Clinical trial NCT03263208: CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-ALL.
Official title: A Study of CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-cell Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: B-cell Acute Lymphocytic Leukemia
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
Collaborators: name: The Pregene (ShenZhen) Biotechnology Company, Ltd.
First posted: 2017-08-28
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: safety as assessed by the occurence of study related adverse events
timeFrame: 30 days
measure: anti-tumor responses of CD19 CAR-T cells
timeFrame: 1 year
Secondary outcomes:
measure: Persistence of the CD19 CAR+ T cells
timeFrame: 1 year
measure: Number of participants who have T cells ablated with cetuximab
timeFrame: 1 year
Other outcomes:
Locations:
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
Study officials:
References: