Ignite Creation Date:
2025-12-25 @ 1:32 AM
Ignite Modification Date:
2026-02-20 @ 6:25 PM
Study NCT ID:
NCT03689894
Status:
TERMINATED
Last Update Posted:
2023-11-28
First Post:
2018-09-27
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Ibrutinib Plus Rituximab for cGVHD Following Allo-SCT
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2022-10-13', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D000092122', 'term': 'Bronchiolitis Obliterans Syndrome'}], 'ancestors': [{'id': 'D000092124', 'term': 'Organizing Pneumonia'}, {'id': 'D001989', 'term': 'Bronchiolitis Obliterans'}, {'id': 'D001988', 'term': 'Bronchiolitis'}, {'id': 'D001991', 'term': 'Bronchitis'}, {'id': 'D001982', 'term': 'Bronchial Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D008173', 'term': 'Lung Diseases, Obstructive'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D006086', 'term': 'Graft vs Host Disease'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C551803', 'term': 'ibrutinib'}, {'id': 'D000069283', 'term': 'Rituximab'}], 'ancestors': [{'id': 'D058846', 'term': 'Antibodies, Monoclonal, Murine-Derived'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'sean.hobson@hitchcock.org', 'phone': '2167129120', 'title': 'Director of Clinical Research', 'organization': 'Dartmouth Hitchcock Medical Center'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': 'Participant #1: Assessed over a period of 5 weeks (Time on study 4/12/2019 - 10/14/2019) Participant #2: Assessed over a period of 28 weeks (Time on study 7/29/2020 - 2/10/2021)', 'eventGroups': [{'id': 'EG000', 'title': 'Ibrutinib Plus Rituximab', 'description': 'Rituximab\n\n\\*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)\n\nIbrutinib\n\n* 420 mg (140 mg capsule x3) by mouth daily\n* May be given beyond 3-6 months (for maintenance).\n\nIbrutinib: Subjects will receive oral (PO) Ibrutinib 140 mg once daily with Rituximab 375 mg per meter squared IV weekly x4 (with pre-medications and infusion procedure as per standard protocol) Rituximab Pre-medications:Acetaminophen 650 mg PO; Diphenhydramine 25 mg PO/IV; Dexamethasone 20 mg IV.\n\nIf no adverse events \\>Grade 3+ are noted after 1 week, the Ibrutinib dose schedule will be increased to 280 mg daily. If no adverse events \\>Gr3+ are noted after an additional 1 week, the Ibrutinib dose will be increased to 420 mg daily.\n\nRituximab: Subject will receive an intravenous infusion of 375mg per meter squared weekly for 4 weeks, which may be repeated 8 weeks after initial therapy if only a suboptimal response is achieved.', 'otherNumAtRisk': 2, 'deathsNumAtRisk': 2, 'otherNumAffected': 0, 'seriousNumAtRisk': 2, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'seriousEvents': [{'term': 'Rash', 'notes': 'Developed skin nodules that appear to be ibrutinib-related, warranting discontinuation of drug.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 2, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Evaluate Dose-limiting Toxicities Experienced in Subjects Treated With Ibrutinib Plus Rituximab', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ibrutinib Plus Rituximab', 'description': 'Rituximab\n\n\\*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)\n\nIbrutinib\n\n420 mg (140 mg capsule x3) by mouth daily May be given beyond 3-6 months (for maintenance).'}], 'timeFrame': 'Start of treatment through Week 4 of treatment', 'description': 'During dose escalation, subjects will be assessed for dose-limiting toxicities at each dose level.', 'reportingStatus': 'POSTED', 'populationDescription': '0 patients analyzed. 1 patient withdrawn early and 1 patient not complaint with study procedures.'