Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia

被引:8
|
作者
Allen, Steven L. [1 ]
Kolitz, Jonathan E. [2 ]
Lundberg, Ante S. [3 ]
Bennett, John M. [4 ]
Capizzi, Robert L. [3 ]
Budman, Daniel R. [2 ]
机构
[1] N Shore Univ Hosp, Albert Einstein Coll Med, Monter Canc Ctr, Lake Success, NY 11042 USA
[2] New York Univ, N Shore Univ Hosp, Monter Canc Ctr, Sch Med, Lake Success, NY USA
[3] Antisoma, Cambridge, MA USA
[4] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA
关键词
AML; Phase I; P-glycoprotein; Pgp; Multidrug resistance; SOUTHWEST-ONCOLOGY-GROUP; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; MYELODYSPLASTIC-SYNDROME; POSTREMISSION THERAPY; ANTITUMOR-ACTIVITY; ELDERLY-PATIENTS; GROUP-B; CANCER; INDUCTION;
D O I
10.1016/j.leukres.2009.07.038
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Amonafide-L-malate ( amonafide) is a unique DNA intercalator that maintains activity in the presence of MDR mechanisms, a frequent cause of treatment-failure in secondary AML. 43 patients with relapsed/refractory or secondary AML or CML blast crisis were enrolled into two phase I dose-escalation studies investigating amonafide as monotherapy or in combination with cytarabine. 3/17 patients in the monotherapy trial and 10/26 patients in the combination trial achieved a complete remission. Between both trials responses occurred in 9/20 patients with secondary AML. Both trials demonstrated an acceptable safety profile and significant antileukemic activity in patients with poor-risk AML, especially those with secondary AML. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:487 / 491
页数:5
相关论文
共 50 条
  • [1] A Phase I Study of Selinexor in Combination with Daunorubicin and Cytarabine in Patients with Newly Diagnosed Poor-Risk Acute Myeloid Leukemia
    Sweet, Kendra L.
    Komrokji, Rami S.
    Padron, Eric
    Cubitt, Christopher L.
    Khavarian, Leyla
    List, Alan F.
    Sallman, David
    Sullivan, Daniel
    Chavez, Julio C.
    Shah, Bijal D.
    Lancet, Jeffrey E.
    BLOOD, 2016, 128 (22)
  • [2] Phase I Clinical Trial of Selinexor in Combination with Daunorubicin and Cytarabine in Previously Untreated Poor-Risk Acute Myeloid Leukemia
    Sweet, Kendra
    Komrokji, Rami
    Padron, Eric
    Cubitt, Christopher L.
    Turner, Joel G.
    Zhou, Junmin
    List, Alan F.
    Sallman, David A.
    Dawson, Jana L.
    Sullivan, Daniel M.
    Chavez, Julio
    Shah, Bijal D.
    Lancet, Jeffrey E.
    CLINICAL CANCER RESEARCH, 2020, 26 (01) : 54 - 60
  • [3] Secondary Acute Myeloid Leukemia (sAML) Treated with Amonafide (AS1413) + Cytarabine: Durable Responses in Poor-Risk AML
    Allen, Steven L.
    Erba, Harry P.
    Rizzieri, David A.
    O'Donnell, Margaret
    Powell, Bayard
    Lundberg, Ante S.
    Bennett, John M.
    Capizzi, Robert L.
    BLOOD, 2008, 112 (11) : 1019 - 1020
  • [4] Phase I study of Debio1143 (AT406) in combination with daunorubicin (D) and cytarabine (C) in patients with poor-risk acute myeloid leukemia (AML).
    DiPersio, John F.
    Erba, Harry Paul
    Larson, Richard A.
    Luger, Selina M.
    Mangan, Kenneth Francis
    Tallman, Martin S.
    Brill, Jeffrey Mark
    Vuagniaux, Gregoire
    Rouits, Elisabeth
    Zanna, Claudio
    Sorensen, J. Mei
    JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (15)
  • [5] FLUDARABINE, CYTARABINE AND IDARUBICIN FOR INDUCTION TREATMENT OF POOR-RISK ACUTE MYELOID LEUKEMIA
    Villa, M. R.
    Izzo, G. Nitrato
    Gagliardi, A.
    Improta, S.
    Mastrullo, L.
    HAEMATOLOGICA, 2015, 100 : 81 - 81
  • [6] A phase IIa pharmacokinetic and efficacy study of amonafide (AS1413) in combination with cytarabine in patients with acute myeloid leukemia
    Lundberg, A. S.
    Allen, S. L.
    JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (15)
  • [7] Combination of liposomal daunorubicin (DaunoXome), fludarabine, and cytarabine (FLAD) in patients with poor-risk acute leukemia
    Clavio, M
    Venturino, C
    Pierri, I
    Garrone, A
    Miglino, M
    Canepa, L
    Balleari, E
    Balocco, M
    Michelis, G
    Ballerini, F
    Gobbi, M
    ANNALS OF HEMATOLOGY, 2004, 83 (11) : 696 - 703
  • [8] Combination of liposomal daunorubicin (DaunoXome), fludarabine, and cytarabine (FLAD) in patients with poor-risk acute leukemia
    Marino Clavio
    Claudia Venturino
    Ivana Pierri
    Alberto Garrone
    Maurizio Miglino
    Letizia Canepa
    Enrico Balleari
    Manuela Balocco
    Gian Luca Michelis
    Filippo Ballerini
    Marco Gobbi
    Annals of Hematology, 2004, 83 : 696 - 703
  • [9] Phase I study of amonafide plus cytosine arabinoside (AraC) in patients with poor risk acute myeloid leukemia (AML).
    Allen, SL
    Kolitz, JE
    Lundberg, A
    Champagne, M
    Devost, S
    Dubon, R
    Drouin, M
    Boss, MA
    Grieshaber, CK
    Budman, DR
    JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (16) : 585S - 585S
  • [10] Cyclosporine modulation in poor-risk acute myeloid leukemia
    Beattie, JV
    Petruska, PJ
    BLOOD, 2002, 100 (01) : 366 - 366