Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Multiple myeloma is the second most prevalent blood cancer (10%) after non-hodgkin's
lymphoma. It represents approximately 1% of all cancers and 2% of all cancer deaths. Although
the peak age of onset of multiple myeloma is 70 years of age, recent statistics indicate both
increasing incidence and earlier age of onset.

The historical control 2-year progression-free survival (PFS) is assumed to be 35%. The
proposed therapy of fludarabine, melphalan and bortezomib is expected to improve the PFS by
20%.

Inclusion Criteria:

- Diagnosis of multiple myeloma

- Have a suitable related or unrelated donor

- Age ≥18 but <70 yrs

- KPS of ≥70%

- Recovery from complications of previous therapies

Exclusion Criteria:

- Diagnosis other than multiple myeloma

- Chemotherapy or radiotherapy within 21 days of initiating treatment in this study

- Prior dose-intense therapy requiring HSC support within 56 days of initiating
treatment in this study

- Uncontrolled bacterial, viral, fungal or parasitic infections

- Uncontrolled CNS metastases

- Known amyloid deposition in heart

- Organ dysfunction

- LVEF <40% or cardiac failure not responsive to therapy

- FVC, FEV1, or DLCO <50% of predicted and/or receiving supplementary continuous oxygen

- Evidence of hepatic synthetic dysfunction, or total bilirubin >2x or AST >3x ULN

- Measured creatinine clearance <20 ml/min

- Sensory peripheral neuropathy grade 4 within 14 days of enrollment

- Karnofsky score <70% unless a result of bone disease directly caused by myeloma

- Life expectancy limited by another co-morbid illness

- Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

- Female subject is pregnant or breast-feeding (women) or unwilling to use acceptable
birth control methods (men or women) for twelve months after treatment. Confirmation
that the subject is not pregnant must be established by a negative serum beta-human
chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening.
Pregnancy testing is not required for post-menopausal or surgically sterilized women.

- Documented hypersensitivity to fludarabine or melphalan or to bortezomib, boron or
mannitol or any components of the formulation

- Patients unable or unwilling to provide consent

- Patient has a sustained platelet count of <30 x 10 9/L within 14 days before
enrollment

- Patient has a sustained absolute neutrophil count of <1.0 x10 9/L within 14 days
before enrollment

- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class III or IV heart failure uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities. Prior to study entry, any ECG
abnormality at screening has to be documented by the investigator as not medically
relevant

- Patient has received other investigational drugs with 14 days before enrollment

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study