}, {'type': 'SECONDARY', 'title': 'Assess the Response Rate of cGVHD to Treatment With Ibrutinib Plus Rituximab', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ibrutinib Plus Rituximab', 'description': 'Rituximab\n\n\\*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)\n\nIbrutinib\n\n* 420 mg (140 mg capsule x3) by mouth daily\n* May be given beyond 3-6 months (for maintenance).\n\nIbrutinib: Subjects will receive oral (PO) Ibrutinib 140 mg once daily with Rituximab 375 mg per meter squared IV weekly x4 (with pre-medications and infusion procedure as per standard protocol) Rituximab Pre-medications:Acetaminophen 650 mg PO; Diphenhydramine 25 mg PO/IV; Dexamethasone 20 mg IV.\n\nIf no adverse events \\>Grade 3+ are noted after 1 week, the Ibrutinib dose schedule will be increased to 280 mg daily. If no adverse events \\>Gr3+ are noted after an additional 1 week, the Ibrutinib dose will be increased to 420 mg daily.\n\nRituximab: Subject will receive an intravenous infusion of 375mg per meter squared weekly for 4 weeks, which may be repeated 8 weeks after initial therapy if only a suboptimal response is achieved.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '6 weeks, 3 months, and 6 months after initiation of treatment', 'description': 'Response rate of clinically significant GVHD will be assessed using NIH criteria (from 2014 NIH Consensus Development Project).', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Subject 1 off study before 6 week assessment due to study drug possibly related rash SAE.'}, {'type': 'SECONDARY', 'title': 'Identify Relevant Laboratory Correlates Underlying Clinical Response, or Lack Thereof.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ibrutinib Plus Rituximab', 'description': 'Rituximab\n\n\\*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)\n\nIbrutinib\n\n420 mg (140 mg capsule x3) by mouth daily May be given beyond 3-6 months (for maintenance).'}], 'timeFrame': '6 weeks, 3 months, and 6 months after initiation of treatment', 'description': 'Plasma ST2 and CD4CD25FOXp3 correlates will be measured at identified intervals to determine if either correlate demonstrates an affect on clinical response.', 'reportingStatus': 'POSTED', 'populationDescription': 'Laboratory correlates for this study were not processed or analyzed for any subject enrolled onto this study.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Ibrutinib Plus Rituximab', 'description': 'Rituximab\n\n\\*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)\n\nIbrutinib\n\n420 mg (140 mg capsule x3) by mouth daily May be given beyond 3-6 months (for maintenance).'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'Completed Study Treatment', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'All participants were recruited at a single site, Dartmouth-Hitchcock Norris Cotton Cancer Center in Lebanon New Hampshire. Recruitment extended throughout the life of the study from 4/11/2019 to 07/22/2021.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Ibrutinib Plus Rituximab', 'description': 'Rituximab\n\n\\*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)\n\nIbrutinib\n\n420 mg (140 mg capsule x3) by mouth daily May be given beyond 3-6 months (for maintenance).'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2018-11-28', 'size': 1021177, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2022-09-14T06:46', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 2}}, 'statusModule': {'whyStopped': 'Insufficient accrual', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2019-04-11', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-11', 'completionDateStruct': {'date': '2021-09-20', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-11-03', 'studyFirstSubmitDate': '2018-09-27', 'resultsFirstSubmitDate': '2022-09-16', 'studyFirstSubmitQcDate': '2018-09-27', 'lastUpdatePostDateStruct': {'date': '2023-11-28', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-11-03', 'studyFirstPostDateStruct': {'date': '2018-10-01', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-11-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-09-20', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Evaluate Dose-limiting Toxicities Experienced in Subjects Treated With Ibrutinib Plus Rituximab', 'timeFrame': 'Start of treatment through Week 4 of treatment', 'description': 'During dose escalation, subjects will be assessed for dose-limiting toxicities at each dose level.'}], 'secondaryOutcomes': [{'measure': 'Assess the Response Rate of cGVHD to Treatment With Ibrutinib Plus Rituximab', 'timeFrame': '6 weeks, 3 months, and 6 months after initiation of treatment', 'description': 'Response rate of clinically significant GVHD will be assessed using NIH criteria (from 2014 NIH Consensus Development Project).'}, {'measure': 'Identify Relevant Laboratory Correlates Underlying Clinical Response, or Lack Thereof.', 'timeFrame': '6 weeks, 3 months, and 6 months after initiation of treatment', 'description': 'Plasma ST2 and CD4CD25FOXp3 correlates will be measured at identified intervals to determine if either correlate demonstrates an affect on clinical response.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Chronic Graft-versus-host-disease']}, 'referencesModule': {'references': [{'pmid': '24468835', 'type': 'BACKGROUND', 'citation': 'Jaglowski SM, Devine SM. Graft-versus-host disease: why have we not made more progress? Curr Opin Hematol. 2014 Mar;21(2):141-7. doi: 10.1097/MOH.0000000000000026.'}, {'pmid': '16338616', 'type': 'BACKGROUND', 'citation': 'Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.'}, {'pmid': '20685255', 'type': 'BACKGROUND', 'citation': 'Wolff D, Schleuning M, von Harsdorf S, Bacher U, Gerbitz A, Stadler M, Ayuk F, Kiani A, Schwerdtfeger R, Vogelsang GB, Kobbe G, Gramatzki M, Lawitschka A, Mohty M, Pavletic SZ, Greinix H, Holler E. Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2011 Jan;17(1):1-17. doi: 10.1016/j.bbmt.2010.05.011. Epub 2010 May 26.'}, {'pmid': '25452031', 'type': 'BACKGROUND', 'citation': 'Sarantopoulos S, Blazar BR, Cutler C, Ritz J. B cells in chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2015 Jan;21(1):16-23. doi: 10.1016/j.bbmt.2014.10.029. Epub 2014 Nov 12.'}, {'pmid': '16551963', 'type': 'BACKGROUND', 'citation': 'Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D, Klickstein LB, Levin J, Miller K, Reynolds C, Macdonell R, Pasek M, Lee SJ, Ho V, Soiffer R, Antin JH, Ritz J, Alyea E. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood. 2006 Jul 15;108(2):756-62. doi: 10.1182/blood-2006-01-0233. Epub 2006 Mar 21.'}, {'pmid': '22563089', 'type': 'BACKGROUND', 'citation': 'Arai S, Sahaf B, Narasimhan B, Chen GL, Jones CD, Lowsky R, Shizuru JA, Johnston LJ, Laport GG, Weng WK, Benjamin JE, Schaenman J, Brown J, Ramirez J, Zehnder JL, Negrin RS, Miklos DB. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012 Jun 21;119(25):6145-54. doi: 10.1182/blood-2011-12-395970. Epub 2012 May 4.'}, {'pmid': '23861248', 'type': 'BACKGROUND', 'citation': 'Cutler C, Kim HT, Bindra B, Sarantopoulos S, Ho VT, Chen YB, Rosenblatt J, McDonough S, Watanaboonyongcharoen P, Armand P, Koreth J, Glotzbecker B, Alyea E, Blazar BR, Soiffer RJ, Ritz J, Antin JH. Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial. Blood. 2013 Aug 22;122(8):1510-7. doi: 10.1182/blood-2013-04-495895. Epub 2013 Jul 16.'}, {'pmid': '8739565', 'type': 'BACKGROUND', 'citation': 'Krenger W, Ferrara JL. Graft-versus-host disease and the Th1/Th2 paradigm. Immunol Res. 1996;15(1):50-73. doi: 10.1007/BF02918284.'}, {'pmid': '23886836', 'type': 'BACKGROUND', 'citation': 'Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y, Hessler JD, Liu TM, Chang BY, Larkin KM, Stefanovski MR, Chappell DL, Frissora FW, Smith LL, Smucker KA, Flynn JM, Jones JA, Andritsos LA, Maddocks K, Lehman AM, Furman R, Sharman J, Mishra A, Caligiuri MA, Satoskar AR, Buggy JJ, Muthusamy N, Johnson AJ, Byrd JC. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013 Oct 10;122(15):2539-49. doi: 10.1182/blood-2013-06-507947. Epub 2013 Jul 25.'}, {'pmid': '23045577', 'type': 'BACKGROUND', 'citation': 'Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH. 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PLoS One. 2015 Sep 8;10(9):e0137641. doi: 10.1371/journal.pone.0137641. eCollection 2015.'}, {'pmid': '28924018', 'type': 'BACKGROUND', 'citation': 'Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, Flowers ME, Logan AC, Nakamura R, Blazar BR, Li Y, Chang S, Lal I, Dubovsky J, James DF, Styles L, Jaglowski S. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017 Nov 23;130(21):2243-2250. doi: 10.1182/blood-2017-07-793786. Epub 2017 Sep 18.'}, {'pmid': '23924003', 'type': 'BACKGROUND', 'citation': 'Vander Lugt MT, Braun TM, Hanash S, Ritz J, Ho VT, Antin JH, Zhang Q, Wong CH, Wang H, Chin A, Gomez A, Harris AC, Levine JE, Choi SW, Couriel D, Reddy P, Ferrara JL, Paczesny S. ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death. N Engl J Med. 2013 Aug 8;369(6):529-39. doi: 10.1056/NEJMoa1213299.'}, {'pmid': '21668397', 'type': 'BACKGROUND', 'citation': 'Rozmus J, Schultz KR. Biomarkers in chronic graft-versus-host disease. Expert Rev Hematol. 2011 Jun;4(3):329-42. doi: 10.1586/ehm.11.27.'}, {'pmid': '25150798', 'type': 'BACKGROUND', 'citation': "Burger JA, Keating MJ, Wierda WG, Hartmann E, Hoellenriegel J, Rosin NY, de Weerdt I, Jeyakumar G, Ferrajoli A, Cardenas-Turanzas M, Lerner S, Jorgensen JL, Nogueras-Gonzalez GM, Zacharian G, Huang X, Kantarjian H, Garg N, Rosenwald A, O'Brien S. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2014 Sep;15(10):1090-9. doi: 10.1016/S1470-2045(14)70335-3. Epub 2014 Aug 20."}, {'pmid': '25796139', 'type': 'BACKGROUND', 'citation': 'Lee SJ, Wolff D, Kitko C, Koreth J, Inamoto Y, Jagasia M, Pidala J, Olivieri A, Martin PJ, Przepiorka D, Pusic I, Dignan F, Mitchell SA, Lawitschka A, Jacobsohn D, Hall AM, Flowers ME, Schultz KR, Vogelsang G, Pavletic S. Measuring therapeutic response in chronic graft-versus-host disease. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. The 2014 Response Criteria Working Group report. Biol Blood Marrow Transplant. 2015 Jun;21(6):984-99. doi: 10.1016/j.bbmt.2015.02.025. Epub 2015 Mar 19.'}, {'pmid': '9051246', 'type': 'BACKGROUND', 'citation': 'McQuellon RP, Russell GB, Cella DF, Craven BL, Brady M, Bonomi A, Hurd DD. Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. Bone Marrow Transplant. 1997 Feb;19(4):357-68. doi: 10.1038/sj.bmt.1700672.'}, {'pmid': '12234170', 'type': 'BACKGROUND', 'citation': 'Lee Sk, Cook EF, Soiffer R, Antin JH. Development and validation of a scale to measure symptoms of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2002;8(8):444-52. doi: 10.1053/bbmt.2002.v8.pm12234170.'}, {'pmid': '16980994', 'type': 'BACKGROUND', 'citation': 'Pavletic SZ, Lee SJ, Socie G, Vogelsang G. Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials. Bone Marrow Transplant. 2006 Nov;38(10):645-51. doi: 10.1038/sj.bmt.1705490. Epub 2006 Sep 18.'}, {'pmid': '25153693', 'type': 'BACKGROUND', 'citation': 'Curtis LM, Grkovic L, Mitchell SA, Steinberg SM, Cowen EW, Datiles MB, Mays J, Bassim C, Joe G, Comis LE, Berger A, Avila D, Taylor T, Pulanic D, Cole K, Baruffaldi J, Fowler DH, Gress RE, Pavletic SZ. NIH response criteria measures are associated with important parameters of disease severity in patients with chronic GVHD. Bone Marrow Transplant. 2014 Dec;49(12):1513-20. doi: 10.1038/bmt.2014.188. Epub 2014 Aug 25.'