Combination therapy for patients with primary plasma cell leukemia who cannot undergo transplant

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 study is testing a new combination treatment for patients with primary plasma cell leukemia who can't have a transplant to see if it helps manage their disease better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Drugs / interventions: CAR-T, CART, chemotherapy
• Locations: 1 site (Tianjin)
• Trial ID: NCT05979363 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of a treatment regimen combining Bortezomib, Lenalidomide, and Dexamethasone (VRD) followed by BCMA CAR-T therapy in patients with primary plasma cell leukemia who are ineligible for transplant. It is a single-arm, open-label, phase II study where participants will receive three courses of the VRD regimen, followed by BCMA CAR-T cell infusion, and then three courses of VR consolidation therapy, concluding with VR maintenance therapy. The goal is to assess how well this combination works in managing the disease in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with documented primary plasma cell leukemia who are not eligible for high-dose chemotherapy with autologous stem cell transplant.

Not a fit: Patients 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 approach could provide a new effective treatment option for patients with primary plasma cell leukemia who cannot undergo transplantation.

How similar studies have performed: While there have been studies on CAR-T therapies for various hematological malignancies, this specific combination approach in transplant-ineligible primary plasma cell leukemia is relatively novel.

Eligibility criteria

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.

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: Plasma Cell Leukemia