Arsenic Trioxide and Imatinib Mesylate in Treating Patients With Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

NCT ID: NCT00081133

Last Updated: 2013-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-12-31
• Study Completion Date: 2005-02-28

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, work in 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 their growth. Combining arsenic trioxide with imatinib mesylate may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of arsenic trioxide when given with imatinib mesylate and to see how well they work in treating patients with accelerated phase or blastic phase chronic myelogenous leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolererated dose of arsenic trioxide when administered with imatinib mesylate in patients with accelerated or blastic phase chronic myelogenous leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.
• Determine the rate of complete morphologic remission in the bone marrow of patients treated with this regimen.

OUTLINE: This is a phase I dose-escalation study of arsenic trioxide followed by a phase II study.

• Phase I:

• Induction therapy: Patients receive oral imatinib mesylate once daily on days 1-35 (weeks 1-5) and arsenic trioxide IV over 1-4 hours on days 1-5, 8-12, 15-19, and 22-26 (weeks 1-4).

Patients undergo bone marrow evaluation on week 5. Patients achieving a morphologic remission proceed to consolidation therapy. Patients not achieving morphologic remission receive a second course of imatinib mesylate as above on weeks 6-10 and arsenic trioxide as above on weeks 6-9. Patients are re-evaluated on week 10. Patients achieving morphologic remission proceed to consolidation therapy. Patients not achieving a morphologic remission are removed from study.

• Consolidation therapy: Patients receive oral imatinib mesylate as in induction therapy on approximately weeks 6-11 (or weeks 11-16*) and arsenic trioxide IV over 1-4 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (approximately weeks 6-9 OR weeks 11-14*).

Patients who remain in morphologic remission receive a second course of imatinib mesylate as in induction therapy on approximately weeks 12-17 (or weeks 17-22*) and arsenic trioxide as above (in consolidation therapy) on approximately weeks 12-15 (or weeks 17-20*).

NOTE: *For patients who receive a second course of induction therapy

Cohorts of 6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive arsenic trioxide at the MTD and imatinib mesylate as in phase I.

Treatment in both phases continues in the absence of unacceptable toxicity or disease progression.

After completion of consolidation therapy, patients may continue imatinib mesylate off study at the discretion of the physician. Patients who become candidates for stem cell transplantation at any time during the study are removed from study.

PROJECTED ACCRUAL: A total of 6-43 patients (6-12 for phase I and 37 [including 6 patients from phase I] for phase II) will be accrued for this study within 2 years.

Conditions

Leukemia

Study Design

• Primary Study Purpose: TREATMENT

Interventions

arsenic trioxide

Intervention Type: DRUG

imatinib mesylate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• > 10% blasts in the bone marrow
• No isolated extramedullary disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST ≤ 2 times ULN
• INR and PTT ≤ 1.5 times ULN (except for patients on anticoagulation therapy)

Renal

• Creatinine ≤ 2 times ULN

Cardiovascular

• Baseline QTc intervals < 480 ms
• No chronic arrhythmias
• No active coronary artery disease

Other

• No chronic electrolyte abnormalities
• No prior non-compliance to medical regimens
• No patients who are considered potentially unreliable
• No active serious infection
• No other active malignancies except superficial epithelial cancers
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for at least 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior peripheral blood stem cell or bone marrow transplantation

Chemotherapy

• Prior hydroxyurea allowed
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• More than 4 weeks since prior major surgery and recovered

Other

• Prior anagrelide allowed
• No concurrent warfarin for therapeutic anticoagulation

• Concurrent low molecular weight heparin is allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Ellin Berman, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

CDR0000358923

Identifier Type: REGISTRY

Identifier Source: secondary_id

03-126

Identifier Type: -

Identifier Source: org_study_id