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Dasatinib (Sprycel™) in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)

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ClinicalTrials.gov Identifier: NCT00850382
Recruitment Status : Completed
First Posted : February 25, 2009
Last Update Posted : March 1, 2016
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Hartmut Doehner, University of Ulm

Study Description
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Brief Summary:

This is a Phase Ib/IIa open-labeled multi-center trial evaluating the feasibility of dasatinib given after standard induction therapy with daunorubicin (DNR) and cytarabine (ARA-C), after consolidation therapy with high-dose cytarabine (HDAC), and as single agent in a one-year maintenance therapy in patients with newly diagnosed CBF AML.

82 patients with newly diagnosed CBF AML will be enrolled at AMLSG study centers.

All AML patients will be assessed for the CBF fusion genes via the central laboratory of the AMLSG within 48 hours of diagnosis of AML, and only patients with CBF AML will be enrolled into the study.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Drug: Dasatinib Drug: daunorubicin Drug: Cytarabine Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 89 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Label, Multicenter Phase Ib/IIa Study For the Evaluation of Dasatinib (Sprycel™) Following Induction and Consolida-tion Therapy as Well as in Maintenance Therapy in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)
Study Start Date : June 2009
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dasatinib

Induction cycle(s):

Patients will receive in cycle 1 induction therapy with daunorubicin 60 mg/m2/day administered on days 1 through 3 and cytarabine 200 mg/m2/day administered by continuous IV infusion daily for 7 days (days 1 through 7). Patients will receive dasatinib 100 mg QD on days 8-21. Patients not achieving CR or CRi at the end of cycle 1 will be evaluable to receive a second induction cycle identical in schedule and dosage to the first induction cycle.

Consolidation Cycles 1, 2, 3, 4:

Patients achieving CR or CRi at the end of cycle 1 will receive consolidation therapy for 4 cy-cles. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (>60 years: 1 g/m2) q12h, d 1, 3, 5, administered intravenously over three hours. Patients will receive dasatinib 100 mg QD on days 6-28.

Maintenance therapy:

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

 Drug: Dasatinib

Induction cycle(s):

Dasatinib 100 mg QD on days 8-21.

Consolidation Cycles 1, 2, 3, 4:

Patients will receive dasatinib 100 mg QD on days 6-28.

Maintenance therapy:

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


Drug: daunorubicin

Induction cycle(s):

Daunorubicin 60 mg/m2/day administered on days 1 through 3


Drug: Cytarabine

Induction cycle(s):

Cytarabine 200 mg/m2/day administered by continuous IV infusion daily for 7 days (days 1 through 7).

Consolidation cycles 1, 2, 3, 4:

Consolidation therapy consists of high-dose cytarabine 3 g/m2 (>60 years: 1 g/m2) q12h, d 1, 3, 5, administered intravenously over three hours.


Outcome Measures
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Primary Outcome Measures :
  1. Feasibility as combined endpoint: Rate of ED/HD Rate of pleural/pericardial effusion grade 3/4 Rate of liver toxicity grade 3/4 that does not improve to <= grade 2 within 14 days after discontinuing responsible medication Rate of refractory disease [ Time Frame: after 4 weeks ]

Secondary Outcome Measures :
  1. Cumulative incidence of relapse (CIR) and death (CID) [ Time Frame: After follow-up period of two years ]
  2. Overall survival (os) [ Time Frame: After follow-up period of two years ]

Eligibility Criteria
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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.
  • Age ≥ 18; there is no upper age limit.
  • No prior chemotherapy for leukemia except hydroxyurea for up to 5 days during the diag-nostic 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 poten-tial (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 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 con-tact with women of childbearing potential while taking dasatinib and for 4 weeks 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
  • Severe neurological or psychiatric disorder interfering with ability of giving an informed consent
  • Known positive for HIV
  • Bleeding disorder independent of leukemia
  • No consent for registration, storage and processing of the individual disease-characteristics and course
Contacts and Locations
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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): NCT00850382


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Sponsors and Collaborators
University of Ulm
Investigators
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Principal Investigator: Hartmut Doehner, MD University Hospital of Ulm
More Information
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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: NCT00850382     History of Changes
Other Study ID Numbers: AMLSG 11-08
First Posted: February 25, 2009    Key Record Dates
Last Update Posted: March 1, 2016
Last Verified: February 2016
Keywords provided by Prof. Dr. Hartmut Doehner, University of Ulm:
CBF 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