CD19/CD20 Dual-CAR-T in B-cell Non-Hodgkin's Lymphoma Patients.

B-cell Non-Hodgkin's Lymphoma Clinical Trial

Official title:

A Study of CD19/CD20 Dual CAR-T Cells in the Treatment of Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma(B-NHL)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04697290
• Other study ID #: HXYT-012
• Status: Suspended
• Phase: Early Phase 1
• Start date: March 10, 2022
• Est. completion date: June 10, 2023

Study information

• Verified date: January 2022
• Source: Beijing Tsinghua Chang Gung Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single center, single arm, open-label, phase I study to evaluate the safety and efficacy of CD19/CD20 Dual-CAR-T cells in patients with refractory or relapsed B-NHL.

Description:

This Phase I study is designed as a pilot trial evaluating the safety and efficacy of CD19/CD20 Dual-CAR-T cell therapy in subjects with refractory and relapsed B-NHL. Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of CD19/CD20 Dual-CAR-T cells. Safety and efficacy of CD19/CD20 Dual-CAR-T cells therapy will be monitored. The purpose of current study is to determine the clinical efficacy and safety of CD19/CD20 Dual-CAR-T cells therapy in patients with refractory and relapsed B-NHL.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 12
• Est. completion date: June 10, 2023
• Est. primary completion date: March 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 80 Years

Eligibility

Inclusion Criteria:

1. Age =18 years

2. NHL confirmed by cytology or histology, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, etc.

3. Relapse or refractory after at least second-line treatment;

4. With evaluable target lesions.Measurable target lesions: lymph nodes>1.5x1.0cm, extranodal lesions>1.0x1.0cm;

5. Double positive expression of CD19 / CD20 in B cells;

6. ECOG score 0-2 points;

7. Good organ function:

Blood routine: absolute neutrophil count (ANC) =1.0×109/L; hemoglobin (Hb) =80 g/L; platelet count (PLT) =50×109/L; Blood biochemistry: total bilirubin=3×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)=3×upper limit of normal (ULN); Pulmonary function: =CTCAE Grade 1 dyspnea and SaO2=92% in indoor air environment; Heart function: Left ventricular ejection fraction (LVEF) =50%.

8. Women of childbearing age (15-49 years old) must receive a pregnancy test within 7 days prior to initiation of treatment and the results are negative; male and female patients with fertility must use an effective contraceptive to ensure 3 months after discontinuation of treatment during the study period not pregnant inside;

9. Patients who voluntarily sign informed consent and are willing to comply with treatment plans.

Exclusion Criteria:

1. Active infections that are difficult to control;

2. Active hepatitis B, active hepatitis C, human immunodeficiency virus (HIV) antibody positive, and Treponema pallidum antibody test positive;

3. The tumor invades the central nervous system or primary CNS lymphoma;

4. Anti-GVHD (acute or chronic) treatment is being performed within 4 weeks before apheresis and cell infusion;

5. Have undergone the following treatments:

• Those who have received chemotherapy or radiotherapy 5 days before apheresis;
• Those who have used drugs that stimulate the production of bone marrow hematopoietic cells within 5 days before apheresis;
• Received donor lymphocyte infusion (DLI) within 6 weeks before cell infusion;
• Have received autologous hematopoietic stem cell transplantation (HSCT) 3 months before apheresis, or received allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 12 months;
• Have used any gene therapy products before;

6. History of epilepsy or other central nervous system diseases; or clinically diagnosed as having severe thyroid dysfunction; or active autoimmune diseases;

7. History of other malignant tumors that have not been remission for at least 3 years ;

8. Any of the following cardiovascular diseases occurred within 6 months of the screening period, including NYHA heart function grade III or IV heart failure, cardiovascular angioplasty or stent, myocardial infarction, unstable angina, or other clinical symptoms Significant heart disease;

9. Pregnant or lactating women;

10. The investigator believes that there are other factors that are not suitable for selection or that affect subjects' participation or completion of the study.

Related Conditions & MeSH terms

• B-cell Non-Hodgkin's Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• CD19/CD20 Dual-CAR-T cells
CD19/CD20 Dual-CAR-T cells are prepared via lentiviral infection. 5 days prior to infusion of CAR-T cells, subjects receive fludarabine at dose 30mg/m2/day and cyclophosphamide treatment at dose 250mg/m2 for 3 days and take a rest at least for 2 days before infusion. CD19/CD20 Dual-CAR-T cells will be intravenously infused with a escalated dose of 2E6?6E6?1E7?3E7 cells/kg.

Locations

Country	Name	City	State
China	Beijing Tsinghua Changgung Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Tsinghua Chang Gung Hospital	China Immunotech Pharmaceuticals Co.Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Persistence of CAR-T cells in vivo		6 months
Primary	Percentage of adverse events	Percentage of participants with adverse events.	6months
Primary	Objective remission rate(ORR)	The percentage of participants who achieved complete remission (CR) and partial remission over all participants.	6 months
Secondary	Relapse-Free Survival(RFS )		6 months
Secondary	Overall-Survival(OS)		6 months