Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors

Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor.

You will receive 3 drugs for your GVHD prophylaxis:

Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant.

Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant.

Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.

Inclusion criteria

• Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including myelodysplastic syndrome) that is unlikely to be cured by alternative therapies
• HLA-Matched unrelated donor; or 1-locus HLA-mismatched related or unrelated donor
• ECOG performance status 0-2
• Adequate organ function
• Able to understand and willing to sign a written informed consent document
• Agrees to practice adequate contraception per study requirements

Exclusion criteria

• Pregnant or breastfeeding
• Recipient of prior allogeneic or autologous stem cell transplantation
• Prior abdominal radiation therapy
• HIV-positive on combination antiretroviral therapy
• Seropositive for hepatitis B or C
• Allergies to bortezomib, boron, or mannitol
• Myocardial infarction within last 6 months, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias
• Uncontrolled bacterial, viral or fungal infections
• Seizures or history of seizures
• History of another non-hematologic malignancy unless disease-free for at least 5 years
• Uncontrolled intercurrent illness