A Study of VRd-based Regimen Followed by BCMA CAR-T Therapy in Transplant-Ineligible Patients With New-diagnosed Multiple Myeloma

NCT05860036 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: IIT2022073
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label study to evaluate the efficacy and safety of VRd(Bortezomib, Lenalidomide and Dexamethasone)-based regimen combined with BCMA CAR-T in Chinese transplant-ineligible patients with newly diagnosed multiple myeloma

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability

  The incidence of treatment-emergent adverse events (TEAEs)

  Up to 2 year

• MRD-negative rate

  achieving MRD-negative, as determined by NGS/NGF 3 months after CAR-T cell infusion

  3 months after CAR-T cell infusion

Secondary Outcomes (4)

• Complete response rate (CRR)

  within 1 week after induction therapy, 1 month after the CAR-T cell transfusion, within 1 week after consolidation therapy

• Progression free survival (PFS)

  Up to 2 year

• Overall Survival (OS)

  Up to 5 year

• Duration of Remission(DOR)

  Up to 2 year

Other Outcomes (5)

• The CART cell duration in vivo

  Up to 1 year

• Change from Baseline in Physical status assessed by International Myeloma Working Group Comprehensive Geriatric Assessment (IMWG-CGA) scores

  Baseline up to 5 years

• Change from Baseline in Physical status assessed by activities of daily living (ADL) scores

  Baseline up to 5 years

Study Arms (1)

VRd-based regimen Combined With BCMA CART

EXPERIMENTAL

VRd：Bortezomib, Lenalidomide and Dexamethasone Bortezomib SC 1.3mg/sqm on day 1,8,15,22, Lenalidomide oral 25 mg on day 1-21, and Dexamethasone 40mg on day 1,8,15,22 in a 28-day cycle. Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2-4 x 10\^6 anti-BCMA CAR+T cells/kg. Participants will receive VRD induction, BCMA CAR-T infusion, VR consolidation, R maintenance.

Biological: anti-BCMA CAR-T; Drug: VRd

Interventions

anti-BCMA CAR-T BIOLOGICAL

Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2.0-4.0 x 10\^6 anti-BCMA CAR+T cells/kg.

VRd-based regimen Combined With BCMA CART

VRd DRUG

Bortezomib, Lenalidomide and Dexamethasone

VRd-based regimen Combined With BCMA CART

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤ 75 years.
• Participants with documented NDMM according to IMWG diagnostic criteria.
• Measurable disease, at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
• Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant (ASCT) due to: Ineligible due to advanced age (≥65); or Ineligible evaluated by researchers; or Eastern Cooperative Oncology Group Performance Status grade of 3 or 4; or Repeated hematopoietic stem cell mobilization failure；or Deferral of high-dose chemotherapy with ASCT as initial treatment.
• Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
• All screening blood biochemistry: tests should be performed according to the protocol and within 14 days before enrollment. Screening laboratory values must meet the following criteria: a.TBIL\<2 x upper limit of normal (ULN) (\<3 x ULN in patients with Gilbert's syndrome); b.AST and ALT \<3 x ULN.; c. Creatinine clearance ≥ 30mL/min (calculated using Cockroft-Gault formula).
• Routine blood tests (performed within 7 days, no RBC transfusion, no G-CSF/GM-CSF/platelet agonists, no drug correction within 14 days before screening, no PLT transfusion within 7 days) : WBC ≥ 1.5 x 109/L, ANC ≥ 1.0 x 109/L, Hb ≥ 70 g/L PLT ≥ 75 x 109/L (if BMPC \< 50%) or PLT ≥ 50 x 109/L (if BMPC ≥ 50%).
• Patients must be able to take prophylactic anticoagulant therapy as recommended by the study.
• The woman is not breastfeeding, is not pregnant and agrees not to be pregnant during the study period and for the following 12 months. Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter.

You may not qualify if:

• Primary plasma cell leukemia.
• Documented active amyloidosis.
• Multiple myeloma with central nervous system (CNS) invasion.
• Prior exposure to any BCMA-targeted therapy or CAR-T therapy.
• Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy greater than grade 2 with pain at baseline, regardless of whether they were currently receiving medical therapy.
• Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and BCMA-CART cellular products.
• Seropositive for human immunodeficiency virus (HIV)
• Hepatitis B infection
• Hepatitis C infection
• Life expectancy of \<6 months
• Women who are pregnant or breastfeeding
• Any active gastrointestinal dysfunction that affects the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that may affect the absorption of the studied treatment medication
• Subjects had major surgery within 2 weeks before randomization (for example, general anesthesia), or is not fully recovered from the surgery, or surgery is arranged during study period.
• Received live attenuated vaccine within 4 weeks prior to study treatment.
• According to the researcher's judgment, any condition including but not limited to serious mental illness, medical illness, or other symptoms/conditions that may affect study treatment, compliance, or the capability of providing informed consent.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, China

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: May 16, 2023
• Study Start: April 4, 2023
• Primary Completion: June 1, 2025
• Study Completion (Estimated): March 10, 2028
• Last Updated: August 3, 2025

Record last verified: 2025-07

Locations

CN (1)