B-cell Malignancy
Conditions
Brief summary
This is a single center, single arm, open-lable phase I study to determine the safety and efficacy of CD19-CAR-T cells in patients with refractory and relapsed B-cell malignancies.
Detailed description
This Phase I study is designed as a pilot trial evaluating the safety and of CD19-CAR-T cell therapy in subjects with refractory and relapsed B cell malignancies. Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of CD19-CAR-T cells. Safety and efficacy of CD19-CAR-T cells therapy will be monitored. The purpose of current study is to determine the clinical efficacy and safety of CD19-CAR-T cells therapy in patients with refractory and relapsed B-cell malignancies.
Interventions
BIOLOGICALCD19-CAR-T cells
CD19-CAR-T cells are prepared via lentiviral infection. 5 days prior to infusion of CAR-T cells, subjects receive fludarabine at dose 30mg/m2/day and cyclophosphamide treatment at dose 250mg/m2 for 3 days and take a rest for 2 days before infusion.
Sponsors
China Immunotech (Beijing) Biotechnology Co., Ltd.
Avalon GloboCare Corp.
Hebei Yanda Ludaopei Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Relapsed and refractory CD19 positive B-cell acute malignancies with: * Relapsed after competed remission, could not get competed remission after at more than 1 course of chemotherapy (including MRD≥0.1%); * MRD≥0.1% after allogeneic hematopoietic stem cell transplantation(HSCT), or recurrence after complete remission or MRD ≥ 0.1% after HSCT; * Refractory: at least two courses of chemotherapy did not achieve complete remission or MRD ≥ 0.1%; 2. Patients must have evaluable evidence of disease, including minimal residual disease (MRD); 3. Ph + patients who meet the following criteria can register:Failure to tolerate TKI or TKI treatment failure, or failure to transplant; 4. Ages 1 to 70 years, including boundary values; 5. ECOG score 0-3 points; 6. Women of childbearing age (15-49 years old) must receive a pregnancy test within 7 days prior to initiation of treatment and the results are negative; male and female patients with fertility must use an effective contraceptive to ensure 3 months after discontinuation of treatment during the study period not pregnant inside.
Exclusion criteria
1. patients with organ failure: * Heart: NYHA heart function grade IV; * Liver: Grade C that achieves Child-Turcotte liver function grading; * Kidney: kidney failure and uremia; * Lung: symptoms of respiratory failure; * Brain: a person with a disability; 2. Active infections that are difficult to control; 3. Human immunodeficiency virus (HIV) positive; 4. Liver and kidney function: total bilirubin \> 5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 5 × ULN, serum creatinine clearance rate 60mL / min; 5. GVHD ≥ 2 or anti-GVHD treatment; 6. Received allogeneic cell therapy within 4 weeks, such as donor lymphocyte infusion; 7. Subject received anti-tumor treatment (chemotherapy, mAb, or hormone) for less than 1 week; 8. Central nervous system white blood that is symptomatic or uncontrolled by systemic chemotherapy and intrathecal chemotherapy (a large number of tumor cells in CSF, white blood cell count \>15WBCs/mL); 9. intracranial hypertension or unconsciousness; respiratory failure; diffuse vascular internal coagulation; 10. pregnant or lactating women; 11. The patient does not agree to use effective contraception during the treatment period and for the next 3 months; 12. Patients who participate in other clinical studies at the same time; 13. The investigator believes that there are other factors that are not suitable for inclusion or influence the subject's participation or completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of adverse events | 6 months | Percentage of participants with adverse events. |
| Objective remission rate(ORR) | 6 months | The percentage of participants who achieved complete remission (CR) and partial remission over all participants. |
Secondary
| Measure | Time frame |
|---|---|
| Relapse-Free Survival(RFS ) | 6 months |
| Overall-Survival(OS) | 6 months |
| Persistence of CAR-T cells in vivo | 6 months |
Countries
China
Outcome results
None listed