B-cell Acute Lymphocytic Leukemia
Conditions
Brief summary
The purpose of this study is to infusion CD19 CAR-T cells to the patients with relapsed and refractory CD19+ B cell leukemia, to assess the safety and feasibility of this strategy. The CAR enables the T cell to recognize and kill the leukemic cell through the recognition of CD19, a protein expressed of the surface of the leukemic cell in patients with CD19+ leukemia.
Detailed description
Upon meeting the eligibility requirements and enrolling on study, Subjects will be collected large numbers of peripheral blood mononuclear cells (PBMC) for the generation of the CD19 CAR-T cells. The T cells are isolated from the PBMC, transduced with a lentivirus to express the CD19 CAR as well as a truncated EGFR that has no signaling capacity (noted EGFRt) and expanded in vitro and then administered to subjects. Subjects will have blood tests to assess safety and efficacy, and persistence of the CD19 CAR-T cells on week 4 after their last infusion. Following the 6 months of intensive follow-up, subjects will be evaluated every 10 weeks for 1 year with a physical examination, blood tests, bone marrow aspirate, MRD and persistence of CD19 CAR-T. Some subjects will receive cetuximab for ablation of the genetically modified T cells. Criteria to receive cetuximab include acute toxicities that are life threatening.
Interventions
DRUGFludarabine
Fludarabine 25-30mg/m2/day IV for 3 days(Day-5 to day-3).
DRUGCyclophosphamide
patients will receive a standard pre-conditioning regime with cyclophosphamide 0.6-0.8g/m2/day IV for 2 days(Day-5 to day-4).
BIOLOGICALCD19 CAR-T
CD19 CAR-T cells will be administered after completion of the chemotherapy.
Sponsors
The Pregene (ShenZhen) Biotechnology Company, Ltd.
Henan Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 1\. 2 years to 70 years, expected survival \> 3 months; * 2\. CD19 positive B-cell acute lymphoblastic leukemia; * 3\. ECOG \< 2； * 4\. The tumor load in the bone marrow is less than 60%; * 5\. Cardiac function: 1-2 levels; Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; kidney: Cr≤1.25ULN; Peripheral Blood: WBC ≥ 2.0×109/L, Hb ≥80 g/L, PLT ≥ 30×109/L）; * 6\. No leukemia cells in the central nervous system; * 7\. No serious allergic constitution; * 8\. No other serous diseases that conflicts with the clinical program; * 9\. No other cancer history; * 10\. No serious mental disorder; * 11\. female participants of reproductive potential must have a negative serum pregnancy test; * 12\. Informed consent is signed by a subject or his lineal relation.
Exclusion criteria
* 1\. Pregnant or lactating women; * 2\. Uncontrolled active infection, HIV infection, syphilis serology reaction positive; * 3\. Active hepatitis B or hepatitis C infection; * 4\. Recent or current use of glucocorticoid or other immunosuppressor; * 5\. With severe cardiac, liver, renal insufficiency, diabetes and other diseases; * 6\. Participate in other clinical research in the past three months; previously treatment with any gene therapy products;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| safety as assessed by the occurence of study related adverse events | 30 days | number of participants with adverse events |
| anti-tumor responses of CD19 CAR-T cells | 1 year | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Persistence of the CD19 CAR+ T cells | 1 year | determine duration of in vivo survival of CD19 CAR-T cells |
| Number of participants who have T cells ablated with cetuximab | 1 year | The efficacy of cetuximab to ablate the T cells will be measured by loss of detection of T cells and any associated toxicities as well as facilitating B cell recovery. |
Countries
China
Contacts
Primary ContactYongping Song
Outcome results
None listed