Overview

Efficacy and Toxicity Study of Pomalidomide and Dexamethasone in Patients Who Have Relapsed After Exposure to Lenalidomide and Bortezomib

Status:
Unknown status
Trial end date:
2018-11-01
Target enrollment:
0
Participant gender:
All
Summary
Asian patients with relapsed myeloma after prior treatment with bortezomib and lenalidomide will treatment on pomalidomde and dexamethasone. Baseline, follow-up, survival and toxicity information will be collected.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National University Hospital, Singapore
Collaborator:
Celgene
Treatments:
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Pomalidomide
Thalidomide
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)

1. Serum M-protein ≥ 0.5g/dL, or

2. 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 have failed lenalidomide (based on 1 of the following criteria: a) Refractory to
lenalidomide; or b) no better than stable disease after 3 cycles of lenalidomide) and
relapsed from previous treatment with 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:

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

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

3. Calculated creatinine clearance ≥ 45mL/min or creatinine < 3mg/dL.

8. Female patients who:

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

2. Are surgically sterile

3. 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:

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

2. Agree to completely abstain from heterosexual intercourse, AND

3. 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).

1.1. 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:

1. Adequately treated basal cell or squamous cell skin cancer

2. Carcinoma in situ of the cervix

3. 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.