CD19/CD20 Dual-CAR-T in B-cell Lymphoma Patients

CD19/CD20 Dual-CAR-T for Patients With B-cell Lymphoma

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 and relapsed B-cell lymphoma.

Study Overview

• Status: Completed
• Conditions: B-cell 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 cell lymphoma. 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-cell lymphoma.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hebei
    • Sanhe, Hebei, China, 065200
      • Hebei yanda Ludaopei Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Relapsed and refractory B-cell lymphoma with:

   Relapsed or refractory disease after ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed after autologous or allogeneic hematopoietic stem cell transplantation (ASCT);

2. Patients must have evaluable evidence of disease, including minimal residual disease (MRD);
3. Double positive expression of CD19 / CD20 in B cells;
4. Ages 1 to 80 years, including boundary values;
5. ECOG score 0-3 points;
6. 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;
7. Patients who voluntarily sign informed consent and are willing to comply with treatment plans.

Exclusion Criteria:

1. patients with organ failure:

   • Heart: NYHA heart function grade IV;
   • Liver: Grade C that achieves Child-Turcotte liver function grading;
   • Kidney: kidney failure and uremia;
   • Lung: symptoms of respiratory failure;
   • Brain: a person with a disability;
2. Active infections that are difficult to control;
3. Human immunodeficiency virus (HIV) positive;
4. Liver and kidney function: total bilirubin > 5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 5 × ULN, serum creatinine clearance rate 60mL / min;
5. GVHD ≥ 2 or anti-GVHD treatment;
6. intracranial hypertension or unconsciousness; respiratory failure; diffuse vascular internal coagulation;
7. pregnant or lactating women;
8. The patient does not agree to use effective contraception during the treatment period and for the next 3 months;
9. Patients who participate in other clinical studies at the same time;
10. The investigator believes that there are other factors that are not suitable for inclusion or influence the subject's participation or completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

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 1-6×106 cells/kg.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Relapse-Free Survival(RFS )	6 months
Overall-Survival(OS)	6 months
Persistence of CAR-T cells in vivo	6 months

Collaborators and Investigators

• Sponsor: Hebei Yanda Ludaopei Hospital
• Collaborators: China Immunotech (Beijing) Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): May 10, 2021
• Study Completion (Actual): September 10, 2021

Study Registration Dates

• First Submitted: February 6, 2020
• First Submitted That Met QC Criteria: February 6, 2020
• First Posted (Actual): February 7, 2020

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: March 6, 2022
• Last Verified: August 1, 2021

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, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: HXYT-006

Drug and device information, study documents

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