Ignite Creation Date:
2024-05-05 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002798
Status:
COMPLETED
Last Update Posted:
2013-01-16
First Post:
2000-11-24
Brief Title:
Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A PHASE III STUDY IN CHILDREN WITH UNTREATED ACUTE MYELOGENOUS LEUKEMIA AML OR MYELODYSPLASTIC SYNDROME MDS
Status:
COMPLETED
Status Verified Date:
2013-01
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:
Randomized phase III trial to compare the effectiveness of different chemotherapy regimens with or without bone marrow transplantation in treating children who have acute myelogenous leukemia or myelodysplastic syndrome Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells It is not yet known which treatment regimen is more effective for acute myelogenous leukemia or myelodysplastic syndrome
Detailed Description:
OBJECTIVES
Increase the remission induction rate to greater than 85 in children with untreated acute myelogenous leukemia AML or myelodysplastic syndromes MDS by replacing daunorubicin DNR with idarubicin IDA in intensively timed DCTER chemotherapy dexamethasone cytarabine ARA-C thioguanine etoposide and daunorubicin in the first 4 days of each course
Increase the remission rate further by comparing the efficacy of consolidation chemotherapy with intensively timed IDA DCTERDCTER vs fludarabine FAMP ARA-C and IDA in maintaining remission and in achieving remission in patients with M2 disease 5-29 blasts in marrow at the end of induction chemotherapy
Compare overall survival event-free survival and disease-free survival in patients who receive consolidation with IDA DCTERDCTER vs FAMP ARA-C and IDA
Compare overall survival event-free survival and disease-free survival in patients receiving intensification with the Capizzi II regimen high-dose ARA-C and asparaginase vs those receiving a matched-related allogeneic bone marrow transplantation
Compare overall survival event-free survival and disease-free survival in patients treated with interleukin-2 IL-2 vs standard follow up care after Capizzi II intensification
Determine whether multichannel flow cytometry detection of residual AML on a companion biologic study protocol CCG-B942 predicts outcome and determine whether any of these treatment regimens eliminates minimal residual disease more effectively than another
Register all patients with MDS treated or followed at CCG institutions and capture their biologic historical and outcome data
Determine on a companion biologic study protocol CCG-B972 whether levels of IL-2 soluble receptor sIL-2R and absolute lymphocyte count ALC before during and after therapy correlates with outcome
OUTLINE This is a randomized multicenter study Patients are stratified according to center diagnosis acute myelogenous leukemia vs other and response to induction partial vs complete remission After induction patients with M1M2 marrow are randomized to arm I or II Patients in complete remission after consolidation who have an HLA-identical or 1-antigen mismatched sibling or parent donor are randomly assigned to the allogeneic bone marrow transplantation AlBMT regimen all others in complete remission are nonrandomly assigned to the Capizzi II regimen then are randomly assigned to arms III or IV Patients with refractory anemia RA or RA with ringed sideroblasts with indolent disease may be registered and followed Other patients with myelodysplastic syndromes may receive 2961 chemotherapy or go directly to AlBMT Patients with chloromas granulocytic sarcomas receive optional radiotherapy on arm V
Induction Patients receive idarubicin IV over 30 minutes on days 0-3 cytarabine and etoposide IV continuously on days 0-3 and oral thioguanine twice a day and oral dexamethasone 3 times a day on days 0-3 Patients then begin course 2 which consists of cytarabine etoposide thioguanine and dexamethasone on days 10-13 daunorubicin IV continuously on days 10-13 and filgrastim G-CSF subcutaneously SC beginning on day 16 and continuing until blood counts recover Patients also receive CNS prophylaxistherapy consisting of cytarabine intrathecally IT on days 0 and 14 if no CNS disease at entry or on days 0 5 and 7 if CNS disease present at entry Disease is reassessed on day 28-42 Patients with M1 or M2 marrow proceed to consolidation while those with M3 marrow or progressive disease go off study
