Back to resultsUniversal BCMA-targeted LUCAR-B68 Cells in Patients With Relapsed/Refractory Multiple Myeloma
Primary Purpose
Relapsed/Refractory Multiple Myeloma
Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
LUCAR-B68 cells product
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- The subject voluntarily participates in the clinical study; Fully understand and be Informed of the study and sign the Informed consent (Informed Consent Form, ICF); Willing to follow and able to complete all test procedures; Informed consent must be obtained before initiating any tests or procedures related to the study that are not part of the standard treatment of the subject's disease;
- Subjects ≥ 18 years of age.
- Eastern Cooperative Oncology Group performance status score of 0, 1, or 2;
- Documented initial diagnosis of MM according to IMWG diagnostic criteria.
- Presence of measurable disease at screening.
- Received a PI and an IMiD (except thalidomide).
- Received at least 3 prior lines of therapy for multiple myeloma, undergone at least 1 complete cycle of treatment for each line, unless progressive disease (PD) was documented by IMWG criteria as the best response to the regimen. Also, subjects refractory or intolerant to any PI and any IMiD in their previous treatment afterwards are eligible.
- Expected survival ≥ 3 months.
- Clinical laboratory values meet screening visit criteria
- Fertile women must be negative using a highly sensitive serum pregnancy test (β human chorionic gonadotropin [β -HCG]) at screening time and before initial treatment with cyclophosphamide and fludarabine;
Exclusion Criteria:
- No response to prior BCMA-targeted CAR-T therapy (except in subjects who relapsed after CR to prior CAR-T treatment);
- Prior treatment with any antibody targeting BCMA;
- Known active, or prior history of central nervous system (CNS) involvement, or clinical signs of membrane/spinal membrane involvement of multiple myeloma;
- Serious underlying medical conditions
- Positive of any hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), human immunodeficiency virus antibody (HIV-Ab) at the time of screening;
- Male subjects who have a birth plan during the study period or within 1 year after the study treatment
- Female subjects who are pregnant, breast-feeding, or plan to become pregnant during the study period or within 1 year after the study treatment
- The investigator considered that the subjects were not suitable for any conditions of participation in the study
Sites / Locations
- Second Affiliated Hospital of Xi'an Jiaotong University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LUCAR-B68 cells product
Arm Description
Each subject will receive LUCAR-B68 cells
Outcomes
Primary Outcome Measures
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment
Dose-limiting toxicity (DLT) rate
Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose
Recommended Phase 2 dose (RP2D) finding
RP2D established through ATD+BOIN design
CAR positive NK cells in peripheral blood and bone marrow
CAR positive NK cells in peripheral blood and bone marrow after LUCAR-B68 infusion
CAR transgene levels in peripheral blood
CAR transgene levels in peripheral blood after LUCAR-B68 infusion
Secondary Outcome Measures
Overall response rate (ORR)
The ORR is defined as the percentage of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria
Duration of Response (DOR)
Duration of response (DOR) will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria or death due to any cause, whichever occurs first
Time to Response (TTR)
Time to response (TTR) is defined as the time between date of the initial infusion of LCAR-B38M CAR-T cells and the first efficacy evaluation that the participant has met all criteria for PR or better
Progress Free Survival (PFS)
Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LUCAR-B68 to the first documented disease progression (according to IMWG criteria) 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 LUCAR-B68 to death of the subject
Incidence of anti- LUCAR-B68 antibody
Venous blood samples will be collected to measure LUCAR-B68 positive cell concentrations and the transgenic level of LUCAR-B68, at the time points when anti- LUCAR-B68 antibody serum samples are evaluated
Full Information
NCT ID
NCT05498545
First Posted
August 10, 2022
Last Updated
August 10, 2022
Sponsor
Second Affiliated Hospital of Xi'an Jiaotong University
Collaborators
Nanjing Legend Biotech Co.
