Study on the Safety and Effectiveness of VELCADE® in the Treatment of Graft-Versus-Host Disease

NCT00408928 | Completed Phase 2 Results DMC

• 3 other identifiers: 04U.1772004-19JT 1129
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test the safety and effectiveness of VELCADE® in the treatment of acute graft-versus-host disease (GVHD) that has not responded to steroids or has worsened when the steroid dose was decreased. VELCADE® is a drug that inhibits certain immune reactions that happen when lymphocytes encounter foreign substances. We are doing this research to determine if VELCADE® may be useful in treating GVHD.

Conditions

Graft-versus-Host Disease

Keywords

Graft-versus-Host Disease; bortezomib

Outcome Measures

Primary Outcomes (1)

• Response to Bortezomib (VELCADE®)

  Response is the primary endpoint of this study and will be scored on day 21 (3 weeks after the first dose of VELCADE) and every 3 weeks subsequently. Patients who progress or expire before the end of the study will be considered non-responders. Patients are evaluated for response in an organ if they have AGVHD in that organ at the start of treatment with VELCADE or if AGVHD develops after the start of VELCADE, but before the time period of evaluation. Complete response in an organ is defined as no evidence clinical or biochemical signs of AGVHD. For the overall assessment, it is defined as complete resolution of rash, abnormal LFTs, and absence of diarrhea attributed to AGVHD. Partial response is defined as a one stage decrease in any organ system without worsening in other organ systems.

  Through 30 days post-treatment

Secondary Outcomes (1)

• Number of Toxicities Related to Bortezomib (VELCADE®)

  Through 30 days post-traeatment

Study Arms (1)

Bortezomib for Treatment of GHVD

EXPERIMENTAL

To determine if bortezomib (VELCADE®) will successfully inhibit T-cell responses in clinically acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT).

Drug: Bortezomib

Interventions

Bortezomib DRUG

Bortezomib at 1.3 mg/m2/dose given twice weekly for two weeks followed by a 10-day rest period. If patients have a complete response, they will receive additional cycles of bortezomib.

Also known as: VELCADE, PS-341

Bortezomib for Treatment of GHVD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have undergone an allogeneic HSCT
• Clinical or histological evidence of AGVHD
• Has been treated with a minimum of 2mg/kg of methylprednisolone per day or equivalent dose of steroids and either one of the following:
• Has had a minimum of 3 days of steroids including the day of assignment and has progressive disease.
• Has had a minimum of 7 days of steroids including the day of assignment and has had no response.
• AGVHD progresses at anytime when steroids are tapered to less than 2mg/kg/day of methylprednisolone or its equivalent.
• Performance status ECOG 0-2
• Patients must be willing to use contraception if they have childbearing potential
• Able to give informed consent
• Patients must be \> 18 years of age, with no upper age limit.

You may not qualify if:

• Performance status of ECOG \>2.
• \>Grade3 peripheral neuropathy at the time of enrollment
• Patient has a creatinine clearance (calculated or measured) of \<30mL/min at the time of enrollment.
• Myocardial infarction within 6 months prior to enrollment or has New York Hospital 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/co-investigator as not medically relevant.
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• Female subject is pregnant or breast-feeding.
• Patient has received other investigational drug within 14 days prior to enrollment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study or to obtain informed consent.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: John Wagner, MD
• Organization: Thomas Jefferson University

John.Wagner@jefferson.edu

215-955-8874

Study Officials

• John Wagner, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2006
• First Posted: December 8, 2006
• Study Start: November 1, 2005
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2009
• Last Updated: May 4, 2025
• Results First Posted: November 28, 2013

Record last verified: 2025-05

Locations

US (1)