Consolidation
Arm I Patients receive treatment as in induction therapy plus G-CSF SC beginning on day 16 and continuing until blood counts recover If CSF is clear by day 10 of induction patients receive cytarabine IT on days 0 10 and 35 If CSF is not clear patients receive triple intrathecal therapy TIT cytarabine hydrocortisone methotrexate on days 0 and 10
Arm II Patients receive fludarabine IV over 24 hours on days 0 and 1 cytarabine IV over 72 hours on days 2-4 and idarubicin IV over 15 minutes on days 0-2 G-CSF begins on day 6 and continues until blood counts recover Patients also receive TIT on days -1 and 7 if CSF is not clear on day 10 of induction Patients on both arms are reassessed on day 35 Those patients with M1 marrow proceed to intensification all others are removed from the study
Intensification
Capizzi II regimen Course 1 Patients receive cytarabine IV over 3 hours every 12 hours on days 0 1 7 and 8 and asparaginase IM on days 1 and 8 Course 2 Patients also receive cytarabine IT or TIT on days 0 7 and 14AlBMT regimen Therapy begins within 2-8 weeks of hematologic recovery Patients may receive interim therapy consisting of oral thioguanine for about 2 weeks Patients then receive oral busulfan every 6 hours on days -9 to -6 and cyclophosphamide IV over 1 hour on days -5 to -2 AlBMT is infused over 4 hours beginning 36-48 hours after the last dose of cyclophosphamide Patients in complete remission after completing the Capizzi II regimen proceed to maintenance therapy on arm III
Arm III Patients receive interleukin-2 IV continuously on days 1-4 and 9-18
Arm IV No further treatment
Arm V Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks
Patients are followed monthly for 18 months every 3 months for 1 year and then every 6 months until 5 years from diagnosis
PROJECTED ACCRUAL Approximately 880 patients with de novo acute myelogenous leukemia will be accrued for this study within 4 years It is expected that 178 patients per year will be randomly assigned for consolidation that 39 patients per year will undergo allogeneic bone marrow transplantation while 120 patients per year will receive chemotherapy as intensification and that 102 patients per year will be randomly assigned for polychemotherapy immunomodulation An additional 80 patients with myelodysplastic syndromes will be accrued for this study
Increase the remission induction rate to greater than 85 in children with untreated acute myelogenous leukemia AML or myelodysplastic syndromes MDS by replacing daunorubicin DNR with idarubicin IDA in intensively timed DCTER chemotherapy dexamethasone cytarabine ARA-C thioguanine etoposide and daunorubicin in the first 4 days of each course
Increase the remission rate further by comparing the efficacy of consolidation chemotherapy with intensively timed IDA DCTERDCTER vs fludarabine FAMP ARA-C and IDA in maintaining remission and in achieving remission in patients with M2 disease 5-29 blasts in marrow at the end of induction chemotherapy
Compare overall survival event-free survival and disease-free survival in patients who receive consolidation with IDA DCTERDCTER vs FAMP ARA-C and IDA
Compare overall survival event-free survival and disease-free survival in patients receiving intensification with the Capizzi II regimen high-dose ARA-C and asparaginase vs those receiving a matched-related allogeneic bone marrow transplantation
Compare overall survival event-free survival and disease-free survival in patients treated with interleukin-2 IL-2 vs standard follow up care after Capizzi II intensification
Determine whether multichannel flow cytometry detection of residual AML on a companion biologic study protocol CCG-B942 predicts outcome and determine whether any of these treatment regimens eliminates minimal residual disease more effectively than another
Register all patients with MDS treated or followed at CCG institutions and capture their biologic historical and outcome data
Determine on a companion biologic study protocol CCG-B972 whether levels of IL-2 soluble receptor sIL-2R and absolute lymphocyte count ALC before during and after therapy correlates with outcome
