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Traditional salvage chemotherapy has low efficacy and poor long-term prognosis for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Targeted CD19 CAR-T cell immunotherapy is an effective means of treating R/R B-ALL. Several clinical studies have shown that its remission rate for R/R B-ALL can reach 68-93%. However, long-term follow-up found that the remission time after CD19 CAR-T treatment is short and the relapse rate is high. Therefore, how to ensure the long-term survival of R/R B-ALL patients after remission by CAR-T therapy is an urgent problem to be solved. Some studies have shown that timely bridging allo-HSCT after CAR-T treatment can overcome the risk of relapse and further improve the long-term survival of patients. However, there is currently no randomized controlled study on whether to bridge transplantation after CAR-T. The purpose of this study is to evaluate the efficacy and safety of S1904 in the treatment of relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia with or without bridging to allogeneic hematopoietic stem cell transplantation after remission.
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Inclusion criteria
The subject or guardian understands and voluntarily signs the Informed Consent Form (ICF);
Male or female, aged 12-65 years (including the cutoff value) when signing the informed consent form;
Expected survival period is not less than 12 weeks;
ECOG physical performance score is 0-1 when signing the ICF;
The subject must be diagnosed with relapsed/refractory B-cell acute lymphoblastic leukemia when signing the ICF, and at least one of the following must be met:
For patients with Philadelphia chromosome-positive ALL (Ph+ ALL), in addition to meeting the above relapse or refractory criteria, they should have failed at least two tyrosine kinase inhibitor (TKI) treatments (except for those with T315I mutations), or be unable to tolerate TKI treatment, or have contraindications to TKI treatment;
Bone marrow morphology examination at screening showed that the proportion of primitive immature lymphocytes in the bone marrow was >5%;
Tumor cells in the bone marrow or peripheral blood were CD19 positive by flow cytometry at screening;
Major organ functions must meet the following requirements:
Blood oxygen saturation>92%;
Males and females of childbearing age with fertility must agree to use effective contraceptive measures from the signing of the informed consent form until 2 years after the use of the study drug. Females of childbearing age include premenopausal women and women within 2 years after menopause. The blood pregnancy test of females of childbearing age must be negative at the time of screening.
Exclusion criteria
Isolated extramedullary relapse;
Burkitt's lymphoma/leukemia;
Previous history of CNS disease, including but not limited to epilepsy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, neuropathy (except inactive CNS leukemia);
Previous hematopoietic stem cell transplantation;
History of autoimmune disease requiring systemic immunosuppressive drug treatment within 2 years before signing the ICF (including but not limited to Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, inflammatory bowel disease, vasculitis, psoriasis);
Any uncontrolled active infection at the time of signing the ICF or within 4 weeks before apheresis, requiring antibiotic, antiviral or antifungal treatment;
Previous cell therapy targeting CD19 (autologous or allogeneic);
Received CAR-T therapy or other cell/gene therapy before screening;
Those who tested positive for hepatitis B surface antigen (HBsAg) during screening need to be excluded; if HBsAg is negative but hepatitis B core antibody (HBcAb) is positive, those with peripheral blood hepatitis B virus (HBV) DNA above the detection limit need to be excluded; those who tested positive for hepatitis C virus (HCV) antibody and HCV RNA need to be excluded; those who tested positive for human immunodeficiency virus (HIV) antibody; those who tested positive for cytomegalovirus (CMV) DNA; those who tested positive for human lymphotropic herpes virus (EBV) DNA; those who tested positive for both Treponema pallidum-specific and non-specific antibodies;
Clinically significant cardiovascular disease, including any of the following:
Allergic to any drug component to be used in this study, including but not limited to S1904, clearing drugs (cyclophosphamide, fludarabine), etc.;
Received any study drug treatment or other systemic anti-tumor treatment within 4 weeks before apheresis (or 5 half-lives of the drug, whichever is more appropriate as determined by the researcher);
Received extensive radiotherapy within 4 weeks before signing the ICF, except for local radiotherapy of non-target lesions for symptom relief within 2 weeks before signing the ICF or expected during the study period;
At the time of signing the ICF, except for alopecia and pigmentation, the toxicity caused by previous anti-tumor treatment has not recovered to grade 1 or baseline level (according to NCI-CTCAE version 5.0);
Patients who need to receive systemic corticosteroids (dose equivalent to or higher than 10 mg/day of prednisone) or other immunosuppressive drugs within 2 weeks before signing the ICF or within 2 weeks before apheresis or during the study, except for the following:
Subjects who have undergone major surgery (except routine biopsy) within 4 weeks before signing the ICF, or are expected to undergo major surgery during the study;
Subjects with a history of active tuberculosis infection within 1 year before signing the ICF (except for subjects with a history of active tuberculosis infection more than 1 year ago who are judged by the investigator to have no evidence of active tuberculosis);
Subjects with clinically significant thyroid dysfunction as judged by the investigator;
Subjects with or with a history of interstitial lung disease or interstitial pneumonia;
Subjects with a history of other primary malignant tumors within 5 years before signing the ICF, except for the following:
Subjects who have received attenuated/inactivated vaccines within 4 weeks before signing the ICF, or subjects who are planned to receive attenuated/inactivated vaccines during the screening period;
The researcher believes that the subject's complications or other conditions may affect compliance with the protocol or may be unsuitable for participation in this study;
Pregnancy or lactation.
Primary purpose
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Interventional model
Masking
130 participants in 2 patient groups
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Central trial contact
Yu Wang, MD
Data sourced from clinicaltrials.gov
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