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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00815919
First Posted: December 31, 2008
Last Update Posted: July 22, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
John Koreth, MD, Dana-Farber Cancer Institute
  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
Intervention Model: Single Group Assignment
Masking: None (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 John Koreth, MD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD [ Time Frame: Patients had their cGVHD assessed at Baseline and at 15 weeks or end of therapy ]

    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.



Secondary Outcome Measures:
  • Proportion of Patients Tolerating >50% Steroid Dose Reduction After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD [ Time Frame: After 15 weeks of bortezomib plus prednisone therapy ]
    The participants' total daily steroid dose was recorded at baseline and after a 15 week course of treatment. Starting at a dose of 0.5-1 mg/kg, dose reduction of steroids was permitted after 1 cycle of therapy. The suggested taper was 10-25% every 1-2 weeks. .

  • The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD [ Time Frame: Toxicities were collected from the start of treatment through 15 weeks of therapy or end of study treatmetn ]
    Participants' toxicities were graded based on the CTCAE version 3.0. The toxicities were then given an attribution to the velcade treatment: unrelated, unlikely, possible, probable, definite.

  • Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy [ Time Frame: 1 year after the start of study treatment ]
    Participants who were still being followed 1 year after the start of therapy had their prednisone dose recorded.

  • Overall and cGVHD Progression-free Survival by 1 Year After Therapy [ Time Frame: 2 years ]

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 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
Other Name: Velcade
Drug: Prednisone
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.

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: John Koreth, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00815919     History of Changes
Other Study ID Numbers: 08-191
First Submitted: December 30, 2008
First Posted: December 31, 2008
Results First Submitted: January 17, 2014
Results First Posted: February 28, 2014
Last Update Posted: July 22, 2015
Last Verified: June 2015

Keywords provided by John Koreth, MD, Dana-Farber Cancer Institute:
cGVHD
Velcade
bortezomib

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Prednisone
Bortezomib
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents