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

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ClinicalTrials.gov Identifier: NCT04714593
Recruitment Status : Recruiting
First Posted : January 19, 2021
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
Shanghai Ultra-T Immune Therapeutics Co. LTD
Information provided by (Responsible Party):
Shanxi Province Cancer Hospital

Study Description
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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.

Condition or disease Intervention/treatment Phase
Acute Lymphocytic Leukemia， B-Cell Biological: CD19-CD22 CAR-T cells Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: According to the sequence from the low dose group to the high dose group
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : January 15, 2021
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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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:
  • Fluorine dara marina injection
  • Cyclophosphamide 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:
  • Fluorine dara marina injection
  • Cyclophosphamide 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:
  • Fluorine dara marina injection
  • Cyclophosphamide 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:
  • Fluorine dara marina injection
  • Cyclophosphamide injection


Outcome Measures
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Primary Outcome Measures :
  1. DLT [ Time Frame: Form infusion CAR-T cells to 28 days after infusion ]
    Observe wether dose limiting toxicity will happened in dose escalation phase

  2. ORR [ Time Frame: Form infusion CAR-T cells to 2 years after infusion ]
    The overall response rate after CD19-CD22 CAR-T Cells immunotherapy


Secondary Outcome Measures :
  1. Incidence of various types of adverse recation [ Time Frame: Form infusion CAR-T cells to 2 years after infusion ]
    According to CTCAE 5.0, record the level , type of adverse events, evaluat the correlation of CD19-CD22 CAR-T cells

  2. PFS [ Time Frame: Form infusion CAR-T cells to 2 years after infusion ]
    Progression-free surial

  3. DOR [ Time Frame: Form infusion CAR-T cells to 2 years after infusion ]
    Duration of Response

  4. OS [ Time Frame: Form infusion CAR-T cells to subjects died，assessed up to 60 months ]
    Overall survival

  5. Cmax [ Time Frame: 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 ]
    By measuring the CAR - T cells copy number and the positive rate, peak plasma concentration is determined

  6. Tmax [ Time Frame: 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 ]
    The maximum concentration of time

  7. AUC（0-720d） [ Time Frame: 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 ]
    Area under the plasma concentration versus time curve

  8. Concentration of IL2 level [ Time Frame: 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 ]
    The levels of cytokines（IL2 ）in peripheral blood

  9. Concentration of IL6 level [ Time Frame: 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 ]
    The levels of cytokines（IL6 ）in peripheral blood

  10. Concentration of IL10 level [ Time Frame: 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 ]
    The levels of cytokines（IL10 ）in peripheral blood

  11. Concentration of TNF-α level [ Time Frame: 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 ]
    The levels of cytokines（TNF-α ）in peripheral blood

  12. Concentration of IFN-γ level [ Time Frame: 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 ]
    The levels of cytokines（IFN-γ ）in peripheral blood


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04714593


Contacts
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Contact: Liping Su, M.D. 13835158122 ext +86 sulp2005@sohu.com

Locations
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China, Shanxi
Hematology Department of ShanXi Cancer Hospital Recruiting
Taiyuan, Shanxi, China, 030013
Contact: Tao Guan, PhD    +8613509717461    395714554@qq.com   
Sponsors and Collaborators
Shanxi Province Cancer Hospital
Shanghai Ultra-T Immune Therapeutics Co. LTD
Investigators
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Principal Investigator: Liping Su, M.D. Hematology Department of ShanXi Cancer Hospital
More Information
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Responsible Party: Shanxi Province Cancer Hospital
ClinicalTrials.gov Identifier: NCT04714593    
Other Study ID Numbers: CAR-T SXZL02
First Posted: January 19, 2021    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Plan to Share Clinical Study Report within six months after the study completed
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Within six months after the study completed
Access Criteria: Research site

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
 Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists