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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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Leukemia

Thank you

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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of one of the following:

- Chronic myelogenous leukemia (CML) in one of the following phases:

- Blastic phase*

- Accelerated phase*

- No appropriate donors for stem cell transplantation NOTE: *Must have
received high-dose (600-800 mg/day) imatinib mesylate of no more than
3 months duration

- Acute lymphoblastic leukemia

- Philadelphia chromosome positive by cytogenetic confirmation

- Patients with only bcr-abl-positive disease by polymerase chain
reaction are not eligible

- > 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Ellin Berman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

03-126

NCT ID:

NCT00081133

Start Date:

December 2003

Completion Date:

February 2005

Related Keywords:

  • Leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • recurrent adult acute lymphoblastic leukemia
  • untreated adult acute lymphoblastic leukemia
  • Blast Crisis
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Philadelphia Chromosome

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021