Nctid:
NCT06235398
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-10-04"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D000009190", "term"=>"Myelodysplastic Syndromes"}, {"id"=>"D000013577", "term"=>"Syndrome"}], "ancestors"=>[{"id"=>"D000004194", "term"=>"Disease"}, {"id"=>"D000010335", "term"=>"Pathologic Processes"}, {"id"=>"D000001855", "term"=>"Bone Marrow Diseases"}, {"id"=>"D000006402", "term"=>"Hematologic Diseases"}], "browseLeaves"=>[{"id"=>"M16355", "name"=>"Syndrome", "asFound"=>"Syndrome", "relevance"=>"HIGH"}, {"id"=>"M14164", "name"=>"Preleukemia", "relevance"=>"LOW"}, {"id"=>"M12145", "name"=>"Myelodysplastic Syndromes", "asFound"=>"Myelodysplastic Syndrome", "relevance"=>"HIGH"}, {"id"=>"M5134", "name"=>"Bone Marrow Diseases", "relevance"=>"LOW"}, {"id"=>"M9490", "name"=>"Hematologic Diseases", "relevance"=>"LOW"}, {"id"=>"T3993", "name"=>"Myelodysplastic Syndromes", "asFound"=>"Myelodysplastic Syndrome", "relevance"=>"HIGH"}], "browseBranches"=>[{"name"=>"Symptoms and General Pathology", "abbrev"=>"BC23"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Neoplasms", "abbrev"=>"BC04"}, {"name"=>"Blood and Lymph Conditions", "abbrev"=>"BC15"}, {"name"=>"Rare Diseases", "abbrev"=>"Rare"}]}}, "protocolSection"=>{"designModule"=>{"phases"=>["PHASE2"], "studyType"=>"INTERVENTIONAL", "designInfo"=>{"allocation"=>"NA", "maskingInfo"=>{"masking"=>"NONE"}, "primaryPurpose"=>"TREATMENT", "interventionModel"=>"SINGLE_GROUP"}, "enrollmentInfo"=>{"type"=>"ESTIMATED", "count"=>55}}, "statusModule"=>{"overallStatus"=>"NOT_YET_RECRUITING", "startDateStruct"=>{"date"=>"2024-02-01", "type"=>"ESTIMATED"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2023-08", "completionDateStruct"=>{"date"=>"2028-02-01", "type"=>"ESTIMATED"}, "lastUpdateSubmitDate"=>"2024-01-23", "studyFirstSubmitDate"=>"2024-01-23", "studyFirstSubmitQcDate"=>"2024-01-23", "lastUpdatePostDateStruct"=>{"date"=>"2024-01-31", "type"=>"ACTUAL"}, "studyFirstPostDateStruct"=>{"date"=>"2024-01-31", "type"=>"ACTUAL"}, "primaryCompletionDateStruct"=>{"date"=>"2028-02-01", "type"=>"ESTIMATED"}}, "outcomesModule"=>{"primaryOutcomes"=>[{"measure"=>"Disease-free survival", "timeFrame"=>"2 years after transplantation"}], "secondaryOutcomes"=>[{"measure"=>"Overall survival", "timeFrame"=>"2 years after transplantation"}, {"measure"=>"Non-relapse mortality", "timeFrame"=>"2 years after transplantation"}, {"measure"=>"Cumulative incidence of transformation into acute myeloid leukemia from inclusion", "timeFrame"=>"2 years after inclusion"}, {"measure"=>"Incidence of acute Graft versus Host Disease (GvHD) and grading", "timeFrame"=>"100 days after transplantation"}, {"measure"=>"Incidence of chronic GvHD and grading", "timeFrame"=>"2 years after transplantation"}, {"measure"=>"Percentage of engraftment", "timeFrame"=>"3 months after transplantation", "description"=>"Engraftment is defined by hematological recovery and donor chimerism \\> 95%"}, {"measure"=>"Percentage of graft failure", "timeFrame"=>"2 years after transplantation", "description"=>"Graft failure is defined by acute or late rejection and non-engraftment"}, {"measure"=>"Incidence of severe infections", "timeFrame"=>"3 months after transplantation", "description"=>"Severe infections are defined by Common Terminology of Adverse Events (CTAE) grade 3-4"}, {"measure"=>"Incidence of severe infections", "timeFrame"=>"6 months after transplantation", "description"=>"Severe infections are defined by Common Terminology of Adverse Events grade 3-4"}, {"measure"=>"Incidence of severe infections", "timeFrame"=>"12 months after transplantation", "description"=>"Severe infections are defined by Common Terminology of Adverse Events grade 3-4"}, {"measure"=>"Incidence of severe infections", "timeFrame"=>"24 months after transplantation", "description"=>"Severe infections are defined by Common Terminology of Adverse Events grade 3-4"}, {"measure"=>"Incidence of cardiac events", "timeFrame"=>"1 month after transplantation", "description"=>"CTAE grade 2-4"}, {"measure"=>"Incidence of cardiac events", "timeFrame"=>"3 months after transplantation", "description"=>"CTAE grade 2-4"}]}, "oversightModule"=>{"oversightHasDmc"=>true, "isFdaRegulatedDrug"=>false, "isFdaRegulatedDevice"=>false}, "conditionsModule"=>{"conditions"=>["Myelodysplastic Syndromes"]}, "descriptionModule"=>{"briefSummary"=>"Three recent prospective \"transplant/no transplant\" studies concluded to an advantage of OS with transplantation in patients with high or intermediate-2 IPSS risk (not significant in Kröger's study). No prospective randomized trial has assessed the pre-transplant therapy in MDS patients yet but some information can be extracted from these 3 recent studies. In the French study (n=162), 72% patients with a donor received HSCT, previously treated by hypomethylating agent (HMA) in 71% of them. There was a trend to a better survival in patients achieving a complete remission with pre-graft therapy (HR: 0.55, p=0.088) and higher risk of death in unresponsiveness patients transformed into AML (HR: 2.36, p=0.008). In Nakamura's study (n=384), 83% of patients with a donor were transplanted, previously treated by HMA in 68%2. The multivariable Cox model for Overall Survival (OS) and Leukemia-free survival showed an excess risk in patients treated by HMA. Moreover, responders still have a higher risk of mortality as compared to patients who did not receive any pre-graft therapy (HR: 2.417, p=0.0054). In the German study, the aim was to initiate azacytidine at inclusion and to transplant patients after 4 cycles if a donor was identified1. Among 170 registered patients, 162 initiated 5-aza but 36% of them were \"lost during this pre-graft therapy\" before allocation to \"donor\" or \"no-donor\" arm, for different reasons including death (n=12). After 4 cycles of 5-aza, 79/81 patients \"donor arm\" were transplanted. The multivariable analysis showed remission status did not influence OS. Those 3 previous clinical trials thus suggest that a substantial number of patients planned for transplantation are not transplanted nowadays while no evidence of HMA benefit before HSCT has been clearly identified. This phase 2 study aim to assess the feasibility of upfront HSCT in patients with high risk MDS in order to increase the probability to be transplanted and to achieve a subsequent remission and better survival."}, "eligibilityModule"=>{"sex"=>"ALL", "stdAges"=>["ADULT", "OLDER_ADULT"], "maximumAge"=>"70 years", "minimumAge"=>"50 years", "healthyVolunteers"=>false, "eligibilityCriteria"=>"Inclusion Criteria:\n\n* Age ≥ 50 and ≤ 70 years\n* An HLA (Human Leukocyte Antigen) matched sibling donor or familial haplo-identical donor has been identified\n* The disease fulfills at least one of the following criteria:\n\n * Intermediate-2 or high risk according to classical International Prognostic Scoring System (IPSS)\n * Intermediate-1 risk if marrow fibrosis \\> grade I or poor risk cytogenetics according to R IPSS or classified high or very high risk according to Revised International Prognostic Scoring System (R IPSS) or if the MDS is therapy-related neoplasm\n* Usual criteria for Hematopoietic Stem Cell Transplantation (HSCT):\n\n * Eastern Cooperative Oncology Group Score (ECOG) ≤ 2\n * No severe and uncontrolled infection\n * Cardiac function compatible with high dose of cyclophosphamide Left Ventricular Function (LVF) \\> 50%\n * Adequate organ function: ASAT and ALAT ≤ 2.5N, total bilirubin ≤ 2N, creatinine clearance ≥ 30 ml/min (according to Cockroft formula)\n* In case of transplantation with a haploidentical donor, absence of donor specific antibody (DSA) detected in the patient with a MFI \\>1000 (antibodies directed towards the distinct haplotype between donor and recipient)\n* Contraception methods must be prescribed for women of childbearing age during all the study. If cyclophosphamide is used, effective contraceptive methods for men during all their participation in the study\n* With health insurance coverage\n* With a written informed consent signed\n\nExclusion Criteria:\n\n* Marrow blast \\> 15% at time of inclusion\n* MDS with excess blast \\>10% and NPM1 mutation or a recurrent genetic abnormality related to Acute Myeloid Leukemia (AML) (WHO 2022)\n* Chemotherapy (AML like intensive chemotherapy or demethylating agent) to treat MDS at the current stage\n* Disponibility of an unrelated donor 10/10 (MUD) in absence of geno-identical donor\n* Patient with uncontrolled infection\n* Cancer in the last 5 years (except basal cell carcinoma of the skin or \"in situ\" carcinoma of the cervix\n* Renal failure with creatinine clearance \\<30ml / min (according to Cockroft formula)\n* With contraindications to treatments used during the research\n* Uncontrolled coronary insufficiency, recent myocardial infarction \\<6 month, current manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular ejection fraction \\<50%\n* With heart failure according to NYHA (II or more)\n* Patient with seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive PCR Hepatitis B Virus or Hepatitis C Virus\n* Yellow fever vaccine or any alive vaccine within 2 months before transplantation\n* Pregnancy (β-HCG positive) or breast-feeding\n* Who have any debilitating medical or psychiatric illness, which would preclude giving well understand informed consent or optimal treatment and follow-up\n* Under protection by law (tutorship or curatorship)"}, "identificationModule"=>{"nctId"=>"NCT06235398", "acronym"=>"FIRST ALLO MDS", "briefTitle"=>"Upfront Related Donor Transplantation in Patients With Myelodisplatic Syndrome : a Phase 2 Trial", "organization"=>{"class"=>"OTHER", "fullName"=>"Assistance Publique - Hôpitaux de Paris"}, "officialTitle"=>"Upfront Related Donor Transplantation in Patients With Myelodisplatic Syndrome : a Phase 2 Trial", "orgStudyIdInfo"=>{"id"=>"APHP221273"}}, "armsInterventionsModule"=>{"armGroups"=>[{"type"=>"EXPERIMENTAL", "label"=>"Adults with Myelodysplasic Syndrome diagnosis", "description"=>"Adults (Age ≥ 50 and ≤ 70 years) patients with MDS diagnosis for whom transplantation is indicated from a related donor identified.", "interventionNames"=>["Biological: Hematopoietic stem-cell transplantation"]}], "interventions"=>[{"name"=>"Hematopoietic stem-cell transplantation", "type"=>"BIOLOGICAL", "description"=>"Upfront related donor transplantation", "armGroupLabels"=>["Adults with Myelodysplasic Syndrome diagnosis"]}]}, "contactsLocationsModule"=>{"centralContacts"=>[{"name"=>"Marie Robin, Dr", "role"=>"CONTACT", "email"=>"marie.robin@aphp.fr", "phone"=>"+33142499639"}, {"name"=>"Jérôme Lambert, Dr", "role"=>"CONTACT", "email"=>"jerome.lambert@u-paris.fr", "phone"=>"+33142499742"}]}, "ipdSharingStatementModule"=>{"ipdSharing"=>"UNDECIDED"}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"Assistance Publique - Hôpitaux de Paris", "class"=>"OTHER"}, "responsibleParty"=>{"type"=>"SPONSOR"}}}}
