study of chemotherapy in combination with all-trans retinoic acid (atra) with or without gemtuzumab ozogamicin in patients with acute myeloid leukemia (aml) and mutant nucleophosmin-1 (npm1) gene mutation

Conditions: Acute Myeloid Leukemia

Summary: randomized phase-iii, two-arm, open-label, multi-center study in adult patients with aml and npm1 mutation. before amendment no. 4 (december 2013): primary efficacy objective: * evaluation of efficacy based on event-free survival (efs) after induction and consolidation chemotherapy plus all-trans retinoic acid (atra) with or without gemtuzumab ozogamicin (go) in adult patients with acute myeloid leukemia (aml) and mutant nucleophosmin-1 (npm1) after amendment no. 4 (december 2013): primary efficacy objective: * evaluation of efficacy based on overall survival (os) after induction and consolidation chemotherapy plus all-trans retinoic acid (atra) with or without gemtuzumab ozogamicin (go) in adult patients with acute myeloid leukemia (aml) and mutant nucleophosmin-1 (npm1)


Eligibility criteria:
inclusion criteria: * patients with confirmed diagnosis of acute myeloid leukemia according to the world health organization (who) classification. * presence of npm1 mutation as assessed in one of the central amlsg reference laboratories. * age ≥ 18 years. there is no upper age limit. * no prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis if needed for up to 5 days during the diagnostic screening phase. * non-pregnant and non-nursing. women of childbearing potential (wocbp) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 miu/ml within 72 hours prior to registration. * female patients in the reproductive age and male patients must agree to avoid getting pregnant or to father a child while on therapy and within one year after the last dose of chemotherapy. * women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control: one highly effective method (e.g., iud, hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (e.g., latex condom, diaphragm, or cervical cap). * "women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months. * men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy. * signed written informed consent. exclusion criteria: * aml with other recurrent genetic changes (according to who 2008): * aml with t(8;21)(q22;q22); runx1-runx1t1 * aml with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); cbfb-myh11 * aml with t(15;17)(q22;q12); pml-rara (or other translocations involving rara) * aml with t(9;11)(p22;q23); mllt3-mll (or other translocations involving mll) * aml with t(6;9)(p23;q34); dek-nup214 * aml with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); rpn1-evi1. * performance status who \> 2. * patients with ejection fraction \< 50% by muga or echo scan within 14 days of day 1. * organ insufficiency: * creatinine \> 1.5x upper normal serum level * bilirubin, ast or alp \> 2.5x upper normal serum level, not attributable to aml * heart failure nyha iii/iv * severe obstructive or restrictive ventilation disorder. * uncontrolled infection. * severe neurological or psychiatric disorder interfering with ability of giving an informed consent. * patients with a "currently active" second malignancy other than non-melanoma skin cancers. patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year. * known positive for hiv, active hbv, hcv, or hepatitis a infection. * bleeding disorder independent of leukemia. * no consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation.

Keywords: adult patients npm1 mutation