Ignite Creation Date:
2025-12-24 @ 1:58 PM
Ignite Modification Date:
2026-02-13 @ 1:08 PM
Study NCT ID:
NCT02891395
Status:
COMPLETED
Last Update Posted:
2025-12-22
First Post:
2016-09-01
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Efficacy and Safety of Nilotinib in Patients With a Chronic Disease of the Graft Against the Host
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006086', 'term': 'Graft vs Host Disease'}], 'ancestors': [{'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068877', 'term': 'Imatinib Mesylate'}, {'id': 'C498826', 'term': 'nilotinib'}], 'ancestors': [{'id': 'D001549', 'term': 'Benzamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001565', 'term': 'Benzoates'}, {'id': 'D000146', 'term': 'Acids, Carbocyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D010879', 'term': 'Piperazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011743', 'term': 'Pyrimidines'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 65}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-12-24', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-07', 'completionDateStruct': {'date': '2017-07-26', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-12-15', 'studyFirstSubmitDate': '2016-09-01', 'studyFirstSubmitQcDate': '2016-09-01', 'lastUpdatePostDateStruct': {'date': '2025-12-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2016-09-07', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-07-26', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Response rate at 3 months (complete and partial remission) after salvage treatment with Nilotinib in patients with chronic GVHD who failed Imatinib Mesylate (IM)', 'timeFrame': 'Between Baseline and minimum 12 weeks of treatment', 'description': 'Response rate at 3 months (complete and partial remission) after salvage treatment with Nilotinib in patients with chronic GVHD who failed Imatinib Mesylate (IM)'}], 'secondaryOutcomes': [{'measure': 'Best response to IM within 12 months and the duration of this response', 'timeFrame': 'From 12 to 52 weeks of Imatinib Mesylate treatment'}, {'measure': 'Best response rate to Nilotinib within 12 months and the duration of this response', 'timeFrame': 'From 12 to 52 weeks of Nilotinib treatment'}, {'measure': 'use of systemic secondary treatment due to intolerance to IM', 'timeFrame': 'From baseline to 12 weeks of IM treatment', 'description': 'measure intolerance by IM failure'}, {'measure': 'use of systemic secondary treatment due to intolerance to Nilotinib', 'timeFrame': 'From baseline to 12 weeks of Nilotinib treatment', 'description': 'measure intolerance by Nilotinib failure'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['allogeneic stem cell transplantation', 'imatinib Mesylate', 'Nilotinib'], 'conditions': ['Graft Versus Host Disease']}, 'referencesModule': {'references': [{'pmid': '36624161', 'type': 'RESULT', 'citation': 'Srour M, Alsuliman T, Labreuche J, Bulabois CE, Chevallier P, Daguindau E, Forcade E, Francois S, Guillerm G, Coiteux V, Turlure P, Beguin Y, Yakoub-Agha I, Magro L. Nilotinib efficacy and safety as salvage treatment following imatinib intolerance and/or inefficacy in steroid refractory chronic graft-versus-host-disease (SR-cGVHD): a prospective, multicenter, phase II study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Bone Marrow Transplant. 2023 Apr;58(4):401-406. doi: 10.1038/s41409-022-01898-x. Epub 2023 Jan 9.'}]}, 'descriptionModule': {'briefSummary': 'Open label non-randomized multicenter phase 2 trial with direct individual benefice', 'detailedDescription': 'Induction phase: Imatinib mesylate - starting with 100 mg/day with increase of 100 mg/day each other week up to maximum tolerable dose or 400 mg/day whichever occurred first. For the responders and in absence of toxicity, the treatment will be maintained up to one year. Patients, who discontinue imatinib mesylate at 3 months for lack of response (no response = stable disease), those who experience progression at any time, those who relapse after an initial response at any time or those who discontinue for toxicity at any time, will go to the salvage phase.\n\nSalvage phase:\n\nNilotinib - starting with 200 mg/day with increase of 200 mg/day each other week up to maximum tolerable dose or 800 mg/day whichever occurred first. In absence of toxicity, the treatment will be maintained up to one year.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nInduction phase (IM):\n\n* Patients aged ≥18 years to 75 years\n* Patients who underwent allo-SCT for a hematological disorder\n* Body weight ≥ 40 Kg.\n* Confirmed diagnosis of cGVHD resistant to at least one systemic immunosuppressive therapy. The diagnosis of cGHVD should be based on the NIH Working Group Consensus (www.asbmt.org/gvhd/index.htm). Grading of cGVHD will be based on clinical manifestations including:\n\n 1. ocular, oral and mucosal symptoms;\n 2. performance status;\n 3. evaluation of pulmonary functions;\n 4. cutaneous evaluation;\n 5. evaluation of musculo-skeletal manifestations;\n 6. evaluation of liver involvement;\n* Any source of hematopoietic stem cell is allowed\n* Both myeloablative and nonmyeloablative conditioning regimens are authorized.\n* Absence of contra-indications to the use of IM or Nilotinib\n* Patient having French health care coverage\n* Female patients of childbearing potential must have before initiation of study drug and agree to have efficient contraceptive precautions throughout the trial and for 3 months after the end of the trial.\n* Signed informed consent.\n\nSalvage phase (Nilotinib) :\n\nPatients enrolled in the first phase and who failed to IM:\n\n* Patients, who discontinue imatinib mesylate at 3 months for lack of response (no response = stable disease),\n* those who experience progression at any time,\n* those who relapse after an initial response at any time\n* or those who discontinue for toxicity at any time.\n\nExclusion Criteria:\n\n* Patient developing acute GVHD (whether early or "late onset" form)\n* First episode of cGVHD\n* Patient who received IM or Nilotinib treatment or any other TKI after transplant 3 months before the inclusion on the study\n* Patient treated by TKI for a GVHD\n* Contra-indication to IM or Nilotinib\n* Neutropenia \\< 0.5 G/L\n* Uncontrolled systemic infection which can be associated, according to the investigator, to an enhanced risk of patient\'s death during the first month of treatment\n* Severe neurological or psychiatric disorders\n* Pregnancy or lactation\n* Known uncontrolled arrhythmias or symptomatic heart disease or left ventricular ejection fraction \\< 40% (cardiac tests as clinically indicated)\n* Recurrence of cancer for which the transplant was done except for presence of minimal residual disease by PCR\n* Patients with secondary malignancy ≤ 2 years prior study-entry except:\n\n * Basal cell carcinoma of the skin\n * Squamous cell carcinoma of the skin\n * Carcinoma in situ of the cervix\n * Carcinoma in situ of the breast\n * Prostate cancer (Tumor, Node, Metastasis \\[TNM\\] stage T1a or T1b)\n* Patients in emergency situation\n* Patients kept in detention\n* Patients unable or unwilling to comply with the protocol requirements'}, 'identificationModule': {'nctId': 'NCT02891395', 'acronym': 'DoubleITK', 'briefTitle': 'Efficacy and Safety of Nilotinib in Patients With a Chronic Disease of the Graft Against the Host', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Lille'}, 'officialTitle': 'Efficacy and Safety of Nilotinib in Patients With a Chronic Disease of the Graft Against the Host (Graft Versus Host, GVH) Did Not Respond to Imatinib Mesylate.', 'orgStudyIdInfo': {'id': '2009_18'}, 'secondaryIdInfos': [{'id': '2012-000770-36', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'open-label', 'description': 'Induction phase: Imatinib mesylate - starting with 100 mg/day with increase of 100 mg/day each other week up to maximum tolerable dose or 400 mg/day whichever occurred first. For the responders and in absence of toxicity, the treatment will be maintained up to one year.\n\nSalvage phase:\n\nNilotinib - starting with 200 mg/day with increase of 200 mg/day each other week up to maximum tolerable dose or 800 mg/day whichever occurred first. In absence of toxicity, the treatment will be maintained up to one year.', 'interventionNames': ['Drug: Imatinib Mesylate and Nilotinib']}], 'interventions': [{'name': 'Imatinib Mesylate and Nilotinib', 'type': 'DRUG', 'description': 'For patients under Imatinib Mesylate: the total length of follow up period for those patients will be for 52 weeks following IM treatment, with a follow up at weeks IM4, IM8, IM12, IM26, IM38 and IM52.\n\nFor patients requiring a salvage phase: after the switch for nilotinib, the total length of follow up period for this phase will be for 52 weeks following nilotinib treatment, with a follow up at weeks nilo4, nilo8, nilo12, nilo26, nilo38 and nilo52.', 'armGroupLabels': ['open-label']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Liège', 'country': 'Belgium', 'facility': 'CHU Sart Tilman', 'geoPoint': {'lat': 50.63373, 'lon': 5.56749}}, {'city': 'Amiens', 'country': 'France', 'facility': "CHU d'Amiens", 'geoPoint': {'lat': 49.9, 'lon': 2.3}}, {'city': 'Angers', 'country': 'France', 'facility': "CHU d'Angers", 'geoPoint': {'lat': 47.47156, 'lon': -0.55202}}, {'city': 'Besançon', 'country': 'France', 'facility': 'CHU Besançon', 'geoPoint': {'lat': 47.24878, 'lon': 6.01815}}, {'city': 'Bordeaux', 'country': 'France', 'facility': 'CHU Bordeaux', 'geoPoint': {'lat': 44.84124, 'lon': -0.58046}}, {'city': 'Brest', 'country': 'France', 'facility': 'Hopital Morvan', 'geoPoint': {'lat': 48.39029, 'lon': -4.48628}}, {'city': 'Caen', 'country': 'France', 'facility': 'CHU Clémenceau', 'geoPoint': {'lat': 49.18585, 'lon': -0.35912}}, {'city': 'Clamart', 'country': 'France', 'facility': 'HIA de Percy', 'geoPoint': {'lat': 48.80299, 'lon': 2.26692}}, {'city': 'Clermont-Ferrand', 'country': 'France', 'facility': 'CHU de Clermont Ferrand', 'geoPoint': {'lat': 45.77969, 'lon': 3.08682}}, {'city': 'Grenoble', 'country': 'France', 'facility': 'CHU Grenoble', 'geoPoint': {'lat': 45.17869, 'lon': 5.71479}}, {'zip': '59037', 'city': 'Lille', 'country': 'France', 'facility': 'Diseases of Blood Service HURIEZ hospital CHRU de LILLE', 'geoPoint': {'lat': 50.63391, 'lon': 3.05512}}, {'city': 'Lille', 'country': 'France', 'facility': 'Centre hospitalier et régional de Lille', 'geoPoint': {'lat': 50.63391, 'lon': 3.05512}}, {'city': 'Lyon', 'country': 'France', 'facility': 'CHU de Lyon', 'geoPoint': {'lat': 45.74906, 'lon': 4.84789}}, {'city': 'Marseille', 'country': 'France', 'facility': 'Institut Paoli Calmettes', 'geoPoint': {'lat': 43.29695, 'lon': 5.38107}}, {'city': 'Montpellier', 'country': 'France', 'facility': 'Hôpital Saint Eloi', 'geoPoint': {'lat': 43.61093, 'lon': 3.87635}}, {'city': 'Nantes', 'country': 'France', 'facility': 'CHU Hotel Dieu', 'geoPoint': {'lat': 47.21725, 'lon': -1.55336}}, {'city': 'Nice', 'country': 'France', 'facility': 'CHU de Nice', 'geoPoint': {'lat': 43.70313, 'lon': 7.26608}}, {'city': 'Paris', 'country': 'France', 'facility': 'Hopital NECKER', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'city': 'Paris', 'country': 'France', 'facility': 'Hôpital pitié Salpetrière', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'city': 'Rouen', 'country': 'France', 'facility': 'Centre Henri Becquerel', 'geoPoint': {'lat': 49.44313, 'lon': 1.09932}}, {'city': 'Strasbourg', 'country': 'France', 'facility': 'CHU de STRASBOURG', 'geoPoint': {'lat': 48.58392, 'lon': 7.74553}}, {'city': 'Toulouse', 'country': 'France', 'facility': 'CHU Purpan', 'geoPoint': {'lat': 43.60426, 'lon': 1.44367}}], 'overallOfficials': [{'name': 'YAKOUB-AGHA Ibrahim, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital, Lille'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Lille', 'class': 'OTHER'}, 'collaborators': [{'name': 'Novartis', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}