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

University of Ulm

Status and phase

Completed

Phase 3

Conditions

Acute Myeloid Leukemia

Treatments

Drug: Gemtuzumab Ozogamicin (Mylotarg)

Drug: standard chemotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT00893399

AMLSG 09-09

Details and patient eligibility

About

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)

Enrollment

600 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.