Tandem High-Dose Therapy With Melphalan and Total Marrow Irradiation (TMI) With Peripheral Blood Progenitor Cell Support and Lenalidomide Maintenance in Multiple Myeloma: A Phase I/II Trial

Inclusion Criteria

Criteria

- Patients with multiple myeloma (stages I-III) will be eligible if they are either in
response, or have stable disease

- Patients with smoldering myeloma are eligible if there is evidence of progressive
disease requiring therapy (>= 25% increase in M protein levels or Bence Jones
excretion; Hgb =< 10.5 g/dl; frequent infections; hypercalcemia; rise in serum
creatinine above normal on two separate occasion)

- Patients with non-quantifiable monoclonal proteins are eligible provided they meet
other criteria for multiple myeloma, or smoldering myeloma, and they have evaluable
or measurable disease by other (radiographic) means

- Unlimited prior chemotherapy regimens allowed

- KPS >= 70%

- Patients with Waldenstrom's macroglobulinemia are not eligible

- Less than 18 months since diagnosis

- No contraindication to the collection of a minimum of 4 x 10^6 CD34+ cells/kg by
apheresis

- All patients must have signed a voluntary, informed consent in accordance with
institutional and federal guidelines

- Adequate hepatic function as demonstrated by bilirubin, =< 1.5 mg/dl, and SGOT and
SGPT < 2.5 x upper limits of normal

- Adequate renal function as demonstrated by: creatinine of measured or calculated
creatinine clearance of > 50 cc/min

- Absolute neutrophil count of > 1000/ul, platelet count of > 100,000/ul

- Cardiac ejection fraction >= 50% by MUGA scan and/or by echocardiogram

- Adequate pulmonary function as demonstrated by FEV1 > 60% and DLCO > 50% of predicted
lower limit

- Hepatitis B antigen, Hepatitis C RNA and HIV antibody tests negative

- No other medical, or psychosocial problems, which in the opinion of the primary
physician or principal investigator would place the patient at unacceptably high risk
from this treatment regimen

- Females of reproductive age not using adequate birth control measures/ or who are
pregnant are not eligible

- History of other malignancies within the last 3 years, as long as patients have
remained in complete remission for at least 2 years, except for non-melanoma skin
cancer and in situ carcinoma of the cervix

- Patients should have finished their prior chemotherapy at least 14 days prior to
cyclophosphamide priming, and should have received their last dose of thalidomide,
dexamethasone, or bisphosphonate > 10 days prior to cyclophosphamide priming

- Pre-treatment tests must have been performed within 6 weeks prior to initiation of
cyclophosphamide; A CBC, platelet count and comprehensive chemistry panel should be
performed within 1 week prior to initiating cyclophosphamide priming

- Known hypersensitivity to Filgrastim or to E. coli derived proteins is an exclusion

- Inability to lie supine in a full body cast for approximately 30 minutes, the
anticipated duration of each treatment session, is an exclusion

- Previous radiation therapy to more than 20% of bone marrow containing areas, or to
any area exceeding 2000 cGy, is an exclusion

- Patients must be fully aware of the teratogenic potential of thalidomide and agree to
fully comply with the mandated guidelines regarding contraception as stated in the
informed consent and the patient warning document attached to the consent form

- Women of childbearing potential must have a negative pregnancy test performed within
24 hours prior to beginning thalidomide, except for woman who have been
postmenopausal for at least 2 years, or underwent hysterectomy

- Use of effective means of contraceptive should be started at least 2 weeks prior to
initiating thalidomide