Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia

PRIMARY OBJECTIVES:

I. Assess whether a combination of all-trans retinoic acid (ATRA [tretinoin]), and arsenic
trioxide (ATO) can produce long-term event-free survival in patients with low-risk untreated
acute promyelocytic leukemia (APL).

II. Assess whether administration of gemtuzumab ozogamicin (GO) at the diagnosis in patients
with high-risk APL (white blood cell [WBC] > 10,000) and if the WBC rises to > 10,000 after
start of treatment (in patients with low-risk disease) will improve complete response (CR)
rate without increasing toxicity in high-risk untreated APL.

OUTLINE:

INDUCTION: Patients receive tretinoin orally (PO) twice daily (BID), arsenic trioxide
intravenously (IV) over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at
weeks 1-4.

CONSOLIDATION: Patients achieving CR receive arsenic trioxide IV 5 days per week during weeks
1-4, 9-12, 17-20, and 25-28 and tretinoin PO BID for 2 weeks on and 2 weeks off. Treatment
repeats every 8 weeks for up to 4 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months.

Inclusion Criteria:

- A diagnosis of APL based on the presence of the PML-RAR-alpha fusion gene by
cytogenetics, polymerase chain reaction (PCR), or POD test

- Ability to understand and the willingness to sign a written informed consent document
indicating that they are aware of the investigational nature of the study

- Patients in whom therapy for APL was initiated on an emergent basis are eligible
(patients may have already started treatment with ATRA, ATO, and/or one dose of
idarubicin due to the urgency to start therapy early)

- Women of child-bearing potential must have a negative serum pregnancy test at
screening; in addition to having a negative pregnancy test confirmed at screening, all
female participants of childbearing potential must have a negative pregnancy test
confirmed within 48 hours prior to dosing with the study drug

- All sexually active subjects (males and females of child-bearing potential) agree to
use 2 effective methods of contraception for the duration of the study

Exclusion Criteria:

- Fridericia corrected QT (QTcF) interval on the electrocardiogram (EKG) greater than
480 milliseconds

- Patients with creatinine > 2.5 times upper limit of normal unless felt to be related
the underlying leukemia by the treating physician or hemolysis or Gilbert's disease

- Patients with total bilirubin >= 2.0 times upper limit of normal unless felt to be
related the underlying leukemia by the treating physician or hemolysis or Gilbert's
disease

- Patients with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3
times upper limit of normal unless felt to be related the underlying leukemia by the
treating physician or hemolysis or Gilbert's disease