Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Multiple Myeloma
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BCMA/GPRC5D double CAR-T 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 |
Biological: BCMA/GPRC5D double CAR-T
BCMA/GPRC5D double CAR-T is a new type CAR-T cells therapy for patients with Multiple Myeloma.
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Outcome Measures
Primary Outcome Measures
- Evaluation of Safety [Up to 2 years after BCMA/GPRC5D double CAR-T infusion]
Count the Incidence of adverse events
- Changes in cytokine level [Up to 2 years after BCMA/GPRC5D double CAR-T infusion]
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) [Up to 2 years after BCMA/GPRC5D double CAR-T infusion]
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) [Up to 2 years after BCMA/GPRC5D double CAR-T infusion]
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) [Up to 2 years after BCMA/GPRC5D double CAR-T infusion]
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) [Up to 2 years after BCMA/GPRC5D double CAR-T infusion]
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) [Up to 2 years after BCMA/GPRC5D double CAR-T infusion]
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) [Up to 2 years after BCMA/GPRC5D double CAR-T infusion]
Defined as the proportion of subjects who achieve sCR, CR, VGPR, and PR.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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;
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Aged 18-75 years, male or female;
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According to IMWG diagnostic criteria, diagnosed with multiple myeloma;
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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.
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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;
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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);
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ECOG performance status score 0 to 2 and expected survival greater than 3 months;
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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:
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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;
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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);
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Any hematopoietic stem cell transplantation within 2 months before screening;
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History of central nervous system diseases;
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known active central nervous system (CNS) involvement or clinical signs of meningeal involvement in multiple myeloma;
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Waldenström macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal proteinopathy, and skin changes) or primary AL amyloidosis at screening;
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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;
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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);
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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);
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unstable systemic diseases judged by the investigator: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
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Patients with acute/chronic graft-versus-host disease (GVHD) within 6 months before screening, or need to receive immunosuppressive agents for GVHD;
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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));
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Neoplastic emergencies (such as spinal cord compression, intestinal obstruction, leukostasis, tumor lysis syndrome, etc.) requiring emergency treatment before screening or reinfusion;
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presence of uncontrollable bacterial, fungal, viral, or other infections requiring antibiotic therapy;
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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.
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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.
- 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shenzhen Qianhai Shekou Free Trade Zone Hospital | Shenzhen | Guangdong | China | 518000 |
Sponsors and Collaborators
- Guangzhou Bio-gene Technology Co., Ltd
Investigators
- Principal Investigator: Yang Xiao, MD, Shenzhen Qianhai Shekou Free Trade Zone Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BG-CT-22-008