Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease - Full Text View

Sponsor:	Dana-Farber Cancer Institute
Collaborator:	Millennium Pharmaceuticals, Inc.
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00815919

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 II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
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:

Drug Information available for: Prednisone Bortezomib

U.S. FDA Resources

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 ]

Estimated Enrollment:	30
Study Start Date:	December 2008
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Given intravenously once a week for the first four weeks of a five week cycle for a total of 3 cycles

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

Contacts

Contact: John Koreth, MBBS, DPhil	617-632-2949	jkoreth@partners.org
Contact: Bhavjot Bindra	617-632-6577	bbindra@partners.org

Locations

United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
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:	Dana-Farber Cancer Institute ( John Koreth, MBBS, DPhil )
Study ID Numbers:	08-191
Study First Received:	December 30, 2008
Last Updated:	January 15, 2010
ClinicalTrials.gov Identifier:	NCT00815919 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

cGVHD
Velcade
bortezomib

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Prednisone
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Bortezomib
Physiological Effects of Drugs

Hormones, Hormone Substitutes, and Hormone Antagonists
Enzyme Inhibitors
Glucocorticoids
Hormones
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses
Graft vs Host Disease

ClinicalTrials.gov processed this record on February 08, 2010