Preclinical and phase i results of decitabine in combination with midostaurin (PKC412) for newly diagnosed elderly or relapsed/refractory adult patients with acute myeloid leukemia

Pharmacotherapy

Volumn 33, Issue 12, 2013, Pages 1341-1352

  Williams, Casey B ^a   Kambhampati, Suman ^b   Fiskus, Warren ^c   Wick, Jo ^b   Dutreix, Catherine ^d   Ganguly, Siddartha ^b   Aljitawi, Omar ^b   Reyes, Ruben ^b   Fleming, Allan ^b   Abhyankar, Sunil ^b   Bhalla, Kapil N ^c   McGuirk, Joseph P ^b  

^a SANFORD RESEARCH   (United States)

^b UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^c HOUSTON METHODIST RESEARCH INSTITUTE   (United States)

^d NOVARTIS PHARMA AG   (Switzerland)

Author keywords

acute myeloid leukemia; DAC; elderly; FLT3 ITD; MS; PKC412

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; CD135 ANTIGEN; MIDOSTAURIN;

ACUTE GRANULOCYTIC LEUKEMIA; ADULT; ADVERSE OUTCOME; AGED; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CANCER COMBINATION CHEMOTHERAPY; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG SAFETY; FEBRILE NEUTROPENIA; FEMALE; FLOW CYTOMETRY; FLT3 GENE; GENE DUPLICATION; GENE EXPRESSION; GRANULOCYTOPENIA; HUMAN; IMMUNOBLOTTING; IN VITRO STUDY; INTERNAL TANDEM DUPLICATION; LUNG EDEMA; LUNG INSUFFICIENCY; MALE; MAXIMUM TOLERATED DOSE; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MUTATIONAL ANALYSIS; NAUSEA; NEUTROPENIA; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PRIMARY CELL LINE; THROMBOCYTOPENIA; TREATMENT RESPONSE;

ACUTE MYELOID LEUKEMIA; DAC; ELDERLY; FLT3-ITD; MS; PKC412;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; AZACITIDINE; CELL LINE, TUMOR; COHORT STUDIES; DRUG SYNERGISM; FEMALE; FLOW CYTOMETRY; FMS-LIKE TYROSINE KINASE 3; HUMANS; LEUKEMIA, MYELOID, ACUTE; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MUTATION; RECURRENCE; STAUROSPORINE;

EID: 84895490922     PISSN: 02770008     EISSN: 18759114     Source Type: Journal    
DOI: 10.1002/phar.1316     Document Type: Article

References (52)

1. Yates JW, Wallace HJ Jr, Ellison RR, Holland JF,. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep 1973; 57 (4): 485-8.
2. Roboz GJ,. Novel approaches to the treatment of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2011; 2011: 43-50.
3. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009; 361 (13): 1249-59.
4. Mandelli F, Vignetti M, Suciu S, et al. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. J Clin Oncol 2009; 27 (32): 5397-403.
5. Buchner T, Berdel WE, Haferlach C, et al. Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol 2009; 27 (1): 61-9.
6. Marcucci G, Haferlach T, Dohner H,. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol 2011; 29 (5): 475-86.
7. Pollyea DA, Kohrt HE, Medeiros BC,. Acute myeloid leukaemia in the elderly: a review. Br J Haematol 2011; 152 (5): 524-42.
8. Menzin J, Lang K, Earle CC, Kerney D, Mallick R,. The outcomes and costs of acute myeloid leukemia among the elderly. Arch Intern Med 2002; 162: 1597-603.
9. Burnett AK, Milligan D, Prentice AG, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 2007; 109 (6): 1114-24.
10. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010; 28 (4): 562-9.
11. Blum W, Garzon R, Klisovic RB, et al. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of DAC. Proc Natl Acad Sci USA 2010; 107 (16): 7473-8.
12. Cashen AF, Schiller GJ, O'Donnell MR, DiPersio JF,. Multicenter, phase II study of DAC for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol 2010; 28 (4): 556-61.
13. McDevitt MA,. Clinical applications of epigenetic markers and epigenetic profiling in myeloid malignancies. Semin Oncol 2012; 39 (1): 109-22.
14. Saied MH, Marzec J, Khalid S, et al. Genome wide analysis of acute myeloid leukemia reveal leukemia specific methylome and subtype specific hypomethylation of repeats. PLoS ONE 2012; 7 (3): e33213.
15. Scandura JM, Roboz GJ, Moh M, et al. Phase 1 study of epigenetic priming with DAC prior to standard induction chemotherapy for patients with AML. Blood 2011; 118 (6): 1472-80.
16. Fischer T, Stone RM, Deangelo DJ, et al. Phase IIB trial of oral MS (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multitargeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol 2010; 28 (28): 4339-45.
17. Stone RM, Fischer T, Paquette R, et al. A phase 1b study of MS (PKC412) in combination with daunorubicin and cytarabine induction and high-dose cytarabine consolidation in patients under age 61 with newly diagnosed de novo acute myeloid leukemia: overall survival of patients whose blasts have FLT3 mutations is similar to those with wild-type FLT3. Blood (ASH Annual Meeting Abstracts) 2009; 114:Abstract 634.
18. Godwin JE, Kopecky KJ, Head DR, et al. A double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group Study (9031). Blood 1998; 91: 3607-15.
19. Kantarjian H, O'Brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome. Cancer 2006; 106: 1090-8.
20. Kantarjian H, Ravandi F, O'Brien S, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood 2010; 116: 4422-9.
21. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol 2003; 21: 4642-9.
22. George P, Bali P, Annavarapu S, et al. Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3. Blood 2005; 105: 1768-76.
23. Balusu R, Fiskus W, Rao R, et al. Targeting levels or oligomerization of nucleophosmin 1 induces differentiation and loss of survival of human AML cells with mutant NPM1. Blood 2011; 118: 3096-106.
24. Sato T, Yang X, Knapper S, et al. FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo. Blood 2011; 117 (12): 3286-93.
25. Chou TC, Talalay P,. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984; 22: 27-55.
26. Murphy KM, Levis M, Hafez MJ, et al. Detection of FLT3 internal tandem duplication and D835 mutations by a multiplex polymerase chain reaction and capillary electrophoresis assay. J Mol Diagn 2003; 5: 96-102.
27. Paschka P, Marcucci G, Ruppert AS, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol 2006; 24: 3904-11.
28. Propper DJ, McDonald AC, Man A, et al. Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. J Clin Oncol 2001; 19: 1485-92.
29. Anderson JE, Kopecky KJ, Willman CL, et al. Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study. Blood 2002; 100: 3869-76.
30. Giles F, Rizzieri D, Karp J, et al. Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. J Clin Oncol 2007; 25: 25-31.
31. Kantarjian HM, Erba HP, Claxton D, et al. Phase II study of single agent clofarabine in previously untreated older adult patients with acute myelogenous leukemia (AML) and unfavorable prognostic factors. J Clin Oncol 2010; 28 (4): 549-55.
32. Rowe JM, Tallman MS,. How I treat acute myeloid leukemia. Blood 2010; 116 (17): 3147-56.
33. Trifilio SM, Rademaker AW, Newman D, et al. Mitoxantrone and etoposide with or without intermediate dose cytarabine for the treatment of primary induction failure or relapsed acute myeloid leukemia. Leuk Res 2012; 4: 394-6.
34. Rowe JM, Kim HT, Cassileth PA, et al. Adult patients with acute myeloid leukemia who achieve complete remission after 1 or 2 cycles of induction have a similar prognosis: a report on 1980 patients registered to 6 studies conducted by the Eastern Cooperative Oncology Group. Cancer 2010; 116 (21): 5012-21.
35. Lubbert M, Ruter B, Claus R,. Continued low-dose DAC (DAC) is an active first-line treatment in all cytogenetic subgroups of older AML patients: Results of the FR00331 multicenter phase II study. Blood (ASH Annual Meeting Abstracts) 2007; 110: 300.
36. Pemmaraju N, Kantarjian H, Ravandi F, Cortes J,. FLT3 inhibitors in the treatment of acute myeloid leukemia. Cancer 2011; 117: 3293-304.
37. Fathi AT, Chabner BA,. FLT3 inhibition in acute myeloid leukemia: a record of trials and tribulations. Oncologist 2011; 16: 1162-74.
38. Amadori S,. New agents for the treatment of acute myeloid leukemia: midostaurin. Haematol Meet Rep 2008; 2: 159-61.
39. Weisberg E, Boulton C, Kelly LM, et al. Cancer Cell 2002; 1: 433-43.
40. Nordigården A, Kraft M, Eliasson P, et al. BH3-only protein Bim more critical than Puma in tyrosine kinase inhibitor-induced apoptosis of human leukemic cells and transduced hematopoietic progenitors carrying oncogenic FLT3. Blood 2009; 113: 2302-11.
41. Bali P, George P, Cohen P, et al. Superior activity of the combination of histone deacetylase inhibitor LAQ824 and the FLT-3 kinase inhibitor PKC412 against human acute myelogenous leukemia cells with mutant FLT-3. Clin Cancer Res 2004; 10: 4991-7.
42. Lyons J, Bayar E, Fine G, et al. DAC: development of a DNA methyltransferase inhibitor for hematological malignancies. Curr Opin Investig Drugs 2003; 4: 1442-50.
43. George P, Bali P, Cohen P, et al. Cotreatment with 17-allylamino- demethoxygeldanamycin and FLT-3 kinase inhibitor PKC412 is highly effective against human acute myelogenous leukemia cells with mutant FLT-3. Cancer Res 2004; 64: 3645-52.
44. Debierre-Grockiego F,. Anti-apoptotic role of STAT5 in haematopoietic cells and in the pathogenesis of malignancies. Apoptosis 2004; 9: 717-28.
45. Woodgett JR,. Recent advances in the protein kinase B signaling pathway. Curr Opin Cell Biol 2005; 17: 150-7.
46. Yang JY, Chang CJ, Xia W, et al. Activation of FOXO3a is sufficient to reverse mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor chemoresistance in human cancer. Cancer Res 2010; 70: 4709-18.
47. Swords R, Freeman C, Giles F,. Targeting the FMS-like tyrosine kinase 3 in acute myeloid leukemia. Leukemia 2012; 26: 2176-85.
48. Stone RM, DeAngelo DJ, Klimek V, et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood 2005; 105: 54-60.
49. Levis M,. FLT3/ITD AML and the law of unintended consequences. Blood 2011; 117 (26): 6987-90.
50. Pratz KW, Sato T, Murphy KM, Stine A, Rajkhowa T, Levis M,. FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood 2010; 115 (7): 1425-32.
51. Saunthararajah Y, Triozzi P, Rini B, et al. p53-Independent, normal stem cell sparing epigenetic differentiation therapy for myeloid and other malignancies. Semin Oncol 2012; 39 (1): 97-108.
52. Makishima H, Sugimoto Y, Szpurka H, et al. CBL mutation-related patterns of phosphorylation and sensitivity to tyrosine kinase inhibitors. Leukemia 2012; 26: 1547-54.