Relapsed/Refractory Multiple Myeloma
Conditions
Brief summary
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 LCAR-BCDR cell preparations in relapsed/refractory multiple myeloma subjects who received adequate standard therapy.
Detailed description
The research plan stipulates that "four dose groups will be conducted, namely 30×10\^6, 100×10\^6, 200×10\^6, and 400×10\^6". The research team held a SET meeting and decided to increase the dose escalation to 600×10\^6 and 800×10\^6, and obtained ethical approval from all sites.
Interventions
BIOLOGICALLCAR-BCDR cells product
Before treatment with LCAR-BCDR cells, subjects will receive a conditioning regimen
Sponsors
Shanghai Changzheng Hospital
Nanjing Legend Biotech Co.
First Affiliated Hospital of Wenzhou Medical University
Beijing Boren Hospital
Zhejiang Provincial People's Hospital
Shanghai Fourth People's Hospital Tongji University
Institute of Hematology & Blood Diseases Hospital, China
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. 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; 2. Subjects ≥ 18 years of age. 3. Documented initial diagnosis of MM according to IMWG diagnostic criteria. 4. Presence of measurable disease at screening. 5. Received a PI and an IMiD (except thalidomide). 6. 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. 7. Expected survival ≥ 3 months. 8. Clinical laboratory values meet screening visit criteria 9. 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
1. No response to prior BCMA-targeted CAR-T therapy (except in subjects who relapsed after CR to prior CAR-T treatment). 2. Prior treatment with any antibody targeting BCMA. 3. Diagnosed or pretreated for an invasive malignancy other than multiple myeloma. 4. Prior anti-tumor treatment (before pretreatment) with insufficient washout period. 5. Known active, or prior history of central nervous system (CNS) involvement, or clinical signs of membrane/spinal membrane involvement of multiple myeloma. 6. 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. 7. Serious underlying medical conditions 8. Male subjects who have a birth plan during the study period or within 1 year after the study treatment. 9. Female subjects who are pregnant, breast-feeding, or plan to become pregnant during the study period or within 1 year after the study treatment. 10. The investigator considered that the subjects were not suitable for any conditions of participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, severity, and type of treatment-emergent adverse events (TEAEs) | Minimum 2 years after LCAR-BCDR infusion (Day 1) | 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. |
| Recommended Phase 2 dose (RP2D) finding | 30 days after LCAR-BCDR infusion (Day 1) | RP2D established through ATD+BOIN design |
| CAR positive T cells in peripheral blood and bone marrow | Minimum 2 years after LCAR-BCDR infusion (Day 1) | CAR positive T cells in peripheral blood and bone marrow after LCAR-BCDR infusion |
| CAR transgene levels in peripheral blood and bone marrow | Minimum 2 years after LCAR-BCDR infusion (Day 1) | CAR transgene levels in peripheral blood and bone marrow after LCAR-BCDR infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Minimum 2 years after LCAR-BCDR infusion (Day 1) | The ORR is defined as the percentage of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria. |
| Progression-free survival (PFS) | Minimum 2 years after LCAR-BCDR infusion (Day 1) | Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LCAR-BCDR to the first documented disease progression (according to IMWG criteria) or death (due to any cause), whichever occurs first |
| Overall Survival (OS) | Minimum 2 years after LCAR-BCDR 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 |
| Incidence of anti-LCAR-BCDR antibody | Minimum 2 years after LCAR-BCDR infusion (Day 1) | Venous blood samples will be collected to measure LCAR-BCDR positive cell concentrations and the transgenic level of LCAR-BCDR, at the time points when anti-LCAR-BCDR antibody serum samples are evaluated |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORWeijun Fu, PhD
Shanghai Changzheng Hospital
Outcome results
None listed