Clinical trial NCT04655677: A Study of C-CAR039 Treatment in Subjects With r/r NHL SubjectsNon-Hodgkin's Lymphoma
Official title: A Phase 1 Study Evaluating Safety and Efficacy of C-CAR039 Treatment in Subjects With Relapsed and/or Refractory NHL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Non-Hodgkin's Lymphoma
Keywords: CD19/CD20-directed CAR-T cells
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai AbelZeta Ltd.
First posted: 2020-12-07
Enrollment: 10
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-NHL patients.

Detailed description: The study will include the following sequential phases: Screening, Apheresis and C-CAR039 manufacturing, Baseline testing, Lymphodepleting, C-CAR039 infusion, and Follow-up Visit.

Eligibility criteria: Criteria: Inclusion Criteria:

1. Age 18-70 years (include 18 and 70), male or female;
2. Expected survival ≥ 12 weeks
3. ECOG score 0-2
4. CD19 or CD20 positive B-NHL confirmed by cytology or histology according to WHO2016 criteria, including DLBCL, PMBCL, tFL, FL and MCL
5. Relapsed or refractory disease after ≥ 2 lines (for FL, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (ASCT);
6. 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;
7. No contraindications of apheresis.
8. At least one measurable lesion according to Lugano 2014 criteria;
9. Adequate organ and bone marrow function
10. The patient volunteered to participate in the study and signed the Informed Consent.

Exclusion Criteria:

1. Malignant tumors other than diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma within 5 years before screening, except fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical operation and breast ductal carcinoma in situ after radical operation;
2. Active HIV, HBV, HCV 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 therapy
4. Any other uncontrolled active disease that hinders participation in the trial;
5. Any situation that the investigator believes would compromise the safety of the subject or interfere with the purpose of the study;
6. 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 C-CAR039 infusion;
7. Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment;
8. Patients who have previously been infected with tuberculosis.
9. Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of C-CAR039;
10. Patients with central nervous system involvement;
11. Any systemic antitumor therapy performed within 2 weeks before enrollment;
12. Those with medical conditions that prevent them from signing the written informed consent or from complying with the study procedures; or those who are unwilling or unable to comply with the study requirements;
13. Other conditions was considered unsuitable for enrollment by the investigator.

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: Up to 24 months after C-CAR039 infusion
Secondary outcomes:
measure: Maximum concentration of C-CAR039 in the peripheral blood (Cmax)
timeFrame: Up to 24 Months after C-CAR039 infusion
measure: Time to maximum concentration of C-CAR039 in the peripheral blood (Tmax)
timeFrame: Up to 24 Months after C-CAR039 infusion
measure: Tlast of C-CAR039 in the peripheral blood after infusio (Tlast)
timeFrame: Up to 24 Months after C-CAR039 infusion
measure: AUC0h-28d of C-CAR039 in the peripheral blood (AUC0-28d)
timeFrame: Up to 28 days after C-CAR039 infusion
measure: Overall response rate (ORR)
timeFrame: Up to 24 Months after C-CAR039 infusion
measure: Duration of response (DOR)
timeFrame: Up to 24 Months after C-CAR039 infusion
measure: Progression-free survival (PFS)
timeFrame: Up to 24 Months after C-CAR039 infusion
measure: Overall survival (OS)
timeFrame: Up to 24 Months after C-CAR039 infusion
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing/China
Study officials:
affiliation: Peking Union Medical College Hospital
name: Daobin Zhou, PhD&MD
role: PRINCIPAL_INVESTIGATOR
References: