Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

Brief Title

Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

Official Title

A Phase II Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy Plus Dasatinib (NSC #732517) and Continuation Therapy With Dasatinib Alone in Newly Diagnosed Patients With Core Binding Factor Acute Myeloid Leukemia (AML)

Brief Summary

      This phase II trial studies 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, by
      stopping them from dividing, or by stopping them from spreading. 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.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the safety and tolerability of dasatinib 100 mg/day given after intensive
      induction (daunorubicin hydrochloride [daunorubicin]/cytarabine), and consolidation
      chemotherapy (high-dose cytarabine) and as single agent in maintenance therapy to newly
      diagnosed patients with core binding factor acute myeloid leukemia (AML).

      II. 30-day survival rate during induction (the lack of early/hypoplastic death).

      III. The absence of pleural or pericardial effusion, and absence of liver toxicity that
      exceeds grade 2.

      SECONDARY OBJECTIVES:

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

      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 (WBC) count and hemogram, and performance status on clinical outcomes.

      OUTLINE:

      INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride intravenously (IV)
      on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib orally (PO)
      once daily (QD) 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 QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 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 up to 10 years from study entry.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

30 Day Survival Rate

Secondary Outcome

 Event-free Survival

Condition

Acute Myeloid Leukemia

Intervention

Cytarabine

Study Arms / Comparison Groups

 Treatment (daunorubicin hydrochloride, cytarabine, dasatinib)

Description:  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 PO QD 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 QD 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 QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

61

Start Date

December 14, 2010

Completion Date

March 15, 2021

Primary Completion Date

July 1, 2013

Eligibility Criteria

        Inclusion Criteria:

          -  Documentation of disease as assessed by the Alliance reference laboratory at the Ohio
             State University per Cancer and Leukemia Group B (CALGB) 20202, molecular diagnosis of
             core-binding factor (CBF) acute myeloid leukemia (AML) by reverse transcriptase
             polymerase chain reaction (RT-PCR) positive for RUNX1-RUNX1T1 fusion transcript
             resulting from t(8;21)(q22;q22) (or a variant form) or CBFB-MYH11 fusion transcript
             resulting from inv(16)(p13.1q22) or t(16;16)(p13.1;q22) (any % bone marrow or blood
             blasts render the diagnosis of CBF AML based on the World Health Organization [WHO]
             classification)

          -  No prior chemotherapy for leukemia or myelodysplasia with the following exceptions:

               -  Emergency leukapheresis

               -  Emergency treatment for hyperleukocytosis with hydroxyurea,

               -  Cranial radiotherapy (RT) for central nervous system (CNS) leukostasis (one dose
                  only),

               -  Growth factor/cytokine support/non-cytotoxic molecular-targeted agents

          -  AML patients with a history of antecedent myelodysplasia (MDS) remain eligible for
             treatment on this trial

          -  Patients who have developed therapy related myeloid neoplasm (t-MN) after prior
             radiation therapy or chemotherapy for another cancer or disorder are eligible

          -  Left ventricular ejection fraction >= lower limit of institutional normal by
             multigated acquisition (MUGA) or echocardiogram (ECHO) scan

          -  Patients must not have had myocardial infarction within 6 months of registration

          -  Patients must not have had ventricular tachyarrhythmia within 6 months of registration

          -  Patients must have no major conduction abnormality (unless a cardiac pacemaker is
             present)

          -  Bilirubin must not be < 2.5 times upper limit of normal

          -  Patients must be non-pregnant and non-nursing; 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 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., intrauterine device [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, before she begins
             dasatinib therapy, during treatment and at least 12 weeks after treatment is complete;
             "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

          -  Patients with congenital long QT syndrome or non-congenital corrected QT (QTc)
             prolongation (defined as a QTc interval consistently equal to or greater than 480
             msecs) that cannot be corrected by infusion of electrolytes and/or discontinuation of
             other medications prior to start of treatment are excluded
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Guido Marcucci, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT01238211

Organization ID

NCI-2011-02615

Secondary IDs

NCI-2011-02615

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Guido Marcucci, Principal Investigator, Alliance for Clinical Trials in Oncology

Verification Date

January 2023