Multiple Myeloma
Conditions
Interventions
XVRD:Selinexor, Bortezomib, Lenalidomide, Dexamethasone
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Willing and able to written informed consent (ICF); 2. Aged >= 18 years; 3. Newly diagnosed multiple myeloma as defined by IMWG (Rajkumar, Dimopoulos et al. 2014) , measurable disease as defined IMWG 2016 criteria (Table 5) (Kumar, Paiva et al. 2016), and meet at least one of the following criteria: (1) Serum M-protein (SPEP) >= 5 g/L, if the MM type is IgA/IgD, that can be substituted by IgA/IgD quantitative level; (2) 24 hours-urinary M-protein excretion >= 0.2 g (200 mg); (3) Serum FLC >= 100 mg/L with abnormal FLC ratio (FLC Normal ratio: 0.26 to 1.65); 4. According to mSMART 3.0 definition for high risk multiple myeloma: (1) High risk genetic abnormalities t(4;14), t(14;16), t(14;20), Del 17p, p53 mutation or 1q + ; (2) R-ISS Stage 3; (3) High Plasma Cell S-phase; (4) GEP: High risk signature; 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. ECOG PS 3 allowed, if caused by myeloma; 6. Patients must have received no prior chemotherapy for multiple myeloma. Patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis). Patients must have received no prior steroid treatment for myeloma with the exception of a maximum of 14 days of treatment for symptom control; 7. Adequate hepatic function: total bilirubin = 30 mL/min (calculated using the formula of Cockroft-Gault); 9. Adequate hematopoietic function within 7 days prior to C1D1 and met the following criteria: White blood cell (WBC) count >= 1.5 x 10^9/L, Absolute neutrophil count (ANC) >= 1.0 x 10^9/L, Hemoglobin (Hb) >= 85 g/L and Platelet count (PLT) >= 75 x 10^9/L (patients whom = 50 x 10^9/L (patients whose >= 50% of bone marrow nucleated cells are plasma cells); 10. Patients could not receive hematopoietic growth factor treatment within 2 weeks prior to screening. These growth factors include Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), Granulocyte macrophages-colony stimulating factor (GM-CSF), Platelet agonist, etc (Eltrombopag, Thrombopoietin (TPO), Interleukin-11); 11. Patients receive transfusions of blood products: (1) At least 2 weeks elapsed between the screening hemoglobin assessment and the last red blood cell infusion; (2)And at least 1 week elapsed between the screening platelet assessment and the last platelet infusion; 12. Patients must be able to take prophylactic anticoagulant therapy as recommended by the study; 13. Female patients of childbearing potential must meet below two criteria: (1) Must agree to use effective contraception methods since signature in ICF, throughout the study and for 3 months following the last dose of study treatment; (2) Must have a negative serum pregnancy test at screening. Note: A woman is considered of childbearing potential following menarche and until becoming postmenopausal (defined as no menstrual period for a minimum of 12 months) or permanently sterile (having undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy). A woman who is taking oral contraceptive or using intrauterine device is considered of childbearing potential. Male patients (including those who have received vasectomy) must use a condom if
Exclusion criteria
Exclusion criteria: 1. Plasma cell leukemia; 2. Documented active amyloidosis; 3. Involvement of the central nervous system(CNS) by Multiple myeloma; 4. Prior exposure to a SINE compound, including ATG-010; 5. Currently, whether or not the patient is on medication, > Grade 2 peripheral neuropathy or >= Grade 2 painful neuropathy at baseline; 6. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and Selinexor (ATG-010); 7. Active, unstable cardiovascular function, as indicated by the presence of: (1) Symptomatic ischemia; (2) Uncontrolled clinically significant conduction abnormalities (eg, patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded); (3) Congestive heart failure of New York Heart Association Class >= 3 or known left ventricular ejection fraction < 40%; (4) Myocardial infarction within 6 months prior to C1D1; 8. Known positive serology for HIV or HIV seropositivity; 9. Known active hepatitis A, B, or C infection; eg. positive for HCV RNA or HBV-DNA; 10. Women who are pregnant or nursing; 11. Life expectancy of less than 6 months; 12. Any active gastrointestinal dysfunction interfering with the patients ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment; 13. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent; 14. Contraindication to any of the required concomitant drugs or supportive treatments; 15. Has any concurrent diseases or complications that is likely to interfere with the study procedures; 16. Patients unwilling or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ATG-010 Maximum Tolerated Dose (MTD);ATG-010 Recommended dose for phase II;Minimal residual disease negative remission; | — |
Secondary
| Measure | Time frame |
|---|---|
| CR rate: complete response (CR) and stringent complete response (sCR);12 months Overall Survival;12 months Progression-Free Survival;DOR: Duration from the first observation of at least PR to time of disease progression, or deaths due to disease progression, whichever occurs first;Objective Response Rate + minimal response (MR);Safety and tolerability; | — |
Countries
China
Contacts
Public ContactZhongjun Xia
Sun Yat-sen University Cancer Center
Outcome results
None listed