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 (CAREMM-002)

Safety and Efficiency of VRd Combining BCMA CAR-T Regimen for Transplant-ineligible Patients With Primary Plasma Cell Leukemia: a Prospective, Single-arm, Single-center, Phase II Study.

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

Study Overview

• Status: Recruiting
• Conditions: Plasma Cell Leukemia
• Intervention / Treatment: Biological: anti-BCMA CAR-T; Drug: VRD-based regimen

Detailed Description

The study is a prospective, single-arm, single-centre, phase II study designed to evaluate the efficacy and safety of treatment with VRD-based regimen combined with BCMA CAR-T in transplant-ineligible patients with primary plasma cell leukemia. Patients received 3 courses of induction therapy with VRD-based regimen followed by infusion of BCMA CAR-T cells. Patients then received 3 courses of VR consolidation therapy, followed by VR maintenance therapy.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gang An, PhD&MD; Phone Number: 86-022-23909171; Email: angang@ihcams.ac.cn

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
    • Contact: Gang AN, PhD&MD; Phone Number: 008613502181109; Email: angang@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 75 years.
2. 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).
3. 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.
4. 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.
5. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
6. 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).
7. 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%).
8. Patients must be able to take prophylactic anticoagulant therapy as recommended by the study.
9. 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.

Exclusion Criteria:

1. Documented active amyloidosis.
2. Documented with central nervous system (CNS) invasion.
3. Prior exposure to any BCMA-targeted therapy or CAR-T therapy.
4. 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.
5. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and BCMA-CART cellular products.
6. Seropositive for human immunodeficiency virus (HIV)
7. Hepatitis B infection
8. Hepatitis C infection
9. Life expectancy of <6 months
10. Women who are pregnant or breastfeeding
11. 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
12. 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.
13. Received live attenuated vaccine within 4 weeks prior to study treatment.
14. 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.
15. Necessary medication or supportive therapy is contraindicated with study treatment.
16. Any diseases or complications that may interfere with the study.
17. Patients are not willing to or cannot comply with study scheme.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VRD-based Regimen Combined With BCMA CART; 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; 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.; Drug: VRD-based regimen; Bortezomib, Lenalidomide and Dexamethasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Progression free survival is defined as the time from the date of diagnosis to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first	Up to 2 year
Overall Survival (OS)	Overall survival is measured from the date of diagnosis to the date of the participant's death.	Up to 5 year
Complete response rate (CRR)	CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response accoording to the IMWG criteria	within 1 week after induction therapy, 1 month after the CAR-T cell transfusion, within 1 week after consolidation therapy
Duration of Remission(DOR)	Duration from the first evaluation of at least partial remission (PR) to the onset of disease progression or death due to disease progression (whichever occurs first)	Up to 2 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Physical status assessed by International Myeloma Working Group Comprehensive Geriatric Assessment (IMWG-CGA) scores	The IMWG-CGA was calculated by combining age, activities of daily living (ADL), instrumental ADL (IADL), and Charlson Comorbidity Index (CCI), which ranges from 0 to 5 with higher scores indicating worse physical condition and greater weakness.	Baseline up to 5 years
Change from Baseline in Physical status assessed by activities of daily living (ADL) scores	The ADL includes 4 items (transfer, bed mobility, toileting, and eating), which range from 0 to 6 scores. A higher score represents worse physical condition and greater weakness.	Baseline up to 5 years
Change from Baseline in Physical status assessed by instrumental activities of daily living (IADL) scores	The IADL includes 5 items (cooking, cleaning, transportation, laundry, and managing finances), which range from 0 to 8 scores. A higher score represents worse physical condition and greater weakness.	Baseline up to 5 years
Change from Baseline in Physical status assessed by Charlson Comorbidity Index (CCI)	The CCI estimates the number and the severity of comorbidities, including nineteen diseases with a score varying from 1 to 6 for each of them in accordance to their severity. The score can range from 0 to 37. A higher score represents more severe comorbidities.	Baseline up to 5 years
The duration of CART cell in vivo	The copies of BCMA-CART DNA in peripheral blood with qPCR method	Up to 1 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: July 29, 2023
• First Submitted That Met QC Criteria: July 29, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Multiple Myeloma; Leukemia; Leukemia, Plasma Cell
• Other Study ID Numbers: IIT2023034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes