manufacturing.

Sponsors & Collaborators

• Beijing GoBroad Hospital: lead
• The General Hospital of Western Theater Command: collaborator
• Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai: collaborator
• Shanghai Liquan Hospital: collaborator
• Central People's Hospital of Zhanjiang: collaborator
• First Affiliated Hospital of Guangxi Medical University: collaborator

Study Sites (4)

Beijing GoBroad Hospital

Beijing, Beijing Municipality, 102206, China

RECRUITING

Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai

Shanghai, Shanghai Municipality, 200435, China

RECRUITING

Shanghai Liquan Hospital

Shanghai, Shanghai Municipality, 201418, China

RECRUITING

The General Hospital of Western Theater Command PLA

Chengdu, Sichuan, 610083, China

NOT YET RECRUITING

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Shaocong Miao

CONTACT

86+18831006667; miaosc@gobroadhealthcare.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Dept of Hemato-Oncology and Immunotherapy

Study Record Dates

• First Submitted: June 20, 2025
• First Posted: July 17, 2025
• Study Start: July 9, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 26, 2025

Record last verified: 2025-07

Locations

CN (4)