study of low-dose cytarabine and etoposide with or without all-trans retinoic acid in older patients not eligible for intensive chemotherapy with acute myeloid leukemia and npm1 mutation

Conditions: Acute Myeloid Leukemia (AML)

Summary: this is a randomized, phase-iii, two-arm, open-label, multi-center study in adult patients with aml and npm1 mutation ineligible for intensive chemotherapy. sample size: 144 patients investigator's sites: 50-55 sites in germany and austria (2-10 patients per trial site are expected to be included into the trial) estimated treatment duration of an individual patient: 8 months (follow-up period per patient will last additional 2 years)


Eligibility criteria:
inclusion criteria: * patients with confirmed diagnosis of acute myeloid leukemia according to the world health organization (who) classification (including de novo aml, t-aml and s-aml) * presence of npm1 mutation as assessed in one of the central amlsg reference laboratories. * age \> 60 years. there is no upper age limit. * no prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis if needed for up to 10 days during the diagnostic screening phase. * signed written informed consent * men must give their informed consent that they do not father a baby and must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy. (while on therapy and for 3 month after the last dose of chemotherapy) * who performance status ≤ 3 * patients not eligible for intensive chemotherapy according to at least one of the following criteria * hct-ci score \>2 * patient's decision * age ≥ 75 years exclusion criteria: the presence of any of the following will exclude a patient from study enrollment: * all other aml subtypes, in particular those 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 * no consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician and all other treating physicians about study participation * bleeding disorder independent of leukemia * uncontrolled infection * known positive for hiv, hbv or hcv * 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) * 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.

Keywords: aml npm1 mutation elderly patients (>60 years) unfit for intensive chemotherapy