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

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

  • ORG STUDY ID: 11-107
  • NCT ID: NCT01397734

Conditions

  • Chronic Myelogenous Leukemia

Interventions

DrugSynonymsArms
Arsenic trioxideCohort 1

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalPatients who are receiving Imatinib as part of their standard of care therapy for CML.
  • Arsenic trioxide
Cohort 2ExperimentalPatients who are receiving Dasatinib as part of their standard of care therapy for CML.
  • Arsenic trioxide
Cohort 3ExperimentalPatients 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Adverse Events as a Measure of Safety and Toxicity
Time Frame:1, 2, 6, 12 months
Safety Issue:
Description:To assess the safety and toxicity of arsenic in combination with TKI therapy for chronic phase CML patients

Secondary Outcome Measures

Measure:Disease Response
Time Frame:1, 2, 6, 12 months
Safety Issue:
Description:To assess disease response after combined therapy arsenic trioxide and imatinib (cohort 1), dasatinib (cohort 2) or nilotinib (cohort 3) by bone marrow cytogenetic assessment and serial BCR-ABL QPCR from peripheral blood and bone marrow measurements. Rates of major and complete cytogenetic and molecular responses will be determined.
Measure:PML Expression
Time Frame:1, 6, 12 months
Safety Issue:
Description:To assess whether combined therapy with arsenic and imatinib, dasatinib or nilotinib results in decreased PML expression on the CML stem cell compartment, and decreased capacity of CML stem cells to maintain long term proliferative capacity.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Beth Israel Deaconess Medical Center

Trial Keywords

  • CML
  • Chronic myelogenous leukemia
  • Chronic Myeloid leukemia
  • Arsenic
  • Arsenic trioxide
  • Imatinib
  • Dasatinib
  • Nilotinib
  • TKI
  • Tyrosine kinase inhibitor

Last Updated

September 6, 2018