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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
Full 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 lymphoblastic leukemia (B-ALL), particularly those who have failed or relapsed after CD19- or CD22-targeted CAR-T or antibody-based immunotherapy.
In the Phase I portion of the study, a 3+3 dose-escalation design will be employed to evaluate safety and determine the optimal dose of Nanobody-Based CD5 CAR-T cells. Three dose levels will be tested: 0.3 × 10⁶ cells/kg, 1.0 × 10⁶ cells/kg, and 2.0 × 10⁶ cells/kg. The recommended Phase II dose (RP2D) will be established based on safety data, dose-limiting toxicities (DLTs), and preliminary efficacy outcomes.
The Phase II portion will then focus on evaluating the efficacy of Nanobody-Based CD19/CD22 Tandem Dual CAR-T therapy at the RP2D, with key endpoints including overall response rate (ORR), duration of response (DOR), disease-free survival (DFS), and overall survival (OS). Safety assessments, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), will also be conducted throughout the study.
This study seeks to address the unmet clinical need for effective treatment options in patients with R/R B-ALL, particularly those who have exhausted prior CD19- or CD22-directed therapies.
Enrollment
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Volunteers
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:
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 criteria
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:
History of autoimmune diseases requiring systemic immunosuppressive therapy within 2 years prior to signing the ICF, including but not limited to:
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:
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:
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:
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:
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.
Primary purpose
Allocation
Interventional model
Masking
30 participants in 1 patient group
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Central trial contact
MENG LV, MD, PhD
Data sourced from clinicaltrials.gov
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