Acute Lymphoblastic Leukemia With Failed Remission
Conditions
Keywords
Acute Lymphoblastic Leukemia, Refractory and relapsed, Chimeric antigen receptor T-cell therapy
Brief summary
Refractory and relapsed (R/R) acute lymphoblastic leukemia (ALL) patients with active disease always have a dismal outcome. Chimeric antigen receptor (CAR) T-cell therapy targeting to Cluster of Differentiation Antigen 19 (CD19) has been proved as a potent approach to attain remission in B-cell R/R patients. Therefore, the investigators conduct atrial to evaluate the the efficacy and safety of locally producing CAR T cells targeting CD19, and to analyze the outcome of enrolled B-cell ALL patients with active disease or persistent residual disease.
Interventions
BIOLOGICALCAR T-cell therapy
All enrolled patients will initially enter Arm A and receive CD19-targeted CAR T-cell therapy at a target dose of 5\~10×10E6 cells/kg after a lymphodepleting regimen consisting of fludarabine (30 mg/m²/day, days -5 to -3) and cyclophosphamide (300 mg/m²/day, days -5 to -3). Patients with an available eligible donor who consent to randomization will enter the RCT component and be randomized in a 2:1 ratio to Arm B1 (CAR T-cell therapy alone) or Arm B2 (CAR T-cell therapy followed by allo-HCT); all other patients will remain in Arm A.
Sponsors
The First Affiliated Hospital of Soochow University
Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
The Second People's Hospital of Huai'an
Third Military Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Diagnosed as CD19+ B-cell acute lymphoblastic leukemia; * Fail to achieve remission, or with persistent residual disease after at least 2 cycles of consolidation; * With an estimated survival of higher than 3 months (according to investigator's judgement); * Sufficient organ function: left ventricular ejection fractions≥ 0.5 by echocardiography, creatinine \< 1.6 mg/dL, aspartate aminotransferase/aspartateaminotransferase \< 3 x upper limit of normal, bilirubin \<2.0 mg/dL; * Karnofsky performance status ≥ 60 or ECOG ≤ 2.
Exclusion criteria
* Intolerant to immunosuppressive chemotherapies; * With active infection or other uncontrolled complications; * With history of seizure; * Active hepatitis B or hepatitis C infection and HIV infection; * Pregnant or lactating women, or patients refusing to take effective contraception measures; * Other contraindications that considered inappropriate to participate in this trial (according to investigator's judgement).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Completeremission | 1 month post infusion | defined as less than 5% blasts in the bone marrow without myelosuppression, no circulating blasts in peripheral blood, and the absence of extramedullary disease, regardless of cell count recovery |
| Minimal residual disease response | 1 month post infusion | defined as less than 0.01% bone marrow blasts assessed by multiparameter flow cytometry, and absence of genetic aberrants assessed by karyotype analysis or molecular detection |
| Leukemia-free survival | 3 year post infusion | calculating from the day of CAR T-cell infusion to death, disease progression or the end of follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 3 year post infusion | calculating from the day of CAR T-cell infusion to death or the end of follow-up |
| Cumulative incidence of relapse | 3 year post infusion | calculating from the day of CAR T-cell infusion to disease progression or the end of follow-up |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORDepei Wu, M.D., Ph.D.
The First Affiliated Hospital of Soochow University
Outcome results
None listed