adult patients with AML and NPM1 mutation
Conditions
Interventions
Trade Name: Mylotarg®
Product Name: Gemtuzumab Ozogamicin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Gemtuzumab Ozogamicin
CAS Number: 220578-59-6
Concentration un
Sponsors
University of Ulm
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Both female and male patients meeting the mentioned inclusion and exclusion criteria will be included in this clinical trial, because the risk to get AML does not depend on a patient’s gender. Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study • Patients with confirmed diagnosis of acute myeloid leukemia according to the World Health Organization (WHO) classification • Presence of NPM1 mutation as assessed in one of the central AMLSG reference laboratories. • Age = 18 years. There is no upper age limit. • No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis if needed for up to 5 days during the diagnostic screening phase. • Non-pregnant and non-nursing. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration. • Female patients in the reproductive age and male patients must agree to avoid getting pregnant or to father a child while on therapy and within one year after the last dose of chemotherapy. Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control - one highly effective method (e.g., IUD, hormonal, tubal ligation, or partner’s vasectomy), and one additional effective method (e.g., latex condom, diaphragm, or cervical cap). ). “Women of childbearing potential” is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months. Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy. • Signed written informed consent 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 441 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 147
Exclusion criteria
Exclusion criteria: The presence of any of the following will exclude a patient from study enrollment: • 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 • Performance status WHO >2 • Patients with ejection fraction 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) • Uncontrolled infection • 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. • Known positive for HIV,active HBV, HCV, or Hepatitis A infection • Bleeding disorder independent of leukemia • 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. • No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Efficacy Objective • Evaluation of efficacy based on overall survival (OS) after induction and consolidation chemotherapy plus all-trans retinoic acid (ATRA) with or without gemtuzumab ozogamicin (GO) in adult patients with acute myeloid leukemia (AML) and mutant nucleophosmin-1 (NPM1);Secondary Objective: Secondary Efficacy Objectives • Evaluation of efficacy based on complete remission (CR) rates, event-free survival, cumulative incidences of relapse (CIR) and death (CID) in CR Safety and QoL Objectives • Evaluation of safety based on toxicity induced by gemtuzumab ozogamicin (GO) • Evaluation of safety based on duration of neutropenia and leukopenia after consolidation therapy, incidence of infection, 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: End of Study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: • Rates of complete remission after induction therapy (CR) • Cumulative incidences of relapse (CIR) and death in CR (CID) • Event free survival • Days in hospital during each cycle and during the whole intervention Safety Endpoints • Rate of ED/HD • Type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 3.0), timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during different treatment cycles • Incidence of infection after induction and consolidation therapy • Duration of neutropenia and thrombocytopenia after induction and consolidation therapy 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: Continuous assessment for safety is performed. QOL + secondary Efficacy endpoint assessments are performed at the end of study. | — |
Countries
Austria, Germany
Contacts
Public ContactAMLSG clinical trial office
University of Ulm
Outcome results
None listed