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

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

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.

Study Overview

• Status: Suspended
• Conditions: B-cell Non-Hodgkin's Lymphoma
• Intervention / Treatment: Biological: CD19/CD20 Dual-CAR-T cells

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Tsinghua Changgung Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 80 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 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 for at least 2 days before infusion.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective remission rate(ORR)	The percentage of participants who achieved complete remission (CR) and partial remission over all participants.	6 months
Percentage of adverse events	Percentage of participants with adverse events.	6months

Secondary Outcome Measures

Outcome Measure	Time Frame
Relapse-Free Survival(RFS )	6 months
Overall-Survival(OS)	6 months

Other Outcome Measures

Outcome Measure	Time Frame
Persistence of CAR-T cells in vivo	6 months

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital
• Collaborators: China Immunotech Pharmaceuticals Co.Ltd.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 10, 2022
• Primary Completion (ANTICIPATED): March 10, 2023
• Study Completion (ANTICIPATED): June 10, 2023

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 5, 2021
• First Posted (ACTUAL): January 6, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 14, 2022
• Last Update Submitted That Met QC Criteria: January 29, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: HXYT-012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No