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

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

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)

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.