Phase III Study of Chemotherapy in Combination With ATRA With or Without Gemtuzumab Ozogamicin in Patients With Acute Myeloid Leukemia and NPM1 Gene Mutation

AMLSG 09-09

Randomized Phase-III, two-arm, open-label, multi-center study in adult patients with AML and NPM1 mutation. Before Amendment No. 4 (December 2013): Primary Efficacy Objective: * Evaluation of efficacy based on event-free survival (EFS) 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) After Amendment No. 4 (December 2013): 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)

2010-05-12

2021-09-01

2021-09-01

Completed

Early phase I

600

Inclusion Criteria: * 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. Exclusion Criteria: * 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 \< 50% by MUGA or ECHO scan within 14 days of day 1. * 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. * 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. * 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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 600, 'type': 'ACTUAL'}}

2023-02-27