Lenalidomide After Donor Stem Cell Transplant and Bortezomib in Treating Patients With High Risk Multiple Myeloma

PRIMARY OBJECTIVES:

I. Identify the maximal tolerated dose (MTD) and safety of lenalidomide up to 10mg following
non-myeloablative allogeneic stem cell transplant for multiple myeloma.

SECONDARY OBJECTIVES:

I. Assess safety and tolerability of weekly bortezomib following non-myeloablative
allogeneic stem cell transplant.

II. Obtain estimates of non-relapse mortality. III. Obtain estimates of acute and chronic
graft-versus-host disease (GVHD). IV. Obtain estimates of 1 year relapse and survival.

OUTLINE: This is a dose-escalation study of lenalidomide.

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate on days -5 to -3 and undergo
total body irradiation (TBI) on day -1.

TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant (SCT) on day 0.

GVHD PROPHYLAXIS: Patients receive standard GVHD prophylaxis comprising cyclosporine orally
(PO) twice daily (BID) beginning on day -1 with taper beginning on day 100, mycophenolate
mofetil PO BID on days 1-56, and bortezomib subcutaneously (SC) weekly from day 1 to day 91.

MAINTENANCE THERAPY: Beginning on day 100, patients receive lenalidomide PO daily on days
1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up monthly for 1 year
post-transplant.

Inclusion Criteria:

- Symptomatic multiple myeloma by International Myeloma Working Group (IMWG) criteria
according to the most recent updated version (International Myeloma Workshop [IMW]
meeting in Paris 2011)

- Must have received at least 3 of the following classes of anti-myeloma agents either
alone or in combination: glucocorticoids, immunomodulatory drugs including
thalidomide, proteasome inhibitors, alkylating chemotherapy, or anthracyclines

- Must meet any of these criteria for high risk disease:

- Relapse or progressive disease according to uniform response criteria within 2
years after starting first-line therapy or within 2 years after autologous stem
cell transplant

- Failure to achieve partial response (PR) within 6 months of staring first-line
therapy

- Presence of high risk cytogenetic features (t(14;16), t(14;20), deletion 17p)

- Chromosome 14 translocations other than to chromosome 11

- Chromosome 1p deletion and 1q amplification

- MyPRS gene expression score equal or higher than 45.2

- High risk 70 gene expression profile (MyPRS GEP70TM)

- Any other high risk genetic profile that is determined by future IMWG consensus
or by internal myeloma panel consensus; for the latter, any additional criteria
will be submitted as an addendum

- Diagnosis with multiple myeloma between the ages of 18-50

- Must have achieved at least a minor response to any previous regimen according to
adapted European Group for Blood and Marrow Transplantation (EBMT) criteria

- Must have suitable matched sibling or matched unrelated donor for stem cell source

- Must be transplant-eligible per institution guidelines

- Must have estimated glomerular filtration rate (eGFR) by Modification of Diet in
Renal Disease (MDRD) formula or Cockroft-Gault formula of 50mL/min or higher

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

- Females of childbearing potential must have negative serum or urine pregnancy test
and use acceptable birth control methods

- Able to take aspirin daily as prophylactic anticoagulation (patients intolerant to
acetylsalicylic acid [ASA] may use warfarin or low molecular weight heparin)

Exclusion Criteria:

Participants must not:

- Have known hypersensitivity to thalidomide or lenalidomide

- Have progressive disease at the time of transplant

- Uncontrolled concurrent significant medical or psychological co-morbidity

- Grade 3 peripheral neuropathy

- Known seropositive for or active viral infection with human immunodeficiency virus
(HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are
seropositive because of hepatitis B virus vaccine are eligible

- Be females who are pregnant

- Recent (within 3 years) history of other malignancies, excluding basal cell carcinoma
or squamous cell carcinoma of the skin

- Be currently enrolled in another investigational treatment protocol