Trial Information

APL-R2007: Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)

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.

1. 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.

2. 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 who are not
eligible for allogenic or autologous transplantation, receive various cycles with ATO +
ATRA combined or not with Mylotarg.

If PCR post-consolidation is positive and patient is eligible for allogenic TPH, should
be done a allogenic TPH.

If patient is no eligible for allogenic TPH or dont has compatible donor, will be
administrate one cycle of MTZ + Ara-C and collect stem cells. Autologous
transplantation will be done if after this cycle, a molecular remission is obtained. No
molecular remission or no enough stem cells collection, patient follows treatment with
subsequent cycles of ATO + ATRA combined or no with Mylotarg.

3. ATO + ATRA combined or no with Mylotarg Patients no eligible to autologous TPH or
allogenic TPH follows treatment with subsequent cycles of ATO + ATRA combined or no
with Mylotarg.

If Mylotarg is no possible, treatment will be with subsequent cycles of ATO + ATRA.

ATO + ATRA + Mylotarg: Mylotarg 6 mg/m2 day 1, ATO 0.15 mg/kg days 1 to 5 and 8 to 12, and
ATRA 45 mg/m2/d days 1 to 15. Doses of mylotarg should be reduced to 3 mg/m2 in patients
aged over 60 years. Administration of 3 cycles with a month interval, follow of 3 to 6
cycles of ATO + ATRA without Mylotarg. After, ATRA 45 mg/m2/d 15 days every 3 months until
complete two years of maintenance.

ATO + ATRA: ATO 0.15 mg/kg days 1 to 5 and 8 to 12, and ATRA 45 mg/m2/d days 1 to 15, every
29 days. Administration of 9 cycles, and followed by ATRA 45 mg/m2/d during 15 days every 3
months until complete two years of maintenance.