CD5 CAR T-cell therapy for relapsed or refractory T-cell malignancies

CD5 Chimeric Antigen Receptors (CAR) T Cells in Subjects With Relapsed or Refractory T-Cell Malignancies: a Multi-center, Open-label, Non-randomized, Phase 1/2 Clinical Trial

This study is testing a new CAR T-cell therapy for people with hard-to-treat T-cell cancers to see if it is safe and how well it works.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 1 Year to 70 Years
• Sex: All
• Sponsor: Beijing GoBroad Hospital (Academic / other)
• Drugs / interventions: CAR T, chemotherapy, CAR-T
• Locations: 4 sites (Beijing, Beijing Municipality and 3 other locations)
• Trial ID: NCT06316856 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of CD5 Chimeric Antigen Receptor (CAR) T-cell therapy in patients with relapsed or refractory CD5+ T-cell malignancies. It employs a multi-center, open-label, non-randomized design, utilizing a Bayesian optimal interval (BOIN) approach to determine the optimal biological dose of CAR T-cells. Participants will receive either autologous or donor-derived CD5 CAR T-cells, with the primary objective being to assess dose-limiting toxicities and adverse events within the first 28 days of treatment. The study aims to identify the recommended phase 2 dose based on safety and tolerability outcomes.

Who should consider this trial

Good fit: Ideal candidates include patients aged 1-70 with CD5+ T-cell malignancies who have exhausted standard treatment options.

Not a fit: Patients with severe allergies or those who do not meet the eligibility criteria for CD5+ malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with limited prognosis due to relapsed or refractory T-cell malignancies.

How similar studies have performed: Other studies utilizing CAR T-cell therapy have shown promising results, indicating potential success for this novel approach.

Eligibility criteria

Inclusion Criteria:

Only patients who meet all the following criteria can be included:

1. 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.

Exclusion Criteria:

Patients with at least one of the following conditions are excluded:

1. 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.

Where this trial is running

Beijing, Beijing Municipality and 3 other locations

• Beijing GoBroad Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai — Shanghai, Shanghai Municipality, China (Recruiting)
• Shanghai Liquan Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• The General Hospital of Western Theater Command PLA — Chengdu, Sichuan, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Shaocong Miao

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