R/R B-lineage acute lymphoblastic leukemia
Conditions
Interventions
Single arm:anti-CD19 and anti-CD22 dual targeting CAR-T cells
Sponsors
Shanghai Children's Medical Center, Affiliated to Shanghai Jiaotong University, School of Medicine
Eligibility
Sex/Gender
All
Age
No minimum to 20 Years
Inclusion criteria
Inclusion criteria: Cohort 1 (Safety run-in stage): Patients must have relapsed or refractory B-ALL meeting the following disease-specific criteria: 1.Patients with hematological relapse who did not achieve remission (>5% blasts in bone marrow) after two or more courses of remission induction treatment or those with refractory leukemia with minimal residual disease >1% at the end of remission induction and persistent >0.1% after consolidation treatment who are ineligible for allogeneic stem cell transplant (alloSCT), or 2.Patients who have relapsed post alloSCT at least 100 days, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment, or 3.Patients who have failed prior CD19 CAR-T therapy, or 4.Patients with Ph+ ALL if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed or refractory disease after treatment with at least 2 different TKIs, or 5.Patients with high-risk genetic subtypes with relapsed or refractory leukemia, e.g., hypodiploid 5 WBC/ml CSF, with blasts on cytospin), patients with combined testicular disease, or patients with combined other extramedullary involvement. Cohort 2 (Phase II) 1. Patients must have relapsed or refractory B-ALL meeting the following disease-specific criteria: 1)Patients with hematological relapse who did not achieve remission (>5% blasts in bone marrow) after two or more courses of remission induction treatment or those with refractory leukemia with minimal residual disease >1% at the end of remission induction and persistent > 0.1% after consolidation treatment, or 2)Patients who have relapsed post alloSCT at least 100 days, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment, or 3)Patients who have failed prior CD19 CAR-T therapy, or 4)Patients with Ph+ ALL if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed or refractory disease after treatment with at least 2 different TKIs, or 5)Patients with high-risk genetic subtypes with relapsed or refractory leukemia, e.g., hypodiploid 5 WBC/ml CSF, with blasts on cytospin), patients with isolated testicular disease, patients with both isolated and testicular relapse, and patients with other isolated extramedullary disease. 3.Patients with positive fusion gene of MLL or ZNF384 may bridge to the allogeneic stem cell transplant (alloSCT) after CAR-T therapy, and 4.Patients who have failed prior CD19 CAR-T therapy may bridge to the allogeneic stem cell transplant (alloSCT) after CAR-T therapy. 5.Patients with B-cell recovery in bone marrow within 4 month after CART cell infusion were randomized to a second course of CART therapy or allo-SCT. Eligibility Criteria for Safety run-in stage and Phase II Study 1.Aged = 500/µl at the time of cell collection for CAR-T production, if absolute lymphocyte count < 500/µl at the time of cell collecti
Exclusion criteria
Exclusion criteria: All Cohorts: Subjects will not be included in the study if any of the following criteria applies: Current autoimmune disease, or history of autoimmune disease with potential CNS involvement Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis) History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease free for >= 3 years. Pulmonary function: Patients with pre-existing severe lung disease (FEV1 or FVC 28% O2 supplementation or active pulmonary infiltrates on chest X-ray at the time scheduled for T cell infusion Cardiac function: Fractional shortening 3 times upper limit of normal or an AST or ALT > 5 times upper limit of normal, unless due to leukemic liver infiltration in the estimation of the investigator Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy Active Hepatitis B (HBsAg positive) or Hepatitis C (PCR positive), or known infection with human immunodeficiency virus (HIV) Committal to an institution on judicial or official order
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Minimal Residual Disease, MRD;overall survive;event-free survival;B cell aplasia; | — |
Countries
China
Contacts
Public ContactBenshang Li
Shanghai Children's Medical Center affiliated to school of medicine, Shanghai Jiaotong University
Outcome results
None listed