Targeting CD19 and CD22 CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Acute B Lymphocytic Leukemia

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

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

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphocytic Leukemia， B-Cell
• Intervention / Treatment: Biological: CD19-CD22 CAR-T cells

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 .

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Liping Su, M.D.; Phone Number: +86 13835158122; Email: sulp2005@sohu.com

Study Locations

• China
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Recruiting
      • Hematology Department of ShanXi Cancer Hospital
      • Contact: Tao Guan, PhD; Phone Number: +8613509717461; Email: 395714554@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose Group; CD19-CD22 CAR-T cells injection, infused only once,3-6 subjects of low dose group will be intravenously infuse with 0.5×10^6 CAR+T cells/kg.	Biological: CD19-CD22 CAR-T cells; A autologous doping CAR - T cells injection targets with CD19 and CD22，fluorine dara marina injection(30 mg/m2，QD×3d) and cyclophosphamide injection (300 mg/m2，QD×3d)will be used to remove the lymphocyte before infusion CD19-CD22 CAR-T cells .; Other Names: Cyclophosphamide injection; Fluorine dara marina injection
Experimental: Amplification Dose Group; CD19-CD22 CAR-T cells injection, infused only once.After determined maximum tolerated dose,15 subjects of amplification dose group will be intravenously infuse with 0.5-5.0×10^6 CAR+Tcells/kg.	Biological: CD19-CD22 CAR-T cells; A autologous doping CAR - T cells injection targets with CD19 and CD22，fluorine dara marina injection(30 mg/m2，QD×3d) and cyclophosphamide injection (300 mg/m2，QD×3d)will be used to remove the lymphocyte before infusion CD19-CD22 CAR-T cells .; Other Names: Cyclophosphamide injection; Fluorine dara marina injection
Experimental: Middle Dose Group; CD19-CD22 CAR-T cells injection, infused only once,3-6 subjects of low dose group will be intravenously infuse with 2×10^6 CAR+T cells/kg.	Biological: CD19-CD22 CAR-T cells; A autologous doping CAR - T cells injection targets with CD19 and CD22，fluorine dara marina injection(30 mg/m2，QD×3d) and cyclophosphamide injection (300 mg/m2，QD×3d)will be used to remove the lymphocyte before infusion CD19-CD22 CAR-T cells .; Other Names: Cyclophosphamide injection; Fluorine dara marina injection
Experimental: High Dose Group; CD19-CD22 CAR-T cells injection, infused only once,3-6 subjects of low dose group will be intravenously infuse with 5×10^6 CAR+T cells/kg.	Biological: CD19-CD22 CAR-T cells; A autologous doping CAR - T cells injection targets with CD19 and CD22，fluorine dara marina injection(30 mg/m2，QD×3d) and cyclophosphamide injection (300 mg/m2，QD×3d)will be used to remove the lymphocyte before infusion CD19-CD22 CAR-T cells .; Other Names: Cyclophosphamide injection; Fluorine dara marina injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	Observe wether dose limiting toxicity will happened in dose escalation phase	Form infusion CAR-T cells to 28 days after infusion
ORR	The overall response rate after CD19-CD22 CAR-T Cells immunotherapy	Form infusion CAR-T cells to 2 years after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free surial	Form infusion CAR-T cells to 2 years after infusion
DOR	Duration of Response	Form infusion CAR-T cells to 2 years after infusion
OS	Overall survival	Form infusion CAR-T cells to subjects died，assessed up to 60 months
Cmax	By measuring the CAR - T cells copy number and the positive rate, peak plasma concentration is determined	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
Tmax	The maximum concentration of time	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
AUC（0-720d）	Area under the plasma concentration versus time curve	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
Incidence of various types of adverse recation	According to CTCAE 5.0, record the level , type of adverse events, evaluat the correlation of CD19-CD22 CAR-T cells	Form infusion CAR-T cells to 2 years after infusion
Concentration of IL2 level	The levels of cytokines（IL2 ）in peripheral blood	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
Concentration of IL6 level	The levels of cytokines（IL6 ）in peripheral blood	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
Concentration of IFN-γ level	The levels of cytokines（IFN-γ ）in peripheral blood	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
Concentration of IL10 level	The levels of cytokines（IL10 ）in peripheral blood	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
Concentration of TNF-α level	The levels of cytokines（TNF-α ）in peripheral blood	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

Collaborators and Investigators

• Sponsor: Shanxi Province Cancer Hospital
• Collaborators: Shanghai Ultra-T Immune Therapeutics Co. LTD
• Investigators: Principal Investigator: Liping Su, M.D., Hematology Department of ShanXi Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 15, 2021
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 17, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, B-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: CAR-T SXZL02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Plan to Share Clinical Study Report within six months after the study completed
• IPD Sharing Time Frame: Within six months after the study completed
• IPD Sharing Access Criteria: Research site
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No