A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd)-Based Regimen Followed by BCMA CAR-T Therapy in Transplant-Ineligible Patients With Primary Plasma Cell Leukemia

NCT05979363 | Recruiting Phase 2 FDA Drug

• 1 other identifier: IIT2023034
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label study to evaluate the efficacy and safety of VRD-based regimen combined with BCMA CAR-T in transplant-ineligible patients with primary plasma cell leukemia

Conditions

Plasma Cell Leukemia

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 after consolidation treatment

  within 1 week after consolidation treatment

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 duration of CART cell 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-based induction, BCMA CAR-T infusion, VR consolidation, VR maintenance.

Biological: anti-BCMA CAR-T; Drug: VRD-based regimen

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-based regimen 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 primary plasma cell leukemia according to IMWG diagnostic criteria (circulating plasma cells ≥5%, determined by morphology on peripheral blood smear; or absolute value of peripheral blood tumorigenic plasma cells exceeds 2×10\^9/L).
• 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:

• Documented active amyloidosis.
• Documented 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.
• Necessary medication or supportive therapy is contraindicated with study treatment.

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

RECRUITING

MeSH Terms

Conditions

Leukemia, Plasma Cell

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Gang An, PhD&MD

CONTACT

86-022-23909171; angang@ihcams.ac.cn

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: July 29, 2023
• First Posted: August 7, 2023
• Study Start: August 14, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)