Ignite Creation Date:
2024-05-05 @ 10:23 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002514
Status:
COMPLETED
Last Update Posted:
2023-06-18
First Post:
1999-11-01
Brief Title:
Stem Cell Transplantation Compared With Standard Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia in First Remission
Sponsor:
Eastern Cooperative Oncology Group
Organization:
Eastern Cooperative Oncology Group
Study Overview
Official Title:
Phase III Randomized Trial of Autologous and Allogeneic Stem Cell Transplantation Versus Intensive Conventional Chemotherapy in Acute Lymphoblastic Leukemia in First Remission
Status:
COMPLETED
Status Verified Date:
2023-06
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:
RATIONALE Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die Combining chemotherapy with allogeneic or autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells It is not yet known whether stem cell transplantation is more effective than standard chemotherapy in treating acute lymphoblastic leukemia
PURPOSE This randomized phase III trial is studying how well stem cell transplantation works compared to standard combination chemotherapy in treating patients with acute lymphoblastic leukemia in first remission
PURPOSE This randomized phase III trial is studying how well stem cell transplantation works compared to standard combination chemotherapy in treating patients with acute lymphoblastic leukemia in first remission
Detailed Description:
OBJECTIVES
Compare the duration of complete remission CR and survival in patients with acute lymphoblastic leukemia in first remission treated with allogeneic or autologous stem cell transplantation SCT vs conventional consolidation and maintenance chemotherapy
Compare the overall treatment outcomes in patients treated with these regimens
Determine the effect of imatinib mesylate given after induction therapy in Philadelphia Ph chromosome-positive patients in CR
Determine the benefit of allogeneic or autologous SCT after imatinib mesylate in Ph chromosome-positive patients
Determine the benefit of additional imatinib mesylate administered after allogeneic or autologous SCT in Ph chromosome-positive patients
Determine the minimal residual disease in Ph chromosome-positive patients before and after treatment with imatinib mesylate
Determine the clinical resistance to imatinib mesylate caused by BCR-ABL gene amplification or mutation in Ph chromosome-positive patients
OUTLINE This is a randomized multicenter study Patients are stratified according to age 50 and under vs over 50 time to achieve complete remission CR 4 weeks or less vs more than 4 weeks and Philadelphia Ph chromosome status positive vs negative
First induction therapy Patients receive daunorubicin DNR IV over 15-30 minutes and vincristine VCR IV over 3-5 minutes on days 1 8 15 and 22 oral prednisone PRED once daily on days 1-28 and asparaginase ASP IV over 30 minutes or intramuscularly on days 17-28 Patients with CNS leukemia at presentation also receive methotrexate MTX intrathecally IT via an Ommaya reservoir weekly until the CSF is clear Patients without CNS leukemia at presentation receive MTX IT on day 23 only
Second induction therapy Beginning immediately after first induction therapy patients receive cyclophosphamide CTX IV over 30 minutes on days 1 15 and 29 cytarabine ARA-C IV over 30 minutes on days 1-4 8-11 15-18 and 22-25 and oral mercaptopurine MP once daily on days 1-28 Patients with CNS leukemia at presentation also undergo concurrent craniospinal irradiation Patients without CNS leukemia at presentation receive MTX IT on days 1 8 15 and 22 Patients with Ph chromosome-positive status receive oral imatinib mesylate once daily for at least 28 days days 1-28
Patients with Ph chromosome-positive status and CR after second induction therapy proceed to group I for autologous or allogeneic stem cell transplantation SCT Patients with Ph chromosome-negative status and CR after second induction therapy proceed to group II
Group I Ph chromosome-positive patients
Autologous SCT Patients receive high-dose consolidationmobilization chemotherapy comprising ARA-C IV over 3 hours on days 1-3 and mitoxantrone IV immediately after ARA-C administration on days 1 and 2 Patients also receive filgrastim G-CSF subcutaneously SC once daily beginning on day 5 and continuing until blood counts recover
Patients then undergo peripheral blood stem cell collection or bone marrow harvesting
