Clinical trial NCT04714593: Targeting CD19 and CD22 CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Acute B Lymphocytic Leukemia
Official title: A Clinical Study to Evaluate the Safety and Effectiveness of CD19- BCMA CAR - T Cells Immunotherapy in Patients With Relapsed or Refractory Acute B Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Acute Lymphocytic Leukemia， B-Cell
Lead sponsor: Shanxi Province Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Ultra-T Immune Therapeutics Co. LTD
First posted: 2021-01-19
Enrollment: 24
Sex: ALL
Minimum age (years): 6
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: According to the sequence from the low dose group to the high dose group
Primary purpose: TREATMENT

Brief summary: Evaluation the safety,tolerability, preliminary efficacy,and PK/PD of CD19-CD22 CAR-T cells for the treatment of acute B lymphocytic leukemia.

Detailed description: A non randomized study ,plans to enrollment 24 subjects of acute B lymphocytic leukemia .The subjects will divide into low, medium and high dose groups，to evaluate the safety and tolerability of CD19-CD22 CAR - T cells，to evaluate the preliminary efficacy and observe PK/PD parameters of CD19-CD22 CAR -T cells immunotherapy in patients with relapsed or refractory acute B lymphocytic leukemia .

Eligibility criteria: Inclusion Criteria:

1. 6-70 - year - old male or female subjects (including 6 years old and 70 years old, 6-18 subjects use only the recommended dose of treatment);
2. The Clinical diagnosis of recurrent/refractory acute B lymphocytic leukemia, after at least 2 courses of treatment, has not been achieved partial response, still in the continuous phase and progress, including the MRD positive, or recurrent intramedullary patients；
3. Bone marrow samples inspection by using flow cytometry or organization pathology ，the cell membrane surface antigen CD19 and/or CD22 positive；
4. ECOG physical status score of 0 to 2 points;
5. Expected lifetime is more than 12 weeks;
6. The clinical laboratory test results of screening phase meet the following criteria: (7 days before the inspection without blood transfusion) Hb≥60 g/L (allowed to use recombinant human erythropoietin); PLT≥ 50 x 10 \^ 9 / L ; ALC≥0.3×10\^9/L; ANC≥0.75×10\^9/L (allowed to use granulocyte colony stimulating factor); AST≤3ULN,ALT≤3ULN,TBIL≤2ULN；Ccr≥30 mL/min/1.73 m2；
7. Cardiopulmonary function: left ventricular ejection fraction \> 40%; Baseline blood oxygen saturation \> 95%;
8. Has a history of allogeneic/allogeneic hematopoietic stem cell transplantation patients: transplantation in 3 months ago, no grade 2 or more active graft versus host disease (GVHD), more than a month without immune inhibitors.

Exclusion Criteria:

1. The active hepatitis b, HBV - DNA detection lower limit of the subjects above research center; Hepatitis c virus (HCV) antibody positive and peripheral blood HCV - RNA positive subjects; Antibodies to HIV positive subjects; Early syphilis screening antibody positive;
2. The other clinical significance of active virus, bacterial infection, or failing to control systemic fungal infection;
3. Any instability of systemic disease, including but not limited to, unstable angina, cerebrovascular accident, or transient ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York heart association (NYHA) classification level III or higher congestive heart failure, drug control of serious arrhythmia, liver, kidney or metabolic diseases, as well as the standard treatment cannot control high blood pressure;
4. In past two years, because of autoimmune diseases such as crohn's disease, rheumatoid arthritis and systemic lupus erythematosus (sle), etc.) causing end-organ damage, or need systemic application of immunosuppressive drugs;
5. Had a history of the central nervous system diseases, such as epilepsy, serious brain damage, dementia, Parkinson's disease, psychosis,etc which influence the appraising of test,;
6. Diagnosed with other active malignancy in past five years(the basal or scaly skin cancer, superficial bladder cancer, breast cancer in situ, which has been cured and does not require follow-up treatment are not included );
7. Known allergic to cyclophosphamide, fluorine dara marina or CAR - T cell s including accessories, DMSO ;
8. Patients with pregnancy or lactation, patients do not want to take effective contraceptive measures within 6months after infusion CAR-T cells;
9. The other situations that researchers determined doesn't fit to participate in this study.

Primary outcomes:
measure: DLT
timeFrame: Form infusion CAR-T cells to 28 days after infusion
measure: ORR
timeFrame: Form infusion CAR-T cells to 2 years after infusion
Secondary outcomes:
measure: Incidence of various types of adverse recation
timeFrame: Form infusion CAR-T cells to 2 years after infusion
measure: PFS
timeFrame: Form infusion CAR-T cells to 2 years after infusion
measure: DOR
timeFrame: Form infusion CAR-T cells to 2 years after infusion
measure: OS
timeFrame: Form infusion CAR-T cells to subjects died，assessed up to 60 months
measure: Cmax
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Tmax
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: AUC（0-720d）
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of IL2 level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of IL6 level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of IL10 level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of TNF-α level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
measure: Concentration of IFN-γ level
timeFrame: Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24
Other outcomes:
Locations:
city: Taiyuan
country: China
facility: Hematology Department of ShanXi Cancer Hospital
state: Shanxi
Study officials:
affiliation: Hematology Department of ShanXi Cancer Hospital
name: Liping Su, M.D.
role: PRINCIPAL_INVESTIGATOR
References: