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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Ulm
Sponsor:
Information provided by (Responsible Party):
Dr. Richard Schlenk, University of Ulm
ClinicalTrials.gov Identifier:
NCT00893399
First received: May 5, 2009
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

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)

Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Gemtuzumab Ozogamicin (Mylotarg)
Drug: standard chemotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Study of Chemotherapy in Combination With ATRA With or Without Gemtuzumab Ozogamicin in Patients With Acute Myeloid Leukemia and NPM1 Gene Mutation

Resource links provided by NLM:


Further study details as provided by University of Ulm:

Primary Outcome Measures:
  • Overall survival (OS) [ Time Frame: four years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rates of complete remission after induction therapy (CR) [ Time Frame: not later than 56 days ] [ Designated as safety issue: No ]
  • Cumulative incidences of relapse (CIR) and death in CR (CID) [ Time Frame: four years ] [ Designated as safety issue: No ]
  • Event-free survival (EFS) [ Time Frame: four years ] [ Designated as safety issue: No ]
  • Days in hospital during each cycle and during the whole intervention [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Type, frequency, severity, timing and relatedness of AEs and laboratory abnormalities observed during different treatment cycles [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Incidence of infection after induction and consolidation therapy [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Duration of neutropenia and thrombocytopenia after induction and consolidation therapy [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • 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] [ Time Frame: two years after completion of therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 588
Study Start Date: February 2010
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
chemotherapy in combination with ATRA with gemtuzumab ozogamicin
Drug: Gemtuzumab Ozogamicin (Mylotarg)

Induction Cycle 1, 2: GO 3mg/m² by intravenous infusion (IVI) on day 1 (total dose 3 mg/m2). Start after etoposide IVI. No dose reduction is foreseen in elderly (> 60 yrs) patients.

Consolidation 1: GO 3mg/m² by intravenous infusion (IVI) on day 1 (total dose 3 mg/m2). Start after first dose of high-dose cytarabine. No dose reduction is foreseen in elderly (> 60 yrs) patients.

Consolidation 2, 3: no GO

Drug: standard chemotherapy
Idarubicin, Etoposide, Cytarabine, ATRA, Pegfilgrastim
Active Comparator: 2
chemotherapy in combination with ATRA without gemtuzumab ozogamicin
Drug: standard chemotherapy
Idarubicin, Etoposide, Cytarabine, ATRA, Pegfilgrastim

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00893399

Contacts
Contact: Richard F Schlenk, MD 004973150045900 richard.schlenk@uniklinik-ulm.de

  Show 54 Study Locations
Sponsors and Collaborators
University of Ulm
Investigators
Principal Investigator: Richard F Schlenk, MD University of Ulm
  More Information

No publications provided

Responsible Party: Dr. Richard Schlenk, Prof. Dr., University of Ulm
ClinicalTrials.gov Identifier: NCT00893399     History of Changes
Other Study ID Numbers: AMLSG 09-09
Study First Received: May 5, 2009
Last Updated: January 24, 2014
Health Authority: Germany: Paul-Ehrlich-Institute

Keywords provided by University of Ulm:
adult patients
NPM1 mutation

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Gemtuzumab
Tretinoin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Keratolytic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on July 20, 2014