The Safety and Efficacy of Double-target CART-19 and 20 Cells in Non-Hodgkin's Lymphoma (NHL)

Study Overview
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Brief Summary
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This is a study for patients who have been previously treated for NHL. The purpose of this study is to determine the safety and feasibility of double-target CART-19 and 20 cells to the patients with relapsed and refractory CD19+/CD20+ NHL.

Official Title
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The Safety and Efficacy of Double-target CART-19 and 20 Cells in Relapse and Refractory Patients With CD19+/CD20+ Non-Hodgkin's Lymphoma (NHL)

Conditions
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Non-hodgkin Lymphoma,B Cell

Intervention / Treatment
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* Biological: CART-19 and 20 cells
* Drug: Cyclophosphamide
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 to 75 years old (including 18 and 75) Diagnosed as R/R NHL CD19/CD20 positive confirmed by cell flow cytometry or immunohistochemistry Having at least one measurable lesions World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2 Life expectancy no less than 3 months enough main organ function Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and 12 months after this study Agreeing to sign the written informed consents Exclusion Criteria: Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 12 months Active GVHD History of severe pulmonary dysfunction Active malignant tumor need be treated at the same time Uncontrolled active acute/chronic infection Severe autoimmune diseases or congenital immunodeficiency Untreated active hepatitis HIV-positive, AIDS patients and syphilis infection History of severe allergies to biological products Patients with a history of mental illness Pregnant or lactating women; (female participants of reproductive potential must have a negative serum or urine pregnancy test) Researchers think of that does not fit to participate in the study, or other cases that affect the clinical trial results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: double-target CART-19 and 20<br>Patients will receive a pre-conditioning with cyclophosphamide and fludarabine before infusion of double-target CART-19 and 20 cells. The double-target CART-19 and 20 cells are to be administered on day0. | Biological: CART-19 and 20 cells<br>* Double-target CART-19 and 20 cells will be administered on day0 after completion of the chemotherapy.<br>Drug: Cyclophosphamide<br>* patients will receive a standard pre-conditioning regime with cyclophosphamide 500mg/m2/day IV for 2 days(Day-3 to day-2).<br>Drug: Fludarabine<br>* Fludarabine 25mg/m2/day IV for 3 days (Day-4 to day-2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety as assessed by the occurrence of study related adverse events | monitor the occurrence of study related adverse events | from the date of recieving intravenous CART cells up to one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | the proportion of patients benefit from the therapy | 28 days and 3 months after recieving intravenous CART cells | 
| peripheral blood CART cell copy number | The highest concentration of CART cells in peripheral blood, the time to reach the highest concentration, and the area under the curve at 28 days after recieving intravenous CART cells | from the date of recieving intravenous CART cells up to one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-Hodgkin's lymphoma, CART