Study of Chemotherapy in Combination With All-trans Retinoic Acid (ATRA) With or Without Gemtuzumab Ozogamicin in Patients With Acute Myeloid Leukemia (AML) and Mutant Nucleophosmin-1 (NPM1) Gene Mutation
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Drug: Gemtuzumab Ozogamicin (Mylotarg)Drug: standard chemotherapy
- Registration Number
- NCT00893399
- Lead Sponsor
- University of Ulm
- Brief Summary
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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 600
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Patients with confirmed diagnosis of acute myeloid leukemia according to the World Health Organization (WHO) classification.
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Presence of NPM1 mutation as assessed in one of the central AMLSG reference laboratories.
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Age ≥ 18 years. There is no upper age limit.
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No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis if needed for up to 5 days during the diagnostic screening phase.
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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.
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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.
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Signed written informed consent.
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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.
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Performance status WHO > 2.
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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.
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Uncontrolled infection.
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Severe neurological or psychiatric disorder interfering with ability of giving an informed consent.
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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.
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Known positive for HIV, active HBV, HCV, or Hepatitis A infection.
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Bleeding disorder independent of leukemia.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Gemtuzumab Ozogamicin (Mylotarg) chemotherapy in combination with ATRA with gemtuzumab ozogamicin 1 standard chemotherapy chemotherapy in combination with ATRA with gemtuzumab ozogamicin 2 standard chemotherapy chemotherapy in combination with ATRA without gemtuzumab ozogamicin
- Primary Outcome Measures
Name Time Method Overall survival (OS) four years
- Secondary Outcome Measures
Name Time Method Type, frequency, severity, timing and relatedness of AEs and laboratory abnormalities observed during different treatment cycles 6 months Days in hospital during each cycle and during the whole intervention 6 months Incidence of infection after induction and consolidation therapy 6 months Rates of complete remission after induction therapy (CR) not later than 56 days Cumulative incidences of relapse (CIR) and death in CR (CID) four years Event-free survival (EFS) four years Duration of neutropenia and thrombocytopenia after induction and consolidation therapy 6 months 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 [49] two years after completion of therapy
Trial Locations
- Locations (60)
Medizinische Universitäts Graz
🇦🇹Graz, Austria
Universitätsklinikum Innsbruck
🇦🇹Innsbruck, Austria
Krankenhaus der Barmherzigen Schwestern Linz Betriebsgesellschaft m.b.H.
🇦🇹Linz, Austria
Krankenhaus der Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
Krankenhaus der Elisabethinen Linz
🇦🇹Linz, Austria
Salzburger Landeskliniken
🇦🇹Salzburg, Austria
Hanuschkrankenhaus Wien
🇦🇹Wien, Austria
Klinikum Aschaffenburg-Alzenau
🇩🇪Aschaffenburg, Germany
Ubbo-Emmius-Klinik Aurich
🇩🇪Aurich, Germany
Helios Klinikum Bad Saarow
🇩🇪Bad Saarow, Germany
Scroll for more (50 remaining)Medizinische Universitäts Graz🇦🇹Graz, Austria