Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)

• Status: Completed
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

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 (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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PETHEMA Foundation
• Treatments: Arsenic Trioxide

Criteria

Inclusion Criteria:

• ECOG ≤ 3.

• Patients in first or subsequent hematological or molecular relapse of APL

• Persistence of a positive PCR (positive PCR after 3 consolidation cycles of first line therapy).

• Diagnostic measures Confirmation of relapse by RT-PCR of PML/RARa, cytogenetics, FISH or positive PGM3.

• Age over 18 years (No upper age limit)

• Informed consent of the patient

Exclusion Criteria:

• ECOG 4.

• Heart failure NYHA grade III and IV.

• Renal or hepatic failure WHO grade ³III

• Positive HIV.

• Psychological dysfunction

• Associated active neoplasia

• Pregnancy.

• Arsenic Hypersensibility.

• QTc-interval prolonged over 460 msec before therapy (normal electrolytes, no other drugs prolonging the QT-interval )