Phase 2 Study of Bortezomib (Velcade) for the Treatment of Steroid Refractory Chronic Graft-vs-Host Disease

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the
study:

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

- ≥18 years old.

- Able to understand and sign informed consent.

- Diagnosis of steroid-refractory cGVHD is defined as either failure to improve after 2
months or progression after 1 month of standard steroid based therapy.

- No previous treatment with Bortezomib for cGVHD

- ECOG PS<3

- Total Bilirubin ≤ 1.5x ULN

- Life expectancy > 3months.

- Female subject is either post-menopausal or surgically sterilized or willing to use
an acceptable method of birth control for the duration of the study and through a
minimum of 30 days after the last dose of bortezomib.

- Male subject agrees to use an acceptable method for contraception for the duration of
the study and through a minimum of 30 days after the last dose of study drug.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the
study.

- Patient has a platelet count of <50x 10^9/L within 14 days before enrollment.

- Patient has an absolute neutrophil count of <1.0 x 10^9/L within 14 days before
enrollment.

- Patient has a calculated or measured creatinine clearance of <30 mL/minute within 14
days before enrollment.

- Patients with Total Bilirubin > 1.5x ULN

- Patient has ≥ Grade 2 peripheral neuropathy 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 (see section 8.4), 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 hypersensitivity to bortezomib, boron or mannitol.

- Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum β-human chorionic gonadotropin
(β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
required for post-menopausal or surgically sterilized women.

- 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.

- Primary malignancy (for which the transplant was received ) not in remission

- 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.

- Radiation therapy within 3 weeks before randomization. Enrollment of subjects who
require concurrent radiotherapy (which must be localized in its field size) should be
deferred until the radiotherapy is completed and 3 weeks have elapsed since the last
date of therapy.