Pomalidomide-Cyclophosphamide-Dexamethasone (PCD) Versus Pomalidomide-Dexamethasone (PD) in Relapse or Refractory Myeloma

Inclusion Criteria:

1. Multiple myeloma, diagnosed according to standard criteria, with relapsing andrefractory disease at study entry

2. Patients must have evaluable multiple myeloma with at least one of the following (within 21 days of starting treatment)

3. Serum M-protein ≥ 0.5g/dL, or

4. In subjects without detectable serum M-protein, Urine M-protein ≥ 200mg/24 hour,or serum free light chai (sFLC) > 100mg/L (involved light chain) and an abnormalkappa/Lambda ratio

5. Can receive up to 6 lines of prior treatment. (Induction therapy followed by stem celltransplantation and consolidation/maintenance therapy will be considered as one lineof treatment)

6. Must be relapse refractory to prior lenalidomide and bortezomib. Refractoriness isdefined as disease progression on treatment or progression within 6 months after thelast dose of a given therapy. Relapse is defined according to the criteria of IMWG

7. Males and females ≥ 18 years of age or > country's legal age for adult consent

8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2

9. Patients must meet the following clinical laboratory criteria with 21 days of startingtreatment:

10. Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is >50%)

11. Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanineaminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.

12. Calculated creatinine clearance ≥ 30mL/min or creatinine < 3mg/dL.

13. Female patients who:

14. Are naturally postmenopausal for at least 2 year before enrolment

15. Are surgically sterile

16. If they are of childbearing potential**, agree to

• adhere to the pomalidomide pregnancy prevention risk management program inAppendix 8 :

• All women of childbearing potential must agree to have two negativepregnancy test within 10-14 days and 24hrs before commencing pomalidomideand use two reliable methods of contraception simultaneously or practicecomplete abstinence from any heterosexual intercourse during the followingtime periods related to this study: 1) for at least 28 days before startingstudy; 2) while participating in the study; 3) dose interruptions; and 4)for at least 28 days after study treatment discontinuation. The two methodsof reliable contraception must include one highly effective method and oneadditional effective method to prevent pregnancy, not plan on conceivingchildren during or within 6 months following pomalidomide. (See Appendix 8Pregnancy Prevention and Risk Management Program)

9. Male patients, even if surgically sterilized (i.e. status post-vasectomy), who:

10. Agree to practice effective barrier contraception during the entire studytreatment period and through 28 days after the last dose of study treatment, OR

11. Agree to completely abstain from heterosexual intercourse, AND

12. Must also adhere to the guidelines of the pomalidomide pregnancy prevention andrisk management program

13. Written informed consent in accordance with federal, local and institutionalguidelines

• A female of childbearing potential (FCBP) is defined as a sexually mature womanwho: 1 has not undergone a hysterectomy or bilateral oophorectomy or 2, has notbeen naturally post-menopausal (amenorrhea following cancer therapy does not ruleout childbearing potential) for at least 24 consecutive months (I.E, has hadmenses at any time in the preceding 24 consecutive months).

Exclusion Criteria:

1. Female patients who are lactating or pregnant

2. Multiple Myeloma of IgM subtype

3. Glucocorticoid therapy (prednisolone > 30mg/day or equivalent) within 14 days prior toinformed consent obtained

4. POEMS syndrome

5. Plasma cell leukemia or circulating plasma cells ≥ 2 x 109/L

6. Waldenstrom's Macroglobulinaemia

7. Patients with known amyloidosis

8. Chemotherapy with approved or investigation anticancer therapeutics within 21 daysprior to starting pomalidomide treatment

9. Focal radiation therapy within 7 days prior to start of pomalidomide. Radiationtherapy to an extended field involving a significant volume of bone marrow within 21days prior to start of pomalidomide

10. Immunotherapy (excluding steroids) 21 days prior to start of pomalidomide

11. Major surgery (excluding kyphoplasty) within 28 days prior to start of pomalidomide

12. Active congestive heart failure (New York Heart Association [NYHA] Class III or IV),symptomatic ischaemia, or conduction abnormalities uncontrolled by conventionalintervention. Myocardial infarction within 4 months prior to informed consent obtained

13. Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patientswith hepatitis B surface antigen or core antibody receiving and responding toantiviral therapy directed at hepatitis B: these patients are allowed)

14. Patients with known cirrhosis

15. Second malignancy within the past 3 years except:

16. Adequately treated basal cell or squamous cell skin cancer

17. Carcinoma in situ of the cervix

18. Breast carcinoma in situ with full surgical resection

19. Patients with myelodysplastic syndrome

20. Patients with steroid or lenalidomide hypersensitivity

21. Prior treatment with pomalidomide

22. Ongoing graft-versus-host disease

23. Patients with pleural effusions requiring thoracentesis or ascites requiringparacentesis within 14 days prior to starting pomalidomide treatment

24. Contraindication to any of the required concomitant drugs or supportive treatments

25. Any clinically significant medical disease or psychiatric condition that, in theinvestigator's opinion, may interfere with protocol adherence or a patient's abilityto give informed consent.