Relapsed/Refractory B-cell Malignancies
Conditions
Brief summary
Phase Ib Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of the CD19/CD20 Dual-Target in vivo CAR-T Lentiviral product in the Treatment of Relapsed/Refractory B-cell Malignancies
Detailed description
This is an open-label, dose expansion study to assess the safety, tolerability, and efficacy of CD19/CD20 Dual-Target in vivo CAR-T Lentiviral product in adult patient with relapsed or refractory B cell Malignancies. Subjects who meet the eligibility criteria will receive a single dose of CD19/CD20 Dual-Target in vivo CAR-T Lentiviral product. The study will include the following sequential phases: screening, bridging therapy (if needed), treatment, and follow-up.
Interventions
BIOLOGICALCD19/CD20 Dual-Target in vivo CAR-T Lentiviral
Prior to infusion of theCD19/CD20 Dual-Target in vivo CAR-T Lentiviral product, subjects may receive bridging therapy if needed.
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Nanjing Legend Biotech Co.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects voluntarily participate in clinical studies; Fully informed of this study and signed informed consent; Informed consent form must be obtained prior to initiation of any study-related tests or procedures that are not part of the standard treatment for the subject's disease; Good compliance and cooperation with follow-up. 2. Age greater than or equal to 18. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. At least one measurable tumor lesion. 5. Eligible subjects shall meet the criteria and qualification requirements of any one of the expansion cohorts as follows: * Cohort 1: Relapsed or refractory large B-cell lymphoma patients who have received at least one line of systemic therapy and have not undergone CAR-T therapy; * Cohort 2: High-risk large B-cell lymphoma patients in the first-line setting (who have completed 2 cycles of standard first-line systemic immunochemotherapy); * Cohort 3: Relapsed or refractory mantle cell lymphoma patients treated with at least two lines of systemic therapy; * Cohort 4: Exploratory cohort including relapsed or refractory indolent lymphoma and other B-cell malignancies. 6. Life expectancy≥ 3 months 7. Clinical laboratory values meet screening visit criteria 8. 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. Prior treatment with lentiviral vector-based gene therapies; 3. Patients who are positive for hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), and human immunodeficiency virus antibody (HIV-Ab). 4. Known life-threatening allergic reaction, hypersensitivity reaction, or intolerance to study drug excipients and related excipients, including but not limited to DMSO; or those with a history of severe allergic reactions in the past (such as hypersensitivity reactions, or those with severe immune-related reactions such as the need for glucocorticoids to prevent anaphylaxis as assessed by the investigator). 5. Lactating women;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, severity, and category of treatment-emergent adverse events (TEAEs) | Through study completion, an average of 2 years afterCD19/CD20 Dual-Target in vivo CAR-T Lentiviral 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. |
| Objective response rate (ORR) and complete response (CR) rate (or the proportion of subjects achieving very good partial response [VGPR] or better) assessed per protocol-specified efficacy evaluation criteria stratified by disease type | Through study completion, an average 2 years after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion (Day 1) | Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via CD19/CD20 Dual-Target in vivo CAR-T Lentiviral cell infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Further evaluation of efficacy endpoints stratified by disease subtype: Time to Response (TTR) | Through study completion, an average 2 years after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion (Day 1) | Time to Response (TTR) is defined as the time from the date of first infusion of CD19/CD20 Dual-Target in vivo CAR-T Lentiviral to the date of the first response evaluation of the subject who has met all criteria for CR or PR |
| Further evaluation of efficacy endpoints stratified by disease subtype: Duration of Response (DOR) | Through study completion, an average 2 years after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral 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 |
| Further evaluation of efficacy endpoints stratified by disease subtype: Progression Free Survival (PFS) | Through study completion, an average 2 years after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion (Day 1) | Progression Free Survival (PFS) is defined as the time from the date of first infusion of the CD19/CD20 Dual-Target in vivo CAR-T Lentiviral to the first documented disease progression or death, whichever occurs first. |
| Further evaluation of efficacy endpoints stratified by disease subtype: Overall Survival (OS) | Through study completion, an average 2 years after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion (Day 1) | Overall Survival (OS) is defined as the time from the date of first infusion of CD19/CD20 Dual-Target in vivo CAR-T Lentiviral to death of the subject |
| Pharmacokinetics in peripheral blood | Through study completion, an average of 2 years after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion (Day 1) | CAR positive T cells and CAR transgene percentage of in peripheral blood after CD19/CD20 Dual Target in vivo CAR -T Lentiviral infusion. |
| Pharmacokinetics in bone marrow | Through study completion, an average of 2 years after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion (Day 1) | CAR positive T cells and CAR transgene levels of in bone marrow after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion. |
| Immunogenicity assessment of CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion. | Through study completion, an average 2 years after CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion (Day 1) | The incidence of Anti- CD19/CD20 Dual-Target in vivo CAR-T Lentiviral antibody in patients who received CD19/CD20 Dual-Target in vivo CAR-T Lentiviral infusion |
Countries
China
Contacts
CONTACTLei Fan
PRINCIPAL_INVESTIGATORLei Fan
The First Affiliated Hospital with Nanjing Medical University
Outcome results
None listed