Pomalidomide or Lenalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma Previously Treated With Lenalidomide

PRIMARY OBJECTIVES:

I. To assess the confirmed response rate of the combination of lenalidomide and dexamethasone
in patients with relapsed myeloma who have previously become refractory to lenalidomide. (Arm
A) II. To assess the confirmed response rate of the combination of pomalidomide and
dexamethasone in patients with relapsed myeloma who have previously become refractory to
lenalidomide. (Arm B)

SECONDARY OBJECTIVES:

I. To assess the toxicity in each arm in patients with relapsed myeloma who have previously
received lenalidomide.

II. To assess the response rates with pomalidomide and dexamethasone in patients relapsing on
lenalidomide and dexamethasone. (Arm A) III. To assess time to progression and overall
survival with each approach.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive lenalidomide orally (PO) daily on days 1-21 and dexamethasone PO on
days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity. Patients experiencing progressive disease may crossover to arm B.

ARM B: Patients receive pomalidomide PO daily on days 1-21 and dexamethasone as in arm A.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Calculated creatinine clearance >= 30 ml/min by Cockcroft-Gault formula

- Absolute neutrophil count >= 1000uL

- (Untransfused) platelet count >= 50000/uL

- Hemoglobin >= 8.0 g/dL

- Relapsed myeloma that previously became refractory to lenalidomide, after initial
response of partial response or better to the drug; refractory is defined as
progression on treatment with a dose of at least 10 mg daily for lenalidomide; greater
than or equal to 180 days must have elapsed since previous lenalidomide therapy was
stopped

- Measurable disease of multiple myeloma as defined by at least ONE of the following:

- Serum monoclonal protein >= 1.0 g/dL

- >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis

- Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio

- Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

- Previously treated; NOTE: no limit to prior therapy provided there is adequate
residual organ function

- Provide informed written consent

- Females of childbearing potential (FCBP)* must have a negative serum pregnancy test
with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within
24 hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be filled
within 7 days as required by Revlimid Risk Evaluation and Mitigation Strategy [REMS]),
and must either commit to continued abstinence from heterosexual intercourse or begin
TWO acceptable methods of birth control, one highly effective method and one
additional effective method AT THE SAME TIME, at least 28 days before she starts
taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree
to use a latex condom during sexual contact with a FCBP even if they have had a
successful vasectomy; all study participants must be registered into the Revlimid REMS
program, and be willing and able to comply with the requirements of Revlimid REMS
program

- A female of childbearing potential is a sexually mature woman who: 1) has not
undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any
time in the preceding 24 consecutive months)

- Willing to return to Mayo Clinic enrolling institution for follow-up

Exclusion Criteria:

- Residual toxicity of > grade 1 from prior therapy

- Other active malignancy < 1 year prior to registration; EXCEPTIONS: non-melanotic skin
cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior
malignancy, they must not be receiving other specific treatment for their cancer

- Any of the following:

- Pregnant women

- Nursing women (lactating females must agree not to breast feed while taking
lenalidomide)

- Men or women of childbearing potential who are unwilling to employ adequate
contraception (condoms, diaphragm, birth control pills, injections, intrauterine
device [IUD], or abstinence, etc.)

- Other co-morbidity which would interfere with patient's ability to participate in
trial, e.g. uncontrolled infection, uncompensated heart or lung disease

- Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered
investigational; NOTE: bisphosphonates are considered to be supportive care rather
than therapy, and are thus allowed while on protocol treatment

- New York Heart Association classification III or IV

- Diagnosed active deep vein thrombosis (DVT) that has not been therapeutically
anticoagulated