ArticleBlood2007
Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
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Who cites it
151 citing papers in PubMed, 387 citations in OpenAlex.
- A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease.American journal of hematology · 2019Trial
- Exposure-Response Analysis of Alvocidib (Flavopiridol) Treatment by Bolus or Hybrid Administration in Newly Diagnosed or Relapsed/Refractory Acute Leukemia Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy.Annals of hematology · 2016Trial
- Trial
- Final results of EFC6663: a multicenter, international, phase 2 study of alvocidib for patients with fludarabine-refractory chronic lymphocytic leukemia.Leukemia research · 2015Trial
- Mitochondrial priming of chronic lymphocytic leukemia patients associates Bcl-xL dependence with alvocidib response.Leukemia · 2014Trial
- Impact of targeted therapy on outcome of chronic lymphocytic leukemia patients with relapsed del(17p13.1) karyotype at a single center.Leukemia · 2014Trial
- A pharmacokinetic/pharmacodynamic model of tumor lysis syndrome in chronic lymphocytic leukemia patients treated with flavopiridol.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Trial
- Trial
- Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia.Leukemia & lymphoma · 2011Trial
- Consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia: final analysis of CALGB 10101.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010Trial
- Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia.Leukemia research · 2010Trial
- Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Trial
- Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with previously treated chronic lymphocytic leukaemia.British journal of haematology · 2009Trial
- Development and validation of a highly sensitive liquid chromatography/mass spectrometry method for simultaneous quantification of lenalidomide and flavopiridol in human plasma.Therapeutic drug monitoring · 2008Trial
- Phenotypic screening converges on CDK9 inhibition as a therapeutic strategy in translocation renal cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- The oral CDK9 inhibitor voruciclib combined with venetoclax for patients with relapsed/refractory acute myeloid leukemia.Blood neoplasia · 2025Article
- Phase I first-in-human dose escalation study of the oral casein kinase 1α and cyclin dependent kinase 7/9 inhibitor BTX A51 in advanced MDS and AML.Journal of hematology & oncology · 2025Article
- Updates on the Treatment of Richter's Syndrome, Including Novel Combination Approaches.Cancers · 2025Review
- A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies.Blood advances · 2025Article
91 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Despite promising preclinical studies with the cyclin-dependent kinase inhibitor flavopiridol in chronic lymphocytic leukemia (CLL) and other diseases, previous clinical trials with this agent have been disappointing. The discovery of differential protein binding of flavopiridol in human and bovine serum contributed to an effective pharmacokinetic-derived schedule of administration of this agent. On the basis of pharmacokinetic modeling using our in vitro results and data from a previous trial, we initiated a phase 1 study using a 30-minute loading dose followed by 4 hours of infusion administered weekly for 4 of 6 weeks in patients with refractory CLL. A group of 42 patients were enrolled on 3 cohorts (cohort 1, 30 mg/m2 loading dose followed by 30 mg/m2 4-hour infusion; cohort 2, 40 mg/m2 loading dose followed by 40 mg/m2 4-hour infusion; and cohort 3, cohort 1 dose for treatments 1 to 4, then a 30 mg/m2 loading dose followed by a 50 mg/m2 4-hour infusion). The dose-limiting toxicity using this novel schedule was hyperacute tumor lysis syndrome. Aggressive prophylaxis and exclusion of patients with leukocyte counts greater than 200x10(9)/L have made this drug safe to administer at the cohort 3 dose. Of the 42 patients treated, 19 (45%) achieved a partial response with a median response duration that exceeds 12 months. Responses were noted in patients with genetically high-risk disease, including 5 (42%) of 12 patients with del(17p13.1) and 13 (72%) of 18 patients with del(11q22.3). Flavopiridol administered using this novel schedule has significant clinical activity in refractory CLL. Patients with bulky disease and high-risk genetic features have achieved durable responses, thereby justifying further study of flavopiridol in CLL and other diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.