Study of Pomalidomide, Cyclophosphamide, Dexamethasone in Relapsed/Refractory Multiple Myeloma

This is an open label, single center, phase II study of a combination of pomalidomide, daily
low dose oral cyclophosphamide, and dexamethasone in patients with relapsed/refractory
multiple myeloma. The three oral drugs will be given in 28-day cycles: Pomalidomide 4 mg
daily x 21 days; cyclophosphamide 50 mg BID x 21 days; and dexamethasone 40 mg weekly x 3 (20
mg weekly if the patient aged ≥ 75 years old). Subjects meeting eligibility criteria with ANC
< 1000/µL and platelet count < 50,000/µL will start at dose level -1 of both pomalidomide (3
mg daily) and cyclophosphamide (50 mg daily). G-CSF and platelet transfusion support is
permitted if needed.

Dose reduction for hematologic toxicity will begin with cyclophosphamide and then
subsequently alternate with pomalidomide until a subject cannot tolerate dose level -2 of
both agents - in which case subject would come off study. If subject has 2 or more concurrent
toxicities that are potentially attributable to both agents (e.g. hematologic toxicity) then
dose modification guidelines will be followed with dose reduction being done sequentially
with one agent at a time, unless in the opinion of the investigator, both agents required
concurrent dose reduction.

Inclusion Criteria:

Disease related:

- Patients must have a history of symptomatic multiple myeloma according to the IMWG
criteria

- Patients must have received at least two prior lines of therapy and also must be
refractory to lenalidomide.

- Patient has relapsed or relapsed/refractory MM.

- Patients must currently have measurable disease, as defined as:

1. Serum M-protein ≥ 0.5 g/dL

2. Urine M-protein ≥ 200 mg/24 hours

3. Serum free light chain assay: involved FLC level ≥ 10 mg/dl provided serum FLC
ratio is abnormal

4. If no monoclonal protein is detected, then > 30% monoclonal bone marrow plasma
cells

Demographic:

- Male or female adults ≥ 18 years old

- Able to sign informed consent and to comply with the protocol

- Life expectancy > 12 weeks

- ECOG performance status ≤ 2

- All study participants must be registered into the mandatory POMALYST REMS program,
and be willing and able to comply with the requirements of the POMALYST REMS program.

Laboratory

- ANC ≥ 1000/µL

- Platelets ≥ 50,000/µL (Patients with plasma cells 50% of bone marrow nucleated cells,
and platelets ≥ 30,000/µL will be permitted regardless of the baseline ANC)

- Cr < 3

- AST ≤ 2.5 x ULN

- ALT ≤ 2.5 x ULN

- Serum Bilirubin ≤ 1.5 x ULN (except patients with Gilbert's syndrome who must have a
total bilirubin of <3 time ULN)

Other

- Females of childbearing potential must have a negative serum or urine pregnancy test
with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within
24 hours of starting pomalidomide and must either commit to continued abstinence from
heterosexual intercourse or begin TWO acceptable methods of birth control at least 28
days before taking pomalidomide.

Exclusion Criteria:

- Previous treatment with pomalidomide

- Patients who received chemotherapy or radiation therapy to 30% of marrow-bearing bone
within ≤ 2 weeks or experimental agent/therapy within 4 weeks prior to starting study
treatment; or who have not yet recovered from side effects of such therapies

- Known hypersensitivity to thalidomide or lenalidomide

- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide, lenalidomide or similar drugs

- Other concurrent severe and/or uncontrolled medical conditions including abnormal
laboratory values that could cause unacceptable safety risks or compromise compliance
with the protocol

- Patients for whom prophylactic anticoagulation therapy is not an option unless due to
thrombocytopenia

- Patients who received allogenic stem cell transplantation < 12 months prior to
entering the study or show evidence of active graft-versus-host disease that requires
immunosuppressive therapy

- Patients with existing peripheral neuropathy grade > 2

- Patients with an active malignancy requiring treatment in the next 12 months (except
for basal or squamous cell carcinoma, or in situ cancer of the cervix or breast, and
asymptomatic prostate cancer)

- Patients with known positivity for HIV or active hepatitis B or C

- Corticosteroid therapies of > 20 mg/day prednisone, > 4 mg/day dexamethasone, > 80
mg/day hydrocortisone, or equivalent. Oral, inhaled, or topical steroids are allowed
during study as long as it does not exceed 80 mg/day hydrocortisone.