Plasma Cell Leukemia
Conditions
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
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.
Interventions
BIOLOGICALanti-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.
Bortezomib, Lenalidomide and Dexamethasone
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | Up to 2 year | The incidence of treatment-emergent adverse events (TEAEs) |
| MRD-negative rate | within 1 week after consolidation treatment | achieving MRD-negative, as determined by NGS/NGF after consolidation treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) | within 1 week after induction therapy, 1 month after the CAR-T cell transfusion, within 1 week after consolidation therapy | 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 |
| Progression free survival (PFS) | Up to 2 year | 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 |
| Overall Survival (OS) | Up to 5 year | Overall survival is measured from the date of diagnosis to the date of the participant's death. |
| Duration of Remission(DOR) | Up to 2 year | 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Physical status assessed by International Myeloma Working Group Comprehensive Geriatric Assessment (IMWG-CGA) scores | Baseline up to 5 years | 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. |
| Change from Baseline in Physical status assessed by activities of daily living (ADL) scores | Baseline up to 5 years | 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. |
| Change from Baseline in Physical status assessed by instrumental activities of daily living (IADL) scores | Baseline up to 5 years | 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. |
| Change from Baseline in Physical status assessed by Charlson Comorbidity Index (CCI) | Baseline up to 5 years | 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. |
| The duration of CART cell in vivo | Up to 1 year | The copies of BCMA-CART DNA in peripheral blood with qPCR method |
Countries
China
Contacts
Primary ContactGang An, PhD&MD
Outcome results
None listed