Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002701
Status:
UNKNOWN
Last Update Posted:
2013-09-20
First Post:
1999-11-01
Brief Title:
Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Promyelocytic Leukemia
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
INDUCTION WITH ALL-TRANS RETINOIC ACID IN COMBINATION WITH IDARUBICIN AND INTENSIVE CONSOLIDATION FOLLOWED BY BONE MARROW TRANSPLANTATION OR A RANDOMIZED MAINTENANCE TREATMENT DEPENDING UPON THE AMOUNT OF MINIMAL RESIDUAL DISEASE IN ACUTE PROMYELOCYTIC LEUKEMIA
Status:
UNKNOWN
Status Verified Date:
2006-11
Last Known Status:
ACTIVE_NOT_RECRUITING
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:
RATIONALE Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy to kill tumor cells It is not yet known which regimen of combination chemotherapy with or without bone marrow transplantation is more effective in treating promyelocytic leukemia
PURPOSE Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens with or without bone marrow transplantation in treating patients who have promyelocytic leukemia
PURPOSE Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens with or without bone marrow transplantation in treating patients who have promyelocytic leukemia
Detailed Description:
OBJECTIVES
Determine the complete remission CR rate in patients with acute promyelocytic leukemia treated with induction comprising tretinoin ATRA and idarubicin IDA
Determine the presence of the promyelocyte-retinoic acid receptor alpha PML-RARa transcript using polymerase chain reaction PCR in patients with CR after 3 sequential consolidation regimens comprising cytarabine ARA-C plus IDA followed by mitoxantrone plus etoposide and then IDA ARA-C and thioguanine
Determine the percentage of patients who complete the protocol including PML-RARa-positive patients treated with post-consolidation bone marrow transplantation BMT and PML-RARa-negative patients treated with maintenance comprising mercaptopurine MP plus methotrexate MTX vs ATRA only vs MP plus MTX alternating with ATRA vs observation only
Compare the disease-free survival DFS and overall survival of these patients treated with these regimens
Determine the rate and type of grade 4 toxicity treatment-related mortality and time to granulocyte and platelet recovery associated with each phase of treatment in these patients
Determine the DFS and overall survival of PML-RARa-positive patients who are ineligible for BMT and are treated with maintenance comprising MP plus MTX alternating with ATRA
Compare the quality of life of patients treated with these regimens
OUTLINE This is a randomized multicenter study
Induction Patients receive oral tretinoin ATRA twice daily beginning on day 1 and continuing for 30-90 days and idarubicin IDA IV over 15 minutes on days 2 4 and 8 ATRA is discontinued before day 90 in the presence of complete remission CR at day 30 or 60 unacceptable toxicity or disease progression or in the absence of at least a partial remission at day 60 Patients who achieve CR during induction proceed to consolidation
Consolidation
First consolidation Within 2 weeks after achieving CR patients receive cytarabine ARA-C IV over 6 hours followed 3 hours later by IDA IV over 15 minutes on days 1-4
Second consolidationWithin 4-6 weeks after initiation of first consolidation patients receive mitoxantrone IV over 30 minutes and etoposide IV over 1 hour beginning 12 hours after initiation of mitoxantrone infusion on days 1-5
Third consolidationWithin 4-6 weeks after initiation of second consolidation patients receive ARA-C subcutaneously every 8 hours and oral thioguanine every 8 hours on days 1-5 and IDA IV over 15 minutes on day 1
Patients proceed to group A if they are promyelocyte-retinoic acid receptor alpha PML-RARa-negative after recovery from third consolidation Patients proceed to allogeneic bone marrow transplantation BMT on group B if they are PML-RARa-positive achieve CR are under age 55 and have an HLA-A -B and -DR identical chronic myelomonocytic leukemia nonreactive family donor after recovery from third consolidation Patients proceed to autologous BMT on group B if they are PML-RARa-positive achieve CR and have no identical family donor or are age 55 and over after recovery from third consolidation Patients proceed to arm III of group A if they are PML-RARa-positive and ineligible for BMT after recovery from third consolidation
Group A maintenance Patients are stratified according to participating center and initial white blood cell count Patients are randomized to 1 of 4 treatment arms
Arm I Patients receive oral mercaptopurine MP daily and oral methotrexate MTX weekly
Arm II Beginning 3 months after recovery from third consolidation patients receive oral ATRA on days 1-15
Treatment on arms I and II continues every 3 months for 2 years in the absence of disease progression or unacceptable toxicity
Arm III Patients receive 1 course of arm I treatment alternated by 1 course of arm II treatment Alternating treatment continues every 3 months for 2 years in the absence of disease progression or unacceptable toxicity
Arm IV Patients undergo observation only
Group B Eligible patients receive conditioning comprising cyclophosphamide CTX IV for 2 days followed by total body irradiation or oral busulfan on days -9 to -6 and CTX on days -5 to -2 Autologous or allogeneic bone marrow is infused on day 0 within 4 months after initiation of third consolidation
Quality of life is assessed at baseline after induction after each consolidation regimen and then every 3 months beginning after treatment on group A or B
Patients are followed every 3 months
PROJECTED ACCRUAL A total of 750 patients will be accrued for this study within 75 years
Determine the complete remission CR rate in patients with acute promyelocytic leukemia treated with induction comprising tretinoin ATRA and idarubicin IDA
Determine the presence of the promyelocyte-retinoic acid receptor alpha PML-RARa transcript using polymerase chain reaction PCR in patients with CR after 3 sequential consolidation regimens comprising cytarabine ARA-C plus IDA followed by mitoxantrone plus etoposide and then IDA ARA-C and thioguanine
Determine the percentage of patients who complete the protocol including PML-RARa-positive patients treated with post-consolidation bone marrow transplantation BMT and PML-RARa-negative patients treated with maintenance comprising mercaptopurine MP plus methotrexate MTX vs ATRA only vs MP plus MTX alternating with ATRA vs observation only
Compare the disease-free survival DFS and overall survival of these patients treated with these regimens
Determine the rate and type of grade 4 toxicity treatment-related mortality and time to granulocyte and platelet recovery associated with each phase of treatment in these patients
Determine the DFS and overall survival of PML-RARa-positive patients who are ineligible for BMT and are treated with maintenance comprising MP plus MTX alternating with ATRA
Compare the quality of life of patients treated with these regimens
OUTLINE This is a randomized multicenter study
Induction Patients receive oral tretinoin ATRA twice daily beginning on day 1 and continuing for 30-90 days and idarubicin IDA IV over 15 minutes on days 2 4 and 8 ATRA is discontinued before day 90 in the presence of complete remission CR at day 30 or 60 unacceptable toxicity or disease progression or in the absence of at least a partial remission at day 60 Patients who achieve CR during induction proceed to consolidation
Consolidation
First consolidation Within 2 weeks after achieving CR patients receive cytarabine ARA-C IV over 6 hours followed 3 hours later by IDA IV over 15 minutes on days 1-4
Second consolidationWithin 4-6 weeks after initiation of first consolidation patients receive mitoxantrone IV over 30 minutes and etoposide IV over 1 hour beginning 12 hours after initiation of mitoxantrone infusion on days 1-5
Third consolidationWithin 4-6 weeks after initiation of second consolidation patients receive ARA-C subcutaneously every 8 hours and oral thioguanine every 8 hours on days 1-5 and IDA IV over 15 minutes on day 1
Patients proceed to group A if they are promyelocyte-retinoic acid receptor alpha PML-RARa-negative after recovery from third consolidation Patients proceed to allogeneic bone marrow transplantation BMT on group B if they are PML-RARa-positive achieve CR are under age 55 and have an HLA-A -B and -DR identical chronic myelomonocytic leukemia nonreactive family donor after recovery from third consolidation Patients proceed to autologous BMT on group B if they are PML-RARa-positive achieve CR and have no identical family donor or are age 55 and over after recovery from third consolidation Patients proceed to arm III of group A if they are PML-RARa-positive and ineligible for BMT after recovery from third consolidation
Group A maintenance Patients are stratified according to participating center and initial white blood cell count Patients are randomized to 1 of 4 treatment arms
Arm I Patients receive oral mercaptopurine MP daily and oral methotrexate MTX weekly
Arm II Beginning 3 months after recovery from third consolidation patients receive oral ATRA on days 1-15
Treatment on arms I and II continues every 3 months for 2 years in the absence of disease progression or unacceptable toxicity
Arm III Patients receive 1 course of arm I treatment alternated by 1 course of arm II treatment Alternating treatment continues every 3 months for 2 years in the absence of disease progression or unacceptable toxicity
Arm IV Patients undergo observation only
Group B Eligible patients receive conditioning comprising cyclophosphamide CTX IV for 2 days followed by total body irradiation or oral busulfan on days -9 to -6 and CTX on days -5 to -2 Autologous or allogeneic bone marrow is infused on day 0 within 4 months after initiation of third consolidation
Quality of life is assessed at baseline after induction after each consolidation regimen and then every 3 months beginning after treatment on group A or B
Patients are followed every 3 months
PROJECTED ACCRUAL A total of 750 patients will be accrued for this study within 75 years
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EORTC-06952 | None | None | None |
| ITA-GIMEMA-AIEOP-1 | None | None | None |