Phase I Study of Bortezomib With or Without Total Marrow Irradiation (TMI) Using Intensity Modulated Radiation Therapy (IMRT) in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With High Risk Multiple Myeloma

Inclusion Criteria:

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

- Recipients must have histopathologically confirmed diagnosis of multiple myeloma

- Age:

- Stratum I (TMI containing arm): 18-60 years of age

- Stratum II (non TMI arm): 18-70 years of age

- Patients with primary progressive disease on induction therapy with new targeted
therapies

- Relapsed/refractory disease on new targeted therapies, i.e. thalidomide,
lenalidomide, bortezomib, or other new novel agents such as carfilzomib, pomalidomide

- Patients with relapsed multiple myeloma following previous autologous stem cell
transplant

- Plasma cell leukemia at diagnosis

- High-risk patients with presence of chromosome 17p deletion (> 60%) in the bone
marrow by fluorescence in situ hybridization (FISH); patients are not required to
have prior autologous stem cell transplant

- Able to lie supine for approximately 60 minutes, the anticipated duration of each
treatment session

- Performance status evaluated by Eastern Cooperative Oncology Group (ECOG) or
Karnofsky Performance Scales (KPS) patients must have a score of 0-II (ECOG) or >=
70% (KPS)

- Cardiac ejection fraction >= 50% by multiple gate acquisition (MUGA) scan and/or by
echocardiogram

- Forced expiratory volume in one second (FEV1) >= 50%

- Diffusing lung capacity for carbon monoxide (DLCO) >= 50%

- Creatinine clearance or glomerular filtration rate (GFR) >= 60 ml/min

- Serum bilirubin =< 2.0 mg/dl

- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic
transaminase (SGPT) =< 2.5 times the institutional upper limits of normal

- Pre-treatment tests must be performed within 30 days prior to enrollment

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

- Patients with no previous radiation or up to a maximum 2000 cGy to non thoracic-spine
and rib bone lesions or < 20% of bone marrow are eligible for TMI conditioning
regimen

- Patients with previous history of irradiation at any dose to thoracic-spine, ribs or
>= 20% of bone marrow cannot undergo TMI and will be eligible for bortezomib,
fludarabine, and melphalan regimen

Stratum II); patients can be enrolled on stratum II at their physician's discretion or if
patients decline radiation therapy

DONOR: Any matched sibling donor (matched at HLA A, B, C by intermediate resolution typing
and HLA-DRB1 by high resolution typing), or unmatched unrelated donor (matched at HLA A,
B, C, DRB1 by high resolution typing) will be considered a suitable donor

Exclusion Criteria:

- Patients with peripheral neuropathy greater than grade II

- Major medical or psychiatric disorders that would seriously compromise patient
tolerance of this regimen

- Human immunodeficiency virus (HIV) infection, active hepatitis B or C infection, or
evidence of liver cirrhosis

- Active viral, bacterial or fungal infection unless adequately treated. For fungal
infection, patient should have completed full course of antifungal therapy with
resolution of infection.

- Patients with radiographic changes including pulmonary disease, including but not
limited to: pulmonary nodules, infiltrates, pleural effusion are excluded unless
cleared by pulmonary biopsy showing no evidence for pulmonary infection

- Patients with renal insufficiency or cr clearance < 60 ml/min

DONOR: Donors will be excluded if for medical or psychological reasons they are unable to
tolerate the procedure of peripheral stem cell donation