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

Plain-language summary

This study evaluates chemotherapy combined with All-Trans Retinoic Acid (ATRA), with or without Gemtuzumab Ozogamicin (Mylotarg), in Acute Myeloid Leukemia (AML) patients carrying an NPM1 gene mutation. It included patients over 18 with a confirmed NPM1 mutation. It was a Phase 3 study and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 3

Status

Completed

Sponsor

University of Ulm

Intervention

Gemtuzumab Ozogamicin (Mylotarg), standard chemotherapy

Start date

5/12/2010

Estimated completion

9/1/2021

Countries

Austria, Germany

Related genes

Locations

• Graz, Austria
• Innsbruck, Austria
• Linz, Austria
• Linz, Austria
• Linz, Austria
• Salzburg, Austria
• Vienna, Austria
• Aschaffenburg, Germany
• Aurich, Germany
• Bad Saarow, Germany
• Berlin, Germany
• Berlin, Germany
• Berlin, Germany
• Bochum, Germany
• Bonn, Germany
• Braunschweig, Germany
• Bremen, Germany
• Darmstadt, Germany
• Düsseldorf, Germany
• Essen, Germany
• Esslingen am Neckar, Germany
• Flensburg, Germany
• Frankfurt-Höchst, Germany
• Freiburg im Breisgau, Germany
• Fulda, Germany
• Giessen, Germany
• Goch, Germany
• Göttingen, Germany
• Hamburg, Germany
• Hamburg, Germany
• Hamm, Germany
• Hanau, Germany
• Hanover, Germany
• Hanover, Germany
• Heilbronn, Germany
• Homburg, Germany
• Karlsruhe, Germany
• Kiel, Germany
• Lebach, Germany
• Lemgo, Germany

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Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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.