Relapsed or Refractory Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, BCMA, GPRC5D
Brief summary
This is a single arm, single center clinical study evaluating the safety and efficacy of CAR-T treatment for relapsed or refractory multiple myeloma.
Detailed description
This study is a single arm, single center study targeting patients with relapsed or refractory multiple myeloma (r/rMM). The study plans to enroll 40 subjects, with a sample size based on actual occurrence and a dosage of 3×10\^6/kg±20%\ 1×10\^7/kg ±20% CAR positive T cells.
Interventions
BIOLOGICALBCMA/GPRC5D dual CAR-T
BCMA/GPRC5D dual CAR-T is a new type CAR-T cells therapy for patients with Relapsed or Refractory Multiple Myeloma.
Sponsors
Guangzhou Bio-gene Technology Co., Ltd
Shenzhen Qianhai Shekou Free Trade Zone Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Patients or their guardians understand and voluntarily sign an informed consent form and are expected to complete the follow-up examinations and treatments related to the study. * 2\. Aged 18-75 years, any gender. * 3\. Diagnosed with multiple myeloma according to IMWG diagnostic criteria. * 4\. Documented evidence that the patient's multiple myeloma is refractory or relapsed, defined as: * a) Refractory: No response to salvage therapy (no response defined as no achievement of minimal response \[MR\] or disease progression during treatment), or disease progression within 60 days of the last treatment, or patients who achieved MR or higher but experienced disease progression. * b) Relapsed: No response to any treatment, including no achievement of MR or higher in any prior treatment, but with minimal changes in M-protein without clinical progression or relapse as per the progression definition. * 5\. Measurable disease at screening based on 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 diagnosed with light-chain multiple myeloma in the absence of measurable disease in serum or urine: serum immunoglobulin free light chain ≥10 mg/dL and an abnormal κ/γ free light chain ratio, extramedullary measurable lesions, or presence of tumor cells in bone marrow biopsy. * 6\. Patients have recovered from toxicity of prior treatment, with CTCAE toxicity grade ≤2 (unless the abnormality is related to the tumor or is deemed stable by the investigator with no significant impact on safety or efficacy). * 7\. ECOG performance status score of 0-2 and an expected survival of more than 3 months. * 8\. Adequate organ function, including: * ALT (alanine transaminase) ≤3 times the upper limit of normal (ULN). * AST (aspartate transaminase) ≤3 times ULN. * Total bilirubin ≤1.5 times ULN. * Serum creatinine ≤1.5 times ULN or creatinine clearance ≥30 mL/min (calculated by Cockcroft-Gault formula). * Oxygen saturation ≥92%. * Left ventricular ejection fraction (LVEF) ≥45%, confirmed by echocardiography with no evidence of pericardial effusion and no clinically significant electrocardiographic findings. * No clinically significant pleural effusion. * 9\. Establishing a required venous access for collection without any leukapheresis contraindications.
Exclusion criteria
* 1\. Diagnosis or treatment of invasive malignancies other than multiple myeloma within 3 years, unless the malignancy has been curatively treated and there is no known active disease within 3 years before enrollment, or unless the patient has been fully treated for non-melanoma skin cancer with no evidence of disease. * 2\. Prior treatment with the following anti-cancer therapies (before leukapheresis for CAR-T cell production): received targeted therapy, epigenetic therapy, or investigational drug treatment within 14 days or at least 5 half-lives (whichever is shorter); received monoclonal antibody therapy within 21 days; received proteasome inhibitor therapy within 14 days; received immunomodulatory drug therapy within 7 days; received radiation therapy within 14 days (excluding bone marrow radiation ≤5% of bone marrow reserve). * 3\. Underwent hematopoietic stem cell transplantation within 2 months prior to screening. * 4\. History of central nervous system disorders. * 5\. Clinical signs of active central nervous system (CNS) involvement or manifestations of multiple myeloma meningeal involvement. * 6\. Diagnosed with Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), or primary AL amyloidosis. * 7\. Positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA quantification, positive for hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, cytomegalovirus (CMV) DNA, syphilis test, or Epstein-Barr virus DNA. * 8\. History of severe allergies (defined as Grade 2 or higher reactions) or known hypersensitivity to any active ingredients, excipients, mouse-derived products, or heterologous proteins included in this trial, including the conditioning regimen. * 9\. Severe cardiac diseases, including but not limited to severe arrhythmias, unstable angina, extensive myocardial infarction, New York Heart Association class III or IV heart failure, myocardial infarction within ≤6 months prior to screening, coronary artery bypass grafting (CABG) performed, except for non-vascular vagal syncope or dehydration, severe non-ischemic cardiomyopathy, and resistant hypertension. * 10\. Unstable systemic diseases, as judged by the investigator, including but not limited to severe liver, kidney, or metabolic diseases requiring drug treatment. * 11\. Had acute or chronic graft-versus-host disease (GVHD) within 6 months prior to screening or required immunosuppressive treatment for GVHD. * 12\. Active autoimmune or inflammatory neurological diseases (e.g., Guillain-Barré syndrome, amyotrophic lateral sclerosis) and clinically significant active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome) at screening. * 13\. Requires emergency treatment for tumor emergencies at screening (e.g., spinal cord compression, intestinal obstruction, leukostasis, tumor lysis syndrome). * 14\. Has uncontrollable bacterial, fungal, viral, or other infections requiring antibiotic treatment. * 15\. Received blood transfusions or hematopoietic cytokine drugs affecting the patient's blood counts within 2 weeks prior to screening for planned CAR-T cell production, as determined by the investigator to affect cell preparation. * 16\. Receiving steroids or immunosuppressive drugs within 2 weeks of screening for planned CAR-T cell production: * a) Steroids: Received systemic corticosteroid treatment within 2 weeks of screening and judged by the investigator to require long-term systemic corticosteroid treatment (excluding inhalation or topical use); and received systemic corticosteroid treatment within 72 hours before cell infusion (excluding inhalation or topical use). * b) Immunosuppressive drugs: Receiving immunosuppressive drugs within 2 weeks of screening. * 17\. Underwent major surgery (excluding diagnostic surgery and biopsy) within 4 weeks prior to screening or has unhealed surgical wounds before enrollment. * 18\. Received (attenuated) live virus vaccines within 4 weeks before screening. * 19\. Has severe mental illness. * 20\. History of alcohol abuse or substance abuse. * 21\. Pregnant or lactating women and participants planning to become pregnant within 2 years after cell infusion or their partners planning to become pregnant within 2 years after cell infusion. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in cytokine level | Up to 2 years after BCMA/GPRC5D dual CAR-T infusion | Calculate the change of cytokine level in peripheral blood by flow cytometry after BCMA/GPRC5D dual CAR-T infusion. Cytokines include IL-2、IL-6、IL-10、IFN-γ |
| Evaluation of Safety | Up to 2 years after BCMA/GPRC5D dual CAR-T infusion | Count the Incidence of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate(CR) | Up to 2 years after BCMA/GPRC5D dual CAR-T infusion | 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(SCR) | Up to 2 years after BCMA/GPRC5D dual CAR-T infusion | 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(VGPR) | Up to 2 years after BCMA/GPRC5D dual CAR-T infusion | 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(PR) | Up to 2 years after BCMA/GPRC5D dual CAR-T infusion | Subjects who met the following requirements: * （1） A decrease of ≥ 50% in serum M protein and ≥ 90% or\<200 mg/24h in urine M protein; * （2） 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%; * （3） 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; * （4） In addition to the above criteria, if there is a baseline presence of soft tissue plasmacytomas, it is required that the sum of the maximum vertical diameter product (SPD) of the measurable lesion be reduced by ≥ 50%. |
| Minimal response(MR) | Up to 2 years after BCMA/GPRC5D dual CAR-T infusion | 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(OR) | Up to 2 years after BCMA/GPRC5D dual CAR-T infusion | Defined as subjects who achieve sCR, CR, VGPR, and PR. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYang Xiao, MD
Shenzhen Qianhai Shekou Free Trade Zone Hospital
Outcome results
None listed