A Study of C-CAR066 in Subjects With r/r Diffuse Large B Cell Lymphoma Who Received CD19 CAR-T Therapy

Phase 1

Completed

• Conditions: Diffuse Large B Cell Lymphoma
• Interventions: Drug: C-CAR066

• Registration Number: NCT04316624
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Brief Summary

This is a single-center, non-randomized and dose-escalation study to evaluate the safety and efficacy of C-CAR066 in treatment of r/r DLBCL who received CD19 CAR-T therapy.

Detailed Description

This study plans to enroll 10 patients to assess the safety and efficacy of C-CAR066. Subjects who meet the eligibility criteria will receive a single dose of C-CAR066 injection.

The study will include the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), C-CAR066 infusion and Follow-up Visit.

Study Timeline

• Study Start: 2019-09-29
• Status Verified: 2020-03
• Study First Submitted: 2020-03-15
• Study First Submitted QC: 2020-03-18
• Study First Posted: 2020-03-20
• Primary Completion: 2023-02-08
• Study Completion: 2023-02-08
• Last Update Submitted: 2023-07-17
• Last Update Posted: 2023-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

1. The patient volunteered to participate in the study, and signed the Informed Consent
2. Age 18-75 years old, male or female
3. Patients diagnosed with diffuse large B-cell lymphoma (DLBCL, De novo or transformed) histologically according to the 2016 WHO Classification, at least one measurable lesion(LDi≥1.5 cm)
4. r/r DLBCL patients who received prior CD19 CAR-T therapy, and positive for CD20
5. At least 2 weeks from last treatment (radiation, chemotherapy, mAb, etc) to apheresis
6. Adequate organ and bone marrow fuction
7. No contraindications of apheresis
8. Expected survival time > 3 months
9. ECOG scores 0 - 1

Exclusion Criteria

1. Have a history of allergy to cellular products

2. Patients with cardiac insufficiency classified as Class III or IV according to the New York Heart Association (NYHA) Heart Function Classification Standard

3. A history of craniocerebral trauma, consciousness disorder, epilepsy, cerebral ischemia or hemorrhagic cerebrovascular disease

4. Patients with active CNS involvement

5. Patients with autoimmune disease, immunodeficiency, or other treatment requiring inhibitors

6. Severe active infection (except simple urinary tract, bacterial pharyngitis), or currently receiving intravenous antibiotics. However, prophylactic antibiotics, antiviral and antifungal treatments are allowed

7. Live vaccination within 4 weeks before peripheral blood apheresis

8. HIV, HBV, HCV and TPPA / RPR infections, and HBV carriers

9. Have a history of alcoholism, drug addiction and mental illness

10. Non-sterile subjects had any of the following: a) being pregnant / lactating; or b) having a pregnancy plan during the trial; or c) having fertility without taking effective contraception

11. Patients with severe fludarabine or cyclophosphamide hypersensitivity

12. The patient has a history of other primary cancers, except for the following:

    1. Non-melanoma such as skin basal cell carcinoma cured by resection
    2. Cured carcinoma in situ such as cervical, bladder or breast cancer

13. The investigators believe that there are other circumstances that are not suitable for the trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
C-CAR066	C-CAR066	Autologous C-CAR066 (CD20-directed CAR T-cell) administered by intravenous (IV) infusion

Primary Outcome Measures

Name	Time	Method
The incidence of adverse events	Up to 12 weeks after C-CAR066 infusion	The incidence of treatment-emergent adverse events (TEAEs)

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	Up to 24 months after C-CAR066 infusion	The percentage of subjects who achieved complete response and partial response
Complete response rate (CRR)	Up to 24 months after C-CAR066 infusion	The percentage of subjects who achieved complete response
Overall survival (OS)	Up to 24 months after C-CAR066 infusion	Time from C-CAR066 infusion to death from any cause
Duration of response (DOR)	Up to 24 months after C-CAR066 infusion	The time from the date of first response (PR or CR) to the date of disease progression or death after C-CAR066 infusion
Progression free survival (PFS)	Up to 24 months after C-CAR066 infusion	The time from C-CAR066 infusion to the date of progression as assessed by Lugano 2014 criteria or death

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, China