Ignite Creation Date:
2025-12-24 @ 12:19 PM
Ignite Modification Date:
2026-01-17 @ 2:19 AM
Study NCT ID:
NCT01830361
Status:
COMPLETED
Last Update Posted:
2020-08-06
First Post:
2013-03-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Trial to Assess the Efficacy of Midostaurin (PKC412) in Patients With c-KIT or FLT3-ITD Mutated t(8;21) AML
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015470', 'term': 'Leukemia, Myeloid, Acute'}], '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'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C059539', 'term': 'midostaurin'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-03-13', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-08', 'completionDateStruct': {'date': '2019-10-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-08-05', 'studyFirstSubmitDate': '2013-03-25', 'studyFirstSubmitQcDate': '2013-04-09', 'lastUpdatePostDateStruct': {'date': '2020-08-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2013-04-12', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2019-10-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Event-free Survival', 'timeFrame': '2-year Event-free Survival'}], 'secondaryOutcomes': [{'measure': 'Time to relapse', 'timeFrame': '2-years'}, {'measure': 'Overall survival', 'timeFrame': '2-years'}, {'measure': 'Relapse-free survival', 'timeFrame': '2-years'}, {'measure': 'morphologic and molecular CR rate', 'timeFrame': '2-years'}, {'measure': 'incidence of AEs/SAEs', 'timeFrame': 'until 30 days after end of treatment'}, {'measure': 'MRD kinetics (molecular residual disease)', 'timeFrame': '2-years', 'description': 'molecular diagnostics of markers in peripheral blood / bone marrow'}, {'measure': 'Cumulative incidence of relapse', 'timeFrame': '2-year'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['AML', 'Acute Myeloid Leukemia', 'c-KIT', 'FLT3-ITD', 't(8;21)', 'chemotherapy', 'midostaurin'], 'conditions': ['Acute Myeloid Leukemia']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'http://www.sal-aml.org', 'label': 'Website Study Alliance Leukemia (coordinating study group)'}]}, 'descriptionModule': {'briefSummary': 'To assess the efficacy of tyrosine-kinase inhibitor midostaurin in c-KIT or FLT3-ITD mutated t(8;21) AML. To assess the efficacy of midostaurin depending on the type of c-KIT mutation', 'detailedDescription': 'AML patients displaying t(8;21) have a relatively favourable outcome. Nevertheless, only approximately 50% of patients carrying this cytogenetic aberration are alive at 5 years. This suggests that some patients have more aggressive leukemic phenotypes and indicates the need for treatment optimization with novel therapies.\n\nThe mutated KIT gene as well as the FLT3-ITD mutation have recently been identified as factors most likely to explain the heterogeneous clinical outcomes within the group of t(8;21) AML. The FLT3 and c-KIT genes encode type III receptor tyrosine kinases (RTK) with important and partly redundant functions in early hematopoietic stem cells. Various activating mutations have been described for both genes. For c-KIT, the incidence ranges from 17 to 48% depending on the source population and type of mutations determined. It has been consistently shown that in AMLs with t(8;21), mutated c-KIT is associated with a dramatically increased risk of relapse and reduced overall survival compared to their unmutated counterparts. The FLT3-ITD mutation has a similar negative effect on prognosis in the patient group of t(8;21) mutated AMLs as c-KIT.\n\nPKC412 (midostaurin) is known to inhibit the c-KIT RTK activity as well as the FLT3 kinase, both in patients with ITD and TKD mutations. It should therefore be possible to abrogate the negative impact of pathologically increased c-KIT or FLT3-ITD activity on relapse and overall survival by using midostaurin in this patient population. Aim of the proposed clinical trial is to prove the efficacy of midostaurin in c-KIT or FLT3-ITD mutated t(8;21)- AMLs in an open-label one-arm design.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Diagnosis of c-KIT mutated t(8;21) AML i.e.\n\n 1. \\>20% myeloid blasts in bone marrow and/or peripheral blood at initial diagnosis\n 2. Plus cytogenetic diagnosis of aberration t(8;21)/AML1-ETO\n 3. Plus mutation of c-KIT gene (mut-KIT17 or mut-KIT8) or FLT3-ITD mutation or both c-KIT and FLT3-ITD mutations\n* Chemoresponsive disease as determined by early bone marrow assessment on day 14-16 after first cycle of induction therapy with cytarabine in combination with daunorubicine or idarubicine, or mitoxantrone- Fit for further intensive chemotherapy\n* Age 18-65 years\n* ECOG performance status of 0-2\n* Life expectancy of at least 12 weeks\n\nExclusion Criteria:\n\n* Primary refractory or previously relapsed AML\n* Non-eligibility for high-dose cytarabine based consolidation, e.g. intolerance to cytarabine\n* Inability to swallow oral medications\n* Symptomatic congestive heart failure\n* Bilirubin \\>2.5 x upper limit of normal'}, 'identificationModule': {'nctId': 'NCT01830361', 'acronym': 'MIDOKIT', 'briefTitle': 'Trial to Assess the Efficacy of Midostaurin (PKC412) in Patients With c-KIT or FLT3-ITD Mutated t(8;21) AML', 'organization': {'class': 'OTHER', 'fullName': 'Technische Universität Dresden'}, 'officialTitle': 'A Single-arm Phase II Trial to Assess the Efficacy of Midostaurin (PKC412) Added to Standard Primary Therapy in Patients With Newly Diagnosed c-KIT or FLT3-ITD Mutated t(8;21) AML', 'orgStudyIdInfo': {'id': 'TUD-MIDOKI-052'}, 'secondaryIdInfos': [{'id': '2011-002567-17', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'midostaurin (PKC412), capsules', 'description': 'midostaurin 50 mg (two 25 mg capsules) is given in combination with the second of two induction cycles and in combination with three cycles of high-dose cytarabine (HiDAC) consolidation chemotherapies and maintenance treatment in patients with c-kit or FLT3-ITD positive t(8;21) AML in an open-label one-arm design. The first cycle of induction is not part of the study.', 'interventionNames': ['Drug: midostaurin (PKC412)']}], 'interventions': [{'name': 'midostaurin (PKC412)', 'type': 'DRUG', 'otherNames': ['Rydapt'], 'description': 'Midostaurin 50 mg (2 capsules) twice daily days 8-21 in induction II + consolidation I-III; maintenance treatment twice daily continuously for 12 months', 'armGroupLabels': ['midostaurin (PKC412), capsules']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Chemnitz', 'country': 'Germany', 'facility': 'Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III', 'geoPoint': {'lat': 50.8357, 'lon': 12.92922}}, {'city': 'Dresden', 'country': 'Germany', 'facility': 'Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I', 'geoPoint': {'lat': 51.05089, 'lon': 13.73832}}, {'city': 'Erlangen', 'country': 'Germany', 'facility': 'Universitätsklinikum Erlangen, Medizinische Klinik 5', 'geoPoint': {'lat': 49.59099, 'lon': 11.00783}}, {'city': 'Frankfurt am Main', 'country': 'Germany', 'facility': 'Klinikum der Johann-Wolfgang-Goethe Universität', 'geoPoint': {'lat': 50.11552, 'lon': 8.68417}}, {'city': 'Heidelberg', 'country': 'Germany', 'facility': 'Universitätsklinikum Heidelberg', 'geoPoint': {'lat': 49.40768, 'lon': 8.69079}}, {'city': 'Jena', 'country': 'Germany', 'facility': 'Universitätsklinikum Jena, Klinik für Innere Medizin II', 'geoPoint': {'lat': 50.92878, 'lon': 11.5899}}, {'city': 'Marburg', 'country': 'Germany', 'facility': 'Universitätsklinikum Gießen und Marburg GmbH', 'geoPoint': {'lat': 50.80904, 'lon': 8.77069}}, {'city': 'Münster', 'country': 'Germany', 'facility': 'Universitätsklinikum Münster', 'geoPoint': {'lat': 51.96236, 'lon': 7.62571}}, {'city': 'Nuremberg', 'country': 'Germany', 'facility': 'Städtisches Klinikum Nord', 'geoPoint': {'lat': 49.45421, 'lon': 11.07752}}, {'city': 'Regensburg', 'country': 'Germany', 'facility': 'Klinikum der Universität Regensburg', 'geoPoint': {'lat': 49.01513, 'lon': 12.10161}}], 'overallOfficials': [{'name': 'Christoph Röllig, Prof. Dr.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Medizinische Fakultät der TU Dresden, Medizinische Klinik und Poliklinik I'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Technische Universität Dresden', 'class': 'OTHER'}, 'collaborators': [{'name': 'Novartis Pharmaceuticals', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}