A Phase II study of Selinexor (KPT-330) combined with bortezomib and dexamethasone (SVd) for induction and
consolidation for patients with progressive or refractory Multiple Myeloma.

- The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.

- Age ≥ 18 years at the time of signing the informed consent form.

- Able to adhere to the study visit schedule and other protocol requirements.

- Documented diagnosis of multiple myeloma and measurable disease (serum M-protein ≥ 5 g/L or urine M-protein ≥ 200 mg/24 hours or abnormal FLC ratio with involved free light chain (FLC) > 100 mg/L);

- Documented progression as per the IMWG uniform response criteria (Durie, 2006) during or after the anti-myeloma regimen; or never achieved a response better than PD after at least 2
cycles of their previous anti-myeloma regimen.

- At least one prior anti-myeloma regimen. Induction therapy followed by autologous stem cell transplant (ASCT) and consolidation/ maintenance will be considered as one regimen.

- Normal renal function with a Creatinine Clearance > 30mL/min according to the Modification of Diet in Renal Disease (MDRD) equation for estimation of Glomerular Filtration Rate (GFR)

- WHO performance status score of 0, 1 or 2 (see Appendix B).

- Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing
potential. Acceptable methods of contraception are condoms with contraceptive foam, oral,
implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm
with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout
the study and for three months following the last dose.

- All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.

- All subjects must agree not to share medication.

- Prior resistance/refractory disease to bortezomib

- Systemic AL amyloidosis

- Non secretory myeloma

- Known CNS involvement

- Absolute neutrophil count (ANC) <1.0 x 109/L, unless related to MM.

- Platelet count < 50 x 109/L.

- Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L).

- Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human
erythropoietin use is permitted).

- Significant hepatic dysfunction (Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal
(ULN) or serum total bilirubin > 2 x ULN unless due to inheritable syndrome such as Gilbert’s)

- Prior history of malignancies, other than MM, unless the subject has been free of the disease
for ≥ 5 years. Exceptions include the following:

o Basal or squamous cell carcinoma of the skin.

o Carcinoma in situ of the cervix or breast.

o Incidental histological finding of prostate cancer (TNM stage of T1a or T1b).

- Hypersensitivity to bortezomib or dexamethasone (this includes ≥ Grade 3 rash during prior
bortezomib therapy).

- Peripheral neuropathy ≥ Grade 2 at time of registration.

- Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell
transplant less than 12 months prior to initiation of study treatment

- Congestive heart failure (NY Heart Association Class III or IV) (see appendix C).

- Myocardial infarction within 12 months prior to starting study treatment

- Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.

- Subjects who received any of the following within the last 14 days of initiation of study
treatment:

o Major surgery (kyphoplasty is not considered major surgery).

o Use of any anti-myeloma drug therapy at the time of registration in the trial.

- Use of any investigational agents within 28 days or five half-lives (whichever is longer) of
treatment.

- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent
the subjects from signing the informed consent form.

- Any active uncontrolled infections

- Pregnant or breastfeeding females.

- Known human immunodeficiency virus (HIV) positivity, active infectious hepatitis A, B or C or
chronic hepatitis B or C.

 Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.