Patients receive preparative therapy comprising total body irradiation twice daily 5-10 hours apart on days -6 to -4 and high-dose etoposide VP-16 IV over 4 hours on day -3 Male patients also undergo radiotherapy boost to the testes on day -6
Patients undergo autologous SCT on day 0 and receive sargramostim GM-CSF SC once daily beginning 6 hours after the completion of SCT and continuing until blood counts recover
Allogeneic SCT Patients receive the preparative regimen as in autologous SCT and then undergo allogeneic SCT on day 0 Patients receive GM-CSF as in autologous SCT
Post-SCT imatinib mesylate therapy After recovery from autologous or allogeneic SCT patients receive oral imatinib mesylate once daily Imatinib mesylate therapy continues in the absence of disease progression or unacceptable toxicity
Group II Ph chromosome-negative patients
Intensification therapy Beginning 4 weeks after the completion of the second induction therapy patients receive high-dose MTX IV over 2 hours on days 1 8 and 22 leucovorin calcium IV every 6 hours for 4 doses and then orally every 6 hours for 12 doses beginning 22-24 hours after each MTX infusion and ASP IV over 30 minutes on days 2 9 and 23
Patients who are 50 years of age with a histocompatible donor proceed to allogeneic SCT and undergo allogeneic SCT as in group I Patients who are 50 years of age without an appropriate donor are randomized to 1 of 2 treatment arms
Arm I conventional consolidationmaintenance therapy
Conventional consolidation therapy During course 1 patients receive ARA-C IV over 30 minutes and VP-16 IV over 1 hour on days 1-5 VCR IV on days 1 8 15 and 22 and oral dexamethasone on days 1-28 During course 2 which begins 4 weeks after initiation of course 1 or when blood counts recover patients receive ARA-C and VP-16 as in course 1 During course 3 which begins 4 weeks after initiation of course 2 or when blood counts recover patients receive DNR IV on days 1 8 15 and 22 CTX IV over 30 minutes on day 29 ARA-C IV over 30 minutes on days 31-34 and 38-41 and oral thioguanine on days 29-42 During course 4 which begins 8 weeks after initiation of course 3 or when blood counts recover patients receive treatment as in course 2
Maintenance therapy Beginning 4 weeks after initiation of course 4 of consolidation therapy or when blood counts recover patients receive oral MP daily MTX orally or IV once weekly VCR IV once every 12 weeks and oral PRED for 5 days every 12 weeks Maintenance therapy continues for 25 years after initiation of intensification therapy
Arm II autologous SCT Patients undergo autologous SCT as in group I with the exception of high-dose consolidationmobilization chemotherapy
Patients are followed every 6 months for 2 years
PROJECTED ACCRUAL Approximately 40 patients per year will be accrued for group I Philadelphia Ph chromosome-positive patients of this study Approximately 550 patients will be accrued for group II Ph chromosome-negative patients of this study within 5 years
Compare the duration of complete remission CR and survival in patients with acute lymphoblastic leukemia in first remission treated with allogeneic or autologous stem cell transplantation SCT vs conventional consolidation and maintenance chemotherapy
Compare the overall treatment outcomes in patients treated with these regimens
Determine the effect of imatinib mesylate given after induction therapy in Philadelphia Ph chromosome-positive patients in CR
Determine the benefit of allogeneic or autologous SCT after imatinib mesylate in Ph chromosome-positive patients
Determine the benefit of additional imatinib mesylate administered after allogeneic or autologous SCT in Ph chromosome-positive patients
Determine the minimal residual disease in Ph chromosome-positive patients before and after treatment with imatinib mesylate
Determine the clinical resistance to imatinib mesylate caused by BCR-ABL gene amplification or mutation in Ph chromosome-positive patients
OUTLINE This is a randomized multicenter study Patients are stratified according to age 50 and under vs over 50 time to achieve complete remission CR 4 weeks or less vs more than 4 weeks and Philadelphia Ph chromosome status positive vs negative
First induction therapy Patients receive daunorubicin DNR IV over 15-30 minutes and vincristine VCR IV over 3-5 minutes on days 1 8 15 and 22 oral prednisone PRED once daily on days 1-28 and asparaginase ASP IV over 30 minutes or intramuscularly on days 17-28 Patients with CNS leukemia at presentation also receive methotrexate MTX intrathecally IT via an Ommaya reservoir weekly until the CSF is clear Patients without CNS leukemia at presentation receive MTX IT on day 23 only
