Adult patients (>60) with AML and NPM1 mutation ineligible for intensive chemotherapy
Conditions
Sponsors
University Hospital Ulm
Eligibility
Sex/Gender
All
Inclusion 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 (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
Exclusion criteria
Exclusion criteria: •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 |
|---|---|
| Main Objective: Primary Efficacy Objective 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 ;Secondary Objective: Secondary Efficacy Objectives Evaluation of efficacy based on complete remission (CR) rates, event-free survival (EFS), and cumulative incidences of relapse and deaths in CR Safety and QoL Objectives • Evaluation of safety based on toxicity • Evaluation of safety based on duration of neutropenia and leukopenia after each treatment cycle, incidence of infections, duration of hospitalization • Assessment of quality of live ;Primary end point(s): Primary Efficacy Endpoint Overall Survival (OS) ;Timepoint(s) of evaluation of this end point: at the end of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints •Rates of CR •Cumulative incidences of relapse (CIR) and death in CR (CID) •Event-free survival (EFS) Safety Endpoints •Rate of early deaths (ED)/hypoplastic deaths (HD) •Type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4.0), timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during different treatment cycles •Incidence of infection after each treatment cycle •Duration of neutropenia and thrombocytopenia as well as duration of hospitalization after each treatment cycle QoL Endpoint •Quality of life 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.;Timepoint(s) of evaluation of this end point: Safety will be monitored by internal and external supervision. After cohorts of 25 patients, the analyses of the safety end points will be performed and results will be sent to the internal monitoring board (principle investigator, chairs of the AMLSG, biostatistician, AMLSG Steering Committee). Twelve-monthly, a study report comprising the safety end point report, a summary as well as a complete list of serious adverse events (SAE), results of blinded central versus on-site disease assessment and a summary of study con-duct to assess protocol adherence will be sent to the external Data Monitoring and Safety Board (DMSB). The DMSB will have to answer within 1 month with a common statement concerning the further conduct of the study. | — |
Countries
Austria, Germany
Contacts
Public ContactAMLSG Clinical Trials Office
University Hospital Ulm
Outcome results
None listed