Recurrent or refractory multiple myeloma
Conditions
Interventions
100mg Bisthianostat Group:100mg Bisthianostat + 4mg Ixazomib + 20mg Dexamethasone
200mg Bisthianostat Group:200mg Bisthianostat + 4mg Ixazomib + 20mg Dexamethasone
400mg Bisthianostat Group:400mg Bisthianostat + 4mg Ixazomib + 20mg Dexamethasone
600mg Bisthianostat Group:600mg Bisthianostat + 4mg Ixazomib + 20mg Dexamethasone
Dose expansion group:X mg Bisthianostat + 4mg Ixazomib + 20mg Dexamethasone
Sponsors
Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Subjects fully understand the purpose, nature, method and possible adverse reactions of the trial, voluntarily participate in this clinical trial, and sign the informed consent form; 2. Male or female subjects aged 18-75 years (including boundary value); 3. Patients with terminal line multiple myeloma who have been fully treated by the standard treatment scheme (at least received proteasome inhibitors and immunomodulators in the past), and meet the following criteria for recurrent or refractory multiple myeloma: Refractory multiple myeloma: invalid for the first treatment or salvage treatment (invalid definition: failure to achieve minimal remission, or disease progression during treatment); Or disease progression within 60 days after the last treatment; ?Recurrent multiple myeloma: the patient has received treatment in the past, but the disease is progressing, and rescue treatment needs to be started and does not meet the criteria for refractory multiple myeloma; 4. Subjects must have any of the following measurable lesions: serum M protein = 5 g/L, urine M protein = 200 mg/24h, affected serum free light chain (FLC) = 100 mg/L and abnormal ratio; 5. According to the score of American Eastern Cooperative Oncology (ECOG) (Appendix 2), the physical condition is 0-2. 6. Estimated survival time = 3 months. 7. Subjects have proper bone marrow reserves and organ functions: Absolute neutrophil count (ANC) = 1.0 × 109/L, and PEG-FEGERSTINE was not used within 21 days before enrollment, and non PEG-G-CSF or GM-CSF were not used within 7 days before enrollment; Platelet = 50 × 109/L, and no platelet transfusion was conducted within 7 days before enrollment; Hemoglobin = 60 g/L, and no red blood cell infusion was conducted within 7 days before enrollment; Total bilirubin = 1.5 times the upper limit of normal value (ULN). In case of liver metastasis or Gilbert syndrome, total bilirubin = 3 × ULN ALT and AST = 2.5 × ULN, ALT or AST = 5 in case of liver metastasis × ULN The creatinine clearance rate estimated according to Cockcroft Gault formula (Appendix 3) is = 30 mL/min; International standardized ratio (INR) or plasma prothrombin time (PT) = 1.5 × ULN Left ventricular ejection fraction (LVEF) = 50%; ECG is basically normal, QTcF (corrected by Fridericia formula, see Appendix 4) = 450ms (female), = 470ms (male); 8. The fertile subjects (male or female) must agree to use a medically approved contraceptive measure (such as IUD, contraceptives or condoms) during the trial and within 3 months after the last administration; The serum human chorionic gonadotropin test of fertile women must be negative within 7 days before the first administration, and must be non lactating.
Exclusion criteria
Exclusion criteria: 1. The subjects were secondary plasma cell leukemia (proportion of peripheral plasma cells = 5%); 2. Known allergic history to the active ingredient or its excipients (pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, sodium dodecyl sulfate, magnesium stearate, povidone, and opamide) of becenoltal tablets, or dexamethasone and isazomi; 3. Participated in other clinical trials within 28 days before the first administration; 4. Subjects who have undergone major surgery or severe trauma within 28 days before the first administration, or who are expected to undergo major surgery (except vertebroplasty) during the trial; 5. Persons receiving other anti-tumor treatment within 14 days before the first administration (except prednisone = 20mg/day and its equivalent dose of steroid hormone); 6. Subjects who plan to receive hematopoietic stem cell transplantation, or who received autologous hematopoietic stem cell transplantation within 100 days before the first administration, or who received allogeneic hematopoietic stem cell transplantation within 6 months before the first administration, or who have graft versus host reaction (GVHD) and need immunosuppressive therapy; 7. Known uncontrolled or symptomatic active central nervous system metastasis; 8. Have a history of serious cardiovascular and cerebrovascular diseases, including but not limited to: Serious cardiac rhythm or conduction abnormality, such as ventricular arrhythmia requiring clinical intervention, ? - ? degree atrioventricular block, etc; Thromboembolic events requiring therapeutic anticoagulation, or subjects with venous filters; According to the standards of New York Heart Association (NYHA), patients with Class III~IV cardiac insufficiency (Appendix 5); Acute coronary syndrome, Grade III-IV congestive heart failure, aortic dissection, stroke or other cardiovascular and cerebrovascular events of Grade 3 or above occurred within 6 months before the first administration; Hypertension that cannot be controlled clinically (after standard antihypertensive treatment, the blood pressure cannot be controlled at systolic pressure<140 mmHg and/or diastolic pressure<90 mmHg); Any factor that increases the risk of QTcF prolongation or arrhythmia, such as torsade de pointes, hypokalemia, and congenital long QT syndrome; 9. Cannot swallow capsules or suffer from diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, gastrectomy or small bowel resection, symptomatic inflammatory bowel disease, partial or complete intestinal obstruction. 10. Subjects who are taking (or cannot stop taking 1 week before the first administration) any strong inhibitor of CYP1A2, strong inhibitor or strong inducer of CYP3A4, antiarrhythmic drugs, drugs that may prolong QT interval (Annexes 6 and 7), or need to continue to receive these drugs during the study period; 11. HIV infection, active HBV and HCV infection (HbsAg positive; or HbsAg negative but HbcAb positive, and HBV DNA exceeds the upper limit of normal value; HCV antibody positive, and HCV RNA positive); 12. Acute active infections requiring intravenous anti infection treatment; 13. Any other malignant tumor was diagnosed within 3 years before entering the study, except for basal cell or squamous cell skin cancer or cervical carcinoma in situ that was stable after adequate treatment; 14. Subjects with known psychological or mental disorders that may affect the complianc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Security check; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) characteristics;IMWG diagnostic criteria for multiple myeloma;Ac-H3 level in PBMC; | — |
Countries
China
Contacts
Public ContactJian Hou
Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Outcome results
None listed