Clinical Trial: Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: APL-R2007: Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)
Brief Summary:
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
Detailed Summary:
Induction ATO 0.15 mg/kg/día IV in continuous perfusion 1-2 hours/day until complete response (CR) or maximum of 60 days.
Oral hydroxyurea treatment (initial dose 2 g/day)is recommended in patients with leucocyte counts at relapse >10x109/L or in the two first weeks of induction.
Isolated molecular relapsed patients will be treated with ATO (same dose) 5 days at week, during 6 weeks.
Consolidation ATO 0.15 mg/kg/día IV 5 days at week, during 5 weeks, combined with oral ATRA 45 mg/m²/day during the same 5 weeks.
Post-consolidation therapy TPH (autologous or allogenic) in candidate patients. In case of molecular remission, is recommended autologous-TPH.
Patients no candidates to auto-TPH or alo-TPH, should will follow treatment with ATO cycles + ATRA +/- Mylotarg.
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Option Alo-TPH If PCR post-consolidation is negative is recommended auto-TPH. However, if alo-TPH is decided, it will be done immediately without preceding chemotherapy.
If PCR post-consolidation is positive, should done alo-TPH.
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Option Auto-TPH If PCR post-consolidation is negative it will be administered one cycle of MTZ + Ara-C follow by auto-TPH.
In cas of failure: a) if patient has autologous stem cells preserved (PCR negative) are suitable for auto-TPH; b) patients with HLA-compatible donor who are suitable for allogenic stem cell transplantation should be transplanted; c) Patients wh
Sponsor: PETHEMA Foundation
Current Primary Outcome:
- 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 ]
Original Primary Outcome:
- Evaluate the hematological and molecular remission rate after induction and consolidation with ATO
- Evaluate the induction mortality with ATO in monotherapy
- Evaluate the hematological and molecular relapse rate in patients treated with autologous transplantation, allogenic transplantation or ATO + ATRA +/- Mylotarg
Current Secondary Outcome:
- 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 ]
Original Secondary Outcome:
- Evaluate kinetics of the MDR of PML/RARa during and after ATO
- Evaluate the mortality related with postremission treatment
- Side effects of ATO and the different treatments post-consolidation
- Overall survival
Information By: PETHEMA Foundation
Dates:
Date Received: July 19, 2007
Date Started: July 2007
Date Completion:
Last Updated: October 27, 2014
Last Verified: October 2014
