Relapse or Refractory Multiple Myeloma

Primary Objectives To assess the progression free survival (PFS) for PCD compared to PD in patients who have relapsed and have previously been treated with bortezomib and lenalidomide. Secondary Objectives To assess the following: 1) Overall Response Rate (ORR) 2) Overall Survival (OS) 3) Duration of Response (DOR) 4) Safety and Tolerability

POMALYST

Pomalidomide

capsule

4
3
2
1

End Points – Efficacy
Primary endpoint:
-Progression free survival (PFS) is defined as the time from commencement of treatment with either PCD or PD to disease progression or death due to any cause, whichever occurs first.

Secondary endpoints:
-Overall response rate (ORR) is defined as the percentage of patients enrolled that achieve a complete response (CR), or stringent complete response (sCR), or very good partial response (VGPR), or partial response (PR) based on the International Myeloma Working Group criteria anytime from commencement of treatment to the end of study.
-Overall survival (OS) is defined as the time from commencement of treatment to the date of death.
-Duration of response (DOR) is defined as the time from first evidence of PR or VGPR, or CR, or sCR to confirmation of disease progression or death due to any cause.

End Points – Safety
Safety is assessed on the basis of the frequency and severity of adverse events. Adverse events were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events Version 4.03. Safety assessments was based on reported adverse events, clinical laboratory tests (haematologic testing and serum chemical testing), vital signs, physical examinations and ECOG performance status

Inclusion Criteria
1. Multiple myeloma, diagnosed according to standard criteria, with relapsing and refractory disease at study entry
2. Patients must have evaluable multiple myeloma with at least one of the following (within 21 days of starting treatment)
a. Serum M-protein ≥ 0.5g/dL, or
b. 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 abnormal kappa/Lambda ratio
3. Can receive up to 6 lines of prior treatment. (Induction therapy followed by stem cell transplantation and consolidation/maintenance therapy will be considered as one line of treatment)
4. Must be relapse refractory to prior lenalidomide and bortezomib. Refractoriness is defined as disease progression on treatment or progression within 6 months after the last dose of a given therapy. Relapse is defined according to the criteria of IMWG
5. Males and females ≥ 18 years of age or > country’s legal age for adult consent
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
7. Patients must meet the following clinical laboratory criteria with 21 days of starting treatment:
a. Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is >50%)
b. Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
c. Calculated creatinine clearance ≥ 30mL/min or creatinine < 3mg/dL.
8. Female patients who:
a. Are naturally postmenopausal for at least 2 year before enrolment
b. Are surgically sterile
c. If they are of childbearing potential**, agree to
- adhere to the pomalidomide pregnancy prevention risk management program in Appendix 8 :
- All women of childbearing potential must agree to have two negative pregnancy test within 10-14 days and 24hrs before commencing pomalidomide and use two reliable methods of contraception simultaneously or practice complete abstinence from any heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study; 2) while participating in the study; 3) dose interruptions; and 4) for at least 28 days after study treatment discontinuation. The two methods of reliable contraception must include one highly effective method and one additional effective method to prevent pregnancy, not plan on conceiving children during or within 6 months following pomalidomide. (See Appendix 8 Pregnancy Prevention and Risk Management Program)

9. Male patients, even if surgically sterilized (i.e. status post-vasectomy), who:
a. Agree to practice effective barrier contraception during the entire study treatment period and through 28 days after the last dose of study treatment, OR
b. Agree to completely abstain from heterosexual intercourse, AND
c. Must also adhere to the guidelines of the pomalidomide pregnancy prevention and risk management program
10. Written informed consent in accordance with federal, local and institutional guidelines

** A female of childbearing potential (FCBP) is defined as a sexually mature woman who: 1 has not undergone a hysterectomy or bilateral oophorectomy or 2, has not been naturally post-menopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (I.E, has had menses 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 to informed 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 days prior to starting pomalidomide treatment
9. Focal radiation therapy within 7 days prior to start of pomalidomide. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days 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 conventional intervention. Myocardial infarction within 4 months prior to informed consent obtained
13. Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed)
14. Patients with known cirrhosis
15. Second malignancy within the past 3 years except:
a. Adequately treated basal cell or squamous cell skin cancer
b. Carcinoma in situ of the cervix
c. Breast carcinoma in situ with full surgical resection
16. Patients with myelodysplastic syndrome
17. Patients with steroid or lenalidomide hypersensitivity
18. Prior treatment with pomalidomide
19. Ongoing graft-versus-host disease
20. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to starting pomalidomide treatment
21. Contraindication to any of the required concomitant drugs or supportive treatments
22. Any clinically significant medical disease or psychiatric condition that, in the investigator’s opinion, may interfere with protocol adherence or a patient’s ability to give informed consent.