A Study of C-CAR066 in Subjects With r/r Diffuse Large B Cell Lymphoma Who Received CD19 CAR-T Therapy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: C-CAR066 Autologous C-CAR066 (CD20-directed CAR T-cell) administered by intravenous (IV) infusion |
Drug: C-CAR066
Single infusion of C-CAR066 at a target dose of 1.0-9.0x 10^6 CAR+T cells/kg. Divided into three dose levels: low (1.0-3.0×10^6 CAR+T cells/kg), medium (3.0-6.0×10^6 CAR+T cells/kg) and high (6.0-9.0×10^6 CAR+T cells/kg).
|
Outcome Measures
Primary Outcome Measures
- incidence of adverse events [up to 12months after C-CAR066 infusion]
the incidence of treatment-emergent adverse events (TEAEs)
Secondary Outcome Measures
- objective response rate [up to 12 months after C-CAR066 infusion]
the percentage of subjects who achieved complete response and partial response
Other Outcome Measures
- complete response rate [up to 12 months after C-CAR066 infusion]
the percentage of subjects who achieved complete response
- Duration of response [up to 12 months after C-CAR066 infusion]
- Progression free survival [up to 12 months after C-CAR066 infusion]
- overall survival [up to 12months after C-CAR066 infusion]
time to death from any cause
- duration of C-CAR066 in vivo [up to 12months after C-CAR066 infusion]
duration of detectable C-CAR066 in vivo evaluate by qPCR
- duration CD20+ B-cell aplasia [up to 12 months after C-CAR066 infusion]
duration of CD20+ B-cell aplasia post C-CAR066 infusion
Eligibility Criteria
Criteria
Inclusion Criteria:
-
The patient volunteered to participate in the study, and signed the Informed Consent;
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Age 18-75 years old, male or female;
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Subjects diagnosed with diffuse large B-cell lymphoma (DLBCL) histologically according to the 2016 edition of the WHO Lymphocytic Tumor Classification Standard;
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At least one measurable lesion(LDi≥ 1.5 cm);
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r/r patients who received prior CD19 CAR-T therapy, and the CD19 CAR-T cell therapy must be at least 3 months from the screening period and positive for CD20;
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At least 2 weeks from the end of treatment regimen (radiation, chemotherapy, mAb, etc) to apheresis;
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Echocardiography showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥50%, no Pericardial effusion and no severe arrhythmia;
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No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air.
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NEUT ≥ 1.0 × 109 / L, PLT ≥ 50 × 109 / L, TBIL ≤ 1.5 times the upper limit of the normal range, Cr ≤ the upper limit of the normal range, ALT, AST ≤ 3 times the upper limit of the normal range;
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No contraindications of peripheral blood apheresis;
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Expected survival time > 3 months;.
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ECOG scores 0 - 1;
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The apheresis was received by laboratory and met the requirements for manufacturing CAR-T cell.
Exclusion Criteria:
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Have a history of allergy to cellular products;
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Patients with cardiac insufficiency classified as Class III or IV according to the New York Heart Association (NYHA) Heart Function Classification Standard;
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A history of craniocerebral trauma, consciousness disorder, epilepsy, cerebral ischemia or hemorrhagic cerebrovascular disease ;
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Patients with active CNS involvement;;
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Patients with autoimmune disease, immunodeficiency, or other treatment requiring inhibitors
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After allogeneic hematopoietic stem cell transplantation;
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Autologous stem cell transplantation within 6 weeks before cell therapy;
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Severe active infection (except simple urinary tract, bacterial pharyngitis), or currently receiving intravenous antibiotics. However, prophylactic antibiotics, antiviral and antifungal treatments are allowed;
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Live vaccination within 4 weeks before peripheral blood apheresis;
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HIV, HBV, HCV and TPPA / RPR infections, and HBV carriers;
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Have a history of alcoholism, drug addiction and mental illness;
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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;
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Patients with severe fludarabine or cyclophosphamide hypersensitivity;
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The patient has a history of other primary cancers, except for the following:
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Non-melanoma such as skin basal cell carcinoma cured by resection;
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Cured carcinoma in situ such as cervical, bladder or breast cancer;
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The investigators believe that there are other circumstances that are not suitable for the trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Hematology & Blood Diseases Hospital | Tianjin | China | 300020 |
Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital
- Shanghai Celluar Biopharmaceutical Group Ltd.
Investigators
- Principal Investigator: Dehui Zou, Institute of Hematology & Blood Diseases Hostipal
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0502-014