Chronic Graft Versus Host DiseasePhase 2NCT00815919
Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease
A Phase 2 study testing bortezomib and Prednisone in people with Chronic Graft Versus Host Disease, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Graft Versus Host Disease
- What is being tested?
- bortezomib and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Jan 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase II Trial of Bortezomib (Velcade) Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease
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.
Read the 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.
- Conditions
- Chronic Graft Versus Host Disease
- Being tested
- bortezomib, Prednisone
- Keywords
- cGVHD, Velcade, bortezomib
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Also called Velcade
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
PrednisoneDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Velcade (bortezomib) | Experimental | Not described Receives: Drug: bortezomib; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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. .
Measured: After 15 weeks of bortezomib plus prednisone therapy
The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
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.
Measured: 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
Participants who were still being followed 1 year after the start of therapy had their prednisone dose recorded.
Measured: 1 year after the start of study treatment
Overall and cGVHD Progression-free Survival by 1 Year After Therapy
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2008 (estimated)
- Study startDec 2008
- Primary completionJan 2012
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, John Koreth, MD, Dana-Farber Cancer Institute
- Investigators
- John Koreth, MBBS, DPhil, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00815919
- Sponsor's protocol ID
- 08-191
- Status last verified
- Jun 2015
- First submitted
- 30 Dec 2008
- Last updated
- 22 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Bortezomib (Velcade) Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT00815919
- Acronym / sponsor ID
- 08-191
- Conditions
- Chronic Graft Versus Host Disease
- Keywords
- cGVHD, Velcade, bortezomib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Dec 2008
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 31 Dec 2008 (estimated)
- Results
- Posted 28 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Velcade (bortezomib) | Experimental | Drug: bortezomib, Drug: Prednisone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bortezomibAlso: VelcadeGiven 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 | Drug | Velcade (bortezomib) |
| PrednisoneTaken 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. | Drug | Velcade (bortezomib) |
Primary outcome
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.
4 secondary outcomes
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 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
Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy
Time frame: 1 year after the start of study treatment
Overall and cGVHD Progression-free Survival by 1 Year After Therapy
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Koreth, MBBS, DPhil principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bortezomib and Prednisone in people with Chronic Graft Versus Host Disease, run by Dana-Farber Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2015.