Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease

This study has been completed.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
John Koreth, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00815919
First received: December 30, 2008
Last updated: January 28, 2013
Last verified: January 2013
  Purpose

The purpose of this research study is to determine the effectiveness of bortezomib (Velcade) plus prednisone for treating chronic graft versus host disease (cGVHD) and the safety of this drug combination in this patient population. Chronic GVHD is a medical condition that may occur after allogeneic stem cell transplantation. The donor's immune system may recognize the participants body (the host) as foreign and attempt to "reject" it. Bortezomib has been used in other research studies, and information from those studies suggests that this drug may help to control the abnormal immune responses that underlie cGVHD.


Condition Intervention Phase
Chronic Graft Versus Host Disease
Drug: bortezomib
Drug: Prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Bortezomib (Velcade) Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To determine the overall response rate after a 15 week course of bortezomib plus prednisone in patients with cGVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the proportion of patients tolerating >50% steroid dose reduction after a 15 week course of bortezomib plus prednisone in patients with cGVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To assess the toxicity of a 15 week course of bortezomib plus prednisone in patients with cGVHD [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To determine the proportion of cGVHD patients requiring prednisone by 1 year after therapy [ Time Frame: 2 yeras ] [ Designated as safety issue: No ]
  • To assess overall and cGVHD progression-free survival by 1 year after therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: December 2008
Study Completion Date: January 2013
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Velcade (bortezomib) Drug: bortezomib
Given intravenously once a week for the first four weeks of a five week cycle for a total of 3 cycles
Other Name: Velcade
Drug: Prednisone
Taken orally once a day. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks.

Detailed Description:
  • Each treatment cycle lasts five weeks, during which time participants will come to the clinic to receive bortezomib intravenously once a week for the first 4 weeks. Prednisone will be taken orally on a daily basis and dose reduction may be initiated after 1 cycle of therapy.
  • During all treatment cycles, participants will have the following: physical exam and blood work. At the end of cycle 3 (week 15) the participants cGVHD will be evaluated. These assessments may include an eye examination, a skin examination, a pulmonary function test and/or, a flexion assessment test.
  • Participants will receive 3 cycles of bortezomib.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
  • 100 days or more past stem cell transplantation
  • Recipients of matched or mismatched, related or unrelated adult donor stem cells
  • Must have cGVHD requiring systemic therapy
  • No addition or subtraction of other immunosuppressive medications. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug. However, if cGVHD occurs during a taper of immune suppression, the medication(s) may not be increased back up to therapeutic level, but will continue a the taper dose for the 15 week study duration
  • Adequate bone marrow, hepatic and renal function as outlined in the protocol
  • Does not require hemodialysis
  • 18 years of age or older
  • ECOG Performance Status of 0-2 or Karnofsky performance score of 70% or greater
  • Life expectancy of more than 3 months

Exclusion Criteria:

  • Systemic steroid therapy in the 4 weeks prior to enrollment
  • Active malignant disease after transplantation. 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 will not be considered in this category
  • Active uncontrolled infection
  • Peripheral neuropathy CTC Grade 1 (or greater) with pain in the 4 weeks before enrollment. Other neurological deficits must be reviewed with the study PI prior to study entry
  • Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Hypersensitivity to bortezomib, boron, or mannitol
  • Female subject is pregnant or breast-feeding
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00815919

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: John Koreth, MBBS, DPhil Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: John Koreth, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00815919     History of Changes
Other Study ID Numbers: 08-191
Study First Received: December 30, 2008
Last Updated: January 28, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
cGVHD
Velcade
bortezomib

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Prednisone
Bortezomib
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013