Clinical trial NCT05318963: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: B-cell Lymphoma Recurrent
B-cell Lymphoma Refractory
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2022-04-08
Enrollment: 14
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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Aged 18-75 years (inclusive).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Histologically confirmed B-cell lymphoma that expresses at least one of CD19/CD20/CD22.
5. At least one measurable tumor lesion determined according to Lugano 2014 criteria.
6. Response to prior therapy is consistent with one of the following:

   1. 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;
   2. 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;
   3. 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;
7. Life expectancy≥ 3 months
8. Clinical laboratory values meet screening visit criteria
9. Adequate organ function;

Exclusion Criteria:

Subject eligible for this study must not meet any of the following criteria:

1. Prior antitumor therapy with insufficient washout period ;
2. 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;
3. With acute or chronic graft-versus-host disease (GvHD);
4. 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).
5. Known life-threatening allergies, hypersensitivity, or intolerance to LCAR-AIO CAR-T cell or its excipients, including DMSO (refer to Investigator's Brochure).
6. Pregnant or lactating women;

Primary outcomes:
measure: Incidence, severity and type of TEAEs (Treatment-emergent Adverse Events)
timeFrame: Minimum 2 years after LCAR-AIO infusion (Day 1)
measure: Pharmacokinetics in peripheral blood
timeFrame: Minimum 2 years after LCAR-AIO infusion (Day 1)
measure: Pharmacokinetics in bone marrow
timeFrame: Minimum 2 years after LCAR-AIO infusion (Day 1)
measure: The recommended Phase II dose (RP2D) for this cell therapy
timeFrame: 30 days after LCAR-AIO infusion
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
measure: Progression-free survival (PFS)
timeFrame: Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
measure: Overall Survival (OS)
timeFrame: Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
measure: Time to Response (TTR)
timeFrame: Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
measure: Duration of Response (DoR)
timeFrame: Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
measure: Immunogenicity assessment of LCAR-AIO cells
timeFrame: Through study completion, minimum 2 years after LCAR-AIO infusion (Day 1)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Gobroad Boren Hospital
state: Beijing
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
References: