Ignite Creation Date:
2025-12-24 @ 11:31 PM
Ignite Modification Date:
2025-12-31 @ 10:09 PM
Study NCT ID:
NCT01076556
Status:
TERMINATED
Last Update Posted:
2015-11-11
First Post:
2010-02-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015451', 'term': 'Leukemia, Lymphocytic, Chronic, B-Cell'}, {'id': 'D015463', 'term': 'Leukemia, Prolymphocytic'}], 'ancestors': [{'id': 'D015448', 'term': 'Leukemia, B-Cell'}, {'id': 'D007945', 'term': 'Leukemia, Lymphoid'}, {'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': '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'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C094397', 'term': 'cytokine inducible SH2-containing protein'}, {'id': 'C077990', 'term': 'alvocidib'}, {'id': 'D003520', 'term': 'Cyclophosphamide'}, {'id': 'D000069283', 'term': 'Rituximab'}], 'ancestors': [{'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D058846', 'term': 'Antibodies, Monoclonal, Murine-Derived'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 9}}, 'statusModule': {'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2010-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-11', 'lastUpdateSubmitDate': '2015-11-10', 'studyFirstSubmitDate': '2010-02-25', 'studyFirstSubmitQcDate': '2010-02-25', 'lastUpdatePostDateStruct': {'date': '2015-11-11', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2010-02-26', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2010-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum-tolerated dose of combination therapy with Cyclophosphamide, Alvocidib, and Rituximab', 'timeFrame': '21 days', 'description': 'Determined using the CTEP Active Version of the CTCAE.'}, {'measure': 'Treatment related adverse events assessed using the CTEP Active Version of the CTCAE', 'timeFrame': 'Up to 5 years'}]}, 'conditionsModule': {'conditions': ['Chronic Lymphocytic Leukemia', 'Prolymphocytic Leukemia', 'Recurrent Small Lymphocytic Lymphoma', 'Refractory Chronic Lymphocytic Leukemia', 'Stage I Chronic Lymphocytic Leukemia', 'Stage I Small Lymphocytic Lymphoma', 'Stage II Chronic Lymphocytic Leukemia', 'Stage II Small Lymphocytic Lymphoma', 'Stage III Chronic Lymphocytic Leukemia', 'Stage III Small Lymphocytic Lymphoma', 'Stage IV Chronic Lymphocytic Leukemia', 'Stage IV Small Lymphocytic Lymphoma']}, 'descriptionModule': {'briefSummary': 'This phase I trial is studying the side effects and the best dose of alvocidib when given together with cyclophosphamide and rituximab in treating patients with high risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can also block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Other find cancer cells and help kill them or carry cancer-killing substances to them. Giving cyclophosphamide, alvocidib, and rituximab together may kill more cancer cells.', 'detailedDescription': 'PRIMARY OBJECTIVES:\n\nI. To determine the dose-limiting toxicity and maximum-tolerated dose of treatment with cyclophosphamide, alvocidib, and rituximab in patients with high-risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.\n\nII. To determine the feasibility of administering this regimen as an outpatient regimen in these patients.\n\nSECONDARY OBJECTIVES:\n\nI. To determine the complete response rate, partial response rate, and minimal-residual disease-negative response rate in patients treated with this regimen.\n\nII. To determine the pharmacokinetics of alvocidib and dexamethasone as part of this regimen.\n\nIII. To determine the immunologic effects of this regimen as measured by serial T-cell and NK-cell number, T-cell function, and immunoglobulin levels.\n\nOUTLINE: This is a dose-escalation study of alvocidib.\n\nPatients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies.\n\nAfter completion of study treatment, patients are followed up for up to 5 years.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Histologically confirmed chronic lymphocytic leukemia (CLL) or B-cell prolymphocytic leukemia\\* (PLL) arising from CLL\n\n * Patients must have documented B-cell lymphocytosis \\> 5 x 10\\^9/L at some point since initial diagnosis of CLL\n * Patients must have B-cells that co-express CD5 with CD19 or CD20\n * Patients who do not have dim sIg or CD23 expression on their leukemia cells should be examined for cyclin D1 over-expression or t(11;14) to rule out mantle cell lymphoma\n* To be considered high risk, patients must meet the following criteria:\n\n * At least 1 of the following:\n\n * 17p deletion\n * 11q deletion\n * Un-mutated IgV\\_H (≥ 98% homology)\n * Age \\> 70 years\n * B\\_2M \\> 4\n * AND at least 1 of the following:\n\n * Progressive or marked splenomegaly and/or lymphadenopathy\n * Anemia (hemoglobin \\< 11 g/dL) or thrombocytopenia (platelets \\< 100,000/mm\\^3)\n * Weight loss exceeding 10% of body weight over preceding 6 months\n * NCI grade 2 or 3 fatigue\n * Fevers \\> 100.5° F or night sweats for \\> 2 weeks without evidence of infection\n * Progressive lymphocytosis, with an increase exceeding 50% over a 2-month period or a doubling time of \\< 6 months\n* No other concurrent hormones, chemotherapy, or radiotherapy except for steroids for new adrenal failure or hormones for nondisease-related conditions (e.g., insulin for diabetes)\n\n * No requirement for chronic corticosteroids\n* ECOG performance status 0-2\n* Creatinine ≤ 2.0 mg/dL\n* Bilirubin ≤ 1.5 times normal unless due to Gilbert disease, hemolysis, or disease infiltration of the liver\n* AST ≤ 2 times normal unless due to hemolysis or disease infiltration of the liver\n* Negative pregnancy test\n* Not pregnant or nursing\n* Fertile patients must use effective contraception\n* No secondary or other malignancy that will limit survival to \\< 2 years\n* No uncontrolled concurrent illness including, but not limited to, any of the following:\n\n * Ongoing or active infection\n * Symptomatic congestive heart failure\n * Unstable angina pectoris\n * Cardiac arrhythmia\n * Psychiatric illness or social situations that would limit compliance with study requirements\n* No uncompensated HIV without adequate CD4 (\\> 200/mm\\^3) and requiring HIV medication\n* No active hepatitis B infection\n* No known G6PD deficiency\n* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to alvocidib, cyclophosphamide, rituximab, or other agents used in this study\n* No prior alvocidib\n* No prior purine analog therapy\n* No more than 1 prior treatment with a biologic or alkylating agent\n* No other concurrent investigational agents'}, 'identificationModule': {'nctId': 'NCT01076556', 'briefTitle': 'Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma', 'organization': {'class': 'NIH', 'fullName': 'National Cancer Institute (NCI)'}, 'officialTitle': 'A Phase I Feasibility Trial of Cyclophosphamide, Alvocidib (Flavopiridol) and Rituximab (CAR) in Patients With High Risk B-cell CLL/SLL', 'orgStudyIdInfo': {'id': 'NCI-2011-01373'}, 'secondaryIdInfos': [{'id': 'NCI-2011-01373', 'type': 'REGISTRY', 'domain': 'CTRP (Clinical Trial Reporting Program)'}, {'id': 'OSU 09089'}, {'id': 'CDR0000666448'}, {'id': 'OSU-09089'}, {'id': 'OSU 09089', 'type': 'OTHER', 'domain': 'Ohio State University Comprehensive Cancer Center'}, {'id': '8267', 'type': 'OTHER', 'domain': 'CTEP'}, {'id': 'P30CA016058', 'link': 'https://reporter.nih.gov/quickSearch/P30CA016058', 'type': 'NIH'}, {'id': 'U01CA076576', 'link': 'https://reporter.nih.gov/quickSearch/U01CA076576', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment (rituximab, cyclophosphamide, alvocidib)', 'description': 'Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1).', 'interventionNames': ['Drug: Alvocidib Hydrochloride', 'Drug: Cyclophosphamide', 'Other: Diagnostic Laboratory Biomarker Analysis', 'Other: Pharmacological Study', 'Biological: Rituximab']}], 'interventions': [{'name': 'Alvocidib Hydrochloride', 'type': 'DRUG', 'otherNames': ['4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5, 7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-, hydrochloride, (-)-cis-', 'Flavopiridol Hydrochloride', 'HL-275', 'HMR 1275', 'L-86-8275', 'L-868275', 'MDL 107,826A', 'MDL-107826A'], 'description': 'Given IV', 'armGroupLabels': ['Treatment (rituximab, cyclophosphamide, alvocidib)']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'otherNames': ['(-)-Cyclophosphamide', '2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate', 'Carloxan', 'Ciclofosfamida', 'Ciclofosfamide', 'Cicloxal', 'Clafen', 'Claphene', 'CP monohydrate', 'CTX', 'CYCLO-cell', 'Cycloblastin', 'Cycloblastine', 'Cyclophospham', 'Cyclophosphamid monohydrate', 'Cyclophosphamidum', 'Cyclophosphan', 'Cyclophosphane', 'Cyclophosphanum', 'Cyclostin', 'Cyclostine', 'Cytophosphan', 'Cytophosphane', 'Cytoxan', 'Fosfaseron', 'Genoxal', 'Genuxal', 'Ledoxina', 'Mitoxan', 'Neosar', 'Revimmune', 'Syklofosfamid', 'WR- 138719'], 'description': 'Given IV', 'armGroupLabels': ['Treatment (rituximab, cyclophosphamide, alvocidib)']}, {'name': 'Diagnostic Laboratory Biomarker Analysis', 'type': 'OTHER', 'description': 'Correlative studies', 'armGroupLabels': ['Treatment (rituximab, cyclophosphamide, alvocidib)']}, {'name': 'Pharmacological Study', 'type': 'OTHER', 'description': 'Correlative studies', 'armGroupLabels': ['Treatment (rituximab, cyclophosphamide, alvocidib)']}, {'name': 'Rituximab', 'type': 'BIOLOGICAL', 'otherNames': ['BI 695500', 'C2B8 Monoclonal Antibody', 'Chimeric Anti-CD20 Antibody', 'IDEC-102', 'IDEC-C2B8', 'IDEC-C2B8 Monoclonal Antibody', 'MabThera', 'Monoclonal Antibody IDEC-C2B8', 'PF-05280586', 'Rituxan', 'Rituximab Biosimilar BI 695500', 'Rituximab Biosimilar PF-05280586', 'Rituximab Biosimilar RTXM83', 'RTXM83'], 'description': 'Given IV', 'armGroupLabels': ['Treatment (rituximab, cyclophosphamide, alvocidib)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '43210', 'city': 'Columbus', 'state': 'Ohio', 'country': 'United States', 'facility': 'Ohio State University Comprehensive Cancer Center', 'geoPoint': {'lat': 39.96118, 'lon': -82.99879}}], 'overallOfficials': [{'name': 'Joseph Flynn', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Ohio State University Comprehensive Cancer Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}