Acute Myeloid Leukemia (AML)
Conditions
Keywords
AML, NPM1 Mutation, elderly patients (>60 years), unfit for intensive chemotherapy
Brief 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)
Interventions
DRUGCytarabine
in all treatment cycles: Cytarabine 20 mg/day, s.c., bid, days 1-7; (total dose 280 mg).
DRUGEtoposide
first treatment cycle Etoposide 50 mg/m²/day, continuously i.v., days 1-3; (total dose 150 mg/m2) treatment cycles 2 to 6 Etoposide 100 mg/day, p.o. or i.v. (over 1 hour), days 1-3; (total dose 300 mg).
in all treatment cycles: ATRA 45 mg/m²/day p.o., days 8-10, ATRA 15 mg/m²/day p.o., days 11-28, with or shortly after meals distributed on 3 doses per day.
Sponsors
German Federal Ministry of Education and Research
University of Ulm
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
61 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| overall survival | 2 years and 8 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| cumulative incidence of relapse | 2 years and 8 months | — |
| cumulative incidence of death in complete remission | 2 years and 8 months | — |
| event-free survival | 2 years and 8 months | — |
| Rate of early deaths (ED)/hypoplastic deaths (HD) | 8 months | — |
| Type, frequency, severity, timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during different treatment cycles | 8 months | adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 4.0 |
| Rate of Complete remission | 8 months | — |
| Duration of neutropenia after each treatment cycle | 8 months | — |
| Duration of thrombocytopenia after each treatment cycle | 8 months | — |
| Duration of hospitalization after each treatment cycle | 8 months | — |
| Quality of life | 2 years and 8 months | assessed by the EORTC Quality of Life Core Questionnaire (QLQ-C30), supplemented by information on self-assessed concomitant diseases, late treatment effects, and demographics according to Messerer et al.33 |
| Incidence of infection after each treatment cycle | 8 months | — |
Countries
Germany
Outcome results
None listed