Clinical trial NCT05149391: A Study of C-CAR039 in Subjects With Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma
Official title: A Phase 1 Study of CD19 and CD20 Targeted Chimeric Antigen Receptor T Cells Therapy (C-CAR039) in Subjects With Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: B Cell Non-Hodgkin's Lymphoma
Keywords: CD19/CD20-directed Chimeric Antigen Receptor T Cells
Lead sponsor: Peking University
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
First posted: 2021-12-08
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-center, open-label study to evaluate the safety and efficacy of C-CAR039 in relapsed and/or refractory B cell Non-Hodgkin's Lymphoma patients.

Detailed description: The study includes the following sequential phases: Screening, Apheresis and C-CAR039 manufacturing, Baseline testing, Lymphodepletion, C-CAR039 infusion, Dose-limiting toxicity observation and Follow-up Visit.

Eligibility criteria: Inclusion Criteria:

1. The patient volunteered to participate in the study and signed the Informed Consent;
2. Age, 18-70 years (include 18 and 70), male or female;
3. Expected survival ≥ 12 weeks
4. Eastern Cooperative Oncology Group score 0-2
5. CD19 or CD20 positive B-Non-Hodgkin's lymphoma confirmed by cytology or histology according to World Health Organization 2016 criteria;
6. Patients with a clear diagnosis of relapsed and/or refractory B-Non-Hodgkin's lymphoma, including Diffuse Large B Cell Lymphoma, Follicular Lymphoma and Mantle Cell Lymphoma. Diffuse Large B Cell Lymphoma includes the following types:

   1. Diffuse Large B Cell Lymphoma, Non Specifically
   2. Primary Mediastinal B-cell Lymphoma
   3. Transformed Follicular Lymphoma
   4. High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6
   5. High Grade B-Cell Lymphoma, Non Specifically
7. For CD20-positive subjects, they should have received at least one regimen containing anti-CD20-targeted therapy (such as rituximab). If they do not complete the regimen due to intolerance, the cause of intolerance should be recorded;
8. No contraindications of apheresis.
9. At least one measurable lesion according to Lugano 2014 criteria;
10. Adequate organ function and adequate bone marrow reserve

    1. Hemoglobin≥80 g/L
    2. Absolute neutrophil count≥1.0×109/L
    3. Platelet≥50×109/L,
    4. Creatinine≤1.5×upper limit of the normal range (ULN)
    5. Cardiac ejection fraction≥50%
    6. Saturation of Pulse Oxygen\>92%
    7. Total bilirubin≤1.5×ULN
    8. Alanine Aminotransferase/Aspartate Aminotransferase≤3×ULN

Exclusion Criteria:

1. Malignant tumors other than B-Non-Hodgkin's lymphoma within 5 years prior to screening, except cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery;
2. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus or treponema pallidum infection ;
3. Any instability of systemic disease, including but not limited to active infection (except local infection), severe cardiac, liver, kidney, or metabolic disease need treatment;
4. Female subjects who have been pregnant or breastfeeding, or who plan to conceive during or within 1 year after treatment, or male subjects' partner plans to conceive within 1 year after their cell transfusion;
5. Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment;
6. Patients who have been previously infected with tuberculosis;
7. Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of C-CAR039;
8. Patients with central nervous system involvement;

Primary outcomes:
measure: Safety Observation
timeFrame: up to 24 Months. Incidence and severity of adverse events after C-CAR039 infusion according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 criteria, including dose-limiting toxicity (DLT) and laboratory abnormalities.
Secondary outcomes:
measure: Maximum concentration (Cmax) of C-CAR039 in the peripheral blood.
timeFrame: Baseline, Days 4, 7, 10 and weeks 2, 3, 4, 8, 12 and month 6, 9, 12, 15, 18, 21, 24
measure: Time to maximum concentration (Tmax) of C-CAR039 in the peripheral blood.
timeFrame: Baseline, Days 4, 7, 10 and weeks 2, 3, 4, 8, 12 and month 6, 9, 12, 15, 18, 21, 24
measure: Peripheral blood duration of C-CAR039 in the peripheral blood after infusion.
timeFrame: Baseline, Days 4, 7, 10 and weeks 2, 3, 4, 8, 12 and month 6, 9, 12, 15, 18, 21, 24
measure: Area under the curve 0h-28d of C-CAR039 in the peripheral blood.
timeFrame: Baseline, Days 4, 7, 10 and weeks 2, 3, 4
measure: Overall response rate (ORR)
timeFrame: 4 weeks, 12 weeks, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, 24 months
measure: Duration of response (DOR)
timeFrame: up to 24 months
measure: Progression-free survival (PFS)
timeFrame: 4 weeks, 12 weeks, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, 24 months
measure: Overall survival (OS)
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital
Study officials:
References: