Bridging Allogeneic Hematopoietic Stem Cell Transplantation or Not After CD19 CAR - T (S1904) Cell Therapy for r/r B-cell Acute Lymphoblastic Leukemia

NCT06581081 | Recruiting DMC

• 1 other identifier: COMPLETE
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsed Adult ALL; B-cell Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia; Relapsed Pediatric ALL

Outcome Measures

Primary Outcomes (1)

• 2-year event-free survival after randomization

  The time from randomization to MRD positive or relapse or death due to non-relapse causes (whichever occurs first)

  Participants will be followed for an expected average of 2 years

Secondary Outcomes (3)

• 2-year relapse-free survival after randomization

  Participants will be followed for an expected average of 2 years

• Cumulative incidence of relapse

  Participants will be followed for an expected average of 2 years

• 2-year overall survival after randomization

  Participants will be followed for an expected average of 2 years

Study Arms (2)

Bridging to allo-HSCT

EXPERIMENTAL

Subjects enrolled in this study will first receive Senl\_B19 autologous CAR-T (S1904) treatment. If the subject achieves bone marrow leukemia-free state (MLFS) and minimal residual disease (MRD) negative within 12 weeks after S1904 infusion, they will be randomly assigned to the bridging transplant group and the non-bridging transplant group at a ratio of 2:1.

Biological: Senl_B19 autologous CAR-T (S1904) treatment

No bridging to allo-HSCT

OTHER

Subjects enrolled in this study will first receive Senl\_B19 autologous CAR-T (S1904) treatment. If the subject achieves bone marrow leukemia-free state (MLFS) and minimal residual disease (MRD) negative within 12 weeks after S1904 infusion, they will be randomly assigned to the bridging transplant group and the non-bridging transplant group at a ratio of 2:1.

Biological: Senl_B19 autologous CAR-T (S1904) treatment

Interventions

Senl_B19 autologous CAR-T (S1904) treatment BIOLOGICAL

Subjects enrolled in this study will first receive Senl\_B19 autologous CAR-T (S1904) treatment.

Bridging to allo-HSCT; No bridging to allo-HSCT

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Relapse: including relapse within 12 months after the first remission, 2 or more relapses;
• Refractory: including primary refractory, failure to achieve remission after at least 2 courses of induction therapy, or failure to achieve remission after at least 1 course of salvage therapy after the first relapse.
• 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:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×upper limit of normal (ULN);
• Total bilirubin ≤2×ULN;
• Serum creatinine clearance of adult subjects ≥60 mL/min (Cockcroft-Gault formula) or creatinine ≤1.5×upper limit of normal (ULN);
• Serum creatinine for children: no more than 1.2 mg/dL for 10 to 13 years old, no more than 1.5 mg/dL for males aged 13 to 16 years old, no more than 1.4 mg/dL for females aged 13 years and above, and no more than 1.7 mg/dL for males aged 16 years and above.

You may not qualify if:

• 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:
• QTc interval ≥470 ms after heart rate correction (QTc interval calculated by Fridericia formula);
• New York Heart Association (NYHA) grade II or above heart failure;
• Unstable angina or acute myocardial infarction within 6 months before signing the ICF;
• Left ventricular ejection fraction (LVEF) \< 50%;
• Poorly controlled hypertension (systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 95 mm Hg);

Sponsors & Collaborators

• Peking University People's Hospital: lead
• The First Affiliated Hospital of Soochow University: collaborator
• Nanfang Hospital, Southern Medical University: collaborator

Study Sites (1)

Peking University People'S Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Central Study Contacts

Yu Wang, MD

CONTACT

86-88326666; ywyw3172@sina.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: August 29, 2024
• First Posted: August 30, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2029
• Last Updated: March 12, 2025

Record last verified: 2025-03

Locations

CN (1)