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A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by BCMA CAR-T Therapy in Transplant-Ineligible Patients With New-diagnosed Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
anti-BCMA CAR-T
VRD
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 18 years and ≤ 75 years. Participants with documented NDMM according to IMWG diagnostic criteria. 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. 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. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination. 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). 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%). Patients must be able to take prophylactic anticoagulant therapy as recommended by the study. 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: Primary plasma cell leukemia. Documented active amyloidosis. Multiple myeloma with central nervous system (CNS) invasion. Prior exposure to any BCMA-targeted therapy or CAR-T therapy. 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. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and BCMA-CART cellular products. Seropositive for human immunodeficiency virus (HIV) Hepatitis B infection Hepatitis C infection Life expectancy of <6 months Women who are pregnant or breastfeeding 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 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. Received live attenuated vaccine within 4 weeks prior to study treatment. 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. Necessary medication or supportive therapy is contraindicated with study treatment. Any diseases or complications that may interfere with the study. Patients are not willing to or cannot comply with study scheme.

Sites / Locations

  • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

VRD Combined With BCMA CART

Arm Description

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 induction, BCMA CAR-T infusion, VR consolidation, R maintenance.

Outcomes

Primary Outcome Measures

Safety and Tolerability
The incidence of treatment-emergent adverse events (TEAEs)
MRD-negative rate
achieving MRD-negative, as determined by NGS/NGF 3 months after CAR-T cell infusion

Secondary Outcome Measures

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
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
Overall Survival (OS)
Overall survival is measured from the date of diagnosis to the date of the participant's death.
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)

Full Information

First Posted
April 3, 2023
Last Updated
July 12, 2023
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT05860036
Brief Title
A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by BCMA CAR-T Therapy in Transplant-Ineligible Patients With New-diagnosed Multiple Myeloma
Official Title
Safety and Efficiency of VRd Combining BCMA CAR-T Regimen for New-diagnosed Transplant-ineligible Multiple Myeloma Patients: a Prospective, Single-arm, Single-center, Phase II Study.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2023 (Actual)
Primary Completion Date
March 10, 2025 (Anticipated)
Study Completion Date
March 10, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

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

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VRD Combined With BCMA CART
Arm Type
Experimental
Arm Description
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 induction, BCMA CAR-T infusion, VR consolidation, R maintenance.
Intervention Type
Biological
Intervention Name(s)
anti-BCMA CAR-T
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
VRD
Intervention Description
Bortezomib, Lenalidomide and Dexamethasone
Primary Outcome Measure Information:
Title
Safety and Tolerability
Description
The incidence of treatment-emergent adverse events (TEAEs)
Time Frame
Up to 2 year
Title
MRD-negative rate
Description
achieving MRD-negative, as determined by NGS/NGF 3 months after CAR-T cell infusion
Time Frame
3 months after CAR-T cell infusion
Secondary Outcome Measure Information:
Title
Complete response rate (CRR)
Description
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
Time Frame
within 1 week after induction therapy, 1 month after the CAR-T cell transfusion, within 1 week after consolidation therapy
Title
Progression free survival (PFS)
Description
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
Time Frame
Up to 2 year
Title
Overall Survival (OS)
Description
Overall survival is measured from the date of diagnosis to the date of the participant's death.
Time Frame
Up to 5 year
Title
Duration of Remission(DOR)
Description
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)
Time Frame
Up to 2 year
Other Pre-specified Outcome Measures:
Title
The CART cell duration in vivo
Description
The copies of BCMA-CART DNA in peripheral blood with qPCR method
Time Frame
Up to 1 year
Title
Change from Baseline in Physical status assessed by International Myeloma Working Group Comprehensive Geriatric Assessment (IMWG-CGA) scores
Description
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.
Time Frame
Baseline up to 5 years
Title
Change from Baseline in Physical status assessed by activities of daily living (ADL) scores
Description
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.
Time Frame
Baseline up to 5 years
Title
Change from Baseline in Physical status assessed by instrumental activities of daily living (IADL) scores
Description
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.
Time Frame
Baseline up to 5 years
Title
Change from Baseline in Physical status assessed by Charlson Comorbidity Index (CCI)
Description
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.
Time Frame
Baseline up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years and ≤ 75 years. Participants with documented NDMM according to IMWG diagnostic criteria. 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. 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. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination. 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). 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%). Patients must be able to take prophylactic anticoagulant therapy as recommended by the study. 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: Primary plasma cell leukemia. Documented active amyloidosis. Multiple myeloma with central nervous system (CNS) invasion. Prior exposure to any BCMA-targeted therapy or CAR-T therapy. 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. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and BCMA-CART cellular products. Seropositive for human immunodeficiency virus (HIV) Hepatitis B infection Hepatitis C infection Life expectancy of <6 months Women who are pregnant or breastfeeding 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 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. Received live attenuated vaccine within 4 weeks prior to study treatment. 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. Necessary medication or supportive therapy is contraindicated with study treatment. Any diseases or complications that may interfere with the study. Patients are not willing to or cannot comply with study scheme.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gang An, PhD&MD
Phone
86-022-23909171
Email
angang@ihcams.ac.cn
Facility Information:
Facility Name
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
City
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gang An, PhD&MD
Phone
008613502181109
Email
angang@ihcams.ac.cn

12. IPD Sharing Statement

Learn more about this trial

A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by BCMA CAR-T Therapy in Transplant-Ineligible Patients With New-diagnosed Multiple Myeloma

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