Clinical trial NCT04697290: CD19/CD20 Dual-CAR-T in B-cell Non-Hodgkin's Lymphoma Patients.
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)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: EARLY_PHASE1
Conditions: B-cell Non-Hodgkin's Lymphoma
Lead sponsor: Beijing Tsinghua Chang Gung Hospital
Sponsor class: OTHER
Collaborators: name: China Immunotech Pharmaceuticals Co.Ltd.
First posted: 2021-01-06
Enrollment: 12
Sex: ALL
Minimum age (years): 1
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of adverse events
timeFrame: 6months
measure: Objective remission rate(ORR)
timeFrame: 6 months
Secondary outcomes:
measure: Relapse-Free Survival(RFS )
timeFrame: 6 months
measure: Overall-Survival(OS)
timeFrame: 6 months
Other outcomes:
measure: Persistence of CAR-T cells in vivo
timeFrame: 6 months
Locations:
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
state: Beijing
Study officials:
References: