Back to resultsTargeting CD19/CD20/CD22 Triple-targeted Cell in Patients With Relapsed/Refractory B-cell Lymphoma
Primary Purpose
B-cell Lymphoma Recurrent, B-cell Lymphoma Refractory
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
LCAR-AIO cells product
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Lymphoma Recurrent
Eligibility Criteria
Inclusion Criteria:
- 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.
- Aged 18-75 years (inclusive).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histologically confirmed B-cell lymphoma that expresses at least one of CD19/CD20/CD22.
- At least one evaluable tumor lesion in PET-positive lesions determined according to Lugano 2014 criteria.
Response to prior therapy is consistent with one of the following:
- 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;
- 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;
- 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;
- Life expectancy≥ 3 months
- Clinical laboratory values meet screening visit criteria
- Adequate organ function;
Exclusion Criteria:
Subject eligible for this study must not meet any of the following criteria:
- Prior antitumor therapy with insufficient washout period ;
- 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;
- With acute or chronic graft-versus-host disease (GvHD);
- 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).
- Known life-threatening allergies, hypersensitivity, or intolerance to LCAR-AIO CAR-T cell or its excipients, including DMSO (refer to Investigator's Brochure).
- Pregnant or lactating women;
Sites / Locations
- Beijing Gobroad Boren HospitalRecruiting
- Institute of Hematology & Blood Diseases HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LCAR-AIO cells product
Arm Description
Each subject will be given a single-dose LCAR-AIO cells infusion at each dose level.
Outcomes
Primary Outcome Measures
Incidence, severity and type of TEAEs (Treatment-emergent Adverse Events)
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
CAR positive T cells and CAR transgene levels in peripheral blood after LCAR-AIO infusion.
Pharmacokinetics in bone marrow
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
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
Secondary Outcome Measures
Overall Response Rate (ORR)
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)
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)
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)
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)
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
The incidence of Anti-LCAR-AIO antibody in patients who received LCAR-AIO cells infusion
Full Information
NCT ID
NCT05318963
First Posted
March 15, 2022
Last Updated
August 1, 2023
Sponsor
Qiu Lugui
Collaborators
Nanjing Legend Biotech Co.
1. Study Identification
Unique Protocol Identification Number
NCT05318963
Brief Title
Targeting CD19/CD20/CD22 Triple-targeted Cell in Patients With Relapsed/Refractory B-cell Lymphoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 14, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Qiu Lugui
Collaborators
Nanjing Legend Biotech Co.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Lymphoma Recurrent, B-cell Lymphoma Refractory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
LCAR-AIO cells product
Arm Type
Experimental
Arm Description
Each subject will be given a single-dose LCAR-AIO cells infusion at each dose level.
Intervention Type
Biological
Intervention Name(s)
LCAR-AIO cells product
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence, severity and type of TEAEs (Treatment-emergent Adverse Events)
Description
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.
Time Frame
Minimum 2 years after LCAR-AIO infusion (Day 1)
Title
Pharmacokinetics in peripheral blood
Description
CAR positive T cells and CAR transgene levels in peripheral blood after LCAR-AIO infusion.
Time Frame
Minimum 2 years after LCAR-AIO infusion (Day 1)
Title
Pharmacokinetics in bone marrow
Description
CAR positive T cells and CAR transgene levels in bone marrow after LCAR-AIO infusion.
Time Frame
Minimum 2 years after LCAR-AIO infusion (Day 1)
Title
The recommended Phase II dose (RP2D) for this cell therapy
Description
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
Time Frame
30 days after LCAR-AIO infusion
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via LCAR-AIO cell infusion
Time Frame
Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
Title
Progression-free survival (PFS)
Description
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
Time Frame
Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
Title
Overall Survival (OS)
Description
Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-AIO to death of the subject
Time Frame
Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
Title
Time to Response (TTR)
Description
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.
Time Frame
Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
Title
Duration of Response (DoR)
Description
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
Time Frame
Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
Title
Immunogenicity assessment of LCAR-AIO cells
Description
The incidence of Anti-LCAR-AIO antibody in patients who received LCAR-AIO cells infusion
Time Frame
Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Aged 18-75 years (inclusive).
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Histologically confirmed B-cell lymphoma that expresses at least one of CD19/CD20/CD22.
At least one measurable tumor lesion determined according to Lugano 2014 criteria.
Response to prior therapy is consistent with one of the following:
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;
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;
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;
Life expectancy≥ 3 months
Clinical laboratory values meet screening visit criteria
Adequate organ function;
Exclusion Criteria:
Subject eligible for this study must not meet any of the following criteria:
Prior antitumor therapy with insufficient washout period ;
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;
With acute or chronic graft-versus-host disease (GvHD);
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).
Known life-threatening allergies, hypersensitivity, or intolerance to LCAR-AIO CAR-T cell or its excipients, including DMSO (refer to Investigator's Brochure).
Pregnant or lactating women;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Liu
Phone
86-022-23909282
Email
liuwei@ihcams.ac.cn
Facility Information:
Facility Name
Beijing Gobroad Boren Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kai Hu
Phone
15010390336
Email
xiaohu7079@sina.com
First Name & Middle Initial & Last Name & Degree
Kai Hu
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Liu, MD
Phone
86-022-23909282
Email
liuwei@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Lugui Qiu, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Targeting CD19/CD20/CD22 Triple-targeted Cell in Patients With Relapsed/Refractory B-cell Lymphoma
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