Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)
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|ClinicalTrials.gov Identifier: NCT00504764|
Recruitment Status : Completed
First Posted : July 20, 2007
Last Update Posted : October 28, 2014
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
|Condition or disease||Intervention/treatment||Phase|
|Acute Promyelocytic Leukemia||Drug: Arsenic Trioxide Procedure: Autologous Transplantation Procedure: Allogenic Transplantation Drug: ATRA||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||APL-R2007: Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)|
|Study Start Date :||July 2007|
|Actual Primary Completion Date :||October 2014|
|Actual Study Completion Date :||October 2014|
- 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
- Procedure: Autologous Transplantation
- Procedure: Allogenic Transplantation
- Drug: ATRA
Consolidation: ATRA 45 mg/m²/day oral during 5 weeks
- Evaluate the hematological and molecular remission rate after induction and consolidation with ATO [ Time Frame: 1 year ]
- Evaluate the induction mortality with ATO in monotherapy [ Time Frame: 1 year ]
- Evaluate the hematological and molecular relapse rate in patients treated with autologous transplantation, allogenic transplantation or ATO + ATRA +/- Mylotarg [ Time Frame: 1 year ]
- Evaluate kinetics of the MDR of PML/RARa during and after ATO [ Time Frame: 2 years ]
- Evaluate the mortality related with postremission treatment [ Time Frame: 1 year ]
- Side effects of ATO and the different treatments post-consolidation [ Time Frame: 2 years ]
- Overall survival [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00504764
|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 Universitario de Valencia|