Phase II Study of Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy

Inclusion Criteria:

- Previously untreated patients with a morphologic diagnosis of APL, confirmed by
demonstration of t(15;17) using conventional cytogenetics or florescence in situ
hybridization (FISH), or a positive RT-PCR assay for PML-RAR at the subject's local
institution.

- Age ≥18 years. Karnofsky performance status of ≥ 60%.

- Adequate renal function as demonstrated by a serum creatinine ≤ 2.0 mg/dl or a
creatinine clearance of > 60 ml/min.

- Adequate hepatic function as demonstrated by a bilirubin < 2.0 mg/dl (unless
attributable to Gilbert's disease) and an alkaline phosphatase, AST, and ALT ≤ 2.5
times the upper limit of normal.

- Normal cardiac function as demonstrated by a left ventricular ejection fraction ≥ 50%
on echocardiogram or MUGA scan.

- QTc ≤ 500 msec on baseline ECG.

- Negative serum pregnancy test in women of childbearing potential.

- Ability to swallow oral medication.

- Men and women of child-bearing potential must be willing to practice an effective
method of birth control during treatment and at least 4 months after treatment is
finished.

- Patients with central nervous system involvement by APL are eligible and may receive
concomitant treatment with radiation therapy and/or intrathecal chemotherapy in
accordance with standard medical practice.

Exclusion Criteria:

- Previous treatment for APL, except tretinoin, which may be given for up to 7 days
prior to study entry.

- Active serious infections not controlled by antibiotics.

- Pregnant women or women who are breast-feeding.

- Concurrent active malignancy requiring immediate therapy.

- Clinically significant cardiac disease (NY Heart Association Class III or IV),
including chronic arrhythmias, or pulmonary disease.

- Other serious or life-threatening conditions deemed unacceptable by the principal
investigator.