Trial Information

A Phase I/II Study to Determine Safety and Efficacy of Arsenic Trioxide (Trisneox™) in Combination With Imatinib (STI571, Gleevec™) in Patients With Chronic Myelogenous Leukemia in Accelerated or Blastic Phase Disease or Ph+ Acute Lymphoblastic Leukemia

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.