Selinexor in Combination With Immunomodulator （Thalidomide/Pomalidomide/Lenalidomide）in RRMM

Inclusion Criteria:

• Patients must meet all of the following inclusion criteria to be eligible to enroll inthis study:

1. Known and written informed consent (ICF) voluntarily.
2. Age ≥ 18 years and ≤ 75 years.
3. Patients with multiple myeloma who have received first-line treatment (induction,autologous transplantation and maintenance as the same first-line treatment) andachieved at least partial remission in induction.
4. At or after accepting first-line regimen, subjects must have progression disease (PD) recorded which is determined by researcher according to IMWG criteria.
5. Any clinically significant non-hematological toxicities (except for hair loss,peripheral neuropathy, which is otherwise stipulated in Article 13 of theexclusion criteria) that relevant to previous therapies must have resolved to ≤Grade 2 prior to first dose of study drug.
6. Left ventricular ejection fraction#LVEF #≥50% by an echocardiogram or MUGA scanin 42 days before the first administration
7. Adequate hepatic function: total bilirubin < 2× upper limit of normal (ULN) (forpatients with Gilbert's syndrome, a total bilirubin of < 3× ULN is required), AST < 2.5× ULN, and ALT < 2.5× ULN.
8. Adequate renal function: estimated creatinine clearance ≥ 20 mL/min (calculatedusing the formula of Cockroft-Gault).
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
10. Measurable MM as defined by at least one of the following:
11. Serum M-protein (SPEP) ≥ 10 g/L
12. 24 hours-Urinary M-protein excretion ≥ 0.2 g (200 mg)
13. Serum FLC ≥ 100 mg/L with abnormal FLC ratio
14. Expected survival is more than 6 months.
15. Adequate hematopoietic function (no blood transfusion within 2 weeks and noG-CSF/GM-CSF supportive treatment within 1 week prior to screening test):
16. Hemoglobin level ≥ 80 g/L
17. ANC ≥ 1,000/mm3 (1.0×109/L)
18. Platelet count ≥ 75,000/mm3 (75×109/L)
19. Female patients of childbearing potential must meet below two criteria:
20. must agree to use effective contraception methods since signature in ICF,throughout the study and for 3 months following the last dose of studytreatment.
21. must have a negative serum pregnancy test at screening. Note: A woman isconsidered of childbearing potential following menarche and until becomingpostmenopausal (defined as no menstrual period for a minimum of 12 months)or permanently sterile (having undergone a hysterectomy, bilateralsalpingectomy or bilateral oophorectomy). A woman who is taking oralcontraceptive or using intrauterine device is considered of childbearingpotential.
22. Male patients (including those who have received vasectomy) must use a condom ifsexually active with a female of child-bearing potential throughout the study andfor 3 months following the last dose of study treatment.

Exclusion Criteria:

• Patients who meet any of the following criteria will not be enrolled:

1. Asymptomatic (smoldering) MM.
2. Plasma cell leukemia.
3. Documented active amyloidosis.
4. Previously refractory or intolerant to immunomodulators.
5. Pregnancy or breastfeeding.
6. Major surgery was performed within 4 weeks prior to the first study.
7. Patients with active, unstable cardiovascular diseases, fits any of thefollowing:
8. Symptomatic ischemia, or
9. Uncontrolled clinically-significant conduction abnormalities (e.g., patientswith ventricular tachycardia on antiarrhythmics are excluded; patients withfirst-degree atrioventricular (AV) block or asymptomatic left anteriorfascicular block/right bundle branch block (LAFB/RBBB) are allowed), or
10. Congestive heart failure (CHF) of New York Heart Association (NYHA) ≥ Grade 3, or
11. Acute myocardial infarction (AMI) within 3 months prior to the first dose ofstudy drug.
12. Uncontrolled active infection within 1 week prior to the first dose of studydrug.
13. Known HIV positive.
14. Known active hepatitis A, B, or C infection; or known positive for HCV RNA orHBsAg. (Note: patients with HBsAg negative but HBc Ab positive need furtherHBV-DNA test, excluded if HBV-DNA ≥103 , if HBV-DNA # 103 need anti-viral drugs)
15. Prior malignancy that required treatment or has shown evidence of recurrence (except for skin basal-cell carcinoma and in-situ carcinoma including squamouscell carcinoma, bladder cancer in situ, endometrial cancer in situ, cervicalcancer in situ/atypical hyperplasia, prostate cancer incidental finding (T1a orT1b), or breast cancer in situ) within 5 years prior to the first dose of studydrug.
16. Active GI dysfunction interfering with the ability to swallow tablets, or any GIdysfunction that could interfere with absorption of study treatment.
17. Grade ≥ 3 peripheral neuropathy, and Grade ≥ 2 painful neuropathy, within 3 weeksprior to the first dose of study drug.
18. Previous history of deep vein thrombosis.
19. Serious, active psychiatric, or medical conditions which, in the opinion of theInvestigator, could interfere with study treatment.
20. Participation in an investigational anti-cancer clinical study within 3 weeks or 5 half-lives (T1/2) prior to the first dose of study drug.
21. Received ASCT within 12 weeks prior to the first dose of study drug or previousallogeneic stem cell transplantation (no time limitation).
22. Treatment with an approved or trial anticancer drug was given within 4 weeksprior to the first study.
23. Known intolerance to or contraindication for glucocorticoid therapy.
24. Prior exposure to a SINE compound.