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

Phase 2
18 Years
Open (Enrolling)
Chronic Graft-versus-host Disease

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Trial Information

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

Graft vs. host disease represents the most formidable problem following allogeneic
hematopoietic stem cell transplantation for hematological diseases. Chronic
graft-versus-host disease (cGVHD) is the most serious and common long-term complication of
this treatment in patients surviving more than 100 days. Some patients are requiring
immunosuppressive therapy for years. cGVHD is associated with a high degree of morbidity
and mortality and remains a major cause of late death. When standard treatment with
steroids is ineffective or poorly tolerated, effective therapeutic options are limited.
Patients with uncontrolled cGVHD with initial therapy including systemic steroids respond
poorly to second line options. Recent studies have demonstrated Bortezomib safety in the
prophylaxis, and improvement of GVHD suggesting its efficacy.This study is done to evaluate
the potential of bortezomib in treating refractory cGVHD.

Inclusion Criteria:

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

- 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not part of normal medical care, with the understanding that consent may be withdrawn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


- 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

- 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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the effectiveness and safety of the proteasome inhibitor Bortezomib (Velcade) in the treatment of steroid refractory chronic Graft-vs-Host Disease (cGVHD)

Outcome Description:

Total time frame including treatment and follow up is 19 months(Maximum of 6 cycles during initial treatment phase, 6 cycles in maintenance phase, and follow up phase for 6 months). Subjects will be assessed for signs and symptoms of cGVHD on day 1 of every cycle using standardized criteria for diagnosis of cGVHD, new clinical scoring system, and new guidelines for global assessment of chronic GVHD severity per NIH consensus development project on criteria for clinical trials in chronic GVHD. Safety will be assessed in terms of adverse events for 30 days following the last dose to a maximum of 6 months. Adverse events will be recorded through out the trial and will be followed by investigator until resolution.

Outcome Time Frame:

19 months

Safety Issue:


Principal Investigator

Alan Miller, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Charles A. Caner Center, Baylor University Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2010

Completion Date:

March 2014

Related Keywords:

  • Chronic Graft-versus-host Disease
  • Steroid refractory chronic graft vs host disease (cGVHD)
  • Bortezomib
  • Velcade
  • Graft vs Host Disease



Charles A. Cancer Center, Baylor University Medical CenterDallas, Texas  75246