Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Phase 1 / 2 Study
Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Phase 1 / 2 Study
A) Phase 1: To determine the maximal tolerated dose (MTD) of lenalidomide that can be safely
 added to high-dose melphalan prior to autologous stem cell transplantation (ASCT).

 B) Phase 2: To determine whether the addition of high-dose lenalidomide to ASCT followed by
 maintenance standard-dose lenalidomide improves the response rate and duration of response
 for relapsed multiple myeloma (RMM).
Inclusion Criteria:

 -  Patients must have histologically or cytologically confirmed relapsed, primary
 refractory, or relapsed and refractory multiple myeloma.

 -  Patients must have measurable disease as defined by the International Uniform Response
 Criteria,defined as any of the following:

 -  serum M-protein of > = 500mg/dL

 -  urine M-protein of > = 200mg/ 24 hours

 -  involved free light chain > = 10mg/dL provided serum free light chain ratio is
 abnormal

 -  Patients must have received at least one prior line of therapy.

 -  Age > = 18 years.

 -  Life expectancy of greater than 12 weeks.

 -  ECOG performance status > = 2.

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

 -  Patients must have normal organ and marrow function as defined below:

 -  ANC > = 1,000/uL

 -  platelets > = 50,000/uL

 -  total bilirubin < = 1.5 X upper limit of normal

 -  AST(SGOT)/ALT(SGPT) < = 2.5 X upper limit of normal

 -  Cardiac Ejection Fraction > = 45 %

 -  Creatinine clearance > 60 cc/min

 -  Patients must have an adequate number of CD34+ stem cells collected to allow for
 transplantation. This number is defined as ≥ 2 x 106 CD34+ cells / kg body weight. If
 not previously collected and stored, the patient must be willing to undergo stem cell
 mobilization and collection as per standard practice.

 -  The effects of lenalidomide on the developing human fetus at the recommended
 therapeutic dose are unknown; however, it has been shown to be teratogenic other
 primates. Females of childbearing potential (FCBP) must have a negative serum or urine
 pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again
 within 24 hours prior to prescribing lenalidomide (prescriptions must be filled within
 7 days) 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. Should a woman become pregnant or suspect she is pregnant while
 participating in this study, she should inform her treating physician immediately. The
 treating physician will follow the adverse reporting guidelines as outlined in further
 detail below for pregnancies.

 -  Lenalidomide has been shown to carry a risk of thromboembolic events, especially when
 used in combination with either corticosteroids or alkylating chemotherapeutic agents.
 All patients who participate in this study must be willing and able to tolerate
 prophylactic anticoagulation with low-molecular weight heparin (LMWH) for the required
 dates in treatment protocol. Patients also must be able to tolerate low-dose aspirin,
 81 mg daily, during the maintenance phase of the treatment protocol.

 -  Ability to understand and the willingness to sign a written informed consent document.

 Exclusion Criteria:

 -  Patients who have had myeloma therapy within 14 days prior to entering the study or
 those who have not recovered from adverse events due to agents administered more than
 2 weeks earlier. Patients may have received bisphosphonate therapy as part of routine
 myeloma care at any time prior to study entry.

 -  Patients may not be receiving any other investigational agents.

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to lenalidomide (including thalidomide) or melphalan.

 -  Known positive for HIV or infectious hepatitis, type B or C.

 -  Uncontrolled illness including, but not limited to, ongoing or active infection,
 symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
 psychiatric illness/social situations that would limit compliance with study
 requirements.

 -  Pregnant and lactating women are excluded from the study because the risks to an
 unborn fetus or potential risks in nursing infants are unknown.

 -  History of thrombosis or thromboembolic event within last 60 days prior to study
 entry.