drugset / Trial / NCT01822015
Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Phase 0
Completed
55 enrolled
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
NaSingle-groupOpen-labelTreatment
Summary
This pilot clinical trial studies sirolimus, idarubicin, and cytarabine in treating patients with newly diagnosed acute myeloid leukemia. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving sirolimus together with idarubicin and cytarabine may kill more cancer cells.
Timeline
- Start
- 2013-03-15
- Primary completion
- 2019-12-12
- Completion
- 2019-12-12
Publications
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- Background Xu Q, Thompson JE, Carroll M. mTOR regulates cell survival after etoposide treatment in primary AML cells. Blood. 2005 Dec 15;106(13):4261-8. doi: 10.1182/blood-2004-11-4468. Epub 2005 Sep 8.
- Background Castro AF, Rebhun JF, Clark GJ, Quilliam LA. Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner. J Biol Chem. 2003 Aug 29;278(35):32493-6. doi: 10.1074/jbc.C300226200. Epub 2003 Jul 3.
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- Background Hultsch T, Martin R, Hohman RJ. The effect of the immunophilin ligands rapamycin and FK506 on proliferation of mast cells and other hematopoietic cell lines. Mol Biol Cell. 1992 Sep;3(9):981-7. doi: 10.1091/mbc.3.9.981.
- Background Majewski M, Korecka M, Kossev P, Li S, Goldman J, Moore J, Silberstein LE, Nowell PC, Schuler W, Shaw LM, Wasik MA. The immunosuppressive macrolide RAD inhibits growth of human Epstein-Barr virus-transformed B lymphocytes in vitro and in vivo: A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4285-90. doi: 10.1073/pnas.080068597.
- Background Muthukkumar S, Ramesh TM, Bondada S. Rapamycin, a potent immunosuppressive drug, causes programmed cell death in B lymphoma cells. Transplantation. 1995 Aug 15;60(3):264-70. doi: 10.1097/00007890-199508000-00010.
- Background Yamamoto-Yamaguchi Y, Okabe-Kado J, Kasukabe T, Honma Y. Induction of differentiation of human myeloid leukemia cells by immunosuppressant macrolides (rapamycin and FK506) and calcium/calmodulin-dependent kinase inhibitors. Exp Hematol. 2001 May;29(5):582-8. doi: 10.1016/s0301-472x(01)00626-9.
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- Background Zeng Z, Sarbassov dos D, Samudio IJ, Yee KW, Munsell MF, Ellen Jackson C, Giles FJ, Sabatini DM, Andreeff M, Konopleva M. Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML. Blood. 2007 Apr 15;109(8):3509-12. doi: 10.1182/blood-2006-06-030833. Epub 2006 Dec 19.
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- Background Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. doi: 10.1056/NEJMoa066838.
- Background Ansell SM, Inwards DJ, Rowland KM Jr, Flynn PJ, Morton RF, Moore DF Jr, Kaufmann SH, Ghobrial I, Kurtin PJ, Maurer M, Allmer C, Witzig TE. Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group. Cancer. 2008 Aug 1;113(3):508-14. doi: 10.1002/cncr.23580.
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- Background Chiarini F, Grimaldi C, Ricci F, et al. Temsirolimus, An Allosteric mTORC1 Inhibitor, Is Synergistic with Clofarabine in AML and AML Leukemia Initiating Cells. ASH Annual Meeting Abstracts;118:2596-.
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- Background Duran I, Kortmansky J, Singh D, Hirte H, Kocha W, Goss G, Le L, Oza A, Nicklee T, Ho J, Birle D, Pond GR, Arboine D, Dancey J, Aviel-Ronen S, Tsao MS, Hedley D, Siu LL. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Br J Cancer. 2006 Nov 6;95(9):1148-54. doi: 10.1038/sj.bjc.6603419. Epub 2006 Oct 10.
- Background Tabernero J, Rojo F, Calvo E, Burris H, Judson I, Hazell K, Martinelli E, Ramon y Cajal S, Jones S, Vidal L, Shand N, Macarulla T, Ramos FJ, Dimitrijevic S, Zoellner U, Tang P, Stumm M, Lane HA, Lebwohl D, Baselga J. Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol. 2008 Apr 1;26(10):1603-10. doi: 10.1200/JCO.2007.14.5482. Epub 2008 Mar 10.
- Background Recher C, Beyne-Rauzy O, Demur C, Chicanne G, Dos Santos C, Mas VM, Benzaquen D, Laurent G, Huguet F, Payrastre B. Antileukemic activity of rapamycin in acute myeloid leukemia. Blood. 2005 Mar 15;105(6):2527-34. doi: 10.1182/blood-2004-06-2494. Epub 2004 Nov 18.
- Background Greenberg PL, Lee SJ, Advani R, Tallman MS, Sikic BI, Letendre L, Dugan K, Lum B, Chin DL, Dewald G, Paietta E, Bennett JM, Rowe JM. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol. 2004 Mar 15;22(6):1078-86. doi: 10.1200/JCO.2004.07.048.
- Background Park S, Chapuis N, Marcoux FS, et al. RAD001: A Clinico-Biological Phase I GOELAMS trial of Everolimus Association with High Dose Chemotherapy in Late Relapsing AML Patients Under 65 Years of Age. ASH Annual Meeting Abstracts;118:945-.
- Background Barnes JA, Jacobsen E, Feng Y, Freedman A, Hochberg EP, LaCasce AS, Armand P, Joyce R, Sohani AR, Rodig SJ, Neuberg D, Fisher DC, Abramson JS. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica. 2013 Apr;98(4):615-9. doi: 10.3324/haematol.2012.075184. Epub 2012 Nov 9.
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- Background Jacobberger JW, Sramkoski RM, Frisa PS, Ye PP, Gottlieb MA, Hedley DW, Shankey TV, Smith BL, Paniagua M, Goolsby CL. Immunoreactivity of Stat5 phosphorylated on tyrosine as a cell-based measure of Bcr/Abl kinase activity. Cytometry A. 2003 Aug;54(2):75-88. doi: 10.1002/cyto.a.10063.
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Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Sirolimus | Small molecule | — | Oral |
| Background | Cytarabine | Small molecule | — | Intravenous |
| Background | Idarubicin | Small molecule | — | Intravenous |
Indications
acute erythroid leukemia
acute megakaryoblastic leukemia in adult
acute myeloblastic leukemia with maturation
acute myeloblastic leukemia without maturation
acute myeloid leukemia with 11q23 abnormalities
acute myeloid leukemia with t(8;21)(q22;q22) translocation
acute myeloid leukemia, del(5q31-q32)
acute myeloid leukemia, inv(16)(p13.1;q22)
acute myeloid leukemia, t(16;16)(p13.1;q22)
acute myelomonocytic leukemia M4
adult acute monocytic leukemia