Status:
RECRUITING
Nanobody-Based Anti-CD5 CAR-T for Relapsed/Refractory T-ALL/LBL
Lead Sponsor:
Peking University People's Hospital
Collaborating Sponsors:
Hebei Senlang Biotechnology Inc., Ltd.
Conditions:
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Eligibility:
All Genders
3-70 years
Phase:
PHASE1
PHASE2
Brief Summary
To observe the safety and efficacy of Nanobody-Based CD5-targeted chimeric antigen receptor T cells in the treatment of refractory or relapsed T-ALL/LBL.
Detailed Description
This Phase I/II study aims to evaluate the safety, tolerability, and efficacy of Nanobody-Based CD5 Chimeric Antigen Receptor (CAR) T-cell therapy in patients with relapsed or refractory (R/R) T-cell ...
Eligibility Criteria
Inclusion
- The subject or guardian understands and voluntarily signs the informed consent form (ICF).
- Male or female, aged 3-70 years at the time of signing the ICF (inclusive).
- Expected survival of at least 12 weeks.
- ECOG performance status of 0-2 at the time of ICF signing.
- Diagnosis of relapsed/refractory T-cell lymphoblastic leukemia/lymphoma (R/R T-ALL/LBL) confirmed at screening and meeting at least one of the following criteria:
- Bone marrow involvement: Morphologic examination shows ≥5% lymphoblasts, and/or
- Cerebrospinal fluid (CSF) involvement: Tumor cells detected in CSF, and/or
- Extramedullary disease: Presence of measurable lesions (lymph node/mass ≥1.5 cm in axial diameter or extranodal lesion ≥1 cm in axial diameter).
- CD5 expression: Tumor cells in bone marrow, peripheral blood, or CSF are CD5-positive by flow cytometry, and/or lymph node/mass or extranodal lesions are CD5-positive by pathology.
- Adequate major organ function, defined as:
- AST and ALT ≤5× upper limit of normal (ULN).
- Total bilirubin ≤2× ULN.
- Renal function: Serum creatinine clearance ≥60 mL/min (Cockcroft-Gault formula) or creatinine ≤1.5× ULN.
- Blood oxygen saturation \>92%.
- Reproductive health requirements:
- Fertile men and women of childbearing potential must agree to use effective contraception from ICF signing until 2 years after study drug administration.
- Women of childbearing potential (pre-menopausal or within 2 years post-menopause) must have a negative blood pregnancy test at screening.
Exclusion
- History of central nervous system (CNS) diseases, including but not limited to:
- Epilepsy
- Paralysis
- Aphasia
- Stroke
- Severe brain injury
- Dementia
- Parkinson's disease
- Neuropathy
- History of autoimmune diseases requiring systemic immunosuppressive therapy within 2 years prior to signing the ICF, including but not limited to:
- Crohn's disease
- Rheumatoid arthritis
- Systemic lupus erythematosus (SLE)
- Systemic sclerosis
- Inflammatory bowel disease (IBD)
- Vasculitis
- Psoriasis
- Presence of any uncontrolled active infection at the time of signing the ICF or within 4 weeks prior to apheresis that requires antibiotic, antiviral, or antifungal treatment.
- Positive virological or infectious disease markers, including:
- Hepatitis B virus (HBV): Subjects with positive HBsAg or HBcAb-positive at screening must have undetectable HBV DNA in peripheral blood to be eligible; otherwise, they should be excluded.
- Hepatitis C virus (HCV): Subjects with positive HCV antibodies and detectable HCV RNA should be excluded.
- Human immunodeficiency virus (HIV) antibody-positive subjects should be excluded.
- Cytomegalovirus (CMV) DNA test-positive subjects should be excluded.
- Epstein-Barr virus (EBV) DNA test-positive subjects should be excluded.
- Positive serological or non-specific antibodies for Treponema pallidum (syphilis).
- Clinically significant cardiovascular diseases, including any of the following:
- QTc interval ≥480 ms (Fridericia correction formula)
- New York Heart Association (NYHA) Class II or higher heart failure
- Unstable angina or acute myocardial infarction within 6 months prior to signing the ICF
- Left ventricular ejection fraction (LVEF) \<50%
- Poorly controlled hypertension (as determined by the investigator)
- Clinically significant arrhythmias or those requiring antiarrhythmic treatment, including:
- Persistent ventricular tachycardia
- Ventricular fibrillation
- Torsades de pointes
- Complete left bundle branch block
- History of severe hypersensitivity or allergy to any components of the study drug.
- Receipt of any investigational drug therapy or other systemic antitumor therapy within 4 weeks before apheresis (or 5 half-lives of the drug, whichever is longer, as determined by the investigator).
- Receipt of extensive radiotherapy within 4 weeks prior to signing the ICF, except for palliative radiotherapy for non-target lesions within 2 weeks before signing the ICF or as expected during the study.
- Unresolved toxicity from prior antitumor therapy that has not returned to Grade 1 or baseline levels at the time of signing the ICF, except for hair loss and pigmentation (per NCI-CTCAE v5.0).
- Requirement for systemic corticosteroids or other immunosuppressive therapy (≥10 mg/day prednisone or equivalent) within 3 days prior to apheresis or during the study period, except for:
- Intranasal, inhaled, or topical steroids, or localized steroid injections (e.g., intra-articular injections)
- Systemic corticosteroids ≤10 mg/day prednisone (or equivalent physiological dose)
- Steroids as prophylaxis for allergic reactions (e.g., pre-medication before contrast-enhanced CT)
- Steroids used for symptomatic treatment of transfusion-related reactions
- Major surgery within 4 weeks prior to signing the ICF (excluding routine biopsy procedures) or planned major surgery during the study period.
- History of active tuberculosis infection within 1 year prior to signing the ICF, except for subjects with a history of tuberculosis more than 1 year ago, provided that the investigator determines there is no evidence of active tuberculosis.
- History of other primary malignancies within 5 years prior to signing the ICF, except for:
- Adequately treated carcinoma in situ of the cervix
- Localized basal cell carcinoma or squamous cell carcinoma of the skin
- Receipt of live-attenuated or inactivated vaccines within 4 weeks before signing the ICF or planned vaccination during the screening period.
- Any other condition or complication that, in the investigator's judgment, may affect adherence to the study protocol or make the subject unsuitable for participation.
- Pregnancy or lactation.
Key Trial Info
Start Date :
February 14 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2027
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT06874946
Start Date
February 14 2025
End Date
December 31 2027
Last Update
March 13 2025
Active Locations (1)
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1
Peking University People's Hospital
Beijing, Beijing Municipality, China, 100044