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BCMA CAR-T Cell Therapy in High-risk NDMM Patients With Positive MRD After First-line ASCT

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
anti-BCMA CAR-T
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 - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 18 years. Participants with documented NDMM according to IMWG diagnostic criteria. High-risk MM, as determined by R2-ISS(J Clin Oncol, 2022,40(29):3406-3418.), Stage III or Stage IV. Has received 3 to 6 cycles of induction therapy, followed by conditioning regimen and ASCT. Screening must be completed within 100 days of ASCT. For subjects receiving consolidation therapy after ASCT, screening must be completed within 60 days after consolidation therapy, and within 6 months after ASCT. Detectable MRD using EuroFlow or NGS, at 100 days after ASCT (minimum sensitivity of 10-5). 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<1.5 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 > 60mL/min (calculated using the 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 ≥ 85 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. Has received maintenance therapy. 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 BCMA-CART cellular products. Seropositive for human immunodeficiency virus (HIV). Hepatitis B infection. Hepatitis C infection. Life expectancy of <3 months. Women who are pregnant or breastfeeding. 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

BCMA CAR-T in high-risk MM with detectable MRD after first-line ASCT

Arm Description

Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2-4 x 10^6 anti-BCMA CAR+T cells/kg.

Outcomes

Primary Outcome Measures

Safety and Tolerability
The incidence of treatment-emergent adverse events (TEAEs)
MRD-negativity rate
Achieving undetectable MRD, as determined by NGF/NGS 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.

Full Information

First Posted
April 27, 2023
Last Updated
May 4, 2023
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT05846737
Brief Title
BCMA CAR-T Cell Therapy in High-risk NDMM Patients With Positive MRD After First-line ASCT
Official Title
Safety and Efficiency of BCMA CAR-T Cell Therapy in High-risk NDMM Patients With Positive MRD After First-line ASCT: a Prospective, Single-arm, Single-center, Phase II Study.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Anticipated)
Primary Completion Date
May 1, 2025 (Anticipated)
Study Completion Date
May 1, 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 study is a open-label, single-center Phase 2 study to evaluate the efficacy and safety of BCMA CAR-T Cell Therapy in High-risk NDMM Patients With Positive MRD After First-line ASCT. A total of 40 subjects will be enrolled into this study.
Detailed Description
The study is a prospective, single-arm, single-centre, phase II study designed to evaluate the efficacy and safety of BCMA CAR-T Cell Therapy in High-risk NDMM Patients With Positive MRD After First-line ASCT. Patients with detectable MRD after undergoing ASCT MRD will be enrolled in this study.

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
BCMA CAR-T in high-risk MM with detectable MRD after first-line ASCT
Arm Type
Experimental
Arm Description
Autologous BCMA-directed CAR-T cells, infusion intravenously at a target dose of 2-4 x 10^6 anti-BCMA CAR+T cells/kg.
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 2-4 x 10^6 anti-BCMA CAR+T cells/kg.
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-negativity rate
Description
Achieving undetectable MRD, as determined by NGF/NGS 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
1 month after the CAR-T cell transfusion, 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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years. Participants with documented NDMM according to IMWG diagnostic criteria. High-risk MM, as determined by R2-ISS(J Clin Oncol, 2022,40(29):3406-3418.), Stage III or Stage IV. Has received 3 to 6 cycles of induction therapy, followed by conditioning regimen and ASCT. Screening must be completed within 100 days of ASCT. For subjects receiving consolidation therapy after ASCT, screening must be completed within 60 days after consolidation therapy, and within 6 months after ASCT. Detectable MRD using EuroFlow or NGS, at 100 days after ASCT (minimum sensitivity of 10-5). 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<1.5 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 > 60mL/min (calculated using the 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 ≥ 85 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. Has received maintenance therapy. 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 BCMA-CART cellular products. Seropositive for human immunodeficiency virus (HIV). Hepatitis B infection. Hepatitis C infection. Life expectancy of <3 months. Women who are pregnant or breastfeeding. 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
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gang An, PhD&MD
Phone
+86-022-23909171
Email
angang@ihcams.ac.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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BCMA CAR-T Cell Therapy in High-risk NDMM Patients With Positive MRD After First-line ASCT

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