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

NCT01409161 · M.D. Anderson Cancer Center
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Official title
Phase II Study of Treatment of Acute Promyelocytic Leukemia (APL) With ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin (GO)
About this study
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.
Eligibility criteria
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
Study design
Enrollment target: 151 participants
Allocation: na
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2011-10-05
Estimated completion: 2027-12-18
Last updated: 2026-05-20
Interventions
Drug: Arsenic TrioxideDrug: Gemtuzumab OzogamicinOther: Laboratory Biomarker AnalysisDrug: Tretinoin
Primary outcomes
  • Event free survival (The time from the start of treatment to first documentation of disease relapse or death, assessed up to 2 years)
Sponsor
M.D. Anderson Cancer Center · other
With: National Cancer Institute (NCI)
Contacts & investigators
ContactFarhad Ravandi-Kashani · contact · fravandi@mdanderson.org · 713-745-0394
InvestigatorFarhad Ravandi-Kashani · principal_investigator, M.D. Anderson Cancer Center
All locations (5)
M D Anderson Cancer CenterRecruiting
Houston, Texas, United States
MD Anderson Regional Care Center-KatyRecruiting
Houston, Texas, United States
MD Anderson Regional Care Center-Bay AreaRecruiting
Nassau Bay, Texas, United States
MD Anderson Regional Care Center-Sugar LandRecruiting
Sugar Land, Texas, United States
MD Anderson Regional Care Center-The WoodlandsRecruiting
The Woodlands, Texas, United States
Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia · TrialPath