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

Sponsor

OHSU Knight Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00053248

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

5.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Leukemia	Drug: arsenic trioxide Drug: imatinib mesylate	Phase 1/Phase 2

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 .

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Masking:

None (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

Study Start Date :

Oct 1, 2002

Actual Primary Completion Date :

Jun 1, 2005

Actual Study Completion Date :

Jun 1, 2005

Outcome Measures

Primary Outcome Measures

Satey and Tolerability []
Dose-limiting toxicity []
Pharmacokinetics []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	UCLA Department of Medicine, Division of Hematology/Oncology	Los Angeles	California	United States	90095
2	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
3	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239