Clinical trial NCT05498545: 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
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Lead sponsor: Second Affiliated Hospital of Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2022-08-12
Enrollment: 34
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: 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

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. Eastern Cooperative Oncology Group performance status score of 0, 1, or 2;
4. Documented initial diagnosis of MM according to IMWG diagnostic criteria.
5. Presence of measurable disease at screening.
6. Received a PI and an IMiD (except thalidomide).
7. 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.
8. Expected survival ≥ 3 months.
9. Clinical laboratory values meet screening visit criteria
10. 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. Known active, or prior history of central nervous system (CNS) involvement, or clinical signs of membrane/spinal membrane involvement of multiple myeloma;
4. Serious underlying medical conditions
5. 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;
6. Male subjects who have a birth plan during the study period or within 1 year after the study treatment
7. Female subjects who are pregnant, breast-feeding, or plan to become pregnant during the study period or within 1 year after the study treatment
8. 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 LUCAR-B68 infusion (Day 1
measure: Dose-limiting toxicity (DLT) rate
timeFrame: Minimum 2 years after LUCAR-B68 infusion (Day 1)
measure: Recommended Phase 2 dose (RP2D) finding
timeFrame: 30 days after LUCAR-B68 infusion (Day 1)
measure: CAR positive NK cells in peripheral blood and bone marrow
timeFrame: Minimum 2 years after LUCAR-B68 infusion (Day 1)
measure: CAR transgene levels in peripheral blood
timeFrame: Minimum 2 years after LUCAR-B68 infusion (Day 1)
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Minimum 2 years after LUCAR-B68 infusion (Day 1)
measure: Duration of Response (DOR)
timeFrame: Minimum 2 years after LUCAR-B68 infusion (Day 1)
measure: Time to Response (TTR)
timeFrame: Minimum 2 years after LUCAR-B68 infusion (Day 1)
measure: Progress Free Survival (PFS)
timeFrame: 2 years after LUCAR-B68 infusion (Day 1)
measure: Overall Survival (OS)
timeFrame: Minimum 2 years after LUCAR-B68 infusion (Day 1)
measure: Incidence of anti- LUCAR-B68 antibody
timeFrame: Minimum 2 years after LUCAR-B68 infusion (Day 1)
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Second Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
Study officials:
References: