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

Phase 2UnknownNCT03207178

Shanghai Longyao Biotechnology Inc., Ltd.20 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Overall complete remission rate

The complete remission rate will be evaluated by routine methods.

Time frame: Half a year

Secondary Outcomes

The initial effect time

The initial effect time will be recorded.

Time frame: 1 year

The one-year survival rate

The one-year survival rate will be recorded.

Time frame: 1 year

The safety and the tolerability(incidence of treatment-emergent adverse events defined as dose-limited toxicity)

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

Time frame: 1 month

The time to disease progression

The time to disease progression will be counted after complete remission.

Time frame: 1 year

The one-year recurrence

The one-year recurrence will be counted after complete remission.

Time frame: 1 year

The life quality improvement

The life quality improvement will be evaluated by appetite,sleep,pain and mental state.

Time frame: 1 year

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts