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Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Multiple Myeloma

Primary Purpose

Multiple Myeloma in Relapse

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
BCMA/GPRC5D double CAR-T
Sponsored by
Guangzhou Bio-gene Technology Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma in Relapse focused on measuring Multiple Myeloma, BCMA, GPRC5D

Eligibility Criteria

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

Inclusion Criteria: Patients or their guardians understand and voluntarily sign the informed consent form, and are expected to complete the follow-up examination and treatment of study procedures; Aged 18-75 years, male or female; According to IMWG diagnostic criteria, diagnosed with multiple myeloma; Patients with documented multiple myeloma disease as relapsed refractory or primary refractory, defined as: a) relapsed refractory: no response to salvage therapy (no response defined as failure to achieve minimal response [MR] or disease progression on treatment), or disease progression within 60 days of the last treatment, or disease progression in patients who have achieved MR or above remission; b) primary refractory: never achieved MR or above response to any treatment, including never achieved MR or above remission, but M protein changes are not large, patients without evidence of clinical progression and patients who have primary refractory, progressed, and met the definition of progression. the presence of measurable disease at screening as determined by any of the following criteria: serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL or urine M-protein level ≥ 200 mg/24 hours; or diagnosis of light chain multiple myeloma without measurable disease in serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin κ/γ free light chain ratio; extramedullary measurable disease; the presence of tumor cells in the bone marrow as detected; the patient has recovered from the toxicity of previous treatment, that is, CTCAE toxicity grade < 2 (unless the abnormality is tumor-related or judged by the investigator to be stable, it has little effect on safety or efficacy); ECOG performance status score 0 to 2 and expected survival greater than 3 months; Appropriate organ function: alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN); aspartate aminotransferase (AST) ≤ 3 times the ULN; total bilirubin ≤ 1.5 times the ULN; Serum creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 30 mL/min (calculated by Cockcroft-Gault formula); Intraventricular oxygen saturation ≥ 92%; Left ventricular ejection fraction (LVEF) ≥ 45%, no pericardial effusion confirmed by echocardiography, no clinically significant electrocardiographic findings; no clinically significant pleural effusion; 9. venous access for collection can be established, no contraindications for leukocyte collection. Exclusion Criteria: Diagnosis or treatment of another invasive malignancy other than multiple myeloma within 3 years, with the following exceptions: malignancy treated with curative intent and no known active disease ≥ 3 years prior to enrollment; or adequately treated non-melanoma skin cancer with no evidence of disease; previous anticancer therapy (prior to blood collection for CAR-T preparation) as follows: targeted therapy, epigenetic therapy, or investigational agent within 14 days or at least 5 half-lives (whichever is shorter), or invasive investigational medical devices; monoclonal antibody therapy within 21 days; proteasome inhibitor therapy within 14 days; immunomodulator therapy within 7 days; and radiotherapy within 14 days (except for bone marrow reserve with ≤ 5% field coverage); Any hematopoietic stem cell transplantation within 2 months before screening; History of central nervous system diseases; known active central nervous system (CNS) involvement or clinical signs of meningeal involvement in multiple myeloma; Waldenström macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal proteinopathy, and skin changes) or primary AL amyloidosis at screening; Hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive and peripheral blood HBV DNA quantitative detection positive; hepatitis C virus (HCV) antibody positive; human immunodeficiency virus (HIV) antibody positive; cytomegalovirus (CMV) DNA detection positive; syphilis detection positive; Epstein-Barr virus DNA detection positive; Patients with a history of severe allergy [a history of severe allergy is defined as a secondary or above allergic reaction, any of the following clinical manifestations occur when allergic reactions occur: airway obstruction (runny nose, cough, wheezing, dyspnea), tachycardia, hypotension, arrhythmia, gastrointestinal symptoms (nausea, vomiting), incontinence, laryngeal edema, bronchospasm, cyanosis, shock, respiratory, cardiac arrest] or known allergy to any of the active ingredients, excipients or murine products and xenogeneic proteins contained in this trial (including Qinglin regimen); Patients with severe heart disease, including but not limited to severe arrhythmia, unstable angina pectoris, massive myocardial infarction, New York Heart Association class III or IV cardiac insufficiency, myocardial infarction ≤ 6 months before screening or coronary artery bypass grafting (CABG), a history of unexplained syncope and non-vasovagal or dehydration caused by, a history of severe non-ischemic cardiomyopathy, refractory hypertension (refractory hypertension is defined as: the use of reasonable tolerable adequate doses of ≥ 3 antihypertensive drugs (including diuretics) on the basis of lifestyle improvement for > 1 month of blood pressure is still not up to standard or taking ≥ 4 antihypertensive drugs blood pressure can be effectively controlled); unstable systemic diseases judged by the investigator: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment; Patients with acute/chronic graft-versus-host disease (GVHD) within 6 months before screening, or need to receive immunosuppressive agents for GVHD; Patients with active autoimmune or inflammatory diseases of the nervous system (e.g., Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically significant active cerebrovascular disease (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES)); Neoplastic emergencies (such as spinal cord compression, intestinal obstruction, leukostasis, tumor lysis syndrome, etc.) requiring emergency treatment before screening or reinfusion; presence of uncontrollable bacterial, fungal, viral, or other infections requiring antibiotic therapy; Hematopoietic cytokine drugs that have been transfused or have an effect on the hemogram of patients such as erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) within 2 weeks of blood collection scheduled for CAR-T preparation at screening, and have an effect on cell preparation as judged by the investigator. Receiving hormonal or immunosuppressive agents at screening within 2 weeks of blood collection scheduled for CAR-T preparation and having an effect on cell preparation as judged by the investigator. 1) Corticosteroids: subjects who are receiving systemic steroid therapy within 2 weeks of blood collection scheduled for CAR-T at screening and require chronic systemic steroid therapy during treatment as judged by the investigator (except for inhaled or topical use); and subjects who are receiving systemic steroid therapy within 72 hours before cell reinfusion (except for inhaled or topical use); 2) Immunosuppressants: subjects who are receiving immunosuppressive agents within 2 weeks of blood collection scheduled for CAR-T at screening; 17. Patients who have undergone major surgery (except diagnostic surgery and biopsy) within 4 weeks before Qinglin or plan to undergo major surgery during the study period, or whose surgical wounds have not completely healed before enrollment; 18. Patients who have received (attenuated) live viral vaccines within 4 weeks before screening; 19. patients with severe mental illness; 20. Alcoholics or those who have a history of drug abuse; 21. Pregnant or lactating women, and female subjects who plan to become pregnant within 2 years after cell reinfusion or male subjects whose partners plan to become pregnant within 2 years after cell reinfusion; 22. patients who have contraindications to any study procedure or have other medical conditions that may place them at unacceptable risk according to the investigator 's judgment and/or clinical criteria.

Sites / Locations

  • Shenzhen Qianhai Shekou Free Trade Zone HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BCMA/GPRC5D double CAR-T

Arm Description

The study plans to enroll 40 subjects, with a sample size based on actual occurrence and a dosage of 3 × 106/kg ± 20%~1 × 107/kg ± 20% CAR positive T cells

Outcomes

Primary Outcome Measures

Evaluation of Safety
Count the Incidence of adverse events
Changes in cytokine level
Calculate the change of cytokine level in peripheral blood by flow cytometry after CLL1 CAR-T infusion. Cytokines include IL-2、IL-6、IL-10、IFN-γ

Secondary Outcome Measures

Complete response rate(CRR)
Proportion of subjects whose serum and urine immunofixation electrophoresis are negative, and there is no soft tissue plasma cell tumor, with bone marrow plasma cells<5%.
Strict complete response rate(SCRR)
Proportion of subjects who achieved complete response with normal FLC ratio and confirmed absence of clonal plasma cells in bone marrow by immunohistochemistry.
Very good partial response rate(VGPRR)
Proportion of subjects who detected serum and urine M protein in immunofixation, but did not detect it from electrophoresis; Or M protein decrease ≥ 90% and urine M protein<100 mg/24h.
Partial response rate(PRR)
Proportion of subjects who met the following requirements: A decrease of ≥ 50% in serum M protein and ≥ 90% or<200 mg/24h in urine M protein; If M protein in serum and urine cannot be detected, it is required to reduce the difference between affected and unaffected serum FLC by ≥ 50%; If M protein and serum FLC in serum and urine cannot be measured, and the baseline bone marrow plasma cell ratio is ≥ 30%, a reduction of ≥ 50% in the number of bone marrow plasma cells is required; In addition to the above criteria, if there is a baseline presence of soft tissue plasmocytoma, it is required that the sum of the maximum vertical diameter product (SPD) of the measurable lesion be reduced by ≥ 50%.
Minimal response rate(MRR)
Proportion of subjects whose serum M protein decreased by 25%~49% and 24-hour urine M protein decreased by 50%~89%; In addition to the above criteria, if there is a baseline presence of soft tissue plasmocytoma, a measurable reduction in lesion SPD of ≥ 50% is required.
Overall response rate(ORR)
Defined as the proportion of subjects who achieve sCR, CR, VGPR, and PR.

Full Information

First Posted
September 28, 2023
Last Updated
September 28, 2023
Sponsor
Guangzhou Bio-gene Technology Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT06068400
Brief Title
Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Multiple Myeloma
Official Title
A Single-Arm, Single-Center Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 13, 2023 (Actual)
Primary Completion Date
May 31, 2029 (Anticipated)
Study Completion Date
May 31, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guangzhou Bio-gene Technology Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a single arm, single center clinical study evaluating the safety and efficacy of CAR-T treatment for multiple myeloma.
Detailed Description
This study is a single arm, single center study targeting patients with recurrent/refractory multiple myeloma (r/rMM). The study plans to enroll 40 subjects, with a sample size based on actual occurrence and a dosage of 3×106/kg±20%~1×107/kg ±20% CAR positive T cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma in Relapse
Keywords
Multiple Myeloma, BCMA, GPRC5D

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
BCMA/GPRC5D double CAR-T
Arm Type
Experimental
Arm Description
The study plans to enroll 40 subjects, with a sample size based on actual occurrence and a dosage of 3 × 106/kg ± 20%~1 × 107/kg ± 20% CAR positive T cells
Intervention Type
Biological
Intervention Name(s)
BCMA/GPRC5D double CAR-T
Intervention Description
BCMA/GPRC5D double CAR-T is a new type CAR-T cells therapy for patients with Multiple Myeloma.
Primary Outcome Measure Information:
Title
Evaluation of Safety
Description
Count the Incidence of adverse events
Time Frame
Up to 2 years after BCMA/GPRC5D double CAR-T infusion
Title
Changes in cytokine level
Description
Calculate the change of cytokine level in peripheral blood by flow cytometry after CLL1 CAR-T infusion. Cytokines include IL-2、IL-6、IL-10、IFN-γ
Time Frame
Up to 2 years after BCMA/GPRC5D double CAR-T infusion
Secondary Outcome Measure Information:
Title
Complete response rate(CRR)
Description
Proportion of subjects whose serum and urine immunofixation electrophoresis are negative, and there is no soft tissue plasma cell tumor, with bone marrow plasma cells<5%.
Time Frame
Up to 2 years after BCMA/GPRC5D double CAR-T infusion
Title
Strict complete response rate(SCRR)
Description
Proportion of subjects who achieved complete response with normal FLC ratio and confirmed absence of clonal plasma cells in bone marrow by immunohistochemistry.
Time Frame
Up to 2 years after BCMA/GPRC5D double CAR-T infusion
Title
Very good partial response rate(VGPRR)
Description
Proportion of subjects who detected serum and urine M protein in immunofixation, but did not detect it from electrophoresis; Or M protein decrease ≥ 90% and urine M protein<100 mg/24h.
Time Frame
Up to 2 years after BCMA/GPRC5D double CAR-T infusion
Title
Partial response rate(PRR)
Description
Proportion of subjects who met the following requirements: A decrease of ≥ 50% in serum M protein and ≥ 90% or<200 mg/24h in urine M protein; If M protein in serum and urine cannot be detected, it is required to reduce the difference between affected and unaffected serum FLC by ≥ 50%; If M protein and serum FLC in serum and urine cannot be measured, and the baseline bone marrow plasma cell ratio is ≥ 30%, a reduction of ≥ 50% in the number of bone marrow plasma cells is required; In addition to the above criteria, if there is a baseline presence of soft tissue plasmocytoma, it is required that the sum of the maximum vertical diameter product (SPD) of the measurable lesion be reduced by ≥ 50%.
Time Frame
Up to 2 years after BCMA/GPRC5D double CAR-T infusion
Title
Minimal response rate(MRR)
Description
Proportion of subjects whose serum M protein decreased by 25%~49% and 24-hour urine M protein decreased by 50%~89%; In addition to the above criteria, if there is a baseline presence of soft tissue plasmocytoma, a measurable reduction in lesion SPD of ≥ 50% is required.
Time Frame
Up to 2 years after BCMA/GPRC5D double CAR-T infusion
Title
Overall response rate(ORR)
Description
Defined as the proportion of subjects who achieve sCR, CR, VGPR, and PR.
Time Frame
Up to 2 years after BCMA/GPRC5D double CAR-T infusion

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: Patients or their guardians understand and voluntarily sign the informed consent form, and are expected to complete the follow-up examination and treatment of study procedures; Aged 18-75 years, male or female; According to IMWG diagnostic criteria, diagnosed with multiple myeloma; Patients with documented multiple myeloma disease as relapsed refractory or primary refractory, defined as: a) relapsed refractory: no response to salvage therapy (no response defined as failure to achieve minimal response [MR] or disease progression on treatment), or disease progression within 60 days of the last treatment, or disease progression in patients who have achieved MR or above remission; b) primary refractory: never achieved MR or above response to any treatment, including never achieved MR or above remission, but M protein changes are not large, patients without evidence of clinical progression and patients who have primary refractory, progressed, and met the definition of progression. the presence of measurable disease at screening as determined by any of the following criteria: serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL or urine M-protein level ≥ 200 mg/24 hours; or diagnosis of light chain multiple myeloma without measurable disease in serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin κ/γ free light chain ratio; extramedullary measurable disease; the presence of tumor cells in the bone marrow as detected; the patient has recovered from the toxicity of previous treatment, that is, CTCAE toxicity grade < 2 (unless the abnormality is tumor-related or judged by the investigator to be stable, it has little effect on safety or efficacy); ECOG performance status score 0 to 2 and expected survival greater than 3 months; Appropriate organ function: alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN); aspartate aminotransferase (AST) ≤ 3 times the ULN; total bilirubin ≤ 1.5 times the ULN; Serum creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 30 mL/min (calculated by Cockcroft-Gault formula); Intraventricular oxygen saturation ≥ 92%; Left ventricular ejection fraction (LVEF) ≥ 45%, no pericardial effusion confirmed by echocardiography, no clinically significant electrocardiographic findings; no clinically significant pleural effusion; 9. venous access for collection can be established, no contraindications for leukocyte collection. Exclusion Criteria: Diagnosis or treatment of another invasive malignancy other than multiple myeloma within 3 years, with the following exceptions: malignancy treated with curative intent and no known active disease ≥ 3 years prior to enrollment; or adequately treated non-melanoma skin cancer with no evidence of disease; previous anticancer therapy (prior to blood collection for CAR-T preparation) as follows: targeted therapy, epigenetic therapy, or investigational agent within 14 days or at least 5 half-lives (whichever is shorter), or invasive investigational medical devices; monoclonal antibody therapy within 21 days; proteasome inhibitor therapy within 14 days; immunomodulator therapy within 7 days; and radiotherapy within 14 days (except for bone marrow reserve with ≤ 5% field coverage); Any hematopoietic stem cell transplantation within 2 months before screening; History of central nervous system diseases; known active central nervous system (CNS) involvement or clinical signs of meningeal involvement in multiple myeloma; Waldenström macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal proteinopathy, and skin changes) or primary AL amyloidosis at screening; Hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive and peripheral blood HBV DNA quantitative detection positive; hepatitis C virus (HCV) antibody positive; human immunodeficiency virus (HIV) antibody positive; cytomegalovirus (CMV) DNA detection positive; syphilis detection positive; Epstein-Barr virus DNA detection positive; Patients with a history of severe allergy [a history of severe allergy is defined as a secondary or above allergic reaction, any of the following clinical manifestations occur when allergic reactions occur: airway obstruction (runny nose, cough, wheezing, dyspnea), tachycardia, hypotension, arrhythmia, gastrointestinal symptoms (nausea, vomiting), incontinence, laryngeal edema, bronchospasm, cyanosis, shock, respiratory, cardiac arrest] or known allergy to any of the active ingredients, excipients or murine products and xenogeneic proteins contained in this trial (including Qinglin regimen); Patients with severe heart disease, including but not limited to severe arrhythmia, unstable angina pectoris, massive myocardial infarction, New York Heart Association class III or IV cardiac insufficiency, myocardial infarction ≤ 6 months before screening or coronary artery bypass grafting (CABG), a history of unexplained syncope and non-vasovagal or dehydration caused by, a history of severe non-ischemic cardiomyopathy, refractory hypertension (refractory hypertension is defined as: the use of reasonable tolerable adequate doses of ≥ 3 antihypertensive drugs (including diuretics) on the basis of lifestyle improvement for > 1 month of blood pressure is still not up to standard or taking ≥ 4 antihypertensive drugs blood pressure can be effectively controlled); unstable systemic diseases judged by the investigator: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment; Patients with acute/chronic graft-versus-host disease (GVHD) within 6 months before screening, or need to receive immunosuppressive agents for GVHD; Patients with active autoimmune or inflammatory diseases of the nervous system (e.g., Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically significant active cerebrovascular disease (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES)); Neoplastic emergencies (such as spinal cord compression, intestinal obstruction, leukostasis, tumor lysis syndrome, etc.) requiring emergency treatment before screening or reinfusion; presence of uncontrollable bacterial, fungal, viral, or other infections requiring antibiotic therapy; Hematopoietic cytokine drugs that have been transfused or have an effect on the hemogram of patients such as erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) within 2 weeks of blood collection scheduled for CAR-T preparation at screening, and have an effect on cell preparation as judged by the investigator. Receiving hormonal or immunosuppressive agents at screening within 2 weeks of blood collection scheduled for CAR-T preparation and having an effect on cell preparation as judged by the investigator. 1) Corticosteroids: subjects who are receiving systemic steroid therapy within 2 weeks of blood collection scheduled for CAR-T at screening and require chronic systemic steroid therapy during treatment as judged by the investigator (except for inhaled or topical use); and subjects who are receiving systemic steroid therapy within 72 hours before cell reinfusion (except for inhaled or topical use); 2) Immunosuppressants: subjects who are receiving immunosuppressive agents within 2 weeks of blood collection scheduled for CAR-T at screening; 17. Patients who have undergone major surgery (except diagnostic surgery and biopsy) within 4 weeks before Qinglin or plan to undergo major surgery during the study period, or whose surgical wounds have not completely healed before enrollment; 18. Patients who have received (attenuated) live viral vaccines within 4 weeks before screening; 19. patients with severe mental illness; 20. Alcoholics or those who have a history of drug abuse; 21. Pregnant or lactating women, and female subjects who plan to become pregnant within 2 years after cell reinfusion or male subjects whose partners plan to become pregnant within 2 years after cell reinfusion; 22. patients who have contraindications to any study procedure or have other medical conditions that may place them at unacceptable risk according to the investigator 's judgment and/or clinical criteria.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yang Xiao, MD
Phone
13902213175
Email
jdxiao111@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Liya Wei, MD
Phone
18824309836
Email
45000674@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yang Xiao, MD
Organizational Affiliation
Shenzhen Qianhai Shekou Free Trade Zone Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shenzhen Qianhai Shekou Free Trade Zone Hospital
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Xiao, MD
Phone
13902213175
Email
jdxiao111@163.com
First Name & Middle Initial & Last Name & Degree
Liya Wei, MD
Phone
18824309836
Email
45000674@qq.com

12. IPD Sharing Statement

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Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Multiple Myeloma

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