Treatment for transplant-ineligible patients with newly diagnosed multiple myeloma using VRd and CAR-T therapy

Safety and Efficiency of VRd-based Regimen Followed by BCMA CAR-T for New-diagnosed Transplant-ineligible Multiple Myeloma Patients: a Prospective, Single-arm, Single-center, Phase II Study.

This study is testing a new treatment combining VRd and CAR-T therapy for Chinese patients with newly diagnosed multiple myeloma who can't have a transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, CART, chemotherapy
• Locations: 1 site (Tianjin)
• Trial ID: NCT05860036 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label phase II study aimed at evaluating the efficacy and safety of a treatment regimen combining VRd (Bortezomib, Lenalidomide, and Dexamethasone) with BCMA CAR-T therapy in Chinese patients who are ineligible for transplant due to various reasons. Participants will receive three courses of the VRd regimen followed by infusion of BCMA CAR-T cells, and then undergo three courses of VR-based consolidation therapy, concluding with R maintenance therapy. The study focuses on patients with newly diagnosed multiple myeloma who meet specific eligibility criteria.

Who should consider this trial

Good fit: Ideal candidates for this study are Chinese adults aged 18 to 75 with newly diagnosed multiple myeloma who are not eligible for high-dose chemotherapy with autologous stem cell transplant.

Not a fit: Patients who are not diagnosed with multiple myeloma or those who are eligible for high-dose chemotherapy with autologous stem cell transplant may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could provide a new effective option for patients with newly diagnosed multiple myeloma who cannot undergo transplantation.

How similar studies have performed: Other studies have shown promising results with CAR-T therapies in multiple myeloma, indicating that this approach may be effective, although this specific combination is novel.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 75 years.
2. Participants with documented NDMM according to IMWG diagnostic criteria.
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. Primary plasma cell leukemia.
2. Documented active amyloidosis.
3. Multiple myeloma with central nervous system (CNS) invasion.
4. Prior exposure to any BCMA-targeted therapy or CAR-T therapy.
5. 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.
6. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and BCMA-CART cellular products.
7. Seropositive for human immunodeficiency virus (HIV)
8. Hepatitis B infection
9. Hepatitis C infection
10. Life expectancy of \<6 months
11. Women who are pregnant or breastfeeding
12. 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
13. 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.
14. Received live attenuated vaccine within 4 weeks prior to study treatment.
15. 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.
16. Necessary medication or supportive therapy is contraindicated with study treatment.
17. Any diseases or complications that may interfere with the study.
18. Patients are not willing to or cannot comply with study scheme.

Where this trial is running

Tianjin

• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin, China (Recruiting)

Study contacts

• Study coordinator: Gang An, PhD&MD

Conditions Multiple Myeloma