1. Study Identification
Unique Protocol Identification Number
NCT05498545
Brief Title
Universal BCMA-targeted LUCAR-B68 Cells in Patients With Relapsed/Refractory Multiple Myeloma
Official Title
A Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of Universal BCMA-targeted LUCAR-B68 Cells Product in Patients With Relapsed/Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2022 (Anticipated)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
March 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital of Xi'an Jiaotong University
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 Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of Universal BCMA-targeted LUCAR-B68 Cells Product in Patients With Relapsed/Refractory Multiple Myeloma
Detailed Description
This is a prospective, single-arm, open-label, dose-finding and dose-expansion study that evaluates the safety, tolerability, PK, and anti-tumor efficacy of LUCAR-B68 cell preparations in relapsed/refractory multiple myeloma subjects who received adequate standard therapy
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Multiple Myeloma
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
LUCAR-B68 cells product
Arm Type
Experimental
Arm Description
Each subject will receive LUCAR-B68 cells
Intervention Type
Biological
Intervention Name(s)
LUCAR-B68 cells product
Intervention Description
Before treatment with LUCAR-B68 cells, subjects will receive a conditioning regimen
Primary Outcome Measure Information:
Title
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
Description
An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment
Time Frame
Minimum 2 years after LUCAR-B68 infusion (Day 1
Title
Dose-limiting toxicity (DLT) rate
Description
Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose
Time Frame
Minimum 2 years after LUCAR-B68 infusion (Day 1)
Title
Recommended Phase 2 dose (RP2D) finding
Description
RP2D established through ATD+BOIN design
Time Frame
30 days after LUCAR-B68 infusion (Day 1)
Title
CAR positive NK cells in peripheral blood and bone marrow
Description
CAR positive NK cells in peripheral blood and bone marrow after LUCAR-B68 infusion
Time Frame
Minimum 2 years after LUCAR-B68 infusion (Day 1)
Title
CAR transgene levels in peripheral blood
Description
CAR transgene levels in peripheral blood after LUCAR-B68 infusion
Time Frame
Minimum 2 years after LUCAR-B68 infusion (Day 1)
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
The ORR is defined as the percentage of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria
Time Frame
Minimum 2 years after LUCAR-B68 infusion (Day 1)
Title
Duration of Response (DOR)
Description
Duration of response (DOR) will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria or death due to any cause, whichever occurs first
Time Frame
Minimum 2 years after LUCAR-B68 infusion (Day 1)
Title
Time to Response (TTR)
Description
Time to response (TTR) is defined as the time between date of the initial infusion of LCAR-B38M CAR-T cells and the first efficacy evaluation that the participant has met all criteria for PR or better
Time Frame
Minimum 2 years after LUCAR-B68 infusion (Day 1)
Title
Progress Free Survival (PFS)
Description
Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LUCAR-B68 to the first documented disease progression (according to IMWG criteria) or death (due to any cause), whichever occurs first
Time Frame
2 years after LUCAR-B68 infusion (Day 1)
Title
Overall Survival (OS)
Description
Overall Survival (OS) is defined as the time from the date of first infusion of LUCAR-B68 to death of the subject
Time Frame
Minimum 2 years after LUCAR-B68 infusion (Day 1)
Title
Incidence of anti- LUCAR-B68 antibody
Description
Venous blood samples will be collected to measure LUCAR-B68 positive cell concentrations and the transgenic level of LUCAR-B68, at the time points when anti- LUCAR-B68 antibody serum samples are evaluated
Time Frame
Minimum 2 years after LUCAR-B68 infusion (Day 1)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The subject voluntarily participates in the clinical study; Fully understand and be Informed of the study and sign the Informed consent (Informed Consent Form, ICF); Willing to follow and able to complete all test procedures; Informed consent must be obtained before initiating any tests or procedures related to the study that are not part of the standard treatment of the subject's disease;
Subjects ≥ 18 years of age.
Eastern Cooperative Oncology Group performance status score of 0, 1, or 2;
Documented initial diagnosis of MM according to IMWG diagnostic criteria.
Presence of measurable disease at screening.
Received a PI and an IMiD (except thalidomide).
Received at least 3 prior lines of therapy for multiple myeloma, undergone at least 1 complete cycle of treatment for each line, unless progressive disease (PD) was documented by IMWG criteria as the best response to the regimen. Also, subjects refractory or intolerant to any PI and any IMiD in their previous treatment afterwards are eligible.
Expected survival ≥ 3 months.
Clinical laboratory values meet screening visit criteria
Fertile women must be negative using a highly sensitive serum pregnancy test (β human chorionic gonadotropin [β -HCG]) at screening time and before initial treatment with cyclophosphamide and fludarabine;
Exclusion Criteria:
No response to prior BCMA-targeted CAR-T therapy (except in subjects who relapsed after CR to prior CAR-T treatment);
Prior treatment with any antibody targeting BCMA;
Known active, or prior history of central nervous system (CNS) involvement, or clinical signs of membrane/spinal membrane involvement of multiple myeloma;
Serious underlying medical conditions
Positive of any hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), human immunodeficiency virus antibody (HIV-Ab) at the time of screening;
Male subjects who have a birth plan during the study period or within 1 year after the study treatment
Female subjects who are pregnant, breast-feeding, or plan to become pregnant during the study period or within 1 year after the study treatment
The investigator considered that the subjects were not suitable for any conditions of participation in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wan-Hong Zhao, PhD
Phone
86-29-87679459
Email
zhaowanhong68@163.com
Facility Information:
Facility Name
Second Affiliated Hospital of Xi'an Jiaotong University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710000
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Universal BCMA-targeted LUCAR-B68 Cells in Patients With Relapsed/Refractory Multiple Myeloma
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