OUTLINE This is a randomized multicenter study Patients are stratified according to center diagnosis acute myelogenous leukemia vs other and response to induction partial vs complete remission After induction patients with M1M2 marrow are randomized to arm I or II Patients in complete remission after consolidation who have an HLA-identical or 1-antigen mismatched sibling or parent donor are randomly assigned to the allogeneic bone marrow transplantation AlBMT regimen all others in complete remission are nonrandomly assigned to the Capizzi II regimen then are randomly assigned to arms III or IV Patients with refractory anemia RA or RA with ringed sideroblasts with indolent disease may be registered and followed Other patients with myelodysplastic syndromes may receive 2961 chemotherapy or go directly to AlBMT Patients with chloromas granulocytic sarcomas receive optional radiotherapy on arm V
Induction Patients receive idarubicin IV over 30 minutes on days 0-3 cytarabine and etoposide IV continuously on days 0-3 and oral thioguanine twice a day and oral dexamethasone 3 times a day on days 0-3 Patients then begin course 2 which consists of cytarabine etoposide thioguanine and dexamethasone on days 10-13 daunorubicin IV continuously on days 10-13 and filgrastim G-CSF subcutaneously SC beginning on day 16 and continuing until blood counts recover Patients also receive CNS prophylaxistherapy consisting of cytarabine intrathecally IT on days 0 and 14 if no CNS disease at entry or on days 0 5 and 7 if CNS disease present at entry Disease is reassessed on day 28-42 Patients with M1 or M2 marrow proceed to consolidation while those with M3 marrow or progressive disease go off study
Consolidation
Arm I Patients receive treatment as in induction therapy plus G-CSF SC beginning on day 16 and continuing until blood counts recover If CSF is clear by day 10 of induction patients receive cytarabine IT on days 0 10 and 35 If CSF is not clear patients receive triple intrathecal therapy TIT cytarabine hydrocortisone methotrexate on days 0 and 10
Arm II Patients receive fludarabine IV over 24 hours on days 0 and 1 cytarabine IV over 72 hours on days 2-4 and idarubicin IV over 15 minutes on days 0-2 G-CSF begins on day 6 and continues until blood counts recover Patients also receive TIT on days -1 and 7 if CSF is not clear on day 10 of induction Patients on both arms are reassessed on day 35 Those patients with M1 marrow proceed to intensification all others are removed from the study
Intensification
Capizzi II regimen Course 1 Patients receive cytarabine IV over 3 hours every 12 hours on days 0 1 7 and 8 and asparaginase IM on days 1 and 8 Course 2 Patients also receive cytarabine IT or TIT on days 0 7 and 14AlBMT regimen Therapy begins within 2-8 weeks of hematologic recovery Patients may receive interim therapy consisting of oral thioguanine for about 2 weeks Patients then receive oral busulfan every 6 hours on days -9 to -6 and cyclophosphamide IV over 1 hour on days -5 to -2 AlBMT is infused over 4 hours beginning 36-48 hours after the last dose of cyclophosphamide Patients in complete remission after completing the Capizzi II regimen proceed to maintenance therapy on arm III
Arm III Patients receive interleukin-2 IV continuously on days 1-4 and 9-18
Arm IV No further treatment
Arm V Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks
Patients are followed monthly for 18 months every 3 months for 1 year and then every 6 months until 5 years from diagnosis
PROJECTED ACCRUAL Approximately 880 patients with de novo acute myelogenous leukemia will be accrued for this study within 4 years It is expected that 178 patients per year will be randomly assigned for consolidation that 39 patients per year will undergo allogeneic bone marrow transplantation while 120 patients per year will receive chemotherapy as intensification and that 102 patients per year will be randomly assigned for polychemotherapy immunomodulation An additional 80 patients with myelodysplastic syndromes will be accrued for this study
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 |
|---|---|---|---|
| CDR0000064883 | REGISTRY | PDQ Physician Data Query | httpsreporternihgovquickSearchU10CA098543 |
| 2961 | None | None | None |
| U10CA098543 | NIH | None | None |