Pomalidomide for Lenalidomide for Relapsed or Refractory Multiple Myeloma Patients

This is a phase 2, multicenter, open-label and non-randomized study to evaluate the efficacy
and safety of pomalidomide as a replacement for lenalidomide among MM patients who have
failed lenalidomide-containing regimens that include more than steroids within 6 months of
their last dose of lenalidomide. Pomalidomide will replace lenalidomide in a combination
regimen containing an alkylating agent (cyclophosphamide), anthracycline (doxorubicin or
PLD), proteasome inhibitor (bortezomib or carfilzomib) and/or a glucocorticosteroid
(prednisone, dexamethasone or methylprednisolone). Pomalidomide will be administered on days
1-21 of a 28-day cycle, whereas other drugs (anthracyclines, proteasome inhibitors, steroids
or alkylating agents except melphalan) will be administered using the same schedule(s),
dose(s) and drug combination as the last lenalidomide-containing regimen that the patient
received and failed. This study will enroll patients resistant to a lenalidomide-containing
combination regimen as demonstrated by PD while being treated or that has relapsed within 6
months of the last dose of lenalidomide in their last lenalidomide-containing combination
regimen or while on lenalidomide or lenalidomide and steroid maintenance therapy. Forty-five
patients will be enrolled in the study.

The study consists of: 1) a screening period; 2) up to eight 28-day, treatment cycles; 3) a
final assessment to occur 28 days after the end of the last treatment cycle; and 4) a
follow-up period.

Subjects eligible for this study will receive treatment with study drug for a maximum of
eight 28-day treatment cycles, depending on the schedule of their last
lenalidomide-containing regimen. Subjects are to be treated to a maximum response (lowest
level of paraprotein) plus 1 additional cycle, without exceeding a total of 8 cycles, or
complete 8 cycles of therapy without progressing (PD).

Key Inclusion Criteria:

1. Has a diagnosis of MM based on standard criteria as follows:

- Major criteria:

1. plasmacytomas on tissue biopsy

2. bone marrow plasmacytosis (greater than 30% plasma cells)

3. monoclonal immunoglobulin (Ig) spike on serum electrophoresis IgG greater
than 3.5 g/dL or IgA greater than 2.0 g/dL; kappa or lambda light chain
excretion greater than 1 g/day on 24-hour urine protein electrophoresis

- Minor criteria:

1. bone marrow plasmacytosis (10% to 30% plasma cells)

2. monoclonal immunoglobulin present but of lesser magnitude than given under
major criteria

3. lytic bone lesions

4. normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600
mg/dL

- Any of the following sets of criteria will confirm the diagnosis of multiple
myeloma:

- any 2 of the major criteria

- major criterion 1 plus minor criterion 2, 3, or 4

- major criterion 3 plus minor criterion 1 or 3

- minor criteria 1, 2, and 3, or 1, 2, and 4

2. Currently has progressive MM that has relapsed while currently receiving or within 6
months of receiving the maximum tolerated dose of lenalidomide at the physician's
discretion as part of a combination treatment that includes more than just steroids in
a 21-day or a 28-day cycle schedule. MM patients that are relapsed or have refractory
disease, as defined below, are both eligible for enrollment provided they fulfill the
other eligibility criteria:

- Patients are refractory to a lenalidomide combination regimen, when they progress
while currently receiving the lenalidomide combination treatment or within 8
weeks of its last dose.

- Patients are considered relapsed, when they progress between 8 and 26- weeks from
their last dose of lenalidomide as part of a lenalidomide-combination therapy
that includes more than just steroids.

- Prior treatment with four days or less of a total of 400 mg of prednisone (or an
equivalent potency of another steroid) for MM will not be considered a regimen

3. Currently has MM with measurable disease, defined as:

- a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL
and/or

- urine monoclonal protein levels of at least 200 mg/24 hours

- for patients without measurable serum and urine M-protein levels, an abnormal
free light chain ratio (normal value: 0.26 - 1.65)

- Serum free light chain (SFLC) > 100 mg/L (involved light chain) and abnormal ƙ/λ
ratio

4. Patients with previous clotting or thrombotic events must be able to take aspirin
(acetylsalicylic acid, ASA) at 81 or 325 mg /daily as prophylactic anticoagulation
(subjects intolerant to ASA may use warfarin or low molecular weight heparin) and/or
antithrombotic agents.

Key Exclusion Criteria:

1. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal
protein (M-protein) and skin changes (POEMS) syndrome

2. Plasma cell leukemia

3. Primary amyloidosis

4. Non-hematologic malignancy within the past 5 years with the exception of a) adequately
treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)
carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or
less with stable prostate-specific antigen levels; or d) cancer considered cured by
surgical resection or unlikely to impact survival during the duration of the study,
such as localized transitional cell carcinoma of the bladder or benign tumors of the
adrenal or pancreas

5. Impaired cardiac function or clinically significant cardiac diseases, including
myocardial infarction within 6 months prior to enrollment, New York Heart Association
(NYHA) Class II or greater heart failure, uncontrolled angina, clinically significant
pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or
multigated acquisition scan (MUGA) evidence of left ventricular ejection fraction
(LVEF) below institutional normal within 28 days prior to enrollment,
electrocardiographic evidence of acute ischemia or active conduction system
abnormalities. Prior to study entry, any ECG abnormality at Screening has to be
documented by the investigator as not medically relevant.

6. Received the following prior therapy:

- Pomalidomide

- Lenalidomide alone or in combination with steroids in their last treatment
regimen. Interim therapy not containing lenalidomide between their last
lenalidomide-containing regimen and the start of the trial.

- A melphalan-containing regimen as the immediate prior line of treatment

- Chemotherapy within 3 weeks of study drugs (6 weeks for nitrosoureas)

- Corticosteroids (>10 mg /daily prednisone or equivalent) within 3 weeks of study
drugs

- Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic
trioxide or bortezomib within 21 days before study drugs

- Extensive radiation therapy within 28 days before study drugs. Receipt of
localized radiation therapy does not preclude enrollment.

- Use of any other experimental drug or therapy within 28 days of study drugs

7. Known hypersensitivity to compounds of similar chemical or biological composition to
thalidomide and lenalidomide.

8. The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs