Ignite Creation Date:
2025-12-25 @ 12:52 AM
Ignite Modification Date:
2026-01-01 @ 4:46 PM
Study NCT ID:
NCT03263767
Status:
TERMINATED
Last Update Posted:
2022-07-15
First Post:
2017-08-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Post Transplant Cyclophosphamide (PTCY) as Sole Graft Versus Host Disease (GVHD) Prophylaxis for Matched Allotransplant: CYRIC
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': 'C024352', 'term': 'fludarabine'}, {'id': 'D000077866', 'term': 'Clofarabine'}, {'id': 'D003520', 'term': 'Cyclophosphamide'}, {'id': 'D033581', 'term': 'Stem Cell Transplantation'}, {'id': 'D014180', 'term': 'Transplantation'}], 'ancestors': [{'id': 'D000227', 'term': 'Adenine Nucleotides'}, {'id': 'D011685', 'term': 'Purine Nucleotides'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D001087', 'term': 'Arabinonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D009711', 'term': 'Nucleotides'}, {'id': 'D012265', 'term': 'Ribonucleotides'}, {'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D017690', 'term': 'Cell Transplantation'}, {'id': 'D064987', 'term': 'Cell- and Tissue-Based Therapy'}, {'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 47}}, 'statusModule': {'whyStopped': 'Security criteria (MTD)', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2018-01-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-07', 'completionDateStruct': {'date': '2022-06-21', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-07-13', 'studyFirstSubmitDate': '2017-08-21', 'studyFirstSubmitQcDate': '2017-08-23', 'lastUpdatePostDateStruct': {'date': '2022-07-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-08-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-10-21', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of grade 3 and 4 acute GVHD cortico-resistant', 'timeFrame': '100 days after transplantation', 'description': 'acute GVHD will be evaluated from International Mount Sinai criteria'}], 'secondaryOutcomes': [{'measure': 'Engraftment', 'timeFrame': 'one year', 'description': 'number of days in aplasia (neutrophils\\< 0.5 Giga/L and platelets\\<20 G/l, number of transfusions (red blood and platelets)'}, {'measure': 'Engraftment', 'timeFrame': 'one year', 'description': 'chimerism'}, {'measure': 'disease free survival (DFS)', 'timeFrame': 'one year, the last follow-up visit', 'description': 'blood and bone marrow analysis'}, {'measure': 'Overall survival (OS)', 'timeFrame': 'one year, the last follow-up visit', 'description': 'clinical follow-up'}, {'measure': 'graft and relapse free survival', 'timeFrame': 'one year', 'description': 'time between Day O and relapse'}, {'measure': 'chronic GVHD', 'timeFrame': 'one year', 'description': 'chronic GVHD will be assessed with NCI criteria for evaluation of chronic GVHD'}, {'measure': 'non relapse mortality (NRM)', 'timeFrame': 'last follow-up visit', 'description': 'number of death unrelated to relapse or disease progression'}, {'measure': 'Chimerism', 'timeFrame': '1, 2, 3, 6 and 12 months after transplantation', 'description': 'proportion of full and mixed donor chimerism'}, {'measure': 'Immune reconstitution', 'timeFrame': '3, 6 and 12 months after transplantation', 'description': 'lymphocytes, monocytes, T4, T8, Natural Killer (NK), B cells rates'}, {'measure': 'Identification of ghost factors associated with GVHD', 'timeFrame': 'one year', 'description': 'Statistical Models to Identify Subjects with Ghost Prognosis Factors Nguyen JM. 2015'}, {'measure': 'Adverse events of grade 3 and 4 after transplantation', 'timeFrame': 'one year', 'description': 'time of occurring and frequency of grade 3 and grade 4 adverse events (CTCAE criteria)'}, {'measure': 'Infections frequency', 'timeFrame': 'one year', 'description': 'time of occurring and frequency of viral (CytoMegalo Virus, Epstein Barr virus , BKV, adenovirus), bacterial, parasite and yeast infections, evaluated by Polymerase Chain Reaction (PCR), blood and urines cultures, biopsy if applicable'}, {'measure': 'compare OS between patients with ATG and patients without ATG', 'timeFrame': 'one year, last follow-up visit', 'description': 'OS'}, {'measure': 'compare grade 2-4 and 3-4 acute GVHD between patients with ATG and patients without ATG', 'timeFrame': 'one year', 'description': 'acute GVHD will be evaluated from International Mount Sinai criteria'}, {'measure': 'compare chronic GVHD between patients with ATG and patients without ATG', 'timeFrame': 'one year', 'description': 'chronic GVHD will be assessed with NCI criteria for evaluation of chronic GVHD'}, {'measure': 'compare DFS between patients with ATG and patients without ATG', 'timeFrame': 'one year, last follow-up visit', 'description': 'DFS'}, {'measure': 'compare Relapse between patients with ATG and patients without ATG', 'timeFrame': 'one year, last follow-up visit', 'description': 'Relapse'}, {'measure': 'compare NRM between patients with ATG and patients without ATG', 'timeFrame': 'one year, last follow-up visit', 'description': 'NRM'}, {'measure': 'compare Infections frequency between patients with ATG and patients without ATG', 'timeFrame': 'one year', 'description': 'time of occurring and frequency of viral (CytoMegalo Virus, Epstein Barr virus , BKV, adenovirus), bacterial, parasite and yeast infections, evaluated by Polymerase Chain Reaction (PCR), blood and urines cultures, biopsy if applicable'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Peripheral haemopoietic stem cell transplant', 'High dose cyclophosphamide', 'acute GVHD', 'allogenic transplantation', 'RIC (reduced-intensity conditioning)'], 'conditions': ['Graft Versus Host Disease']}, 'descriptionModule': {'briefSummary': 'Acute or chronic graft versus host disease is still the major complication of stem cells transplantation regarding morbidity and mortality.\n\nRecently, high dose cyclophosphamide utilization early after post-transplantation (day+ 3 and +4) not only for patients with HLA- haploidentical donor but also for patients with Human Leukocyte Antigen (HLA)-compatible donor, showed a great control of graft versus host disease after transplantation, allowing to consider stopping immunosuppressive treatment after the transplantation (Neoral=cyclosporine, cell-cept=mycophenolate mofetil). Indeed, this step has already been completed in myeloablative transplantation in adult patients.\n\nThis approach could enable to avoid in the end several complications related to long term immunosuppressive drugs administration, while promoting quicker immunity recovery.', 'detailedDescription': 'The BALTIMORE conditioning regiment will be used in this study with peripheral stem cell transplantation and fludarabine will be replaced by clofarabine for myeloid diseases (Acute Myeloide Leukemia, Myelodysplasia , myelofibrosis, Chronic Myeoloid Leukemia..) because of better antitumoral activity in this setting.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* adults ≤ 70 years old\n* indication to stem cells transplantation with reduced-intensity conditioning regimen\n* with a HLA-compatible familial 10/10 or non-familial donor\n* Written signed informed consent form\n* woman with childbearing potential under efficient control birth method during the trial and up to 12 months after cyclophosphamide stop\n* men under efficient control birth method during the trial and up to 6 months after cyclophosphamide stop\n* Negative serology to B and C hepatitis and to HIV\n* Affiliated to social security\n\nExclusion Criteria:\n\n* \\- Eligible to myeloablative contioning regimen\n* Other progressive malignancy disease or history of prior other malignancy in the last two years, with the exception of: curatively treated basal cell carcinoma or carcinoma in situ of the cervix\n* Progressive mental illness disease\n* Pregnant or Breastfeeding woman\n* woman with childbearing potential without any efficient control birth\n* Serious concomitant infection and not controlled\n* Contra-indications to allogenic transplantation, especially:\n\n * Cardiac: left ventricular ejection fraction \\<45% assessed by transthoracic echography or isotopic method (isotopic gamma-angiography)\n * Respiratory: DLCO limiting fludarabine and busulfan use (DLCO\\< 40% of theorical value)\n * Renal: creatinine clearance \\< 60ml/min (MDRD method)\n * Hepatic: transaminases \\>5 Uper Per Normal (UPN) or bilirubin\\> 2 UPN\n* Contra-indications to cyclophosphamide:\n\n * Urinary tract infections\n * Acute urothelial toxicity due to cytotoxic chemotherapy or to radiotherapy\n * Obstruction of urines flow\n * Pre-existing hemorrhagic cystitis\n * Yellow fever vaccination\n* Cardiac condition preventing high dose cyclophosphamide utilization :\n\n * New York Heart Association (NYHA) functional class II, III or IV\n * Rhythmic, valvular or ischemic cardiomyopathy\n* Minor\n* Patient under guardianship or curatorship\n* Patient under judicial protection\n* Known or suspected hypersensitivity to cyclophosphamide\n* Known or suspected hypersensitivity to rabbit proteins'}, 'identificationModule': {'nctId': 'NCT03263767', 'acronym': 'CYRIC', 'briefTitle': 'Post Transplant Cyclophosphamide (PTCY) as Sole Graft Versus Host Disease (GVHD) Prophylaxis for Matched Allotransplant: CYRIC', 'organization': {'class': 'OTHER', 'fullName': 'Nantes University Hospital'}, 'officialTitle': 'Phase II Study Testing Prophylaxis Feasibility of Graft Versus Host Disease With Only High Dose Cyclophosphamide Post-transplantation for Patients Eligible to a Reduced-intensity Conditioning Regiment Prior to Allogenic Transplantation With a Compatible Familial or Non-familial Donor.', 'orgStudyIdInfo': {'id': 'RC16_0435'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'LYMPHOID HEMOPATHY without ATG', 'description': 'patients with lymphoid hemopathy', 'interventionNames': ['Drug: Fludarabine', 'Radiation: Full body irradiation', 'Drug: Cyclophosphamide', 'Other: stem cell transplantation', 'Other: nuclear cells']}, {'type': 'EXPERIMENTAL', 'label': 'MYELOID HEMOPATHY without ATG', 'description': 'patients with myeloid hemopathy', 'interventionNames': ['Drug: Clofarabine', 'Radiation: Full body irradiation', 'Drug: Cyclophosphamide', 'Other: stem cell transplantation', 'Other: nuclear cells']}, {'type': 'EXPERIMENTAL', 'label': 'LYMPHOID HEMOPATHY witH ATG', 'description': 'patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence', 'interventionNames': ['Drug: Fludarabine', 'Radiation: Full body irradiation', 'Drug: Cyclophosphamide', 'Other: stem cell transplantation', 'Other: nuclear cells', 'Drug: Thymoglobulin Injectable Product']}, {'type': 'EXPERIMENTAL', 'label': 'MYELOID HEMOPATHY with ATG', 'description': 'patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence', 'interventionNames': ['Drug: Clofarabine', 'Radiation: Full body irradiation', 'Drug: Cyclophosphamide', 'Other: stem cell transplantation', 'Other: nuclear cells', 'Drug: Thymoglobulin Injectable Product']}], 'interventions': [{'name': 'Fludarabine', 'type': 'DRUG', 'description': '30 mg/m² Intravenous 5 days from Day-6 to Day-2', 'armGroupLabels': ['LYMPHOID HEMOPATHY witH ATG', 'LYMPHOID HEMOPATHY without ATG']}, {'name': 'Clofarabine', 'type': 'DRUG', 'description': '30 mg/m² Intravenous 5 days from Day-6 to Day-2', 'armGroupLabels': ['MYELOID HEMOPATHY with ATG', 'MYELOID HEMOPATHY without ATG']}, {'name': 'Full body irradiation', 'type': 'RADIATION', 'description': '2 grays at Day-1', 'armGroupLabels': ['LYMPHOID HEMOPATHY witH ATG', 'LYMPHOID HEMOPATHY without ATG', 'MYELOID HEMOPATHY with ATG', 'MYELOID HEMOPATHY without ATG']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'description': '14 mg/kg intravenous 2 days at Day - 6 and day -5', 'armGroupLabels': ['LYMPHOID HEMOPATHY witH ATG', 'LYMPHOID HEMOPATHY without ATG', 'MYELOID HEMOPATHY with ATG', 'MYELOID HEMOPATHY without ATG']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'otherNames': ['hight dose'], 'description': '50 mg/kg intravenous 2 days at day +3 and day +4', 'armGroupLabels': ['LYMPHOID HEMOPATHY witH ATG', 'LYMPHOID HEMOPATHY without ATG', 'MYELOID HEMOPATHY with ATG', 'MYELOID HEMOPATHY without ATG']}, {'name': 'stem cell transplantation', 'type': 'OTHER', 'otherNames': ['graft'], 'description': 'at D0 intraveinous Depending on donor : the stem cells will be extracted from blood (CD34+) or from bone marrow (CD34+ and nuclear cells)', 'armGroupLabels': ['LYMPHOID HEMOPATHY witH ATG', 'LYMPHOID HEMOPATHY without ATG', 'MYELOID HEMOPATHY with ATG', 'MYELOID HEMOPATHY without ATG']}, {'name': 'nuclear cells', 'type': 'OTHER', 'otherNames': ['Donor Lymphocytes Injection (DLI)'], 'description': 'CD3+ cells if needed after transplantation', 'armGroupLabels': ['LYMPHOID HEMOPATHY witH ATG', 'LYMPHOID HEMOPATHY without ATG', 'MYELOID HEMOPATHY with ATG', 'MYELOID HEMOPATHY without ATG']}, {'name': 'Thymoglobulin Injectable Product', 'type': 'DRUG', 'otherNames': ['ATG'], 'description': 'At day -2 2.5 mg/kg for patients inclued after 14 dec 2020', 'armGroupLabels': ['LYMPHOID HEMOPATHY witH ATG', 'MYELOID HEMOPATHY with ATG']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Nantes', 'country': 'France', 'facility': 'Nantes Uh', 'geoPoint': {'lat': 47.21725, 'lon': -1.55336}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Nantes University Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}