Clinical Trial: Single Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia
Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional
Official Title: Molecular Remission With Arsenic Trioxide in Acute Promyelocytic Leukemia: Indian APL Study Group - IAPLSG
Brief Summary: There is very limited data on the use of arsenic trioxide in newly diagnosed patients with acute promyelocytic leukemia. The use of arsenic trioxide was limited to relapsed patients mainly because of the superior efficacy of ATRA as primary therapy for newly diagnosed APML. Though the early study by Niu et al showed 72% remission rates in 11 newly diagnosed patients, the role of arsenic trioxide as primary therapy was limited by the hepatic toxicity seen in this study. Studies from our centre have shown remission rates of 70-75% in newly diagnosed patients with acute promyelocytic leukemia. There was no major toxicity seen related to the administration of arsenic trioxide. Follow up data on these patients continue to show long term remission rates above 70%. These remission rates are similar to the data available in patients with acute promyelocytic leukemia treated with ATRA. Lu et al studied 19 patients treated with oral arsenic (Tetra-arsenic tetra-sulfide) wherein 84% achieved hematological remission with disease free survival of 76% at 3 years. Studies from other groups using arsenic trioxide alone or in combination with ATRA have shown similar remission rates. Arsenic trioxide as primary therapy for patients with newly diagnosed acute promyelocytic leukemia is a very attractive treatment option for developing countries mainly because of the low cost involved along with the favorable toxicity profile. However long term remission data is still not available and the ideal course and duration of treatment still needs to be defined. This multi-center study aims to further clarify the efficacy of this agent in the treatment of newly diagnosed cases of acute promyelocytic leukemia and to study the optimal maintenance regimen.
Detailed Summary:
This multicenter trial will study the clinical and molecular response among patients with newly diagnosed acute promyelocytic leukemia (APL) who fulfill the inclusion and exclusion criteria.
Patients included in this trial should have been diagnosed to have Acute Promyelocytic Leukemia morphologically on FAB criteria. This is sufficient to initiate therapy with arsenic trioxide (ATO) but this diagnosis has to be confirmed using either Fluorescent in situ hybridization (FISH) for t(15;17) or reverse transcriptase polymerase chain reaction assay (RT-PCR) for PML-RARalpha transcripts within 7 days of inclusion into the study.
All these patients would have in the absence of this study received only palliative therapy due to the lack of resources to support standard chemotherapy.
Women who are pregnant will not be considered for this study.
Treatment Protocol: All patients who are included in this study will be initiated on treatment with ATO. Arsenic tri-oxide (10 mg/10ml) will be diluted in 500 ml of Dextrose Saline (only glass bottles to be used) and infused intravenously over 3 - 4 hours once a day.
No premedication is required prior to administration of the drug. The dosage schedule for administration will be as follows:
Adults: 10 mg once a day Children or adults <45kg: 0.15 mg/kg/day (maximum dose = 10mg) once a day
The total courses of therapy will be as follows:
Induction therapy: Induction therapy will be continued till ANC> 1.5 x 10e9/L and Platelet count > 100 x 10e9/L along with the absence of abnormal promyeloc
Sponsor: Christian Medical College, Vellore, India
Current Primary Outcome:
- Measure complete hematological remission rate [ Time Frame: 60 days ]
- Measure complete molecular remission rate [ Time Frame: 3 months ]
- Measure duration of response [ Time Frame: 5 years ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Document early and late toxicities [ Time Frame: 5 years ]
- Measure relapse rates [ Time Frame: 5 years ]
- Measure treatment related mortality [ Time Frame: 60 days ]
Original Secondary Outcome: Same as current
Information By: Christian Medical College, Vellore, India
Dates:
Date Received: August 16, 2007
Date Started: June 2004
Date Completion: July 2009
Last Updated: August 16, 2007
Last Verified: August 2007
