Ignite Creation Date:
2024-05-05 @ 6:34 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00504764
Status:
COMPLETED
Last Update Posted:
2014-10-28
First Post:
2007-07-19
Brief Title:
Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide ATO
Sponsor:
PETHEMA Foundation
Organization:
PETHEMA Foundation
Study Overview
Official Title:
APL-R2007 Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide ATO
Status:
COMPLETED
Status Verified Date:
2014-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Summary Acute promyelocytic leukemia is defined by a characteristic morphology AML FAB M3M3v by the specific translocation t1517 and its molecular correlates PMLRARa and RARaPML 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 PMLRARa 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
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 PMLRARa 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
Detailed Description:
Induction ATO 015 mgkgdía IV in continuous perfusion 1-2 hoursday until complete response CR or maximum of 60 days
Oral hydroxyurea treatment initial dose 2 gdayis recommended in patients with leucocyte counts at relapse 10x109L 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 015 mgkgdía IV 5 days at week during 5 weeks combined with oral ATRA 45 mgm²day 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 mgm2 day 1 ATO 015 mgkg days 1 to 5 and 8 to 12 and ATRA 45 mgm2d days 1 to 15 Doses of mylotarg should be reduced to 3 mgm2 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 mgm2d 15 days every 3 months until complete two years of maintenance
ATO ATRA ATO 015 mgkg days 1 to 5 and 8 to 12 and ATRA 45 mgm2d days 1 to 15 every 29 days Administration of 9 cycles and followed by ATRA 45 mgm2d during 15 days every 3 months until complete two years of maintenance
Oral hydroxyurea treatment initial dose 2 gdayis recommended in patients with leucocyte counts at relapse 10x109L 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 015 mgkgdía IV 5 days at week during 5 weeks combined with oral ATRA 45 mgm²day 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 mgm2 day 1 ATO 015 mgkg days 1 to 5 and 8 to 12 and ATRA 45 mgm2d days 1 to 15 Doses of mylotarg should be reduced to 3 mgm2 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 mgm2d 15 days every 3 months until complete two years of maintenance
ATO ATRA ATO 015 mgkg days 1 to 5 and 8 to 12 and ATRA 45 mgm2d days 1 to 15 every 29 days Administration of 9 cycles and followed by ATRA 45 mgm2d during 15 days every 3 months until complete two years of maintenance
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None