Ignite Creation Date:
2025-12-25 @ 5:05 AM
Ignite Modification Date:
2025-12-26 @ 4:08 AM
Study NCT ID:
NCT00686218
Status:
COMPLETED
Last Update Posted:
2014-08-15
First Post:
2008-05-28
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Panobinostat (LBH589) and Imatinib Mesylate in Treating Patients With Previously Treated Chronic Phase Chronic Myelogenous Leukemia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D015466', 'term': 'Leukemia, Myeloid, Chronic-Phase'}], 'ancestors': [{'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D015464', 'term': 'Leukemia, Myelogenous, Chronic, BCR-ABL Positive'}, {'id': 'D007951', 'term': 'Leukemia, Myeloid'}, {'id': 'D009196', 'term': 'Myeloproliferative Disorders'}, {'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'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068877', 'term': 'Imatinib Mesylate'}, {'id': 'D000077767', 'term': 'Panobinostat'}, {'id': 'D016133', 'term': 'Polymerase Chain Reaction'}, {'id': 'D015153', 'term': 'Blotting, Western'}, {'id': 'D005434', 'term': 'Flow Cytometry'}], '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'}, {'id': 'D006877', 'term': 'Hydroxamic Acids'}, {'id': 'D006898', 'term': 'Hydroxylamines'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D006880', 'term': 'Hydroxy Acids'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D021141', 'term': 'Nucleic Acid Amplification Techniques'}, {'id': 'D005821', 'term': 'Genetic Techniques'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D004586', 'term': 'Electrophoresis'}, {'id': 'D002623', 'term': 'Chemistry Techniques, Analytical'}, {'id': 'D055664', 'term': 'Electrochemical Techniques'}, {'id': 'D015151', 'term': 'Immunoblotting'}, {'id': 'D007118', 'term': 'Immunoassay'}, {'id': 'D007158', 'term': 'Immunologic Techniques'}, {'id': 'D015336', 'term': 'Molecular Probe Techniques'}, {'id': 'D002469', 'term': 'Cell Separation'}, {'id': 'D003584', 'term': 'Cytological Techniques'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D003592', 'term': 'Cytophotometry'}, {'id': 'D005470', 'term': 'Fluorometry'}, {'id': 'D008163', 'term': 'Luminescent Measurements'}, {'id': 'D010783', 'term': 'Photometry'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 9}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2008-05'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-08', 'completionDateStruct': {'date': '2014-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-08-14', 'studyFirstSubmitDate': '2008-05-28', 'studyFirstSubmitQcDate': '2008-05-28', 'lastUpdatePostDateStruct': {'date': '2014-08-15', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2008-05-29', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-03', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum tolerated dose of histone deacetylase inhibitor LBH589 in combination with imatinib mesylate', 'timeFrame': '1 month'}, {'measure': 'Safety and tolerability of histone deacetylase inhibitor LBH589 in combination with imatinib mesylate', 'timeFrame': '4 months'}], 'secondaryOutcomes': [{'measure': 'Effect of treatment with histone deacetylase inhibitor LBH589 in combination with imatinib mesylate on cytogenetic response status and BCR-Abl levels', 'timeFrame': '4 months'}, {'measure': 'Effect of treatment with histone deacetylase inhibitor LBH589 in combination with imatinib mesylate on residual BCR-Abl positive primitive progenitors', 'timeFrame': '4 months'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['chronic phase chronic myelogenous leukemia'], 'conditions': ['Leukemia']}, 'descriptionModule': {'briefSummary': 'RATIONALE: Panobinostat and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.\n\nPURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with imatinib in treating patients with previously treated chronic phase chronic myelogenous leukemia.', 'detailedDescription': 'OBJECTIVES:\n\nPrimary\n\n* To determine the safety and tolerability of LBH589 given in combination with imatinib mesylate in CML patients who are in Major Cytogenetic Remission (MCR) with residual BCR-ABL positive cells after at least 1 year of daily imatinib mesylate treatment.\n* To determine the maximum tolerated dose (MTD) and dose-limiting toxicity of LBH589 given in combination with imatinib mesylate in CML patients.\n\nSecondary\n\n* To study the effect of LBH589 given in combination with imatinib mesylate on cytogenetic response status and BCR-ABL levels in CML patients in major cytogenetic remission on imatinib mesylate treatment.\n\nTertiary\n\n* To study the effect of LBH589 given in combination with imatinib mesylate on residual BCR-ABL positive primitive progenitors in CML patients in major cytogenetic remission on imatinib mesylate treatment.\n\nOUTLINE: This is dose-escalation study of panobinostat.\n\nPatients receive oral panobinostat once daily on days 1, 3 and 5; 8, 10, and 12; 15, 17, and 19; and 22, 24, and 26. Patients also receive oral imatinib mesylate once daily on days 1-28. Treatment repeats every 21 or 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.\n\nAfter completion of study treatment, patients are followed up at 1 month and then every 3 months for up to 1 year.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed\n* CML CP patients who have been treated with and tolerated Imatinib for 1 year or more, have achieved at least major cytogenetic response and continue to be BCR-ABL positive (Patients should be receiving Imatinib at a dose of 400 daily at the time of entry into the study)\n* ANC and PLT need to be in the normal range\n* Serum albumin \\>= 3g/dL\n* AST/SGOT and ALT/SGPT =\\< 2.5 x upper limit of normal (ULN)\n* Serum bilirubin =\\< 1.5 x ULN\n* Serum creatinine =\\< 1.5 x ULN or 24-hour creatinine clearance \\>= 50 ml/min\n* Serum potassium \\>= lower limit of normal (LLN)\n* Serum phosphorus \\>= LLN\n* Serum total calcium (corrected for serum albumin) or serum ionized calcium \\>= LLN\n* Serum magnesium \\>= LLN\n* ECOG performance status of =\\< 2\n\nExclusion Criteria:\n\n* Prior treatment with an HDAC inhibitor\n* Patient who have been treated with Imatinib \\< 1 year or patients are currently being treated with Imatinib at a dose \\> 400 mg daily\n* Impaired cardiac function including any one of the following: Screening ECG with a QTc \\> 450 msec; Patients with congenital long QT syndrome; History or presence of sustained ventricular tachycardia; Any history of ventricular fibrillation or torsades de pointes; Bradycardia defined as heart rate \\< 50 beats per minute (patients with a pacemaker and heart rate \\>= 50 beats per minute are eligible); Patients with a myocardial infarction or unstable angina within 6 months of study entry; Congestive heart failure (NY Heart Association class III or IV); Right bundle branch block and left anterior hemiblock (bifascicular block)\n* Uncontrolled hypertension\n* Concomitant use of drugs with a risk of prolonging the QT interval or inducing torsades de pointes\n* Concomitant use of CYP3A4 inhibitors\n* Patients with unresolved diarrhea \\> CTCAE grade 1\n* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589\n* Other concurrent severe and/or uncontrolled medical conditions\n* Patients who have received chemotherapy, any investigational drug or undergone major surgery \\< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy\n* Concomitant use of any other anti-cancer therapy or radiation therapy\n* Patients being treated with Coumadin (unless patients who require anticoagulation can be switched to a low-molecular weight or standard heparin)\n* Female patients who are pregnant or breast feeding or patients of reproductive potential not willing to use a double method of contraception including a barrier method (i.e. condom) during the study and 3 months after the end of treatment (Women of childbearing potential \\[WOCBP\\] must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589)\n* Male patients whose sexual partners are WOCBP not willing to use a double method of contraception including condom during the study and 3 months after the end of treatment\n* Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin\n* Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required\n* Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent'}, 'identificationModule': {'nctId': 'NCT00686218', 'briefTitle': 'Panobinostat (LBH589) and Imatinib Mesylate in Treating Patients With Previously Treated Chronic Phase Chronic Myelogenous Leukemia', 'organization': {'class': 'OTHER', 'fullName': 'City of Hope Medical Center'}, 'officialTitle': 'A Phase I Dose Escalation Study of LBH589 in Combination With Imatinib Mesylate for Patients With Chronic Myeloid Leukemia in Cytogenetic Remission With Residual Disease Detectable by Q-PCR', 'orgStudyIdInfo': {'id': '07203'}, 'secondaryIdInfos': [{'id': 'P30CA033572', 'link': 'https://reporter.nih.gov/quickSearch/P30CA033572', 'type': 'NIH'}, {'id': 'NOVARTIS-CSTI571AUS275T'}, {'id': 'CDR0000596065', 'type': 'REGISTRY', 'domain': 'PDQ'}, {'id': 'NCI-2010-00528', 'type': 'REGISTRY', 'domain': 'NCI CTRP'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment (panobinostat, imatinib mesylate)', 'description': 'Patients receive oral panobinostat once daily on days 1, 3 and 5; 8, 10, and 12; 15, 17, and 19; and 22, 24, and 26. Patients also receive oral imatinib mesylate once daily on days 1-28. Treatment repeats every 21 or 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.', 'interventionNames': ['Drug: imatinib mesylate', 'Drug: panobinostat', 'Genetic: polymerase chain reaction', 'Genetic: protein expression analysis', 'Genetic: western blotting', 'Other: flow cytometry', 'Other: laboratory biomarker analysis', 'Other: pharmacological study']}], 'interventions': [{'name': 'imatinib mesylate', 'type': 'DRUG', 'otherNames': ['CGP 57148', 'Gleevec', 'Glivec'], 'description': 'Given orally', 'armGroupLabels': ['Treatment (panobinostat, imatinib mesylate)']}, {'name': 'panobinostat', 'type': 'DRUG', 'otherNames': ['Faridak', 'HDAC inhibitor LBH589', 'histone deacetylase inhibitor LBH589', 'LBH589'], 'description': 'Given orally', 'armGroupLabels': ['Treatment (panobinostat, imatinib mesylate)']}, {'name': 'polymerase chain reaction', 'type': 'GENETIC', 'description': 'Testing', 'armGroupLabels': ['Treatment (panobinostat, imatinib mesylate)']}, {'name': 'protein expression analysis', 'type': 'GENETIC', 'description': 'Testing', 'armGroupLabels': ['Treatment (panobinostat, imatinib mesylate)']}, {'name': 'western blotting', 'type': 'GENETIC', 'description': 'Testing', 'armGroupLabels': ['Treatment (panobinostat, imatinib mesylate)']}, {'name': 'flow cytometry', 'type': 'OTHER', 'description': 'Testing', 'armGroupLabels': ['Treatment (panobinostat, imatinib mesylate)']}, {'name': 'laboratory biomarker analysis', 'type': 'OTHER', 'description': 'Testing', 'armGroupLabels': ['Treatment (panobinostat, imatinib mesylate)']}, {'name': 'pharmacological study', 'type': 'OTHER', 'description': 'Testing', 'armGroupLabels': ['Treatment (panobinostat, imatinib mesylate)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '91010-3000', 'city': 'Duarte', 'state': 'California', 'country': 'United States', 'facility': 'City of Hope Medical Center', 'geoPoint': {'lat': 34.13945, 'lon': -117.97729}}, {'zip': '91030', 'city': 'South Pasadena', 'state': 'California', 'country': 'United States', 'facility': 'South Pasadena Cancer Center', 'geoPoint': {'lat': 34.11612, 'lon': -118.15035}}, {'zip': '98109', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}], 'overallOfficials': [{'name': 'Ravi Bhatia, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'City of Hope Medical Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'City of Hope Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}