Targeting CD19 and CD22 CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory B Cell Lymphoma

Lymphoma, B-Cell Clinical Trial

Official title:

A Clinical Study to Evaluate the Safety and Effectiveness of CD19-CD22 CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory B Cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04715217
• Other study ID #: CAR-T SXZL01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 4, 2021
• Est. completion date: October 31, 2025

Study information

• Verified date: December 2023
• Source: Shanxi Province Cancer Hospital
• Contact: Liping Su, M.D.
• Phone: +8613835158122
• Email: sulp2005[@]sohu.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluation the safety,tolerability, preliminary efficacy,and PK/PD of CD19-CD22 CAR-T cells for the treatment of B cell lymphoma.

Description:

A non randomized study ,plans to enrollment 24 subjects of B cell lymphoma .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 B cell lymphoma .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: October 31, 2025
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 70 Years

Eligibility

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 B cell lymphoma, 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. Patients with lymphoma need to have a measurable lesions, measurable target lesions:

lymph node x1.0 > 1.5 cm, outside the junction lesions > x1.0 1.0 cm;

5. ECOG physical status score of 0 to 2 points;

6. Expected lifetime is more than 12 weeks;

7. 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;

8. Cardiopulmonary function: left ventricular ejection fraction > 40%; Baseline blood oxygen saturation > 95%;

9. 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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell

Intervention

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 .

Locations

Country	Name	City	State
China	Hematology Department of ShanXi Cancer Hospital	Taiyuan	Shanxi

Sponsors (2)

Lead Sponsor	Collaborator
Shanxi Province Cancer Hospital	Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DLT	Observe wether dose limiting toxicity will happened in dose escalation phase	Form infusion CAR-T cells to 28 days after infusion
Primary	ORR	The overall response rate after CD19-CD22 CAR-T Cells immunotherapy	Form infusion CAR-T cells to 2 years after infusion
Secondary	Incidence of various types of adverse recation	According to CTCAE 5.0, record the level , type of adverse events, evaluat the correlation of CD19-CD22 CAR-T cells	Form infusion CAR-T cells to 2 years after infusion
Secondary	PFS	Progression-free surial	Form infusion CAR-T cells to 2 years after infusion
Secondary	DOR	Duration of Response	Form infusion CAR-T cells to 2 years after infusion
Secondary	OS	Overall survival	Form infusion CAR-T cells to subjects died,assessed up to 60 months
Secondary	Cmax	By measuring the CAR - T cells copy number and the positive rate, peak plasma concentration is determined	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
Secondary	Tmax	The maximum concentration of time	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
Secondary	AUC(0-720d)	Area under the plasma concentration versus time curve	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
Secondary	Concentration of IL2 level	The levels of cytokines(IL2 )in peripheral blood	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
Secondary	Concentration of IL6 level	The levels of cytokines(IL6 )in peripheral blood	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
Secondary	Concentration of IL10 level	The levels of cytokines( IL10 )in peripheral blood	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
Secondary	Concentration of TNF-a level	The levels of cytokines(TNF-a)in peripheral blood	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
Secondary	Concentration of IFN-? level	The levels of cytokines(IFN-? )in peripheral blood	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