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Trial Evaluating Induction Therapy With Idarubicin and Etoposide Plus Sequential or Concurrent Azacitidine and Maintenance Therapy With Azacitidine (azacitidine)

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ClinicalTrials.gov Identifier: NCT01180322
Recruitment Status : Unknown
Verified August 2013 by Dr. Richard Schlenk, University of Ulm.
Recruitment status was:  Active, not recruiting
First Posted : August 12, 2010
Last Update Posted : September 2, 2013
Sponsor:
Information provided by (Responsible Party):
Dr. Richard Schlenk, University of Ulm

Tracking Information
First Submitted Date  ICMJE August 2, 2010
First Posted Date  ICMJE August 12, 2010
Last Update Posted Date September 2, 2013
Study Start Date  ICMJE November 2010
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2010)
Rates of complete remission (CR) after induction therapy [ Time Frame: 56 days ]
To evaluate the impact of sequential or concurrent addition of 5-azacytidine to intensive induction chemotherapy with idarubicin and etoposide on the CR rate
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2010)
  • Event-free survival [ Time Frame: after two years of follow-up ]
  • Relapse-free survival [ Time Frame: after two years of follow-up ]
  • overall survival [ Time Frame: after two years of follow-up ]
  • days in hospital during each cycle and during the whole intervention [ Time Frame: 6 months ]
  • Rate of early deaths or hypoplastic deaths (ED/HD) [ Time Frame: 56 days ]
  • type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 3.0), timing and relatedness of non-hematological toxicity observed during different treatment cycles [ Time Frame: 6 months ]
  • quality of life [ Time Frame: at the end of therapy (in average 6 months) and once a year in the follow-up ]
    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 [35].
  • duration of leukopenia after each consolidation cycle [ Time Frame: 42 days ]
  • duration of neutropenia after each consolidation cycle [ Time Frame: 42 days ]
  • duration of thrombocytopenia after each consolidation cycle [ Time Frame: 42 days ]
  • duration of leukopenia after each induction cycle [ Time Frame: 28 days ]
  • duration of neutropenia after each induction cycle [ Time Frame: 28 days ]
  • duration of thrombocytopenia after each induction cycle [ Time Frame: 28 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial Evaluating Induction Therapy With Idarubicin and Etoposide Plus Sequential or Concurrent Azacitidine and Maintenance Therapy With Azacitidine
Official Title  ICMJE Randomized Phase-II Trial Evaluating Induction Therapy With Idarubicin and Etoposide Plus Sequential or Concurrent Azacitidine and Maintenance Therapy With Azacitidine
Brief Summary

This is a randomized phase II, four-arm, open-label, multi-center study in adult patients with acute myeloid leukemia (AML) as defined in inclusion/exclusion criteria.

The primary efficacy objective is to evaluate the impact of sequential or concurrent addition of 5-azacytidine to intensive induction chemotherapy with idarubicin and etoposide on the complete remission (CR) rate

Sample size: 336 patients

The treatment duration of an individual patient randomized into one of the three experimental arms (Arm B, C, D) (in case of application of induction, consolidation and maintenance therapy with Azacitidine) is about 30 months.

The treatment duration for patients randomized into the standard arm of the study (Arm A) is about 7 months (in case of application of induction, consolidation and 2-yrs observation as maintenance (without treatment with Azacitidine)).

In case of induction followed by consolidation with allogeneic Stem cell transplantation (SCT) the treatment duration per patient is about 6 months.

Every patient will be followed until month 54 after inclusion into the study. Duration of the study for an individual patient including treatment (induction, consolidation [chemotherapy or allogeneic SCT], maintenance [experimental arm with Azacitidine or observation]) and follow-up period: 54 months

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia (AML)
Intervention  ICMJE
  • Drug: Cytarabine

    Induction therapy:100 mg/m2/day by continuous intravenous (IV) infusion on days 1-7 (total dose 700 mg/m2)

    Consolidation therapy:

    Younger adults (18 to 65 years): 3 g/m2/day by IV infusion over 3 hours every 12 hours on days 1, 2, and 3 (total dose 18 g/m2).

    Elderly patients (>65 years): 1 g/m2/day by IV infusion over 3 hours every 12 hours on days 1, 2, and 3 (total dose 6 g/m2).

  • Drug: Idarubicin

    First induction therapy:

    Arm A, C, D:

    12 mg/m2/day by IV push on days 1,3,5 (total dose 36 mg/m2). For elderly (>65 yrs) patients only two doses of idarubicin are foreseen on days 1+3.

