Targeting CD19/CD20/CD22 Triple-targeted Cell in Patients With Relapsed/Refractory B-cell Lymphoma
Study Details
Study Description
Brief Summary
A phase I, open-label clinical study to evaluate the safety, tolerability, and efficacy of LCAR-AIO, a triple-targeted cell preparation targeting CD19/CD20/CD22, in patients with relapsed/refractory B-cell lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is an open-label, dose-escalation/dose extension study to assess the safety, tolerability, and efficacy of LCAR-AIO in the patient ≥ 18 years of age with relapsed or refractory B cell lymphoma. Subjects who meet the eligibility criteria will receive a single dose of LCAR-AIO injection. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; lymphodepleting chemotherapy), treatment, and follow-up.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LCAR-AIO cells product Each subject will be given a single-dose LCAR-AIO cells infusion at each dose level. |
Biological: LCAR-AIO cells product
before treatment with LCAR-AIO cells, subjects will receive a conditioning regimen (IV infusion of cyclophosphamide 300 mg/m^2 and fludarabine 30mg/m^2 once daily (QD) for 3 days.
|
Outcome Measures
Primary Outcome Measures
- Incidence, severity and type of TEAEs (Treatment-emergent Adverse Events) [Minimum 2 years after LCAR-AIO infusion (Day 1)]
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
- Pharmacokinetics in peripheral blood [Minimum 2 years after LCAR-AIO infusion (Day 1)]
CAR positive T cells and CAR transgene levels in peripheral blood after LCAR-AIO infusion.
- Pharmacokinetics in bone marrow [Minimum 2 years after LCAR-AIO infusion (Day 1)]
CAR positive T cells and CAR transgene levels in bone marrow after LCAR-AIO infusion.
- The recommended Phase II dose (RP2D) for this cell therapy [30 days after LCAR-AIO infusion]
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
Secondary Outcome Measures
- Overall Response Rate (ORR) [Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)]
Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via LCAR-AIO cell infusion
- Progression-free survival (PFS) [Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)]
Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LCAR-AIO to the first documented disease progression (according to Lugano 2014) or death (due to any cause), whichever occurs first
- Overall Survival (OS) [Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)]
Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-AIO to death of the subject
- Time to Response (TTR) [Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)]
Time to Response (TTR) is defined as the time from the date of first infusion of LCAR-AIO to the date of the first response evaluation of the subject who has met all criteria for CR or PR.
- Duration of Response (DoR) [Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)]
Duration of Remission (DoR) is defined as the time from the first documentation of remission (CR or PR) to the first documented relapse evidence of the responders
- Immunogenicity assessment of LCAR-AIO cells [Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)]
The incidence of Anti-LCAR-AIO antibody in patients who received LCAR-AIO cells infusion
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures, and have signed informed consent.
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Aged 18-75 years (inclusive).
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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Histologically confirmed B-cell lymphoma that expresses at least one of CD19/CD20/CD22.
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At least one evaluable tumor lesion in PET-positive lesions determined according to Lugano 2014 criteria.
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Response to prior therapy is consistent with one of the following:
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Primary refractory: it means that the best response to first-line therapy (at least 2 cycles) is PD, or best response to first-line therapy (at least 4 cycles) is SD but the duration is less than 6 months, which is considered to be PD;
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Relapsed or refractory after 2 or more lines of therapy. Refractory is defined that best respond to the most recent treatment regimen (at least 2 cycles) is PD, or best response to the most recent treatment regimen (at least 4 cycles) is SD but the duration is less than 6 months, which is considered to be PD;
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Progression or relapse within 12 months after hematopoietic stem cell transplantation; if salvage therapy is applied after transplantation, the patient must be unresponsive or relapsed to the last line of therapy;
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Life expectancy≥ 3 months
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Clinical laboratory values meet screening visit criteria
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Adequate organ function;
Exclusion Criteria:
Subject eligible for this study must not meet any of the following criteria:
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Prior antitumor therapy with insufficient washout period ;
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Patients who received dual-targeted CAR-T cell therapy (including but not limited to sequential infusion) at any time in the past, or who received CAR-T cell therapy of cameloid origin;
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With acute or chronic graft-versus-host disease (GvHD);
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Patients who are positive for any index of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), or human immunodeficiency virus antibody (HIV- Ab).
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Known life-threatening allergies, hypersensitivity, or intolerance to LCAR-AIO CAR-T cell or its excipients, including DMSO (refer to Investigator's Brochure).
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Pregnant or lactating women;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Gobroad Boren Hospital | Beijing | Beijing | China | |
| 2 | Institute of Hematology & Blood Diseases Hospital | Tianjin | Tianjin | China | 300020 |
Sponsors and Collaborators
- Qiu Lugui
- Nanjing Legend Biotech Co.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BM2L202102