Lenalidomide in Treating Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To determine the efficacy of CC-5013 (lenalidomide) in prolonging time to disease
progression in patients with multiple myeloma after autologous stem cell transplant (ASCT).

SECONDARY OBJECTIVES:

I. To determine if CC-5013 will increase the complete response (CR) rate in patients with
multiple myeloma following ASCT.

II. To compare the progression-free survival (PFS) and overall survival (OS) in patients with
multiple myeloma who have undergone ASCT and who then are randomized to either CC-5013 or
placebo.

III. To determine the feasibility of long-term administration of CC-5013 to multiple myeloma
patients who have undergone ASCT.

OUTLINE:

PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Mobilization of autologous PBSC will be
performed according to institutional guidelines.

AUTOLOGOUS PBSC TRANSPLANTATION (PBSCT): Patients receive melphalan intravenously (IV) over
30-60 minutes on day -2 or -1 or over 2 days on days -3 and -2 or -2 and -1. Patients undergo
autologous PBSCT on day 0.

Patients are then randomized to 1 of 2 maintenance treatment arms. (Note: As of 12/17/09, no
more patients will be randomized between lenalidomide and placebo. Patients who have not been
randomized as of 12/17/09 will be assigned to lenalidomide.)

ARM I: Beginning between day 100-110, patients receive lenalidomide orally (PO) once daily.

ARM II: Beginning between day 100-110, patients receive placebo (PO) once daily.

In both arms, treatment continues in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and
then every 6 months thereafter.

Inclusion Criteria:

- Patients must have active multiple myeloma requiring treatment (Durie-Salmon stage >=
1) and have stable disease or be responsive to at least 2 months of any induction
therapy; patients with smoldering myeloma are not eligible unless the disease has
progressed to >= stage 1

- No more than 12 months of any prior therapy, including CC-5013 and thalidomide

- Within 12 months of initiation of induction therapy

- No prior progression after initial therapy; in addition, no more than two regimens
will be allowed excluding dexamethasone alone

- No prior peripheral blood, bone marrow, or solid organ transplant

- Patients must have peripheral blood stem cell collection of >= 2 x 10^6 cluster of
differentiation (CD)34+ cells/kg (patient body weight) and preferably 5 x 10^6
cells/kg (patient body weight); stem cells may be collected at any time prior to
transplant; peripheral blood stem cell collection may occur before or after
registration

- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Patients must have diffusing capacity of the lung for carbon monoxide (DLCO) > 50%
predicted with no symptomatic pulmonary disease

- Patients must have left ventricular ejection fraction (LVEF) >= 40% by multi gated
acquisition scan (MUGA) or echocardiogram

- Patients must not have uncontrolled diabetes mellitus

- Patients must not have an active serious infection

- Patients must not be human immunodeficiency virus (HIV), hepatitis B surface antigen
(HBSag), or hepatitis (Hep) C positive

- Patients must be non-pregnant and non-nursing; women of childbearing potential must
have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL
10-14 days prior to registration and repeated within 24 hours prior to the first dose
of lenalidomide; in addition, women of childbearing potential taking lenalidomide must
have a pregnancy test performed by the doctor weekly during the first 4 weeks of
treatment, and then every 4 weeks if menses are regular and every 2 weeks if menses
are irregular, and then 30 days following the last dose of lenalidomide; women of
childbearing potential must either commit to continued abstinence from heterosexual
intercourse or begin two acceptable methods of birth control - one highly effective
method (intrauterine device [IUD], hormonal, tubal ligation, or partner's vasectomy),
and one additional effective method (latex condom, diaphragm, or cervical cap) - at
the same time, at least 4 weeks before she begins lenalidomide therapy; "women of
childbearing" potential is defined as a sexually mature woman who has not undergone a
hysterectomy or who has had menses at any time in the preceding 24 consecutive months;
men must agree not to father a child and must use a latex condom during any sexual
contact with women of childbearing potential while taking lenalidomide and for 4 weeks
after therapy is stopped, even if they have undergone a successful vasectomy

- Absolute neutrophil count (ANC) >= 1000/uL

- Platelets >= 100,000/uL

- Creatinine clearance* >= 40 cc/min

- To be calculated by method of Cockcroft-Gault or after 24-hour urine collection

- Creatinine =< 2 mg/dL

- Total bilirubin =< 2 mg/dL

- Aspartate aminotransferase (AST) =< 3 x upper limits of normal

- Alkaline phosphatase =< 3 x upper limits of normal

- Urine (U)-human chorionic gonadotropin (HCG) or serum HCG negative (if patient of
childbearing potential)