Bronchiolitis ObliteransPhase 2NCT01163786
A Proposal to Test the Efficacy and Tolerability of Bortezomib in Pulmonary Chronic GVHD
A Phase 2 study testing Bortezomib in people with Bronchiolitis Obliterans, run by Northwestern University at 1 site in United States.
Trial summary
Approximately 10,000 allogeneic hematopoietic stem cell transplants (HSCT) are performed annually in the US for various indications. Bronchiolitis obliterans (BO) is the most common late noninfectious complication following allogeneic hematopoietic stem cell transplant. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Bronchiolitis Obliterans
- What is being tested?
- Bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Oct 2010to 9 Sep 2015
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
- Day >100 after allogeneic hematopoietic stem cell transplantation
- Underlying cancer in remission
- Decrease in FEV1 of ≥12% from the pre-transplant baseline (FEV1/FVC ratio <0.8)
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- No evidence of acute infection
- ANC >1000
- Platelets >50,000
- Age 18-70
- ECOG performance Status 0-2.
Who cannot join
- Patient has a platelet count of less than 50,000 within 14 days before enrollment.
- Patient has an absolute neutrophil count of less 1000 within 14 days before enrollment.
- Patient has a calculated or measured creatinine clearance of < 20 ml/minute within 14 days before enrollment.
- Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
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- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum b-human chorionic gonadotropin (b-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Inability of give consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Proposal to Test the Efficacy and Tolerability of Bortezomib in Pulmonary Chronic GVHD
Approximately 10,000 allogeneic hematopoietic stem cell transplants (HSCT) are performed annually in the US for various indications. Bronchiolitis obliterans (BO) is the most common late noninfectious complication following allogeneic hematopoietic stem cell transplant. Prognosis of BO in the allogeneic HSCT setting is dismal and there are no therapies proven to be consistently effective. The exact incidence is not clear but may be as high as 30%2 . Risk factors include new or ongoing chronic graft versus host disease (cGVHD), age, antecedent obstructive airways disease and viral infections1. BO is characterized physiologically by progressive irreversible airflow obstruction and pathologically by luminal occlusion of the distal airways due to progressive scarring3. The pathogenesis is not completely understood but the cytokine transforming growth factor-beta 1 (TGF-b1), important for both tissue repair and fibrosis, is thought to play a pivotal role. Bortezomib, an FDA approved proteasomal inhibitor inhibits TGF-b1 signaling in vitro and protects against lung injury/fibrosis in bleomycin mouse model as well as in a mouse model for skin fibrosis. This is consistent with other data in the literature that proteasomal inhibition can prevent the development of fibrosis. Thus the investigators propose to test the safety, tolerability and efficacy of bortezomib in chronic pulmonary GVHD (BO).
- Conditions
- Bronchiolitis Obliterans
- Being tested
- Bortezomib
- Keywords
- Bortezomib GVHD Bronchiolitis Obliterans
- Medical subject headings
- Bronchiolitis Obliterans
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
Each patient will receive 2 cycles of Bortezomib. For each cycle Bortezomib wil be given once a week, 1.3mg/m2 for 4 weeks with 2 weeks between each cycle.
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib | Experimental | Patients will Receive 2 4week cycles of Bortezomib. Each cycle will consist of weekly bortezomib with a 2 week interval between cycles. Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pulmonary Function as Measured by Forced Expiratory Volume in 1 Second (FEV1) Decline
FEV1 will be measured by spirometry assessments at baseline (pre-transplant baseline - prior to pulmonary chronic graft-versus-host disease (p-CGVHD)) during treatment (10 weeks) and at follow up visit 9 (at 12 weeks) and at follow up visit 10 (at 18 weeks) with patients having spirometry tested up to 6 times from screening to the end of the study. FEV1 is reported as slopes computed by dividing difference in FEV1 by time in months.
Measured: Mean time to diagnosis (from transplant to p-CGVHD ) of 3.36 years (+/- 1.88 years) and up to 18 weeks after baseline
Secondary outcomes (2)
Exercise Tolerance- 6 Minute Walk
Patients will have an exercise tolerance assessment defined as a 6 minute walk completed at cycle 1 (week 1) and cycle 2 (week 5) of treatment and visit 9 (12 weeks) and visit 10 (18 weeks).
Measured: Up to 18 weeks from baseline
Short Form (SF)-36 Health Survey
This is a quality of life questionnaire which yields scores for 8 domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health). This questionnaire will be completed by patients on Visit 1 (week 1), Visit 5 (week 5), Visit 8 (week 8), Visit 9 (12 weeks), and Visit 10 (18 weeks).
Questionnaires were scored per the scoring rules for the RAND 36-Item Health Survey (version 1.0) A high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Hence, scale scores represent the average for all items in the scale that the respondent answered.
Measured: up to 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2010 (estimated)
- Study start7 Oct 2010
- Primary completion9 Sep 2015
- Study completion9 Sep 2015
Why it stopped: Study was closed due to low accrual before the accrual goal was reached
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 Bronchiolitis ObliteransStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Robert H. Lurie Cancer Center
- Responsible party
- Sponsor
- Investigators
- Manu Jain, MD, MS, Principal investigator, Northwestern UniversityJayesh Mehta, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01163786
- Sponsor's protocol ID
- NU 09H7
- Other IDs
- NU 09H7, STU00022160
- Status last verified
- Apr 2020
- First submitted
- 7 Jul 2010
- Last updated
- 10 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Proposal to Test the Efficacy and Tolerability of Bortezomib in Pulmonary Chronic GVHD
- ClinicalTrials.gov ID
- NCT01163786
- Acronym / sponsor ID
- NU 09H7
- Conditions
- Bronchiolitis Obliterans
- Keywords
- Bortezomib GVHD Bronchiolitis Obliterans
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was closed due to low accrual before the accrual goal was reached
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Robert H. Lurie Cancer Center
- Study start
- 7 Oct 2010 (actual)
- Primary completion
- 9 Sep 2015 (actual)
- Study completion
- 9 Sep 2015 (actual)
- First posted
- 16 Jul 2010 (estimated)
- Results
- Posted 10 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approximately 10,000 allogeneic hematopoietic stem cell transplants (HSCT) are performed annually in the US for various indications. Bronchiolitis obliterans (BO) is the most common late noninfectious complication following allogeneic hematopoietic stem cell transplant. Prognosis of BO in the allogeneic HSCT setting is dismal and there are no therapies proven to be consistently effective. The exact incidence is not clear but may be as high as 30%2 . Risk factors include new or ongoing chronic graft versus host disease (cGVHD), age, antecedent obstructive airways disease and viral infections1. BO is characterized physiologically by progressive irreversible airflow obstruction and pathologically by luminal occlusion of the distal airways due to progressive scarring3. The pathogenesis is not completely understood but the cytokine transforming growth factor-beta 1 (TGF-b1), important for both tissue repair and fibrosis, is thought to play a pivotal role. Bortezomib, an FDA approved proteasomal inhibitor inhibits TGF-b1 signaling in vitro and protects against lung injury/fibrosis in bleomycin mouse model as well as in a mouse model for skin fibrosis. This is consistent with other data in the literature that proteasomal inhibition can prevent the development of fibrosis. Thus the investigators propose to test the safety, tolerability and efficacy of bortezomib in chronic pulmonary GVHD (BO).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib | Experimental | Drug: BortezomibPatients will Receive 2 4week cycles of Bortezomib. Each cycle will consist of weekly bortezomib with a 2 week interval between cycles. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
- Day >100 after allogeneic hematopoietic stem cell transplantation
- Underlying cancer in remission
Key exclusion criteria (10 listed)
- Patient has a platelet count of less than 50,000 within 14 days before enrollment.
- Patient has an absolute neutrophil count of less 1000 within 14 days before enrollment.
- Patient has a calculated or measured creatinine clearance of < 20 ml/minute within 14 days before enrollment.
- Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
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: VelcadeEach patient will receive 2 cycles of Bortezomib. For each cycle Bortezomib wil be given once a week, 1.3mg/m2 for 4 weeks with 2 weeks between each cycle. | Drug | Bortezomib |
Primary outcome
Change in Pulmonary Function as Measured by Forced Expiratory Volume in 1 Second (FEV1) Decline
Time frame: Mean time to diagnosis (from transplant to p-CGVHD ) of 3.36 years (+/- 1.88 years) and up to 18 weeks after baseline
FEV1 will be measured by spirometry assessments at baseline (pre-transplant baseline - prior to pulmonary chronic graft-versus-host disease (p-CGVHD)) during treatment (10 weeks) and at follow up visit 9 (at 12 weeks) and at follow up visit 10 (at 18 weeks) with patients having spirometry tested up to 6 times from screening to the end of the study. FEV1 is reported as slopes computed by dividing difference in FEV1 by time in months.
2 secondary outcomes
Exercise Tolerance- 6 Minute Walk
Time frame: Up to 18 weeks from baseline
Short Form (SF)-36 Health Survey
Time frame: up to 18 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Ex Vivo-Expanded Regulatory T Cells Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic GVHD
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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.
Manu Jain, MD, MS principal investigator
Northwestern University
Jayesh Mehta, MD principal investigator
Northwestern University
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 in people with Bronchiolitis Obliterans, run by Northwestern University 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 11 inclusion and 10 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: stopped early, as of the sponsor's last update on 10 Apr 2020. 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 10 Apr 2020). 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?
Change in Pulmonary Function as Measured by Forced Expiratory Volume in 1 Second (FEV1) Decline (time frame: Mean time to diagnosis (from transplant to p-CGVHD ) of 3.36 years (+/- 1.88 years) and up to 18 weeks after baseline). 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 10 Apr 2020.