Arsenic Trioxide and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00053248
First received: January 27, 2003
Last updated: May 24, 2012
Last verified: June 2010
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining chemotherapy with imatinib mesylate may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining arsenic trioxide with imatinib mesylate in treating patients who have chronic phase chronic myelogenous leukemia.


Condition Intervention Phase
Leukemia
Drug: arsenic trioxide
Drug: imatinib mesylate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study To Determine The Safety, Tolerability, And Anti-Leukemic Effects of Trisenox (Arsenic Trioxide) In Combination With Gleevec (STI571) In Patients With Resistant Chronic Myelogenous Leukemia In Chronic Phase

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Satey and Tolerability [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: October 2002
Study Completion Date: June 2005
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the safety and tolerability of arsenic trioxide and imatinib mesylate in patients with resistant chronic phase chronic myelogenous leukemia.
  • Determine potential dose-limiting toxic effects in patients treated with this regimen.
  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral imatinib mesylate once daily and arsenic trioxide IV over 1-2 hours on days 1-5 of week 1 and then twice weekly. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 18-24 patients (at least 6 patients for phase I and at least 12 patients for phase II) will be accrued for this study .

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Cytogenetically confirmed Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia, meeting one of the following criteria:

    • Chronic phase

      • Less than 15% blasts in peripheral blood or marrow
      • Less than 30% blasts and promyelocytes in peripheral blood or marrow
      • Less than 20% basophils in blood or marrow
      • Platelet count at least 100,000/mm^3 (unless therapy related)
      • No progressive (increase of at least 10 cm in any 4 of the past 24 weeks) or existing (greater than 10 cm) splenomegaly
    • Complete hematologic response (CHR)

      • No immature myeloid cells in peripheral blood
      • No increased basophils in peripheral blood
      • WBC less than upper limit of normal (ULN)
      • Platelet count less than ULN
      • No major (less than 35% Ph+) or complete (0% Ph+) cytogenetic response after at least 6 months of imatinib mesylate

        • Loss of prior major cytogenetic response or failure to achieve major cytogenetic response

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin less than 1.5 times ULN
  • AST or ALT less than 2.5 times ULN

Renal

  • Creatinine less than 1.5 times ULN

Cardiovascular

  • No New York Heart Association grade III or IV congestive heart failure
  • No untreated symptomatic cardiac ischemia
  • No underlying cardiac arrhythmia, including but not limited to any of the following:

    • Conduction abnormality/atrioventricular heart block
    • Nodal/junctional arrhythmia/dysrhythmia
    • Sinus bradycardia or tachycardia
    • Supraventricular tachycardia
    • Ventricular arrhythmia

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 methods of effective barrier contraception during and for 3 months after study
  • Electrolyte levels (especially potassium and magnesium) normal (CHR patients)
  • No history of noncompliance that would preclude study participation
  • No other concurrent serious, uncontrolled medical condition
  • No grade 2 or greater neuropathy

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Not specified

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • More than 14 days since prior therapy except hydroxyurea, anagrelide hydrochloride, or imatinib mesylate
  • More than 28 days since prior investigational agents
  • No concurrent grapefruit or grapefruit juice
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053248

Locations
United States, California
UCLA Department of Medicine, Division of Hematology/Oncology
Los Angeles, California, United States, 90095
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Michael Mauro, MD OHSU Knight Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00053248     History of Changes
Other Study ID Numbers: CDR0000269319, OHSU-UCLA-0206062, OHSU-HEM-02001-L, OHSU-1096
Study First Received: January 27, 2003
Last Updated: May 24, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by OHSU Knight Cancer Institute:
chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib
Arsenic trioxide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014