Best Practice & Research Clinical Haematology
Volume 19, Issue 2 , Pages 311-320 , June 2006

New agents for the treatment of acute myeloid leukemia

  • Martin S. Tallman, MD (Professor of Medicine)

      Affiliations

    • Corresponding Author InformationTel.: +1 312 695 4540; Fax: +1 312 695 6189.

References 

  1. Tallman MS. Relevance of pathologic classifications and diagnosis of acute myeloid leukemia to clinical trials and clinical practice. Cancer Treatment and Research. 2004;121:45–67
  2. Tallman MS, Gilliland DG, Rowe JM. Drug therapy for acute myeloid leukemia. Blood. 2005;106:1154–1163
  3. Gilliland DG. Targeted therapies in myeloid leukemias. Annals of Hematology. 2004;83(supplement 1):S75–S76
  4. DeAngelo DJ, Stone RM, Durrant ST, et al. Gemtuzumab ozogamicin (Mylotarg) in combination with induction chemotherapy for the treatment of patients with de novo acute myeloid leukemia: two age-specific phase 2 trials. Blood. 2003;102:100a;[abstr 341]
  5. Kell WJ, Burnett AK, Chopra R, et al. A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia. Blood. 2003;102:4277–4283
  6. Petersdorf S, Southwest Oncology Group. Phase III randomized study of induction therapy comprising cytarabine and daunorubicin with versus without gemtuzumab ozogamicin followed by consolidation therapy comprising high-dose cytarabine and post-consolidation therapy comprising gemtuzumab ozogamicin versus no additional therapy in patients with previously untreated de novo acute myeloid leukemia. http://www.cancer.gov/clinicaltrials/SWOG-S0106#ContactInfo_CDR0000360812; 10-25-2005.
  7. Fernandez H, Easton D, Eastern Cooperative Oncology Group. Combination chemotherapy with or without monoclonal antibody therapy followed by stem cell transplantation in treating patients with acute myeloid leukemia. http://www.cancer.gov/ClinicalTrials/view_clinicaltrials.aspx?version=patient&cdrid=258113#ContactInfo_CDR0000258113; 10-25-2005.
  8. Burnett AK, Goldstone AH, Wheatley K. Comparing different chemotherapy regimes and the use of Mylotarg monoclonal antibody in treatment of acute myeloid leukaemia. http://www.cancerhelp.org.uk/trials/trials/trial.asp?freetextsearch=&searchtype=select&trial=4060&trialno=2146&spage=1&objective=0&cancer=0&stage=0&phase=0&treatment=0&location=0; 10-25-2005.
  9. Amadori S. Gemtuzumab ozogamycin (GO) combined with standard intensive chemotherapy versus standard intensive chemotherapy alone for induction/consolidation in patients 61–75 years old with previously untreated AML: a randomized phase III trial of the EORTC—LG. http://www.eortc.be/protoc/details.asp?protocol=06012; 10-25-2005.
  10. List AF, Kopecky KJ, Willman CL, et al. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group Study. Blood. 2001;98:3212–3220
  11. Liu Yin JA, Wheatley K, Rees JK, Burnett AK. Comparison of ‘sequential’ versus ‘standard’ chemotherapy as re-induction treatment, with or without cyclosporine, in refractory/relapsed acute myeloid leukaemia (AML): results of the UK medical research council AML-R trial. British Journal of Haematology. 2001;113:713–726
  12. Daenen S, van der HB, Verhoef GE, et al. Addition of cyclosporin A to the combination of mitoxantrone and etoposide to overcome resistance to chemotherapy in refractory or relapsing acute myeloid leukaemia; a randomised phase II trial from HOVON, the Dutch-Belgian Haemato-oncology Working Group for adults. Leukemia Research. 2004;28:1057–1067
  13. Baer M, George SL, Dodge RK, et al. Phase III study of the multidrug resistance (MDR) modulator PSC-833 in previously untreated acute myeloid leukemia (AML) patients (greater and equal to) 60 years old: correlation of outcome with functional MDR (CALGB studies 9720 and 9760). Blood. 2001;98:461a;[abstr]
  14. Greenberg PL, Lee SJ, Advani R, et al. 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). Journal of Clinical Oncology. 2004;22:1078–1086
  15. Sato W, Fukazawa N, Suzuki T, et al. Circumvention of multidrug resistance by a newly synthesized quinoline derivative, MS-073. Cancer Research. 1991;51:2420–2424
  16. Dantzig AH, Shepard RL, Cao J, et al. Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Research. 1996;56:4171–4179
  17. Green LJ, Marder P, Slapak CA. Modulation by LY335979 of P-glycoprotein function in multidrug-resistant cell lines and human natural killer cells. Biochemical Pharmacology. 2001;61:1393–1399
  18. Cripe LD, Tallman M, Karanes C, et al. A phase II trial of zosuquidar (LY335979), a modulator of P-glycoprotein (Pgp) activity, plus daunorubicin and high-dose cytarabine in patients with newly diagnosed secondary acute myeloid leukemia (AML), refractory anemia with excess blasts in transformation (RAEB-t) or relapsed/refractory AML. Blood. 2001;98:595a;[abstr 2492]
  19. Cripe L, Cooper B, Eastern Cooperative Oncology Group. Phase III randomized study of daunorubicin and cytarabine with or without zosuquidar trihydrochloride in elderly patients with newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts (RAEB) in transformation, or high-risk RAEB. http://www.cancer.gov/ClinicalTrials/view_clinicaltrials.aspx?version=patient&cdrid=257122; 9-27-2005.
  20. Stirewalt DL, Kopecky KJ, Meshinchi S, et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood. 2001;97:3589–3595
  21. Kiyoi H, Naoe T, Nakano Y, et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood. 1999;93:3074–3080
  22. Karp JE, Lancet JE, Kaufmann SH, et al. Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. Blood. 2001;97:3361–3369
  23. Harousseau J-L, Reiffers J, Lowenberg B, et al. Zarnestra(TM) (R115777) in patients with relapsed and refractory acute myelogenous leukemia (AML): results of a multicenter phase 2 study. Blood. 2003;102:177a;[abstr 614]
  24. Lancet JE, Gojo I, Gotlib J, et al. Tipifarnib (ZARNESTRA™) in previously untreated poor-riskAML and MDS: interim results of a phase 2 trial. Blood. 2004;102:176a;[abstr 874]
  25. Erba H, Larson RA, Tallman M. Phase II randomized study of tipifarnib in older patients with previously untreated acute myeloid leukemia. http://www.cancer.gov/clinicaltrials/SWOG-S0432; 10-8-2005.
  26. Luger SM, Rowe JM, Litzow MR. Tipifarnib in treating patients with acute myeloid leukemia in remission. http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=387995&version=Patient; 10-14-2005.
  27. Jiang J, Paez JG, Lee JC, et al. Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML. Blood. 2004;104:1855–1858
  28. Gilliland DG, Kelly L, Curley DP, et al. Therapeutic efficacy of all-trans-retinoic acid (ATRA) combined with the FLT3 inhibitor MLN518 in a murine model of acute promyelocytic leukemia. Blood. 2003;102:66a;[abstr 222]
  29. Knapper S, Burnett AK, Gilkes AF, et al. The in vitro sensitivity of primary AML blasts to two flt3 inhibitors and cytarabine appears independent of flt3 mutation status. Blood. 2003;102:24a;[abstr 74]
  30. Levis MJ, Pham R, Small D. CEP-701, a selective FLT3 tyrosine kinase inhibitor that is cytotoxic to FLT3/ITD-expressing leukemia cells, is synergistic with chemotherapeutic agents in vitro when used in time-sequential fashion. Blood. 2003;102:66a;[abstr 220]
  31. Möllgård L, Bengtzen S, Fioretos T, et al. Effects of the FLT3 inhibitor PKC 412 in combination with cytostatic drugs in vitro in acute myeloid leukemia. Blood. 2004;104:501a;[abstr 1810]
  32. Estey EH, Fisher T, Giles F, et al. A randomized phase II trial of the tyrosine kinase inhibitor PKC412 in patients (pts) with acute myeloid leukemia (AML)/high-risk myelodysplastic syndromes (MDS) characterized by wild-type (WT) or mutated FLT3. Blood. 2003;102:614a;[abstr 2270]
  33. Giles F, Schiffer C, Kantarjian H, et al. Phase 1 study of PKC412, an oral FLT3 kinase inhibitor, in sequential and concomitant combinations with daunorubicin and cytarabine (DA) induction and high-dose cytarabine (HDAra-C) consolidation in newly diagnosed patients with AML. Blood. 2004;11:78a;[abstr 262]
  34. Marcucci G, Bloomfield CD, Balcerzak SP, et al. Phase I trial of genasense™ (G3139, GENTA, INC.), a BCL-2 antisense (AS), in refractory (REF) or relapsed (REL) acute leukemia (AL). Blood. 2000;96:119a;[abstr]
  35. Marcucci G, Stock W, Dai G, et al. Phase I study of oblimersen sodium, an antisense to Bcl-2, in untreated older patients with acute myeloid leukemia: pharmacokinetics, pharmacodynamics, and clinical activity. Journal of Clinical Oncology. 2005;23:3404–3411
  36. Marcucci G, The Cancer and Leukemia Group. CALGB 10201—a phase III study of daunorubicin and cytarabine±G3139 (Genasense™), a Bcl-2 antisense oligodeoxynucleotide, in previously untreated patients with acute myeloid leukemia (AML) ≥60 years. http://www.cancer.gov/clinicaltrials/ft-CALGB-10201/; 4-5-2005.
  37. Moore JO, Seiter K, Kolitz JE, et al. Phase 2 study of oblimersen sodium (G3139; Bcl-2 antisense; Genasense®) plus gemtuzumab ozogamcin (Mylotarg®) in elderly patients with relapsed acute myeloid leukemia (AML). Blood. 2004;104:247a;[abstr 865]
  38. Giles F, Thomas D, Garcia-Manero G, et al. A Phase I and pharmacokinetic study of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients with refractory leukemia. Clinical Cancer Research. 2004;10:2908–2917
  39. Vey N. Update of a phase II trial of VNP40101M (Cloretazine) in acute myeloid leukemia and myelodysplastic syndromes at the sixth international symposium and expert workshops on leukemia and lymphoma, Amsterdam, March 2005. http://www.biospace.com/news_story.aspx?StoryID=19445820&full=1; 10-28-2005.
  40. Sznol M. Phase I study of temozolomide and VNP40101M in patients with relapsed or refractory leukemias. http://www.cancer.gov/clinicaltrials/VION-CLI-036#AlternateTitle_CDR0000405825; 10-29-2005.
  41. No authors listed, Ireland Cancer Center at Case Western Reserve University. Temozolomide and VNP40101M in treating patients with relapsed or refractory leukemias. http://clinicaltrials.gov/ct/screen/BrowseAny?path=%2Fbrowse%2Fby-sponsor%2FINDUSTRY%2FVion%2BPharmaceuticals&recruiting=true; 10-31-2005.
  42. Kantarjian H, Gandhi V, Cortes J, et al. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003;102:2379–2386
  43. Burnett AK, Russell N, Kell JW, et al. A phase 2 evaluation of single agent clofarabine as first line treatment for older patients with AML who are not considered fit for intensive chemotherapy. Blood. 2004;104:248a;[abstr 869]
  44. Faderl S, Gandhi V, O'Brien S, et al. Results of a phase 1–2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005;105:940–947
  45. Faderl S, Gandhi V, Verstovsek S, et al. Clofarabine plus cytarabine (ARA-C) combination is active in newly diagnosed patients (pts)=age 50 with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Blood. 2004;104:250a;[abstr 875]
  46. Hellstrand K, Asea A, Dahlgren C, Hermodsson S. Histaminergic regulation of NK cells. Role of monocyte-derived reactive oxygen metabolites. Journal of Immunology. 1994;153:4940–4947
  47. Brune M, Castaigne S, Catalano J, et al. Improved leukemia-free survival after post-consolidation treatment with histamine dihydrochloride and interleukin-2 in AML: a randomized phase III trial. Blood. 2004;104:78a;[abstr 261]
  48. Recher C, Beyne-Rauzy O, Demur C, et al. Antileukemic activity of rapamycin in acute myeloid leukemia. Blood. 2005;105:2527–2534

PII: S1521-6926(05)00108-8

doi: 10.1016/j.beha.2005.11.006

Best Practice & Research Clinical Haematology
Volume 19, Issue 2 , Pages 311-320 , June 2006

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