Multi-Institutional Prospective Phase II Study of Montelukast for the Treatment of Bronchiolitis Obliterans Following Allogeneic or Autologous Stem Cell Transplantation in Children and Adults
Phase: PHASE2
Conditions: Bronchiolitis Obliterans, Chronic Graft Versus Host Disease, Leukotriene, Montelukast, Stem Cell Transplant
Sponsor: National Cancer Institute (NCI)

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PRECIS ................................................................................................................................................ 4 
7DEOHRI&RQWHQWV ................................................................................................................................. 5 
1 
Introduction .................................................................................................................................. 7 
1.1 
Study Objectives ...............................................................................................................................7 
1.2 
Background and Rationale ..............................................................................................................7 
2 
Eligibility Assessment and Enrollment ..................................................................................... 13 
2.1 
Eligibility Criteria ..........................................................................................................................13 
2.2 
Research Eligibility Evaluation (See Appendix 2) .......................................................................16 
2.3 
Registration Procedure: .................................................................................................................16 
3 
Study Implementation ................................................................................................................ 17 
3.1 
Study Design ....................................................................................................................................17 
3.2 
Drug Administration ......................................................................................................................18 
3.3 
Treatment Modifications ...............................................................................................................18 
3.4 
On Study Protocol Evaluation: Appendix 2 A/B .........................................................................19 
3.5 
Concurrent Therapy for Chronic Graft versus Host Disease: ...................................................24 
3.6 
Criteria for Removal from Protocol Therapy and Off Study Criteria: .....................................26 
3.7 
Off- Protocol Therapy, Off-Study, and Post-protocol therapy Evaluation (Appendix 2A) .....27 
4 
Supportive Care Guidelines ....................................................................................................... 28 
5 
Data Collection and Evaluation ................................................................................................ 29 
5.1 
Data Collection ................................................................................................................................29 
5.2 
Response Criteria: ..........................................................................................................................30 
5.3 
Toxicity Criteria .............................................................................................................................32 
5.4 
Statistical Considerations...............................................................................................................32 
5.5 
Multi-Institutional Guidelines: ......................................................................................................35 
6 
Human Subjects Protections ..................................................................................................... 36 
6.1 
Rationale for patient selection .......................................................................................................36 
6.2 
Participation of Children ...............................................................................................................36 
6.3 
NCI PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT ..............................36 
6.4 
Evaluation of Benefits and Risks/Discomforts: ............................................................................37 
6.5 
Risk/Benefit Analysis ......................................................................................................................37 
6.6 
Consent and Assent Process and Documentation ........................................................................38 
7 
Safety Reporting Requirements and Safety Monitoring Plan .................................................. 39 

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7.1 
Definitions .......................................................................................................................................39 
7.2 
NCI-IRB and NCI Clinical Director Reporting ...........................................................................41 
7.3 
NCI Guidance for Reporting Expedited Adverse Events for Multi-Center Trials ..................42 
7.4 
Data and Safety Monitoring Plan ..................................................................................................43 
7.5 
Abnormal Laboratory Test Results ..............................................................................................43 
7.6 
Withdrawal from Study .................................................................................................................44 
8 
Pharmaceutical Drug Information ........................................................................................... 44 
8.1 
Montelukast (Singulair) .................................................................................................................44 
9 
References: ................................................................................................................................. 47 
10 Appendices .................................................................................................................................. 51 
10.1 
Appendix 1: Performance Scales ...................................................................................................51 
10.2 
Appendix 2A: Required Study Evaluations .................................................................................52 
10.3 
APPENDIX 2B ................................................................................................................................54 
10.4 
Appendix 3: Initial History Guidelines .........................................................................................55 
10.5 
Appendix 4: Chronic GVHD Activity Assessment- Clinician ....................................................57 
10.6 
Appendix 5A: Sign and symptoms of cGVHD .............................................................................61 
10.7 
Appendix 5B: Core set of measures for assessing responses in chronic GVHD trials .............63 
10.8 
Appendix 6: cGVHD score sheet ...................................................................................................64 
10.9 
Appendix 7: Chronic GVHD Manifestations ...............................................................................66 
10.10 Appendix 8: Lung Function Score ................................................................................................67 
10.11 Appendix 9: Physiatry Evaluation: ...............................................................................................68 
10.12 Appendix 10: Chronic GVHD patient symptom scale ................................................................69 
10.13 Appendix 11: Patient Diary for Montelukast (Singulair) ...........................................................70 
10.14 Appendix 12: Chronic GVHD Activity Assessment- Patient Self Report .................................72 
10.15 Appendix 13: QOL and Functional assessment scales ................................................................74 
10.16 Appendix 14: ETIB Policy for Sample Handling.........................................................................76 
10.17 Appendix 15: NIH Problem Report Form....................................................................................80 
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