Clinical trial NCT05376345: BCMA-targeted LCAR-BCDR Cells in Patients With Relapsed/Refractory Multiple Myeloma
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of BCMA-targeted LCAR-BCDR Cells Product in Patients With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2022-05-17
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
timeFrame: Minimum 2 years after LCAR-BCDR infusion (Day 1)
measure: Recommended Phase 2 dose (RP2D) finding
timeFrame: 30 days after LCAR-BCDR infusion (Day 1)
measure: CAR positive T cells in peripheral blood and bone marrow
timeFrame: Minimum 2 years after LCAR-BCDR infusion (Day 1)
measure: CAR transgene levels in peripheral blood and bone marrow
timeFrame: Minimum 2 years after LCAR-BCDR infusion (Day 1)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Minimum 2 years after LCAR-BCDR infusion (Day 1)
measure: Progression-free survival (PFS)
timeFrame: Minimum 2 years after LCAR-BCDR infusion (Day 1)
measure: Overall Survival (OS)
timeFrame: Minimum 2 years after LCAR-BCDR infusion (Day 1)
measure: Incidence of anti-LCAR-BCDR antibody
timeFrame: Minimum 2 years after LCAR-BCDR infusion (Day 1)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Gobroad Boren Hospital
state: Beijing
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
city: Shanghai
country: China
facility: Shanghai Fourth People's Hospital Affiliated to Tongji University
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
Study officials:
References: