Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002700
Status:
COMPLETED
Last Update Posted:
2013-06-12
First Post:
1999-11-01
Brief Title:
Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Organization:
European Organisation for Research and Treatment of Cancer - EORTC
Study Overview
Official Title:
A RANDOMIZED PHASE III TRIAL COMPARING DEXAMETHASONE WITH PREDNISONE IN INDUCTION TREATMENT AND BONE MARROW TRANSPLANTATION WITH INTENSIVE MAINTENANCE TREATMENT IN ADOLESCENT AND ADULT ACUTE LYMPHOBLASTIC LEUKEMIA ALL-4
Status:
COMPLETED
Status Verified Date:
2013-06
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 use different ways to stop tumor cells from dividing so they stop growing or die Combining chemotherapy with radiation therapy may kill more tumor cells Bone marrow transplantation can replace immune cells that were destroyed by chemotherapy
PURPOSE Randomized phase III trial to study the effectiveness of chemotherapy compared with or without bone marrow transplantation in treating patients with acute lymphoblastic leukemia
PURPOSE Randomized phase III trial to study the effectiveness of chemotherapy compared with or without bone marrow transplantation in treating patients with acute lymphoblastic leukemia
Detailed Description:
OBJECTIVES
Compare the remission induction toxicity and duration of remission in patients with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma treated with prednisone vs dexamethasone plus cyclophosphamide daunorubicin and vincristine as induction
Compare the survival and disease-free survival of patients treated with autologous bone marrow transplantation BMT followed by low- or high-intensity maintenance chemotherapy with cranial irradiation after consolidation
Determine the relative and disease-free survival of patients treated with autologous or allogeneic BMT after identical induction consolidation and conditioning regimens
OUTLINE This is a randomized multicenter study Patients are stratified according to center and risk group high vs standard
Induction
Patients are randomized to 1 of 2 treatment arms
Arm IPatients receive daunorubicin IV on days 1-3 and 15 and 16 cyclophosphamide CTX IV on days 1 and 8 vincristine VCR IV on days 1 8 15 and 22 and prednisone IV or orally every 8 hours on days 1-7 and 15-21
Arm II Patients receive daunorubicin CTX and VCR as in arm I and dexamethasone IV or orally on days 1-8 and 15-22
Patients on both arms without CNS disease at presentation receive CNS prophylaxis comprising methotrexate MTX intrathecally IT on days 1 8 15 and 22 Patients on both arms with CNS disease at presentation receive CNS therapy comprising hydrocortisone HC IT and MTX IT alternating with cytarabine ARA-C IT twice a week until CSF clears After induction patients on both arms proceed to consolidation regardless of response
Consolidation
Patients receive ARA-C IV over 2 hours every 12 hours on days 29-34 and mitoxantrone IV on days 33-35 Patients without CNS disease at presentation receive CNS prophylaxis comprising MTX IT on day 29 Patients with CNS disease at presentation receive CNS therapy comprising HC IT and MTX IT alternating with ARA-C weekly for 6 weeks Patients who achieve complete response CR at day 55-60 receive MTX IV on days 64 and 79 leucovorin calcium IV or orally every 6 hours on days 65-67 and 80-82 and asparaginase IV over 1 hour or intramuscularly on days 65 and 80
Standard-risk patients who are under age 20 and achieve CR after day 80 are assigned to arm IV of group A Patients who achieve CR after day 80 and have a genotypically or phenotypically HLA-matched family donor a family donor mismatched at only 1 locus A B or DR or an HLA-matched unrelated donor proceed to group B Patients who achieve CR after day 80 and are eligible for autologous bone marrow transplantation BMT proceed to group A Patients found to be at extremely high risk are taken off study
Group A
Patients are randomized to 1 of 2 treatment arms
Arm III Autologous bone marrow is harvested Patients receive bone marrow ablation comprising CTX IV over 1 hour on days -4 and -3 and total body irradiation on day -1 Autologous bone marrow is reinfused on day 0 Beginning at month 8 4 months after BMT patients receive first maintenance comprising VCR IV doxorubicin IV and dexamethasone IV VAD or VCR IV doxorubicin IV and prednisolone IV VAP on days 1-4 and 29-32 Patients receive second maintenance comprising oral mercaptopurine daily and oral MTX daily beginning at month 10 and continuing through year 3 Patients without CNS disease at presentation receive CNS prophylaxis comprising MTX IT on days 1 and 29 Patients with CNS disease at presentation receive CNS therapy comprising ARA-C IT MTX IT and HC IT beginning at 1 month after BMT and continuing monthly for 1 year and then every 3 months through year 3
Arm IV Patients receive CTX IV and ARA-C IV continuously on day 1 oral mercaptopurine on days 8-28 and oral MTX on days 8 15 and 22 during months 4 7 11 13 17 21 25 and 29 Patients receive MTX IV over 30 minutes on day 1 leucovorin calcium IV or orally every 6 hours on days 2-4 asparaginase IV over 1 hour or intramuscularly on day 2 oral mercaptopurine on days 8-28 and oral MTX on days 8 15 and 22 during months 6 10 12 15 19 23 and 27 Patients receive VAD or VAP as in arm III beginning at month 8 Patients without CNS disease at presentation receive CNS prophylaxis comprising whole brain radiotherapy and MTX IT on day 1 of radiotherapy during month 5 Patients with CNS disease at presentation receive CNS therapy as in arm III
Group B
Allogeneic bone marrow is harvested Patients receive bone marrow ablation as in arm III beginning on day 100 Allogeneic bone marrow is infused over 15-30 minutes on day 0
Patients in groups A and B with CNS disease at presentation undergo radiotherapy to focal infiltration at entry or concurrently with total body irradiation or whole brain radiotherapy during maintenance if no prior CNS irradiation At any time during the study patients who develop marrow relapse more than 5 leukemic blasts in bone marrow on 2 occasions CNS relapse blasts in CSF cranial nerve palsy or CNS mass or testis or other extramedullary relapse are taken off study
PROJECTED ACCRUAL A total of 392 patients will be accrued for this study within approximately 6 years
Compare the remission induction toxicity and duration of remission in patients with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma treated with prednisone vs dexamethasone plus cyclophosphamide daunorubicin and vincristine as induction
Compare the survival and disease-free survival of patients treated with autologous bone marrow transplantation BMT followed by low- or high-intensity maintenance chemotherapy with cranial irradiation after consolidation
Determine the relative and disease-free survival of patients treated with autologous or allogeneic BMT after identical induction consolidation and conditioning regimens
OUTLINE This is a randomized multicenter study Patients are stratified according to center and risk group high vs standard
Induction
Patients are randomized to 1 of 2 treatment arms
Arm IPatients receive daunorubicin IV on days 1-3 and 15 and 16 cyclophosphamide CTX IV on days 1 and 8 vincristine VCR IV on days 1 8 15 and 22 and prednisone IV or orally every 8 hours on days 1-7 and 15-21
Arm II Patients receive daunorubicin CTX and VCR as in arm I and dexamethasone IV or orally on days 1-8 and 15-22
Patients on both arms without CNS disease at presentation receive CNS prophylaxis comprising methotrexate MTX intrathecally IT on days 1 8 15 and 22 Patients on both arms with CNS disease at presentation receive CNS therapy comprising hydrocortisone HC IT and MTX IT alternating with cytarabine ARA-C IT twice a week until CSF clears After induction patients on both arms proceed to consolidation regardless of response
Consolidation
Patients receive ARA-C IV over 2 hours every 12 hours on days 29-34 and mitoxantrone IV on days 33-35 Patients without CNS disease at presentation receive CNS prophylaxis comprising MTX IT on day 29 Patients with CNS disease at presentation receive CNS therapy comprising HC IT and MTX IT alternating with ARA-C weekly for 6 weeks Patients who achieve complete response CR at day 55-60 receive MTX IV on days 64 and 79 leucovorin calcium IV or orally every 6 hours on days 65-67 and 80-82 and asparaginase IV over 1 hour or intramuscularly on days 65 and 80
Standard-risk patients who are under age 20 and achieve CR after day 80 are assigned to arm IV of group A Patients who achieve CR after day 80 and have a genotypically or phenotypically HLA-matched family donor a family donor mismatched at only 1 locus A B or DR or an HLA-matched unrelated donor proceed to group B Patients who achieve CR after day 80 and are eligible for autologous bone marrow transplantation BMT proceed to group A Patients found to be at extremely high risk are taken off study
Group A
Patients are randomized to 1 of 2 treatment arms
Arm III Autologous bone marrow is harvested Patients receive bone marrow ablation comprising CTX IV over 1 hour on days -4 and -3 and total body irradiation on day -1 Autologous bone marrow is reinfused on day 0 Beginning at month 8 4 months after BMT patients receive first maintenance comprising VCR IV doxorubicin IV and dexamethasone IV VAD or VCR IV doxorubicin IV and prednisolone IV VAP on days 1-4 and 29-32 Patients receive second maintenance comprising oral mercaptopurine daily and oral MTX daily beginning at month 10 and continuing through year 3 Patients without CNS disease at presentation receive CNS prophylaxis comprising MTX IT on days 1 and 29 Patients with CNS disease at presentation receive CNS therapy comprising ARA-C IT MTX IT and HC IT beginning at 1 month after BMT and continuing monthly for 1 year and then every 3 months through year 3
Arm IV Patients receive CTX IV and ARA-C IV continuously on day 1 oral mercaptopurine on days 8-28 and oral MTX on days 8 15 and 22 during months 4 7 11 13 17 21 25 and 29 Patients receive MTX IV over 30 minutes on day 1 leucovorin calcium IV or orally every 6 hours on days 2-4 asparaginase IV over 1 hour or intramuscularly on day 2 oral mercaptopurine on days 8-28 and oral MTX on days 8 15 and 22 during months 6 10 12 15 19 23 and 27 Patients receive VAD or VAP as in arm III beginning at month 8 Patients without CNS disease at presentation receive CNS prophylaxis comprising whole brain radiotherapy and MTX IT on day 1 of radiotherapy during month 5 Patients with CNS disease at presentation receive CNS therapy as in arm III
Group B
Allogeneic bone marrow is harvested Patients receive bone marrow ablation as in arm III beginning on day 100 Allogeneic bone marrow is infused over 15-30 minutes on day 0
Patients in groups A and B with CNS disease at presentation undergo radiotherapy to focal infiltration at entry or concurrently with total body irradiation or whole brain radiotherapy during maintenance if no prior CNS irradiation At any time during the study patients who develop marrow relapse more than 5 leukemic blasts in bone marrow on 2 occasions CNS relapse blasts in CSF cranial nerve palsy or CNS mass or testis or other extramedullary relapse are taken off study
PROJECTED ACCRUAL A total of 392 patients will be accrued for this study within approximately 6 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-06951 | None | None | None |
| FRE-LALA-94 | None | None | None |