A Trial of Tandem Autologous Stem Cell Transplants +/- Post Second Autologous Transplant Maintenance Therapy Versus Single Autologous Stem Cell Transplant Followed by Matched Sibling Non-myeloablative Allogeneic Stem Cell Transplant for Patients With Multiple Myeloma (BMT CTN #0102)

Inclusion Criteria:

- Meeting the Durie and Salmon criteria for initial diagnosis of MM

- Stage II or III MM at diagnosis or anytime thereafter

- Symptomatic MM requiring treatment at diagnosis or anytime thereafter

- Received at least three cycles of initial systemic therapy and are within 2-10 months
of initiation of the initial therapy (this time frame excludes the time for
mobilization therapy)

- If receiving chemotherapy-based mobilization regimens, must be able to receive
high-dose melphalan between 2 and 8 weeks after the initiation of mobilization
therapy whether delivered at the transplant center or at a referring center

- Adequate organ function as measured by:

1. Cardiac: Left ventricular ejection fraction at rest greater than 40%

2. Hepatic: Bilirubin less than 2 times the upper limit of normal and ALT and AST
less than 3 times the upper limit of normal

3. Renal: Creatinine clearance greater than 40 ml/min (measured or
calculated/estimated)

4. Pulmonary: DLCO, FEV1, and FVC greater than 50% of predicted value (corrected
for hemoglobin), or O2 saturation greater than 92% of room air

- An adequate autologous graft defined as a cryopreserved PBSC graft containing at
least 4.0 x 106 CD34+ cells/kg patient weight; if prior to enrollment it is known
that a patient will be on the auto-allo arm (i.e., a consenting, eligible HLA-matched
sibling donor is available), the required autograft must contain at least 2.0 x 10^6
CD34+ cells/kg patient weight; the graft may not be CD34+ selected or otherwise
manipulated to remove tumor or other cells; the graft can be collected at the
transplanting institution or by a referring center; for patients without an
HLA-matched sibling donor, the autograft must be stored so that there are two
products each containing at least 2 x 10^6 CD34+ cells/kg patient weight

Exclusion Criteria:

- Never advanced beyond Stage I MM since diagnosis

- Non-secretory MM (absence of a monoclonal protein [M protein] in serum as measured by
electrophoresis and immunofixation and the absence of Bence Jones protein in the
urine defined by use of conventional electrophoresis and immunofixation techniques)

- Plasma cell leukemia

- Karnofsky performance score less than 70%, unless approved by the Medical Monitor or
one of the Protocol Chairs

- Uncontrolled hypertension

- Uncontrolled bacterial, viral, or fungal infections (currently taking medication and
progression of clinical symptoms)

- Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma
in situ; cancer treated with curative intent less than 5 years previously will not be
allowed unless approved by the Medical Monitor or one of the Protocol Chairs; cancer
treated with curative intent more than 5 years previously will be allowed

- Pregnant or breastfeeding

- Seropositive for the human immunodeficiency virus (HIV)

- Unwilling to use contraceptive techniques during and for 12 months following
treatment

- Prior allograft or prior autograft

- Received mid-intensity melphalan (more than 50 mg IV) as part of prior therapy

- Prior organ transplant requiring immunosuppressive therapy