A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by BCMA CAR-T Therapy in Transplant-Ineligible Patients With New-diagnosed Multiple Myeloma
Study Details
Study Description
Brief Summary
This is a single-arm, open-label study to evaluate the efficacy and safety of VRD(Bortezomib, Lenalidomide and Dexamethasone) regimen combined with BCMA CAR-T in Chinese transplant-ineligible patients with newly diagnosed multiple myeloma
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 (Bortezomib, Lenalidomide and Dexamethasone) regimen combined with BCMA CAR-T in Chinese transplant-ineligible patients with newly diagnosed multiple myeloma. Patients received 3 courses of induction therapy with VRd followed by infusion of BCMA CAR-T cells. Patients then received 3 courses of VR consolidation therapy, followed by R maintenance therapy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VRD 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 x 10^6 anti-BCMA CAR+T cells/kg. Participants will receive VRD induction, BCMA CAR-T infusion, VR consolidation, R maintenance. |
Biological: anti-BCMA CAR-T
Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2.0 x 10^6 anti-BCMA CAR+T cells/kg.
Drug: VRD
Bortezomib, Lenalidomide and Dexamethasone
|
Outcome Measures
Primary Outcome Measures
- Safety and Tolerability [Up to 2 year]
The incidence of treatment-emergent adverse events (TEAEs)
- MRD-negative rate [3 months after CAR-T cell infusion]
achieving MRD-negative, as determined by NGS/NGF 3 months after CAR-T cell infusion
Secondary Outcome Measures
- 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 Outcome Measures
- The CART cell duration in vivo [Up to 1 year]
The copies of BCMA-CART DNA in peripheral blood with qPCR method
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years and ≤ 75 years.
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Participants with documented NDMM according to IMWG diagnostic criteria.
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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.
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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.
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Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
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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 ≥ 40mL/min (calculated using Cockroft-Gault formula).
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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%).
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Patients must be able to take prophylactic anticoagulant therapy as recommended by the study.
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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:
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Primary plasma cell leukemia.
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Documented active amyloidosis.
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Multiple myeloma with central nervous system (CNS) invasion.
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Prior exposure to any BCMA-targeted therapy or CAR-T therapy.
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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.
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Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and BCMA-CART cellular products.
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Seropositive for human immunodeficiency virus (HIV)
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Hepatitis B infection
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Hepatitis C infection
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Life expectancy of <6 months
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Women who are pregnant or breastfeeding
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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
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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.
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Received live attenuated vaccine within 4 weeks prior to study treatment.
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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.
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Necessary medication or supportive therapy is contraindicated with study treatment.
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Any diseases or complications that may interfere with the study.
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Patients are not willing to or cannot comply with study scheme.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences | Tianjin | China |
Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CAREMM-001