Randomized Phase III 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 Mutatio
- Conditions
- Adult patients (>60) with AML and NPM1 mutation ineligible for intensive chemotherapyTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2010-023409-37-DE
- Lead Sponsor
- niversity Hospital Ulm
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 144
•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 (see Appendix F)
-Patient’s decision
-age = 75 years
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 29
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 115
•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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Primary Efficacy Objective<br>Evaluation of overall survival after treatment with low-dose cytarabine and etoposide with or without all-trans retinoic acid (ATRA) in patients with acute myeloid leukemia (AML) and nucleophosmin-1 (NPM1) mutation ineligible for intensive treatment<br>;Secondary Objective: Secondary Efficacy Objectives<br>Evaluation of efficacy based on complete remission (CR) rates, event-free survival (EFS), and cumulative incidences of relapse and deaths in CR<br><br>Safety and QoL Objectives<br>•Evaluation of safety based on toxicity <br>•Evaluation of safety based on duration of neutropenia and leukopenia after each treatment cycle, incidence of infections, duration of hospitalization<br>•Assessment of quality of live<br>;Primary end point(s): Primary Efficacy Endpoint<br>Overall Survival (OS)<br>;Timepoint(s) of evaluation of this end point: at the end of the trial
- Secondary Outcome Measures
Name Time Method