Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)
Summary Acute promyelocytic leukemia is defined by a characteristic morphology (AML FAB M3/M3v), by the specific translocation t(15;17) and its molecular correlates (PML/RARa and RARa/PML). Thereby it can be separated from all other forms of acute leukemia.
By all-trans retinoic acid in combination with chemotherapy cure rates of 70 to 80% can be reached. On average, about 10% of patients still die in the early phase of the treatment and about 20 to 30% relapse. Molecular monitoring of the minimal residual disease (MRD) by qualitative nested RT-PCR and quantitative REAL-time PCR of PML/RARa allows to follow the individual kinetics of MRD and to identify patients with an imminent hematological relapse.
A standardized treatment for patients with relapsed APL has not yet been established. With arsenic trioxide (ATO) monotherapy remission rates over 80% were achieved and long-lasting molecular remissions are described. The drug was mostly well tolerated. ATO exerts a dose dependent dual effect on APL blasts, apoptosis in higher and partial differentiation in lower concentrations. ATO was also successfully administered before allogeneic and autologous transplantation. ATO is approved for the treatment of relapsed and refractory APL in Europe and in the USA.
After remission induction, there are several options for postremission therapy Previous studies shows that risk of relapse is higher in patients treated with ATO postremission in monotherapy , than in other that receive ATO plus chemotherapy or transplantation (TPH). Also, compared with chemotherapy, ATO induction and consolidation has a favorable impact in posterior response to transplantation. It is due to a low toxicity or a best quality of remission to TPH. It seems better, for these reasons, the intensification with TPH (autologous or allogenic) in patients with relapsed APL treated with ATO. For another hand, patients no candidates to TPH can be treated with ATO combined with other active agents in APL, as ATRA, anthracyclines o Mylotarg
Acute Promyelocytic Leukemia
Drug: Arsenic Trioxide
Procedure: Autologous Transplantation
Procedure: Allogenic Transplantation
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||APL-R2007: Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)|
- Evaluate the hematological and molecular remission rate after induction and consolidation with ATO [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Evaluate the induction mortality with ATO in monotherapy [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Evaluate the hematological and molecular relapse rate in patients treated with autologous transplantation, allogenic transplantation or ATO + ATRA +/- Mylotarg [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Evaluate kinetics of the MDR of PML/RARa during and after ATO [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Evaluate the mortality related with postremission treatment [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Side effects of ATO and the different treatments post-consolidation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2007|
|Study Completion Date:||October 2014|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Drug: Arsenic Trioxide
Induction ATO 0.15 mg/kg/day IV until CR or a maximum of 60 days In isolated molecular relapse ATO will be administered at same dose, 5 days a week, during 6 weeks.
Consolidation ATO 0.15 mg/kg/day IV 5 days week, during 5 weeks
Please refer to this study by its ClinicalTrials.gov identifier: NCT00504764
Show 85 Study Locations
|Study Chair:||Sanz Miguel Angel, Dr||Hospital La Fe|
|Study Chair:||Esteve Jordi, Dr||Hospital Clinic of Barcelona|
|Study Chair:||Montesinos Pau, Dr||Hospital General de Valencia|