Ignite Creation Date:
2025-12-24 @ 6:43 PM
Ignite Modification Date:
2026-01-02 @ 9:49 AM
Study NCT ID:
NCT04943757
Status:
COMPLETED
Last Update Posted:
2024-10-15
First Post:
2021-06-21
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015470', 'term': 'Leukemia, Myeloid, Acute'}, {'id': 'D015464', 'term': 'Leukemia, Myelogenous, Chronic, BCR-ABL Positive'}, {'id': 'D009190', 'term': 'Myelodysplastic Syndromes'}, {'id': 'D009196', 'term': 'Myeloproliferative Disorders'}, {'id': 'D006086', 'term': 'Graft vs Host Disease'}], 'ancestors': [{'id': 'D007951', 'term': 'Leukemia, Myeloid'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069461', 'term': 'Bendamustine Hydrochloride'}, {'id': 'D003520', 'term': 'Cyclophosphamide'}], 'ancestors': [{'id': 'D002087', 'term': 'Butyrates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D001562', 'term': 'Benzimidazoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 50}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-01-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-10', 'completionDateStruct': {'date': '2024-05-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-10-10', 'studyFirstSubmitDate': '2021-06-21', 'studyFirstSubmitQcDate': '2021-06-21', 'lastUpdatePostDateStruct': {'date': '2024-10-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-06-29', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-05-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Event-free survival analysis [ Time Frame: 1 year ]', 'timeFrame': '1 year', 'description': 'Measure: Kaplan-Meier estimate of death or relapse, or graft failure'}], 'secondaryOutcomes': [{'measure': '- Incidence of Cytokine release syndrome', 'timeFrame': '100 days', 'description': 'Proportion of patients with cytokine release syndrome according to ASBMT Consensus Grading for Cytokine Release Syndrome, 2018'}, {'measure': 'Incidence of HSCT-associated adverse events (safety and toxicity)', 'timeFrame': '100 days', 'description': 'Toxicity assessment is based on NCI CTC AE 5.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Cho et al.'}, {'measure': 'Incidence of acute GVHD grade II-IV', 'timeFrame': '125 days', 'description': 'Cumulative incidence of patients with acute GVHD II-IV grade'}, {'measure': 'Incidence of moderate and severe chronic GVHD', 'timeFrame': '1 year', 'description': 'Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria'}, {'measure': 'Relapse rate analysis', 'timeFrame': '1 year', 'description': 'Cumulative incidence of patients with relapse'}, {'measure': 'Non-relapse mortality analysis', 'timeFrame': '1 year', 'description': 'Cumulative incidence of patients with mortality without hematological relapse of malignancy'}, {'measure': 'Overall survival analysis', 'timeFrame': '1 year', 'description': 'Kaplan-Meier estimate of death from all causes'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Bendamustine', 'Cyclophosphamide', 'Graft-versus-host disease', 'Graft-versus-leukemia effect', 'Refractory', 'Acute Myeloid leukemia', 'Hematopoietic Stem Cell Transplantation', 'Allogeneic'], 'conditions': ['Myeloid Leukemia, Acute', 'Chronic Myeloid Leukemia', 'Myelodysplastic Syndromes', 'Myeloproliferative Neoplasm']}, 'referencesModule': {'references': [{'pmid': '33845259', 'type': 'BACKGROUND', 'citation': 'Moiseev I, Bondarenko S, Morozova E, Vlasova Y, Dotsenko A, Epifanovskaya O, Babenko E, Botina A, Baykov V, Surkova E, Lapin S, Beynarovich A, Borzenkova E, Golosgchapov O, Kanunnikov M, Kudyasheva O, Ovechkina V, Pirogova O, Porunova V, Rudakova T, Smikova O, Smirnova A, Afansyev B. Graft-versus-Host Disease Prophylaxis with Post-Transplantation Bendamustine in Patients with Refractory Acute Leukemia: A Dose-Ranging Study. Transplant Cell Ther. 2021 Jul;27(7):601.e1-601.e7. doi: 10.1016/j.jtct.2021.03.032. Epub 2021 May 7.'}]}, 'descriptionModule': {'briefSummary': 'Prognosis of patients undergoing salvage allogeneic stem cell transplantation for refractory leukemia or other refractory myeloid malignanies is poor. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Despite high frequency of responses and durable remissions after this approach majority of patients develop a serious complication - cytokine release syndrome, which can be life-threatening in some patients. On the other hand post-transplantation cyclophocphamide was reported to abort cytokine release syndrome that sometimes occurs after graft transfusion in patients after haploidentical graft transfusion. The aim of this study is to evaluate if the combination of post-transplantation bendamustine (PTB) and post-transplantation cyclophosphamide (PTCY) facilitates comparable graft-versus leukemia effect to PTB, but with better safety profile and reduced incidence of severe cytokine release syndrome.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients with indication for allogeneic hematopoietic stem cell transplantation\n* Patients with 5-10/10 HLA-matched related or unrelated donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.\n* Peripheral blood stem cells or bone marrow as a graft source\n* Diagnosis:\n\nAcute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms\n\n* Salvage hematopoietic stem cell transplantation defined as:\n* Acute myeloid leukemia: \\>5% of clonal blasts despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: \\>10% of blasts despite previous therapy with -7 or complex karyotype, or p53 mutation Chronic myeloid leukemia: blast crisis or acceleration phase despite at least 3 previous lines of TKIs Myeloprolipherative neoplasms : high tumor burden despite previous therapy, including \\>20 000 WBC/ ul or splenomegaly \\>15 cm\n* No severe concurrent illness\n\nExclusion Criteria:\n\n* Moderate or severe cardiac dysfunction, left ventricular ejection fraction \\<50%\n* Moderate or severe decrease in pulmonary function, FEV1 \\<70% or DLCO\\<70% of predicted\n* Respiratory distress \\>grade I\n* Severe organ dysfunction: AST or ALT \\>5 upper normal limits, bilirubin \\>1.5 upper normal limits, creatinine \\>2 upper normal limits\n* Creatinine clearance \\< 60 mL/min\n* Uncontrolled bacterial or fungal infection at the time of enrollment\n* Requirement for vasopressor support at the time of enrollment\n* Karnofsky index \\<30%\n* Pregnancy\n* Somatic or psychiatric disorder making the patient unable to sign informed consent'}, 'identificationModule': {'nctId': 'NCT04943757', 'acronym': 'PTBCy', 'briefTitle': 'Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies', 'organization': {'class': 'OTHER', 'fullName': 'St. Petersburg State Pavlov Medical University'}, 'officialTitle': 'Graft-versus-host Disease Prophylaxis With Combination of Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies (PTBCy)', 'orgStudyIdInfo': {'id': '05/21-n'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'PTBCy graft-versus-host disease prophylaxis', 'description': 'Days +3 through +4: Bendamustine 50 mg/m2 iv x 2 days; Days +3 through +4: Cyclophosphamide 25 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration', 'interventionNames': ['Drug: Bendamustine Hydrochloride', 'Drug: Cyclophosphamid']}], 'interventions': [{'name': 'Bendamustine Hydrochloride', 'type': 'DRUG', 'description': '50 mg/m2 iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation', 'armGroupLabels': ['PTBCy graft-versus-host disease prophylaxis']}, {'name': 'Cyclophosphamid', 'type': 'DRUG', 'description': '25 mg/kg iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation', 'armGroupLabels': ['PTBCy graft-versus-host disease prophylaxis']}]}, 'contactsLocationsModule': {'locations': [{'zip': '197022', 'city': 'Saint Petersburg', 'country': 'Russia', 'facility': 'RM Gorbacheva Research Institute', 'geoPoint': {'lat': 59.93863, 'lon': 30.31413}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': 'Request for sharing data with the study plan for the data will be evaluated under common conditions by Pavlov University Ethical Committee.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'St. Petersburg State Pavlov Medical University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Vice-director for science RM Gorbacheva Institute', 'investigatorFullName': 'Ivan S Moiseev', 'investigatorAffiliation': 'St. Petersburg State Pavlov Medical University'}}}}