Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00007189

Trial Description

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Title

Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™) in Adult Patients With Newly Diagnosed Core-Binding Factor Acute Myeloid Leukemia (CBF-AML)

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

This is a randomized phase III open-label, multicenter trial evaluating standard induction
therapy (daunorubicin [DNR] and cytarabine [Ara-C]) and consolidation therapy (high-dose
cytarabine [HDAC]) with or without dasatinib in adult patients with newly diagnosed CBF-AML

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Brief Summary in Scientific Language

This is a randomized phase III open-label, multicenter trial evaluating standard induction
therapy (daunorubicin [DNR] and cytarabine [Ara-C]) and consolidation therapy (high-dose
cytarabine [HDAC]) with or without dasatinib in adult patients with newly diagnosed CBF-AML;
in the investigational arm, consolidation therapy is followed by a one-year maintenance
therapy with dasatinib. Patients with molecular disease persistence or molecular relapse as
assessed by quantitative RQ-PCR for the CBF fusion transcripts will be eligible for
hematopoietic stem cell transplantation before overt hematologic relapse occurs. Primary
endpoint is event-free survival.

AML patients will be assessed for the CBF fusion genes in one of two AMLSG central
laboratories within 48 hours of diagnosis, and only patients with CBF-AML will be enrolled.

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Organizational Data

  •   DRKS00007189
  •   2014/11/26
  •   2013/12/11
  •   yes
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Secondary IDs

  •   NCT02013648  (ClinicalTrials.gov)
  •   AMLSG 21-13  (University of Ulm)
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Health Condition or Problem studied

  •   Acute Myeloid Leukemia (AML)
  •   C92.0 -  Acute myeloblastic leukaemia [AML]
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Interventions/Observational Groups

  •   Drug: Dasatinib
  •   Drug: Cytarabine
  •   Drug: Daunorubicin
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
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Primary Outcome

- Event-free Survival; time frame: 4 years; To assess event-free survival (EFS) after intensive induction (daunorubicin and cytarabine) and consolidation (high-dose cytarabine) chemotherapy with or without dasatinib in patients with CBF-AML

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Secondary Outcome

- Cumulative incidence of relapse (CIR); time frame: 4 years
- Cumulative incidence of death (CID); time frame: 4 years
- overall survival; time frame: 4 years
- relapse-free survival; time frame: 4 years
- PIA analysis; time frame: 4 years; Pharmacodynamic inhibition of KIT as assessed by the KIT plasma inhibitory assay (PIA)
- toxicity; time frame: 7 months (standard arm) / 19 months (investigational arm); Type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03), timing and relatedness of non-hematologic toxicity observed during different treatment cycles.

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Countries of Recruitment

  •   Austria
  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2014/07/31
  •   277
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- Core-binding factor (CBF) AML with molecular diagnosis of RUNX1-RUNX1T1 fusion
transcript resulting from t(8;21)(q22;q22) (or a variant form) or of CBFB-MYH11
fusion transcript resulting from inv(16)(p13.1q22)/t(16;16)(p13.1;q22) as assessed in
one of the central AMLSG reference laboratories (Ulm, Hannover)

- Age ≥ 18; there is no upper age limit

- No prior chemotherapy for leukemia except hydroxyurea for up to 5 days during the
diagnostic screening phase

- Non-pregnant and non-nursing. Due to the unknown teratogenic potential of dasatinib
in humans, pregnant or nursing patients may not be enrolled. Women of childbearing
potential (WOCBP) must have a negative serum or urine pregnancy test within a
sensitivity of at least 25 mIU/mL with-in 72 hours prior to registration. 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) - AT THE
SAME TIME, at least four weeks before she begins dasatinib therapy. "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 agree not to father a child and must use a latex condom during any sexual
contact with women of childbearing potential while taking dasatinib and for 3 months
after therapy is stopped, even if they have undergone a successful vasectomy.

- Signed written informed consent.

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Exclusion Criteria

- Performance status WHO >2

- Pulmonary edema and/or pleural/pericardial effusion within 14 days of day 1. If
edema/effusion resolves to CTC Grade ≤1, patients can be treated with dasatinib.

- Patients with ejection fraction <50% by echocardiography within 14 days of day 1

- Organ insufficiency (creatinine >1.5x upper normal serum level; bilirubin, AST or AP
>2.5x upper normal serum level; heart failure NYHA III/IV; severe obstructive or
restrictive ventilation disorder)

- Uncontrolled infection

- 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.

- Severe neurological or psychiatric disorder interfering with ability of giving an
informed consent

- 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 and/or
other physicians involved in the treatment of the patient about study participation.

- No consent for biobanking.

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Addresses

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    • University of Ulm
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    • University of Ulm
    • Hartmut Doehner, Prof. Dr. 
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    • Hartmut Doehner, Prof. Dr. 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   45
  •   2014/11/04
* This entry means the parameter is not applicable or has not been set.