This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The hypothesis of the study is that the administration of flavopiridol prior to or concurrently with vorinostat will block vorinostat-mediated induction of p21CIP1, diminish expression of other anti-apoptotic proteins, and result in extensive induction of apoptosis of leukemic cells with enhanced therapeutic effects.
The specific aims of the study are: (1) Identify recommended phase II doses for the combination of flavopiridol and vorinostat in the treatment of acute leukemia; (2) Determine the safety, toxicities, tolerability, and maximum tolerated dose of the combination; (3) Observe clinical anti-leukemic effects of the combination; (4) Observe pharmacodynamic effects of the combination; (5) Observe the pharmacokinetics of each agent when administered in combination; (5) Observe leukemia gene expression patterns and correlate with response to treatment.
|Holkova, Beata; Yazbeck, Victor; Kmieciak, Maciej et al. (2017) A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma. Leuk Lymphoma 58:1349-1357|
|Corey, Kathleen E; Vuppalanchi, Raj; Vos, Miriam et al. (2015) Improvement in liver histology is associated with reduction in dyslipidemia in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 60:360-7|
|Eaton, J E; Juran, B D; Atkinson, E J et al. (2015) A comprehensive assessment of environmental exposures among 1000 North American patients with primary sclerosing cholangitis, with and without inflammatory bowel disease. Aliment Pharmacol Ther 41:980-90|
|Worthington Jr, Everett L; Berry, Jack W; Hook, Joshua N et al. (2015) Forgiveness-reconciliation and communication-conflict-resolution interventions versus retested controls in early married couples. J Couns Psychol 62:14-27|
|Holkova, Beata; Kmieciak, Maciej; Perkins, E Brent et al. (2014) Phase I trial of bortezomib (PS-341; NSC 681239) and ""nonhybrid"" (bolus) infusion schedule of alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory indolent B-cell neoplasms. Clin Cancer Res 20:5652-62|
|Lo, D J; Farris, A B; Song, M et al. (2013) Inhibition of ?v?6 promotes acute renal allograft rejection in nonhuman primates. Am J Transplant 13:3085-93|
|Jones, Robert; Vuky, Jacqueline; Elliott, Tony et al. (2013) Phase II study to assess the efficacy, safety and tolerability of the mitotic spindle kinesin inhibitor AZD4877 in patients with recurrent advanced urothelial cancer. Invest New Drugs 31:1001-7|
|Al Hawaj, M A; Martin, E J; Venitz, J et al. (2013) Monitoring rFVIII prophylaxis dosing using global haemostasis assays. Haemophilia 19:409-14|
|Noureddin, Mazen; Yates, Katherine P; Vaughn, Ivana A et al. (2013) Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients. Hepatology 58:1644-54|
|Lo, D J; Anderson, D J; Weaver, T A et al. (2013) Belatacept and sirolimus prolong nonhuman primate renal allograft survival without a requirement for memory T cell depletion. Am J Transplant 13:320-8|
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