Clinical Trials /

Sequential Infusion of Anti-CD19 and Anti-CD20 CAR-T Cells Against Relapsed and Refractory B-cell Lymphoma

NCT03207178

Description:

Cluster of differentiation antigen 19(CD19) specifically presents in B lymphocyte cell lines steadily,while not in most normal tissue,including pluripotent hematopoietic stem cells.Cluster of differentiation antigen 20(CD20) presents in 90% of B-cell lymphomas.CD19 antigen is a well-established target for B-cell lymphomas treatment as well as CD20 antigen.Both CD19-targeting CAR T Cells and CD20-targeting CAR T Cells can be used as adoptive cellular immunotherapies for B-cell lymphomas.Though two kinds of single target treatments were proved can induce recession of B-cell lymphomas, the risk of cancer cells to escape and tumor recurrence are still existed. There are no report about combination transfer of two kinds of single target treatments.This research aimed emphasis on safety and therapeutic efficacy evaluation,as well as if combination transfer can decrease recurrence rate.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Sequential Infusion of Anti-CD19 and Anti-CD20 CAR-T Cells Against Relapsed and Refractory B-cell Lymphoma
  • Official Title: Sequential Infusion of Anti-CD19 and Anti-CD20 Chimeric Antigen Receptor(CAR) T Cells Against Relapsed and Refractory B-cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: LYCT-1701
  • NCT ID: NCT03207178

Conditions

  • Recurrent or Refractory B Cell Malignancy

Interventions

DrugSynonymsArms
Mixed CD19/CD20 CAR-T TransferMixed CD19/CD20 CAR-T Transfer

Purpose

Cluster of differentiation antigen 19(CD19) specifically presents in B lymphocyte cell lines steadily,while not in most normal tissue,including pluripotent hematopoietic stem cells.Cluster of differentiation antigen 20(CD20) presents in 90% of B-cell lymphomas.CD19 antigen is a well-established target for B-cell lymphomas treatment as well as CD20 antigen.Both CD19-targeting CAR T Cells and CD20-targeting CAR T Cells can be used as adoptive cellular immunotherapies for B-cell lymphomas.Though two kinds of single target treatments were proved can induce recession of B-cell lymphomas, the risk of cancer cells to escape and tumor recurrence are still existed. There are no report about combination transfer of two kinds of single target treatments.This research aimed emphasis on safety and therapeutic efficacy evaluation,as well as if combination transfer can decrease recurrence rate.

Detailed Description

      To determine:

      Primary Outcome Measure:

      The Overall complete remission rate and one-year survival rate of combination transfer of
      CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is superior to or at least not
      worse than two kinds of single target treatments in the treatment of CD19+/CD20+ B-cell
      lymphomas.

      The risk of cancer recurrence in a year of combination transfer of CD19-targeting CAR T Cells
      and CD20-targeting CAR T Cells is inferior to two kinds of single target treatments.

      Secondary Outcome Measures:

      Evaluate the initial effect time, time to disease progression, and life quality improvement
      of combination transfer compare to single target treatments.

      Evaluate the safety and tolerability of combination transfer compare to single target
      treatments by observation of high fever duration in patients and testing related cell factor
      level in peripheral blood.
    

Trial Arms

NameTypeDescriptionInterventions
Mixed CD19/CD20 CAR-T TransferExperimentalSubjects with CD19+/CD20+ B-cell lymphomas will be infused with CD19-targeting CAR T Cells and CD20-targeting CAR T Cells in one time or in parts
  • Mixed CD19/CD20 CAR-T Transfer

Eligibility Criteria

        Inclusion Criteria:

          -  18 Years to 70 Years, Male and female

          -  Survival time>12 weeks

          -  B cell lymphomas diagnosed by Physical examination,pathological examination,Laboratory
             tests and imaging tests

          -  Chemotherapy failure or recurrent B cell lymphomas

          -  Creatinine< 2.5mg/dl

          -  Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal
             level

          -  Bilirubin<2.0mg/dl

          -  Karnofsky Performance Status>50% at the time of screening

          -  Adequate pulmonary, renal, hepatic, and cardiac function

          -  Fail in autologous or allogenic haemopoietic stem cell transplantation

          -  Free of leukocytes removal contraindications

          -  Voluntarily join CAR-T clinical trial

          -  Understand and sign written informed consent

        Exclusion Criteria:

          -  Pregnant or nursing women or women with pregnancy plan in half a year

          -  Any infectious disease (HIV, active tuberculosis, ect.)

          -  Active hepatitis B, active hepatitis C infection

          -  Feasibility assessment proves that the efficiency of transduction of lymphocyte is
             below 10% or the lymphocyte amplification is below 5 fold with the costimulation of
             cluster of differentiation 3(CD 3)and cluster of differentiation 8(CD 8)

          -  Abnormal vital signs or cannot cooperate with the inspectors

          -  mental or psychological disease cannot cooperate with treatment and curative effect
             evaluation

          -  Highly allergic constitution or history of severe allergies, especially allergy to
             interleukin-2(IL-2)

          -  General infection or local severe infection, or other infection that is not controlled

          -  Dysfunction in lung, heart, kidney and brain

          -  Severe autoimmune diseases

          -  Other symptoms that are not applicable for CAR-T
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall complete remission rate
Time Frame:Half a year
Safety Issue:
Description:The complete remission rate will be evaluated by routine methods.

Secondary Outcome Measures

Measure:The initial effect time
Time Frame:1 year
Safety Issue:
Description:The initial effect time will be recorded.
Measure:The one-year survival rate
Time Frame:1 year
Safety Issue:
Description:The one-year survival rate will be recorded.
Measure:The safety and the tolerability(incidence of treatment-emergent adverse events defined as dose-limited toxicity)
Time Frame:1 month
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Measure:The time to disease progression
Time Frame:1 year
Safety Issue:
Description:The time to disease progression will be counted after complete remission.
Measure:The one-year recurrence
Time Frame:1 year
Safety Issue:
Description:The one-year recurrence will be counted after complete remission.
Measure:The life quality improvement
Time Frame:1 year
Safety Issue:
Description:The life quality improvement will be evaluated by appetite,sleep,pain and mental state.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Shanghai Longyao Biotechnology Inc., Ltd.

Last Updated

June 29, 2017