BCMA-targeted LCAR-BCDR Cells in Patients With Relapsed/Refractory Multiple Myeloma

Phase 1

Recruiting

• Conditions: Relapsed/Refractory Multiple Myeloma
• Interventions: Biological: LCAR-BCDR cells product

• Registration Number: NCT05376345
• Lead Sponsor: Weijun Fu

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

Not available

Study Timeline

• Study First Submitted: 2022-05-12
• Study First Submitted QC: 2022-05-12
• Study First Posted: 2022-05-17
• Study Start: 2022-09-01
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-21
• Last Update Posted: 2023-09-25
• Primary Completion: 2024-06
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LCAR-BCDR cells product	LCAR-BCDR cells product	Each subject will receive LCAR-BCDR cells

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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
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
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

Trial Locations

Locations (6)

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, China

Beijing Gobroad Boren Hospital; 🇨🇳 Beijing, Beijing, China

Shanghai Fourth People's Hospital Affiliated to Tongji University; 🇨🇳 Shanghai, China

The First Affiliated Hospital of Wenzhou Medical University; 🇨🇳 Wenzhou, China

Zhejiang Provincial People's Hospital; 🇨🇳 Hangzhou, Zhejiang, China

Shanghai Changzheng Hospital; 🇨🇳 Shanghai, China