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

Shanghai Longyao Biotechnology

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Recurrent or Refractory B Cell Malignancy

Treatments

Biological: Mixed CD19/CD20 CAR-T Transfer

Study type

Interventional

Funder types

Other

Identifiers

NCT03207178

LYCT-1701

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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