Second induction therapy Beginning immediately after first induction therapy patients receive cyclophosphamide CTX IV over 30 minutes on days 1 15 and 29 cytarabine ARA-C IV over 30 minutes on days 1-4 8-11 15-18 and 22-25 and oral mercaptopurine MP once daily on days 1-28 Patients with CNS leukemia at presentation also undergo concurrent craniospinal irradiation Patients without CNS leukemia at presentation receive MTX IT on days 1 8 15 and 22 Patients with Ph chromosome-positive status receive oral imatinib mesylate once daily for at least 28 days days 1-28
Patients with Ph chromosome-positive status and CR after second induction therapy proceed to group I for autologous or allogeneic stem cell transplantation SCT Patients with Ph chromosome-negative status and CR after second induction therapy proceed to group II
Group I Ph chromosome-positive patients
Autologous SCT Patients receive high-dose consolidationmobilization chemotherapy comprising ARA-C IV over 3 hours on days 1-3 and mitoxantrone IV immediately after ARA-C administration on days 1 and 2 Patients also receive filgrastim G-CSF subcutaneously SC once daily beginning on day 5 and continuing until blood counts recover
Patients then undergo peripheral blood stem cell collection or bone marrow harvesting
Patients receive preparative therapy comprising total body irradiation twice daily 5-10 hours apart on days -6 to -4 and high-dose etoposide VP-16 IV over 4 hours on day -3 Male patients also undergo radiotherapy boost to the testes on day -6
Patients undergo autologous SCT on day 0 and receive sargramostim GM-CSF SC once daily beginning 6 hours after the completion of SCT and continuing until blood counts recover
Allogeneic SCT Patients receive the preparative regimen as in autologous SCT and then undergo allogeneic SCT on day 0 Patients receive GM-CSF as in autologous SCT
Post-SCT imatinib mesylate therapy After recovery from autologous or allogeneic SCT patients receive oral imatinib mesylate once daily Imatinib mesylate therapy continues in the absence of disease progression or unacceptable toxicity
Group II Ph chromosome-negative patients
Intensification therapy Beginning 4 weeks after the completion of the second induction therapy patients receive high-dose MTX IV over 2 hours on days 1 8 and 22 leucovorin calcium IV every 6 hours for 4 doses and then orally every 6 hours for 12 doses beginning 22-24 hours after each MTX infusion and ASP IV over 30 minutes on days 2 9 and 23
Patients who are 50 years of age with a histocompatible donor proceed to allogeneic SCT and undergo allogeneic SCT as in group I Patients who are 50 years of age without an appropriate donor are randomized to 1 of 2 treatment arms
Arm I conventional consolidationmaintenance therapy
Conventional consolidation therapy During course 1 patients receive ARA-C IV over 30 minutes and VP-16 IV over 1 hour on days 1-5 VCR IV on days 1 8 15 and 22 and oral dexamethasone on days 1-28 During course 2 which begins 4 weeks after initiation of course 1 or when blood counts recover patients receive ARA-C and VP-16 as in course 1 During course 3 which begins 4 weeks after initiation of course 2 or when blood counts recover patients receive DNR IV on days 1 8 15 and 22 CTX IV over 30 minutes on day 29 ARA-C IV over 30 minutes on days 31-34 and 38-41 and oral thioguanine on days 29-42 During course 4 which begins 8 weeks after initiation of course 3 or when blood counts recover patients receive treatment as in course 2
Maintenance therapy Beginning 4 weeks after initiation of course 4 of consolidation therapy or when blood counts recover patients receive oral MP daily MTX orally or IV once weekly VCR IV once every 12 weeks and oral PRED for 5 days every 12 weeks Maintenance therapy continues for 25 years after initiation of intensification therapy
Arm II autologous SCT Patients undergo autologous SCT as in group I with the exception of high-dose consolidationmobilization chemotherapy
Patients are followed every 6 months for 2 years
PROJECTED ACCRUAL Approximately 40 patients per year will be accrued for group I Philadelphia Ph chromosome-positive patients of this study Approximately 550 patients will be accrued for group II Ph chromosome-negative patients of this study within 5 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 |
|---|---|---|---|
| EST-4491 | None | None | None |
| E2993 | None | None | None |
| MRC-LEUK-UKALL-XII | None | None | None |