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

NCT00815919 | Completed Phase 2 Results DMC

• 1 other identifier: 08-191
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Graft Versus Host Disease

Keywords

cGVHD; Velcade; bortezomib

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD

  Participants had their cGVHD evaluated per NIH consensus criteria: Complete response: resolution of all reversible manifestations of cGVHD. Partial response: a decrease ≥ 1 point on a 3-point organ-specific scale or 2 points or more on a 10-point global scale without progression in any organ sites. Stable disease: no evidence of cGVHD response without evidence of progressive cGVHD. Progressive cGVHD: increase of ≥ 1 point on an organ-specific 3-point scale, addition of a new immunosuppressive agent prior to the completion of 15 weeks of combination therapy, or requirement an increase in the total daily dose of corticosteroids above a participant's baseline corticosteroid dose during the 15-week combined treatment period. Mixed response: a response in primary sites of cGVHD involvement but interval progressive cGVHD in other organs or sites. Responses were not scored for oral or ocular cGVHD, since topical therapies were permitted during the study.

  Patients had their cGVHD assessed at Baseline and at 15 weeks or end of therapy

Secondary Outcomes (4)

• Proportion of Patients Tolerating >50% Steroid Dose Reduction After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD

  After 15 weeks of bortezomib plus prednisone therapy

• The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD

  Toxicities were collected from the start of treatment through 15 weeks of therapy or end of study treatmetn

• Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy

  1 year after the start of study treatment

• Overall and cGVHD Progression-free Survival by 1 Year After Therapy

  2 years

Study Arms (1)

Velcade (bortezomib)

EXPERIMENTAL

Drug: bortezomib; Drug: Prednisone

Interventions

bortezomib DRUG

Given intravenously at a dose of 1.3 mg/m\^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles

Also known as: Velcade

Velcade (bortezomib)

Prednisone DRUG

Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks.

Velcade (bortezomib)

Eligibility Criteria

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

You may qualify if:

• Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Bortezomib; Prednisone

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: John Koreth, MBBS, DPhil
• Organization: Dana-Farber Cancer Institute

John_Koreth@dfci.harvard.edu

617-632-2949

Study Officials

• John Koreth, MBBS, DPhil

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 30, 2008
• First Posted: December 31, 2008
• Study Start: December 1, 2008
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2013
• Last Updated: July 22, 2015
• Results First Posted: February 28, 2014

Record last verified: 2015-06

Locations

US (1)