Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This phase II trial is studying the side effects and how well giving combination chemotherapy together with dasatinib works in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with dasatinib may kill more cancer cells

Further Study Information

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of dasatinib with intensive induction therapy (daunorubicin hydrochloride and cytarabine), consolidation chemotherapy (high-dose cytarabine), and as single agent in maintenance therapy in patients with newly diagnosed core-binding factor acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

I. To assess clinical outcomes such as event-free survival (EFS), complete response rate (CR), cumulative incidence of relapse (CIR), cumulative incidence of death (CID), disease-free survival (DFS), and overall survival (OS) of patients treated with these regimens.

II. To describe the frequency and severity of adverse events of patients treated on this study during induction, consolidation, and continuation therapy.

III. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell count and hemogram, and performance status on clinical outcomes.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib orally (PO) once daily on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity ≥ 20 % and leukemia blasts ≥ 5%) receive a second course of induction therapy.

INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO once a day on days 6-19. Patients achieving complete response receive consolidation therapy.

CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO once daily on days 6-26. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.

CONTINUATION THERAPY: Patients receive dasatinib PO on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then every year for a up to 10 years.

Eligibility Criteria

Inclusion Criteria:

• Newly diagnosed acute myeloid leukemia (AML)

• Molecular diagnosis of core-binding factor (CBF) AML by RT-PCR positive for any of the following:

• RUNX1-RUNX1T1 fusion transcript resulting from t(8;21)(q22;q22) or a variant form

• CBFB-MYH11 fusion transcript resulting from inv(16)(p13.1q22) ort(16;16)(p13.1;q22) (any % bone marrow or blood blasts render the diagnosis of CBFAML based on the WHO classification)

• AML with a history of antecedent myelodysplasia (MDS) allowed

• Patients who have developed therapy-related myeloid neoplasm (t-MN) after prior radiotherapy or chemotherapy for another cancer or disorder allowed

• Must be registered on CALGB-8461 and CALGB-20202 protocols

• May also be registered on CALGB-9665

• Bilirubin < 2.5 times upper limit of normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must agree to use two acceptable methods of birth control before, during, and for ≥ 12 weeks after treatment is complete:

• One highly effective method (e.g., IUD, hormonal, tubal ligation, or partner's vasectomy)

• One additional effective method (e.g., latex condom, diaphragm, or cervical cap)

• Left ventricular ejection fraction >= lower limit of institutional normal by MUGA or ECHO scan

• No myocardial infarction within 6 months

• No ventricular tachyarrhythmia within 6 months

• No major conduction abnormality (unless a cardiac pacemaker is present)

• No patients with congenital QT syndrome or non-congenital QTc prolongation (≥ 480 msecs) that cannot be corrected by infusion of electrolytes and/or discontinuation of other medications prior to start of treatment

• No concurrent proton pump inhibitors

• No prior chemotherapy for leukemia or myelodysplasia except the following:

• Emergency leukapheresis

• Emergency treatment for hyperleukocytosis with hydroxyurea

• Cranial radiotherapy for CNS leukostasis (one dose only)

• Growth factor and/or cytokine support and/or non-cytotoxic molecular-targeted agents

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Guido Marcucci

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01238211
Information obtained from ClinicalTrials.gov on February 25, 2013