Status:
RECRUITING
Nanobody-Based CD19/CD22 Tandem Dual CAR-T Therapy for R/R B-ALL
Lead Sponsor:
Peking University People's Hospital
Collaborating Sponsors:
Hebei Senlang Biotechnology Inc., Ltd.
Conditions:
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Eligibility:
All Genders
3-65 years
Phase:
PHASE1
PHASE2
Brief Summary
To evaluate the efficacy and safety of Nanobody-Based CD19/CD22 Tandem Dual Chimeric Antigen Receptor (CAR) T-cell therapy in patients with relapsed or refractory B-ALL
Detailed Description
This Phase I/II study aims to evaluate the safety, tolerability, and efficacy of Nanobody-Based CD19/CD22 Tandem Dual CAR-T-cell therapy in patients with relapsed or refractory (R/R) B-cell acute lymp...
Eligibility Criteria
Inclusion
- The subject or their legally authorized representative (guardian) understands the study and voluntarily signs the informed consent form (ICF).
- Male or female, aged 3 to 65 years at the time of signing the ICF (inclusive of the cutoff values).
- Expected survival of at least 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of signing the ICF.
- At the time of signing the ICF, the patient must be diagnosed with R/R B-ALL and meet the following criteria:
- Bone marrow morphological examination at screening shows \>5% blasts in the bone marrow, and/or cerebrospinal fluid (CSF) analysis detects leukemic cells, and/or the presence of measurable extramedullary lesions, defined as:
- Any lymph node or mass with an axial diameter \>1.5 cm Any extranodal lesion with an axial diameter \>1.0 cm
- Flow cytometry confirms CD19 or CD22 positivity in tumor cells from bone marrow, peripheral blood, or cerebrospinal fluid, or pathology confirms CD19 or CD22 positivity in lymph nodes/masses or extranodal lesions.
- Adequate organ function, meeting the following laboratory criteria:
- Liver function:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5× upper limit of normal (ULN) Total bilirubin ≤2× ULN
- Renal function:
- Adults: Serum creatinine clearance ≥60 mL/min (using the Cockcroft-Gault formula) or creatinine ≤1.5× ULN
- Children: Serum creatinine levels must not exceed the following values:
- 10-13 years: ≤1.2 mg/dL Males 13-16 years: ≤1.5 mg/dL Females ≥13 years: ≤1.4 mg/dL Males ≥16 years: ≤1.7 mg/dL Blood oxygen saturation (SpO₂) \>92% on room air. Fertile male and female subjects of reproductive potential must agree to use effective contraception from the time of informed consent until 2 years after administration of the study drug.
- Women of childbearing potential (WOCBP) include premenopausal women and those within 2 years post-menopause.
- A negative blood pregnancy test is required for all female participants of childbearing potential at screening.
Exclusion
- Subjects who meet any of the following criteria will be excluded from the study:
- 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 :
November 14 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2026
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT06880913
Start Date
November 14 2024
End Date
December 31 2026
Last Update
March 18 2025
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Deparment of Hematology, Peking University People's Hospital
Beijing, Beijing Municipality, China, 100044