Clinical trial NCT04316624: A Study of C-CAR066 in Subjects With r/r Diffuse Large B Cell Lymphoma Who Received CD19 CAR-T Therapy
Official title: A Study Evaluating Safety and Efficacy of CBM.CD20 CAR-T(C-CAR066) in Subjects With r/r Diffuse Large B Cell Lymphoma Who Received CD19 CAR-T Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diffuse Large B Cell Lymphoma
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Shanghai AbelZeta Ltd.
First posted: 2020-03-20
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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, 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.

Eligibility criteria: 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

Primary outcomes:
measure: The incidence of adverse events
timeFrame: Up to 12 weeks after C-CAR066 infusion
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 24 months after C-CAR066 infusion
measure: Complete response rate (CRR)
timeFrame: Up to 24 months after C-CAR066 infusion
measure: Duration of response (DOR)
timeFrame: Up to 24 months after C-CAR066 infusion
measure: Progression free survival (PFS)
timeFrame: Up to 24 months after C-CAR066 infusion
measure: Overall survival (OS)
timeFrame: Up to 24 months after C-CAR066 infusion
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hostipal
name: Dehui Zou
role: PRINCIPAL_INVESTIGATOR
References: