Ignite Creation Date:
2025-12-24 @ 6:31 PM
Ignite Modification Date:
2025-12-30 @ 5:24 AM
Study NCT ID:
NCT01120457
Status:
COMPLETED
Last Update Posted:
2015-03-06
First Post:
2010-05-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
First in Human Study to Determine the Safety, Tolerability and Preliminary Efficacy of an Anti-CXCR4 Antibody in Subjects With Acute Myelogenous Leukemia and Selected B-cell Cancers
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015470', 'term': 'Leukemia, Myeloid, Acute'}, {'id': 'D015451', 'term': 'Leukemia, Lymphocytic, Chronic, B-Cell'}, {'id': 'D008224', 'term': 'Lymphoma, Follicular'}], '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': 'D015448', 'term': 'Leukemia, B-Cell'}, {'id': 'D007945', 'term': 'Leukemia, Lymphoid'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System 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': 'D008228', 'term': 'Lymphoma, Non-Hodgkin'}, {'id': 'D008223', 'term': 'Lymphoma'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C581980', 'term': 'ulocuplumab'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 96}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-01', 'completionDateStruct': {'date': '2014-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-03-05', 'studyFirstSubmitDate': '2010-05-07', 'studyFirstSubmitQcDate': '2010-05-10', 'lastUpdatePostDateStruct': {'date': '2015-03-06', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2010-05-11', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and tolerability as monotherapy', 'timeFrame': 'Within the first 7 days for AML', 'description': 'Safety and tolerability measured by incidence of adverse events (AEs), AEs leading to discontinuation, Serious Adverse Events (SAEs), deaths, and laboratory abnormalities'}, {'measure': 'Safety and tolerability as monotherapy', 'timeFrame': 'Within 28 days for the selected B-cell malignancies', 'description': 'Safety and tolerability measured by incidence of adverse events (AEs), AEs leading to discontinuation, Serious Adverse Events (SAEs), deaths, and laboratory abnormalities'}], 'secondaryOutcomes': [{'measure': 'Safety, as measured by vital signs, clinical laboratory tests,ECOG performance status, physical exams, 12 lead ECGs incidence and severity of adverse events', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies', 'description': 'ECOG - Eastern Cooperative Oncology Group ECG - Electrocardiograms'}, {'measure': 'Efficacy- including best overall response (BOR) derived from changes in tumor burden and metabolic response based on FDG-PET (for DLBCL)', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies', 'description': 'FDG-PET - fluoro-2-deoxyglucose positron emission tomography DLBCL - Diffuse Large B-Cell Lymphoma'}, {'measure': 'Immunogenicity measurement for human anti human antibodies (HAHA) -characterizing the immunogenicity of BMS-936564', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies', 'description': 'Subjects will be called as immunogenicity positive/negative to antibodies against BMS-936564 (MDX-1338) using immunogenicity assay, and will be classified as negative, positive baseline, or negative baseline with at least one positive post-treatment. The number and percentage of subjects in each classification will be reported for each dose level.'}, {'measure': 'Maximum observed serum concentration (Cmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Trough observed serum concentration (Cmin) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Time of maximum observed concentration (Tmax) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Half life (T-HALF) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Total body clearance(CLT) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Volume of distribution at steady-state (Vss) of BMS-936564 (MDX-1338) will be derived from serum concentration versus actual time', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Biomarker- characterizing the pharmacodynamic (PD) profiles of BMS-936564 (MDX-1338). The main PD biomarkers are cell trafficking', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}, {'measure': 'Exploratory Biomarkers- are detection of apoptosis, cytokine analyses, CXCR4 expression, ZAP-70 and CD38 expression', 'timeFrame': 'For a maximum of thirteen 28-day cycles for the AML cohort and for a maximum of six 28-day cycles for the B-cell malignancies'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Acute Myelogenous Leukemia', 'Diffuse Large B-Cell Leukemia', 'Chronic Lymphocytic Leukemia', 'Follicular Lymphoma']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'http://www.bms.com/studyconnect/Pages/home.aspx', 'label': 'BMS clinical trial educational resource'}, {'url': 'http://www.bms.com/clinical_trials/Pages/Investigator_Inquiry_form.aspx', 'label': 'Investigator Inquiry form'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to assess the safety and tolerability of BMS-936564 (MDX-1338) in relapsed Acute myelogenous leukemia (AML) and other selected B-cell cancers and to determine the maximum tolerated dose (MTD) of the drug alone in relapsed/refractory AML'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.\n\nInclusion Criteria:\n\nA. Common to All Indications:\n\n* Life expectancy at least 12 weeks\n* ECOG Performance Status of 0-2\n\nB. For Acute myelogenous leukemia (AML) Subjects:\n\n* First Relapse and primary induction failure in AML (M3 excluded)\n* Secondary AML subjects from myelodysplastic syndrome (MDS) or prior chemotherapy are eligible. MDS-only subjects are not eligible\n\nC. For Follicular Lymphoma (FL), Diffuse Large B-Cell Lymphoma (DLBCL) Subjects:\n\n* Must be at least 4 weeks (for FL) or 2 weeks (for DLBCL) since prior cytotoxic, biologic, monoclonal antibody, or investigational therapy\n* Ability to undergo tumor biopsy pre-treatment and at end of monotherapy period (though not mandatory for all subjects)\n* Subjects must have a histologically confirmed diagnosis of relapsed or refractory disease\n\nD. For Chronic lymphocytic leukemia (CLL) Subjects:\n\n* Subjects must have a histologically confirmed diagnosis of relapsed or refractory disease\n* Must be at least 4 weeks since prior cytotoxic, biologic, monoclonal antibody, or investigational therapy, including corticosteroids\n\nExclusion Criteria:\n\nA. Common to All indications:\n\n* Prior anti-CXCR4 therapy including BMS-936564 (MDX-1338)\n* Less than 3 months from prior hematopoietic stem cell transplant\n* Presence of active graft versus host disease\n\nB. For AML Subjects:\n\n* Acute promyelocytic leukemia (M3)\n* Left ventricular ejection fraction \\< institutional limits of normal\n\nC. For FL, DLBCL Subjects:\n\n* (For DLBCL): Inadequate renal function defined as creatinine clearance (by Cockcroft-Gault formula) \\< 60 mL/min\n* Major surgery, not related to debulking procedures, within 21 days of first dose\n* Myocardial infarction within 6 months prior to screening or Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia\n* Myelodysplastic syndrome (MDS)\n\nD. For CLL Subjects:\n\n* No progression to more aggressive B-cell cancers, such as Richter's syndrome\n* Major surgery within 21 days of Cycle 1, Day 1. Patients undergoing debulking procedures and minor surgery are allowed after a recovery period, in the judgment of the Investigator\n* Myocardial infarction within 6 months prior to screening Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia"}, 'identificationModule': {'nctId': 'NCT01120457', 'briefTitle': 'First in Human Study to Determine the Safety, Tolerability and Preliminary Efficacy of an Anti-CXCR4 Antibody in Subjects With Acute Myelogenous Leukemia and Selected B-cell Cancers', 'organization': {'class': 'INDUSTRY', 'fullName': 'Bristol-Myers Squibb'}, 'officialTitle': 'A Phase 1, Open-label, Multicenter Study of BMS-936564 (MDX-1338) in Subjects With Relapsed Acute Myelogenous Leukemia and Selected B-cell Malignancies', 'orgStudyIdInfo': {'id': 'CA212-001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Arm 1: Dose Escalation and Expansion cohort (AML Patients)', 'description': 'Dose Escalation: BMS-936564 0.3-10 mg/kg solution, Intravenous, Single 60 minute infusion as monotherapy 7 days/cycle 1 and with chemotherapy for subsequent cycles (28 days/cycle)\n\nDose Expansion: BMS-936564 maximum tolerated dose (MTD) based on dose escalation, solution, Intravenous, Single 60 minute infusion as monotherapy 7 days/cycle 1 and with chemotherapy for subsequent cycles (28 days/cycle)', 'interventionNames': ['Drug: BMS-936564 (Anti-CXCR4)']}, {'type': 'EXPERIMENTAL', 'label': 'Arm 2: Dose Expansion cohort (DLBCL Patient)', 'description': 'BMS-936564 MTD based on Arm 1, weekly 60 minute infusion in cycle 1 (up to 56 days) and with chemotherapy for subsequent cycles (28 days/cycle)', 'interventionNames': ['Drug: BMS-936564 (Anti-CXCR4)']}, {'type': 'EXPERIMENTAL', 'label': 'Arm 3: Dose Expansion cohort (CLL Patient)', 'description': 'BMS-936564 MTD based on Arm 1, weekly 60 minute infusion in cycle 1 (up to 56 days) and with chemotherapy for subsequent cycles (28 days/cycle)', 'interventionNames': ['Drug: BMS-936564 (Anti-CXCR4)']}, {'type': 'EXPERIMENTAL', 'label': 'Arm 4: Dose Expansion cohort (FL Patient)', 'description': 'BMS-936564 MTD based on Arm 1, weekly 60 minute infusion in cycle 1 (up to 56 days) and with chemotherapy for subsequent cycles (28 days/cycle)', 'interventionNames': ['Drug: BMS-936564 (Anti-CXCR4)']}], 'interventions': [{'name': 'BMS-936564 (Anti-CXCR4)', 'type': 'DRUG', 'otherNames': ['MDX-1338'], 'armGroupLabels': ['Arm 1: Dose Escalation and Expansion cohort (AML Patients)', 'Arm 2: Dose Expansion cohort (DLBCL Patient)', 'Arm 3: Dose Expansion cohort (CLL Patient)', 'Arm 4: Dose Expansion cohort (FL Patient)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35294', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'Uab Comprehensive Cancer Center', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '92093', 'city': 'La Jolla', 'state': 'California', 'country': 'United States', 'facility': 'Uc San Diego Moores Cancer Center', 'geoPoint': {'lat': 32.84727, 'lon': -117.2742}}, {'zip': '90033', 'city': 'Los Angeles', 'state': 'California', 'country': 'United States', 'facility': 'Usc - Norris Comprehensive Cancer Center And Hospital', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '90095', 'city': 'Los Angeles', 'state': 'California', 'country': 'United States', 'facility': 'Ucla-Division Of Hematology/Oncology', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '32224', 'city': 'Jacksonville', 'state': 'Florida', 'country': 'United States', 'facility': 'Mayo Clinic', 'geoPoint': {'lat': 30.33218, 'lon': -81.65565}}, {'zip': '60611', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Northwestern University Feinberg School Of Medicine', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '66205', 'city': 'Westwood', 'state': 'Kansas', 'country': 'United States', 'facility': 'University Of Kansas Cancer Center And Medical Pavillion', 'geoPoint': {'lat': 39.04056, 'lon': -94.6169}}, {'zip': '21287', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'B. Douglas Smith, M.D.', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Dana-Farber Cancer Inst', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'The University Of Texas Md Anderson Cancer Center', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '98109', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'University Of Washington School Of Medicine', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}], 'overallOfficials': [{'name': 'Bristol-Myers Squibb', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Bristol-Myers Squibb'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Bristol-Myers Squibb', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}