Clinical Trials /

Arsenic Trioxide and Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia (CML)

NCT01397734

Description:

In this research study, the investigators are looking to see whether the combination of arsenic trioxide with a tyrosine kinase inhibitor is safe, and what effects it has on chronic myelogenous leukemia.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Arsenic Trioxide</span> and Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia (<span class="go-doc-concept go-doc-disease">CML</span>)

Title

  • Brief Title: Arsenic Trioxide and Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia (CML)
  • Official Title: Targeting of the Leukemia Stem Cell Population With Arsenic Trioxide and Tyrosine Kinase Inhibitors for CML
  • Clinical Trial IDs

    NCT ID: NCT01397734

    ORG ID: 11-107

    Trial Conditions

    Chronic Myelogenous Leukemia

    Trial Interventions

    Drug Synonyms Arms
    Arsenic trioxide Cohort 1, Cohort 2, Cohort 3

    Trial Purpose

    In this research study, the investigators are looking to see whether the combination of
    arsenic trioxide with a tyrosine kinase inhibitor is safe, and what effects it has on
    chronic myelogenous leukemia.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Cohort 1 Experimental Patients who are receiving Imatinib as part of their standard of care therapy for CML. Arsenic trioxide
    Cohort 2 Experimental Patients who are receiving Dasatinib as part of their standard of care therapy for CML. Arsenic trioxide
    Cohort 3 Experimental Patients who are receiving Nilotinib as part of their standard of care therapy for CML. Arsenic trioxide

    Eligibility Criteria

    Inclusion Criteria:

    - Participants must have a diagnosis of chronic myelogenous leukemia as confirmed by
    fluorescent In Situ Hybridization (FISH) for BCR/ABL translocation and/or standard
    cytogenetics analysis.

    - Participants may have received prior hydroxyurea but may not be currently being
    treated with hydroxyurea at the time of study initiation.

    - Participants may have received prior TKI therapy, however must be on a stable dose of
    their current TKI for at least one month prior to enrollment.

    - Participants must demonstrate evidence of persistent disease either by
    cytogenetics/FISH or by PCR for BCR/ABL in the peripheral blood or bone marrow.

    - Greater than or equal to 18 years in age. Because little dosing or adverse event data
    are currently available on the use of Arsenic in participants <18 years of age,
    children are excluded from this study.

    - Life expectancy of greater than 3 months

    - ECOG performance status <2

    - Participants must have normal organ and marrow function as defined below:

    - Bilirubin 2.0 mg/dL

    - Creatinine 2 mg/dL

    - ALT < 2.5 X institutional upper limit of normal

    - AST < 2.5 X institutional upper limit of normal

    - WBC > 2.0 K/uL

    - Platelets >100K

    - Oxygen saturation > 95% on room air

    - The effects of Arsenic on the developing human fetus are unknown. For this reason,
    women of child-bearing potential must have a documented negative pregnancy test; in
    addition, agreement to use adequate contraception (hormonal or barrier method of
    birth control; abstinence) must be documented for both women of child-bearing
    potential and men prior to study entry and for the duration of study participation.
    Should a woman become pregnant or suspect she is pregnant while participating in this
    study, she should inform her treating physician immediately

    - All patients must demonstrate the ability to understand the investigational nature of
    this study and must sign a written informed consent document in accordance with
    institutional and federal guidelines

    Exclusion Criteria:

    - History of acute myocardial infarction, unstable angina, congestive heart failure, or
    arrhythmia within the last three months

    - Participants may not be receiving any other study agent

    - Mean QTc> 450 ms at time of screening

    - Use of potassium wasting diuretics during study treatment

    - Patients should not be taking drugs that are generally accepted to have a risk of
    causing Torsades de Pointes. The following must be discontinued at least 7 days
    prior to enrollment to be eligible: quinidine, procainamide, disopyramide,
    amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin,
    chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride,
    bepridil, droperidol, methadone, chloroquine, domperidone, halofantrine,
    levomethadyl, pentamidine, sparfloxacin, lidoflazine

    - Drugs that are highly dependent on CYP3A4 for metabolism and have a narrow
    therapeutic index (see Appendix A) are allowed but must be used with caution

    - Uncontrolled intercurrent illness including, but not limited to ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia, or psychiatric illness/social situations that would limit compliance with
    study requirements

    - Concurrent and or uncontrolled psychiatric or medical condition which may interfere
    with the study completion.

    - Pregnant women are excluded from this study because the risk of Arsenic to a
    developing fetus is unknown. Because there is an unknown but potential risk of
    adverse events in nursing infants secondary to treatment of the mother with Arsenic,
    breastfeeding should be discontinued if the mother is treated on this clinical trial

    - Individuals with a history of a different malignancy are ineligible except for the
    following circumstances. Individuals with a history of other malignancies are
    eligible if they have been disease-free for at least 5 years and are deemed by the
    investigator to be at low risk for recurrence of that malignancy. Individuals with
    the following cancers are eligible if diagnosed and treated within the past 5 years:
    cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin

    - HIV-positive individuals on combination antiretroviral therapy are ineligible because
    of the potential for pharmacokinetic interactions with TKI therapy and Arsenic. In
    addition, these individuals are at increased risk of lethal infections when treated
    with marrow-suppressive therapy.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of Participants with Adverse Events as a Measure of Safety and Toxicity

    Secondary Outcome Measures

    Disease Response

    PML Expression

    Trial Keywords

    CML

    Chronic myelogenous leukemia

    Chronic Myeloid leukemia

    Arsenic

    Arsenic trioxide

    Imatinib

    Dasatinib

    Nilotinib

    TKI

    Tyrosine kinase inhibitor