Clinical Trials /

Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia

NCT01876953

Description:

This phase I/II trial studies the side effects and best dose of dasatinib when given together with cytarabine and idarubicin hydrochloride and to see how well they work in treating patients with acute myeloid leukemia that is likely to come back or spread. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with cytarabine and idarubicin hydrochloride may be a better treatment for acute myeloid leukemia.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia
  • Official Title: Phase I/II Study of the Combination of Dasatinib With Chemotherapy for High Risk Acute Myeloid Leukemia (AML) Patients

Clinical Trial IDs

  • ORG STUDY ID: 12393
  • SECONDARY ID: NCI-2013-01141
  • NCT ID: NCT01876953

Conditions

  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Recurrent Adult Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Untreated Adult Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
cytarabineARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinosideTreatment (cytarabine, idarubicin, and dasatinib)
idarubicin4-demethoxydaunorubicin, 4-DMDR, DMDR, IDATreatment (cytarabine, idarubicin, and dasatinib)
dasatinibBMS-354825, SprycelTreatment (cytarabine, idarubicin, and dasatinib)

Purpose

This phase I/II trial studies the side effects and best dose of dasatinib when given together with cytarabine and idarubicin hydrochloride and to see how well they work in treating patients with acute myeloid leukemia that is likely to come back or spread. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with cytarabine and idarubicin hydrochloride may be a better treatment for acute myeloid leukemia.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Of the dose levels studied, to determine the maximum tolerated dose of dasatinib when
      given in combination with cytarabine and idarubicin for treatment of high risk acute myeloid
      leukemia (AML). (Phase I)

      II. To determine the anti-tumor activity of dasatinib when given in combination with
      cytarabine and idarubicin, as assessed by complete remission rate (CR) and remission
      duration. (Phase II)

      SECONDARY OBJECTIVES:

      I. To document CR and survival outcomes (overall, event-free). (Phase I)

      II. To estimate the survival probabilities (overall and event-free) and cumulative incidence
      of relapse/progression. (Phase II)

      III. To describe and summarize all toxicities by organ and severity. (Phase II)

      OUTLINE: This is a phase I, dose-escalation study of dasatinib, followed by a phase II study.

      Patients receive cytarabine intravenously (IV) continuously over 168 hours on days 1-7,
      dasatinib orally (PO) once daily (QD) on days 1-7, and idarubicin hydrochloride IV on days
      1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy
      (re-induction therapy) within 1 week in the absence of unacceptable toxicity.

      After completion of study treatment, patients are followed up for 30 days and then every 2
      months for up to 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cytarabine, idarubicin, and dasatinib)ExperimentalPatients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
  • cytarabine
  • idarubicin
  • dasatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients diagnosed with AML meeting one of the following criteria:

               -  Newly diagnosed, age 60 and older

               -  High risk cytogenetics and molecular abnormalities (National Comprehensive Cancer
                  Network [NCCN] criteria)

               -  Relapsed or refractory to prior chemotherapy

               -  Secondary AML

          -  Any prior chemotherapy must have been completed >= 2 weeks prior to day 1 of study
             treatment and the participant must have recovered to eligibility levels from prior
             toxicity

               -  Only one prior regimen is allowed for relapsed AML patients; note one prior
                  regimen is defined as follows:

                    -  Induction chemotherapy followed by consolidation is considered one regimen

                    -  Induction chemotherapy followed by re-induction in case of persistent
                       disease followed by consolidation is considered one regimen

               -  Hydroxyurea is allowed prior to day 1 of study treatment to keep white blood cell
                  (WBC) below 20 K

          -  Karnofsky performance status >= 60%

          -  Total bilirubin < 1.5 x institutional upper limit of normal

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Creatinine < 1.5 x institutional upper limit or normal OR creatinine clearance >= 60
             mL/min for patients with creatinine levels above 1.5 x institutional upper limit of
             normal

          -  Ejection fraction (EF) >= 45%

          -  Ability to understand and sign a written informed consent document

          -  Patients should not be receiving any other investigational agents

        Exclusion Criteria:

          -  Patients with clinically significant illness which would compromise participation in
             the study, including, but not limited to: active or uncontrolled infection, immune
             deficiencies or confirmed diagnosis of human immunodeficiency virus (HIV) infection,
             active hepatitis B, active hepatitis C, or uncontrolled diabetes, uncontrolled
             hypertension, symptomatic congestive heart failure, unstable angina pectoris,
             myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmias; or
             psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Patients with additional (other than AML) currently active primary malignancy other
             than curatively treated carcinoma in situ (CIS) of the cervix, or basal or squamous
             cell carcinoma of the skin; patients are not considered to have a "currently active"
             malignancy if they have completed therapy for a prior malignancy and disease free from
             prior malignancies for > 2 years

          -  Patients with active central nervous system (CNS) disease

          -  Patients with Chronic Myelogenous Leukemia (CML) in Myeloid blasts crisis

          -  Active infections, including opportunistic infections

          -  Women of childbearing potential (WOCBP) who have a positive serum pregnancy test
             within 14 days of the first administration of oral dasatinib
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of dasatinib, determined according to incidence of dose limiting toxicity (DLT), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Time Frame:Up to 42 days
Safety Issue:
Description:Remission rates will be calculated as the percent of evaluable patients that have a confirmed CR, and exact 95% confidence intervals will be calculated for these estimates.

Secondary Outcome Measures

Measure:Remission duration (Phase II)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier.
Measure:Overall survival (Phase II)
Time Frame:Time from start of study therapy until death, or last contact, whichever comes first, assessed up to 2 years
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier.
Measure:Event-free survival (Phase II)
Time Frame:Time from start of study therapy until death, relapse/progression, receipt of anti-leukemia therapy, or last contact, whichever comes first, assessed up to 2 years
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier.
Measure:Cumulative incidence of relapse/progression (Phase II)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Incidence of toxicities, graded according to NCI CTCAE version 4.0(Phase II)
Time Frame:Up to 30 days
Safety Issue:
Description:Observed toxicities will be summarized in terms of type (organ affected or laboratory determination) severity (by NCI CTCAE v4.0), date of onset, duration, reversibility, and attribution. Tables will be created to summarize these toxicities and side effects.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:City of Hope Medical Center

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