    Arm B:

    12 mg/m2/day by IV push on days 6, 8 10 (total dose 36 mg/m2). For elderly (>65 yrs) patients only two doses of idarubicin are foreseen on days 6+8.

    Second induction therapy:

    Arm A, C, D:

    12 mg/m2/day by IV push on days 1 and 3 (total dose 24 mg/m2; for all age groups)

    Arm B:

    12 mg/m2/day by IV push on days 6 and 8 (total dose 24 mg/m2; for all age groups).

  • Drug: Etoposide

    Induction therapy:

    Arm A, C, D:

    100 mg/m²/day by 1-hour IV infusion on days 1,2,3 (total dose 300 mg/m2). On days 1 and 3 start after idarubicin push. For elderly (>65 yrs) patients only two doses of etoposide are foreseen on days 1+3.

    Arm B:

    100 mg/m²/day by 1-hour IV infusion on days 6,7,8 (total dose 300 mg/m2). On days 6 and 8 start after idarubicin push. For elderly (>65 yrs) patients only two doses of etoposide are foreseen on days 6+8.

  • Drug: Azacitidine

    Induction therapy:

    Arm B and C:

    100 mg/m2/day by subcutaneous (SC) injection or 15-minute IV infusion on day 1 to day 5 (total dose 500 mg/m2). Azacitidine is always given prior to idarubicin and etoposide.

    Arm D:

    100 mg/m2/day by SC injection or 15-minute IV infusion on days 4-8 (total dose 500 mg/m2). Azacitidine is always given prior to idarubicin and etoposide.

    Maintenance therapy:

    Arm B, C, D:

    50 mg/m2/day by SC injection on days 1-5 (total dose 250 mg/m2) every 4 weeks. (Maintenance therapy is scheduled for a total duration of 2 years in patients with continuous CR)

  • Drug: Lenograstim

    Consolidation therapy:

    subcutaneously daily beginning on day 10 until neutrophil count > 0.5 x 109/l.

Study Arms  ICMJE
  • Active Comparator: Arm A
    Standard Therapy
    Interventions:
    • Drug: Cytarabine
    • Drug: Idarubicin
    • Drug: Etoposide
    • Drug: Lenograstim
  • Experimental: Arm B
    Investigational Therapy "Azacitidine Prior"
    Interventions:
    • Drug: Cytarabine
    • Drug: Idarubicin
    • Drug: Etoposide
    • Drug: Azacitidine
    • Drug: Lenograstim
  • Experimental: Arm C
    Investigational Therapy "Azacitidine Concurrent"
    Interventions:
    • Drug: Cytarabine
    • Drug: Idarubicin
    • Drug: Etoposide
    • Drug: Azacitidine
    • Drug: Lenograstim
  • Experimental: Arm D
    Investigational Therapy "Azacitidine After"
    Interventions:
    • Drug: Cytarabine
    • Drug: Idarubicin
    • Drug: Etoposide
    • Drug: Azacitidine
    • Drug: Lenograstim
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 11, 2010)
336
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2016
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with suspected diagnosis of acute myeloid leukemia or related precursor neoplasm, or acute leukemia of ambiguous lineage (classified according to the World Health Organization (WHO) classification)
  • Patients considered eligible for intensive chemotherapy
  • WHO performance status of ≤ 2
  • Age ≥ 18 years. There is no upper age limit.
  • No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis
  • 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. "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.
  • Female patients in the reproductive age and male patients must agree to avoid getting pregnant or to father a child while on therapy and for 3 month after the last dose of chemotherapy.
  • Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin one acceptable method of birth control (IUD, tubal ligation, or partner's vasectomy). Hormonal contraception is an inadequate method of birth control.
  • Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy. (while on therapy and for 3 month after the last dose of chemotherapy)
  • Signed written informed consent.

Exclusion Criteria:

-AML with other recurrent genetic abnormalities (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 variant translocations with other RARA gene fusions)

  • AML with NPM1 mutation
  • AML with FLT3 mutation
  • Performance status WHO >2
  • Patients with ejection fraction < 50% by Multi Gated Acquisition Scan (MUGA) or echocardiogram (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 Human immunodeficiency virus (HIV)
  • 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 and/or other physicians involved in the treatment of the patient about study participation.
  • No consent for biobanking.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01180322
Other Study ID Numbers  ICMJE AMLSG 12-09
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Richard Schlenk, University of Ulm
Study Sponsor  ICMJE University of Ulm
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Richard F Schlenk, MD University Hospital of Ulm
PRS Account University of Ulm
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP