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

NCT01397734 | Terminated Phase 1 DMC

• 1 other identifier: 11-107
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Myelogenous Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  To assess the safety and toxicity of arsenic in combination with TKI therapy for chronic phase CML patients

  1, 2, 6, 12 months

Secondary Outcomes (2)

• Disease Response

  1, 2, 6, 12 months

• PML Expression

  1, 6, 12 months

Study Arms (3)

Cohort 1

EXPERIMENTAL

Patients who are receiving Imatinib as part of their standard of care therapy for CML.

Drug: Arsenic trioxide

Cohort 2

EXPERIMENTAL

Patients who are receiving Dasatinib as part of their standard of care therapy for CML.

Drug: Arsenic trioxide

Cohort 3

EXPERIMENTAL

Patients who are receiving Nilotinib as part of their standard of care therapy for CML.

Drug: Arsenic trioxide

Interventions

Arsenic trioxide DRUG

0.15mg/kg/day Arsenic trioxide given IV on days 1-5 of the cycle.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• National Institutes of Health (NIH): collaborator
• Teva Pharmaceuticals USA: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Arsenic Trioxide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Officials

• David E Avigan, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: July 18, 2011
• First Posted: July 20, 2011
• Study Start: September 1, 2011
• Primary Completion: August 6, 2018
• Study Completion: August 6, 2018
• Last Updated: September 6, 2018

Record last verified: 2018-09

Locations

US (1)