A Proposal to Test the Efficacy and Tolerability of Bortezomib in Pulmonary Chronic GVHD

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Northwestern University
Sponsor:
Collaborator:
Robert H. Lurie Cancer Center
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT01163786
First received: July 7, 2010
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Bronchiolitis Obliterans
Drug: Bortezomib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Proposal to Test the Efficacy and Tolerability of Bortezomib in Pulmonary Chronic GVHD

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Change in pulmonary function as measured by FEV1 from baseline and 9 weeks later. [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
    Research subjects will receive 2 4 week cycles of bortezomib with a 1 week holiday between cycles.


Secondary Outcome Measures:
  • Exercise Tolerance- 6 minute walk at baseline and 9 weeks later. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Quality of Life-SF-36 at baseline and 9 weeks later. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: July 2010
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib
Patients will Receive 2 4week cycles of Bortezomib. Each cycle will consist of weekly bortezomib with a 2 week interval between cycles.
Drug: Bortezomib
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.
Other Name: Velcade

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
  • No evidence of acute infection
  • ANC >1000
  • Platelets >50,000
  • Age 18-70
  • ECOG performance Status 0-2.

Exclusion Criteria:

  • 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.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01163786

Contacts
Contact: Manu Jain, MD 312-908-8163
Contact: Study Coordinator 312-695-1301 cancertrials@northwestern.edu

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Manu Jain, MD, MS         
Principal Investigator: Jayesh Mehta, MD         
Sponsors and Collaborators
Northwestern University
Robert H. Lurie Cancer Center
Investigators
Principal Investigator: Manu Jain, MD, MS Northwestern University
Principal Investigator: Jayesh Mehta, MD Northwestern University
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT01163786     History of Changes
Other Study ID Numbers: NU 09H7, NU 09H7, STU00022160
Study First Received: July 7, 2010
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Northwestern University:
Bortezomib GVHD Bronchiolitis Obliterans

Additional relevant MeSH terms:
Bronchiolitis
Bronchiolitis Obliterans
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 10, 2014