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Trial record 1 of 1 for:    AMLSG 21-13
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Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™)

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ClinicalTrials.gov Identifier: NCT02013648
Recruitment Status : Recruiting
First Posted : December 17, 2013
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Hartmut Doehner, University of Ulm

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Drug: Dasatinib Drug: Cytarabine Drug: Daunorubicin Phase 3

Detailed Description:

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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 277 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Study Start Date : July 2014
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : May 2023


Arm Intervention/treatment
Active Comparator: Standard arm

Induction therapy:

Patients will receive induction therapy (one or two cycles) with daunorubicin 60 mg/m2/day administered on days 1-3 and cytarabine 200 mg/m2/day administered by continuous IV infusion on days 1-7. No dose reduction is planned in elderly (>60 years) patients.

Optional second induction cycle:

Patients achieving PR only at the end of cycle 1 will receive a second induction cycle with daunorubicin 50 mg/m2/day administered on days 1-3 and cytarabine 200 mg/m2/day administered by cont. IV infusion daily on days 1-5.

Consolidation therapy:

Patients will receive 4 cycles of consolidation therapy. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (>60 years: 1 g/m2) q12h, days 1-3 administered intravenously over three hours.

Follow-up period:

There is no maintenance therapy in the standard arm. Patients will be closely followed, in particular for molecular disease persistence or molecular relapse.

Drug: Cytarabine
Other Name: ARA-cell

Drug: Daunorubicin
Other Name: Daunoblastin

Experimental: Investigational arm

Induction therapy:

Patients will receive induction therapy (one or two cycles) with daunorubicin 60 mg/m2/day administered on days 1-3 and cytarabine 200 mg/m2/day administered by continuous IV infusion on days 1-7. Patients will receive dasatinib 100 mg once daily (QD) on days 8-21.

Opt. 2nd induction cycle:

Patients achieving PR only at the end of cycle 1 will receive a 2nd induction cycle with daunorubicin 50 mg/m2/day administered on days 1-3 and cytarabine 200 mg/m2/day administered by cont. IV infusion on days 1-5. Patients will receive dasatinib 100 mg QD on days 6-21.

Consolidation therapy:

Patients will receive 4 consolidation cycles. Treatment consists of high-dose cytarabine 3 g/m2 (>60 years: 1 g/m2) q12h, days 1-3 administered IV over 3 hours. Patients will receive dasatinib 100 mg QD on days 4-21.

Maintenance therapy:

Patients completing consolidation therapy will continue to receive single agent dasatinib 100 mg QD for one year (or until relapse).

Drug: Dasatinib
Other Name: Sprycel

Drug: Cytarabine
Other Name: ARA-cell

Drug: Daunorubicin
Other Name: Daunoblastin




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Cumulative incidence of relapse (CIR) [ Time Frame: 4 years ]
  2. Cumulative incidence of death (CID) [ Time Frame: 4 years ]
  3. overall survival [ Time Frame: 4 years ]
  4. relapse-free survival [ Time Frame: 4 years ]
  5. PIA analysis [ Time Frame: 4 years ]
    Pharmacodynamic inhibition of KIT as assessed by the KIT plasma inhibitory assay (PIA)

  6. 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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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02013648


Contacts
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Contact: Hartmut Doehner, Prof. Dr. 0049-731-500- ext 45501 hartmut.doehner@uniklinik-ulm.de
Contact: Peter Paschka, Dr. 0049-731-500 ext 45746 peter.paschka@uniklinik-ulm.de

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Sponsors and Collaborators
University of Ulm
Investigators
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Principal Investigator: Hartmut Doehner, Prof. Dr. University of Ulm

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Prof. Dr. Hartmut Doehner, Prof. Dr., University of Ulm
ClinicalTrials.gov Identifier: NCT02013648     History of Changes
Other Study ID Numbers: AMLSG 21-13
First Posted: December 17, 2013    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018

Keywords provided by Prof. Dr. Hartmut Doehner, University of Ulm:
AML
Dasatinib
Core Binding Factor (CBF)

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Dasatinib
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors