Nanobody-Based CD19/CD22 Tandem Dual CAR-T Therapy for R/R B-ALL

Launched by PEKING UNIVERSITY PEOPLE'S HOSPITAL · Mar 16, 2025

Keywords

ClinConnect Summary

This clinical trial is testing a new treatment called Nanobody-Based CD19/CD22 Tandem Dual CAR-T therapy for patients with a type of blood cancer known as precursor B-cell lymphoblastic leukemia-lymphoma (B-ALL), which has come back after treatment or did not respond to previous therapies. The goal is to see how effective and safe this new therapy is for these patients. The trial is currently recruiting participants who are between the ages of 3 and 65, and who understand the study and voluntarily agree to take part.

To be eligible for this trial, participants need to have a specific type of leukemia that shows certain characteristics in their blood or bone marrow. They should also be in good overall health and have no serious infections or other conditions that could complicate their treatment. If selected, participants can expect to receive the CAR-T therapy and will be monitored closely for any side effects or changes in their condition. This trial offers a potential new option for patients with limited treatment choices, but it is important to discuss any questions or concerns with a healthcare provider before participating.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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:
• 1. 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
• • 2. 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:
• 1. Liver function:
• • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5× upper limit of normal (ULN) Total bilirubin ≤2× ULN
• 2. 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 Criteria:
• Subjects who meet any of the following criteria will be excluded from the study:
• 1. History of central nervous system (CNS) diseases, including but not limited to:
• • Epilepsy
• • Paralysis
• • Aphasia
• • Stroke
• • Severe brain injury
• • Dementia
• • Parkinson's disease
• • Neuropathy
• 2. 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
• • 3. 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.
• 4. 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).
• 5. Clinically significant cardiovascular diseases, including any of the following:
• • 1. QTc interval ≥480 ms (Fridericia correction formula)
• • 2. New York Heart Association (NYHA) Class II or higher heart failure
• • 3. Unstable angina or acute myocardial infarction within 6 months prior to signing the ICF
• • 4. Left ventricular ejection fraction (LVEF) \<50%
• • 5. Poorly controlled hypertension (as determined by the investigator)
• 6. Clinically significant arrhythmias or those requiring antiarrhythmic treatment, including:
• • Persistent ventricular tachycardia
• • Ventricular fibrillation
• • Torsades de pointes
• • Complete left bundle branch block
• • 6. History of severe hypersensitivity or allergy to any components of the study drug.
• • 7. 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).
• • 8. 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.
• • 9. 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).
• 10. 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:
• • 1. Intranasal, inhaled, or topical steroids, or localized steroid injections (e.g., intra-articular injections)
• • 2. Systemic corticosteroids ≤10 mg/day prednisone (or equivalent physiological dose)
• • 3. Steroids as prophylaxis for allergic reactions (e.g., pre-medication before contrast-enhanced CT)
• • 4. Steroids used for symptomatic treatment of transfusion-related reactions
• • 11. Major surgery within 4 weeks prior to signing the ICF (excluding routine biopsy procedures) or planned major surgery during the study period.
• • 12. 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.
• 13. History of other primary malignancies within 5 years prior to signing the ICF, except for:
• • 1. Adequately treated carcinoma in situ of the cervix
• • 2. Localized basal cell carcinoma or squamous cell carcinoma of the skin
• • 14. Receipt of live-attenuated or inactivated vaccines within 4 weeks before signing the ICF or planned vaccination during the screening period.
• • 15. 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.
• • 16. Pregnancy or lactation.