}, {'pmid': '26673811', 'type': 'BACKGROUND', 'citation': 'Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, Offner F, Caballero D, Joao C, Witzens-Harig M, Hess G, Bence-Bruckler I, Cho SG, Bothos J, Goldberg JD, Enny C, Traina S, Balasubramanian S, Bandyopadhyay N, Sun S, Vermeulen J, Rizo A, Rule S. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016 Feb 20;387(10020):770-8. doi: 10.1016/S0140-6736(15)00667-4. Epub 2015 Dec 7.'}, {'pmid': '24881631', 'type': 'BACKGROUND', 'citation': "Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Devereux S, Barr PM, Furman RR, Kipps TJ, Cymbalista F, Pocock C, Thornton P, Caligaris-Cappio F, Robak T, Delgado J, Schuster SJ, Montillo M, Schuh A, de Vos S, Gill D, Bloor A, Dearden C, Moreno C, Jones JJ, Chu AD, Fardis M, McGreivy J, Clow F, James DF, Hillmen P; RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014 Jul 17;371(3):213-23. doi: 10.1056/NEJMoa1400376. Epub 2014 May 31."}, {'pmid': '26639149', 'type': 'BACKGROUND', 'citation': "Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, Bairey O, Hillmen P, Bartlett NL, Li J, Simpson D, Grosicki S, Devereux S, McCarthy H, Coutre S, Quach H, Gaidano G, Maslyak Z, Stevens DA, Janssens A, Offner F, Mayer J, O'Dwyer M, Hellmann A, Schuh A, Siddiqi T, Polliack A, Tam CS, Suri D, Cheng M, Clow F, Styles L, James DF, Kipps TJ; RESONATE-2 Investigators. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015 Dec 17;373(25):2425-37. doi: 10.1056/NEJMoa1509388. Epub 2015 Dec 6."}]}, 'descriptionModule': {'briefSummary': 'Allogeneic stem cell transplant is used to treat a variety of blood cancers. However, graft-versus-host disease (GVHD) is a common condition that may occur after transplant. GVHD happens when the donor cells attack and damage the recipients\' tissue.\n\nThe standard medication to treat chronic graft-versus-host-disease (cGVHD) is corticosteroids. However, there are long-term side effects of steroid therapy, including risk of infection, bone loss and other health problems. In addition, some patients with cGVHD do not respond to standard steroid therapy. In these cases, medications to suppress the immune system may be used.\n\nThe purpose of this study is to learn about the effects, both good and bad, of combining the drugs ibrutinib and rituximab for the treatment of cGVHD.\n\nIbrutinib is Food and Drug Administration (FDA)-approved for the treatment of cGVHD which has not responded to steroid therapy.\n\nRituximab is an investigational drug, which means it is not FDA approved for this particular use. Rituximab is currently approved for treatment of Non-Hodgkin\'s Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), and other conditions, but is not FDA approved for the treatment of cGVHD.\n\nHowever, rituximab has been used in a clinic setting for the treatment of cGVHD in a number of patients over the past few years, and has generally been well tolerated and shown some benefit.\n\nThe combination of ibrutinib and rituximab is being studied in the treatment of certain types of lymphoma and chronic leukemia, but it has not yet been combined for patients with cGVHD. Because ibrutinib is not approved for this use when combined with rituximab, it is considered investigational in this study.\n\nIn this form, the term "study drug" refers to ibrutinib and rituximab.\n\nThis study will involve people who have chronic GVHD, have previously taken corticosteroids, and have either not benefited from treatment with corticosteroids or have been unable to successfully taper off steroids.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Men and women ≥18 years old who are recipients of an allogeneic bone marrow, cord blood or peripheral blood stem cell transplant. (There will be no restrictions based upon underlying disease, donor source, degree of human leukocyte antigen (HLA) match, intensity of pre-transplant conditioning regimen or use of prior donor lymphocyte infusion(s).)\n2. Chronic GVHD that is confirmed by clinical assessment and/or biopsy.\n3. Either steroid-refractory or steroid-dependent cGVHD.\n4. Karnofsky performance status ≥ 60.\n\nExclusion Criteria:\n\n1. History of treatment with a tyrosine kinase inhibitor (eg, imatinib) or other moderate-to-significant Cyclophilin A4 inhibitor within 2 weeks of enrollment.\n2. Renal insufficiency as follows: creatinine \\> 2.5 mg/deciliters (dL) or Creatinine Clearance \\< 30 ml/min.\n3. Hepatic insufficiency as follows: serum bilirubin \\>3 mg/dL or transaminitis \\>3x upper limit of normal (ULN) (unless deemed due to GVHD).\n4. History of cardiac dysrhythmias or known cardiovascular disease without formal Cardiology clearance.\n5. History of cerebro-vascular accident or intracranial hemorrhage within 6 months prior to enrollment.\n6. History of non-intracranial hemorrhage and/or coagulopathy without formal Coagulation clearance.\n7. Uncontrolled infections not responsive to antibiotics, anti-viral medicines, or anti-fungal medicines; or infection requiring systemic treatment that was completed ≤14 days before enrollment.\n8. History of other hematologic malignancy.\n9. History of human immunodeficiency virus (HIV).\n10. History of active hepatitis B virus (HBV) or hepatitis C virus (HCV) without formal Infectious Disease clearance.\n11. Patients incapable of complying with routine follow up schedule or unable to be compliant with study therapy.\n12. Active or within 3 months use of prohibited medications or substances (e.g., illicit drugs).'}, 'identificationModule': {'nctId': 'NCT03689894', 'briefTitle': 'Ibrutinib Plus Rituximab for cGVHD Following Allo-SCT', 'organization': {'class': 'OTHER', 'fullName': 'Dartmouth-Hitchcock Medical Center'}, 'officialTitle': 'Combination Ibrutinib and Rituximab for the Treatment of Chronic Graft-Versus-Host Disease Following Allogeneic Stem Cell Transplant', 'orgStudyIdInfo': {'id': 'D17120'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Ibrutinib plus Rituximab', 'description': 'Rituximab\n\n\\*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)\n\nIbrutinib\n\n* 420 mg (140 mg capsule x3) by mouth daily\n* May be given beyond 3-6 months (for maintenance).', 'interventionNames': ['Drug: Ibrutinib', 'Drug: Rituximab']}], 'interventions': [{'name': 'Ibrutinib', 'type': 'DRUG', 'description': 'Subjects will receive oral (PO) Ibrutinib 140 mg once daily with Rituximab 375 mg per meter squared IV weekly x4 (with pre-medications and infusion procedure as per standard protocol) Rituximab Pre-medications:Acetaminophen 650 mg PO; Diphenhydramine 25 mg PO/IV; Dexamethasone 20 mg IV.\n\nIf no adverse events \\>Grade 3+ are noted after 1 week, the Ibrutinib dose schedule will be increased to 280 mg daily. If no adverse events \\>Gr3+ are noted after an additional 1 week, the Ibrutinib dose will be increased to 420 mg daily.', 'armGroupLabels': ['Ibrutinib plus Rituximab']}, {'name': 'Rituximab', 'type': 'DRUG', 'description': 'Subject will receive an intravenous infusion of 375mg per meter squared weekly for 4 weeks, which may be repeated 8 weeks after initial therapy if only a suboptimal response is achieved.', 'armGroupLabels': ['Ibrutinib plus Rituximab']}]}, 'contactsLocationsModule': {'locations': [{'zip': '03756', 'city': 'Lebanon', 'state': 'New Hampshire', 'country': 'United States', 'facility': 'Dartmouth-Hitchcock Medical Center', 'geoPoint': {'lat': 43.64229, 'lon': -72.25176}}], 'overallOfficials': [{'name': 'John M Hill, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Dartmouth-Hitchcock Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Dartmouth-Hitchcock Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Directory, Allogeneic Transplant Program', 'investigatorFullName': 'John M. Hill, Jr., MD', 'investigatorAffiliation': 'Dartmouth-Hitchcock Medical Center'}}}}