Study of Bexarotene in Patients With Acute Myeloid Leukemia

Bexarotene may be useful in the treatment of Acute Myeloid Leukemia (AML). This is the first study on the use of bexarotene to treat patients with AML. The main purpose of this study is to establish the proper dose of bexarotene when used to treat AML. The side effect profile of bexarotene in patients with AML will also be explored.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Age \>18 years.
* Must have a histologically confirmed diagnosis of non-M3 AML as proven by bone marrow biopsy. Patients with CML in myeloid blast crisis are eligible.
* Willing and able to give informed consent.
* Must have received prior induction therapy with conventional chemotherapy and/or Mylotarg or otherwise not be eligible for conventional chemotherapy
* ECOG performance status of 0-2
* Must have recovered from the toxicities of prior chemotherapy.
* Women of childbearing potential must use effective contraception after enrollment in this study and have a negative pregnancy test within 1 week of study enrollment. They must continue to use effective contraception for 3 months after stopping bexarotene.
* Men must agree to use effective methods of contraception while taking bexarotene and for 3 months after stopping therapy.

Exclusion Criteria:

* History of pancreatitis.
* Active alcohol abuse
* Taken bexarotene in the past.
* WBC \>10,000/uL at the time of enrollment. Patients may be taking hydrea for WBC control at the time of enrollment.
* Cytotoxic chemotherapy or Mylotarg within the past 7 days other than hydrea.
* Significant organ dysfunction: total bilirubin\>3x ULN, AST or ALT\>3x ULN, creatinine\>4mg/dL, on blood pressure supporting medications or mechanical ventilation.
* Serious medical or psychiatric conditions that may compromise the safety of the patient while participating in this study.
* Women of childbearing potential who are pregnant or actively breast feeding.
* Active participant in any other investigational treatment study for their AML.
* Unable/unwilling to perform required follow-up.
* Life expectancy of less than 1 month.
* Use of blood growth factors (G-CSF, GM-CSF, Aranesp, erythropoietin, or Neumega) within 1 week prior to treatment initiation.
* Uncontrolled hyperlipidemia (triglycerides\>1000 while on treatment with triglyceride lowering medications).
* History of myeloablative allogeneic stem cell transplant.
* Known history of HIV.
* Uncontrolled active infection
* Known active CNS involvement with AML

• BACKGROUNDBoehm MF, Zhang L, Badea BA, White SK, Mais DE, Berger E, Suto CM, Goldman ME, Heyman RA. Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. J Med Chem. 1994 Sep 2;37(18):2930-41. doi: 10.1021/jm00044a014. PMID 8071941
• BACKGROUNDBoehm MF, Zhang L, Zhi L, McClurg MR, Berger E, Wagoner M, Mais DE, Suto CM, Davies JA, Heyman RA, et al. Design and synthesis of potent retinoid X receptor selective ligands that induce apoptosis in leukemia cells. J Med Chem. 1995 Aug 4;38(16):3146-55. doi: 10.1021/jm00016a018. PMID 7636877
• BACKGROUNDKizaki M, Dawson MI, Heyman R, Elster E, Morosetti R, Pakkala S, Chen DL, Ueno H, Chao W, Morikawa M, Ikeda Y, Heber D, Pfahl M, Koeffler HP. Effects of novel retinoid X receptor-selective ligands on myeloid leukemia differentiation and proliferation in vitro. Blood. 1996 Mar 1;87(5):1977-84. PMID 8634447
• BACKGROUNDAsou H, Koike M, Elstner E, Cambell M, Le J, Uskokovic MR, Kamada N, Koeffler HP. 19-nor vitamin-D analogs: a new class of potent inhibitors of proliferation and inducers of differentiation of human myeloid leukemia cell lines. Blood. 1998 Oct 1;92(7):2441-9. PMID 9746784
• BACKGROUNDEsteva FJ, Glaspy J, Baidas S, Laufman L, Hutchins L, Dickler M, Tripathy D, Cohen R, DeMichele A, Yocum RC, Osborne CK, Hayes DF, Hortobagyi GN, Winer E, Demetri GD. Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer. J Clin Oncol. 2003 Mar 15;21(6):999-1006. doi: 10.1200/JCO.2003.05.068. PMID 12637463
• BACKGROUNDRizvi N, Hawkins MJ, Eisenberg PD, Yocum RC, Reich SD; Ligand L1069-20 Working Group. Placebo-controlled trial of bexarotene, a retinoid x receptor agonist, as maintenance therapy for patients treated with chemotherapy for advanced non-small-cell lung cancer. Clin Lung Cancer. 2001 Feb;2(3):210-5. doi: 10.3816/clc.2001.n.005. PMID 14700480