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