Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002531
Status:
UNKNOWN
Last Update Posted:
2013-09-17
First Post:
1999-11-01
Brief Title:
Combination Chemotherapy in Treating Adults With Acute Lymphocytic Leukemia
Sponsor:
Johann Wolfgang Goethe University Hospital
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
MULTICENTRE TRIAL OF INTENSIFIED THERAPY FOR ADULT ALL O593
Status:
UNKNOWN
Status Verified Date:
2006-12
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 Combining more than one drug may kill more cancer cells
PURPOSE Randomized phase II trial to study the effectiveness of various combination chemotherapy regimens in treating patients with acute lymphocytic leukemia
PURPOSE Randomized phase II trial to study the effectiveness of various combination chemotherapy regimens in treating patients with acute lymphocytic leukemia
Detailed Description:
OBJECTIVES I Develop risk-adapted therapy for patients with low-risk high-risk T-cell or B-cell acute lymphocytic leukemia ALL II Determine the complete remission rate in these patients treated with the following strategies increased doses of cyclophosphamide during induction and reinduction early use of high-dose cytarabine plus mitoxantrone for high-risk patients and increased doses of methotrexate for B-cell ALL patients III Determine the duration of remission and survival of patients in all risk groups treated with intensified consolidation and subtype-specific chemotherapy IV Compare the effects of intensified vs conventional maintenance therapy in patients of all risk groups
OUTLINE This is a randomized multicenter study Patients are assigned to 1 of 4 treatment groups based on disease status Patients in groups 1-3 with a large leukemic cell mass in particular those with a WBC greater than 25000mm3 andor marked organomegaly receive preinduction therapy comprising oral prednisolone PRDL 3 times a day on days 1-7 and vincristine VCR IV on day 1 Group 1 low-risk acute lymphocytic leukemia ALL First induction therapy Patients receive oral PRDL 3 times a day on days 1-7 of weeks 1-4 asparaginase ASP IV over 30 minutes on days 1-7 of weeks 3 and 4 VCR IV and daunorubicin IV over 30 minutes on day 1 of weeks 1-4 and methotrexate MTX IT on day 1 of week 1 Patients who achieve complete remission CR after first induction therapy proceed to first consolidation therapy on group 1 Second induction therapy Patients receive oral cyclophosphamide CTX IV on day 1 of weeks 5 7 and 9 cytarabine ARA-C IV over 1 hour or subcutaneously on days 3-6 and MTX IT on day 3 of weeks 5-8 and oral mercaptopurine MP on days 1-7 of weeks 5-8 and day 1 of week 9 Patients who achieve CR during second induction therapy undergo prophylactic cranial irradiation 5 days a week for 24 weeks Patients who achieve CR after second induction therapy proceed to group 3 First consolidation therapy Patients receive high-dose MTX IV continuously with leucovorin calcium CF rescue on day 1 ASP IV over 1 hour on day 2 and oral MP on days 1-5 of weeks 13 and 15 and teniposide VM-26 IV over 1 hour and ARA-C IV over 1 hour on days 1-5 of week 17 Triple intrathecal therapy TIT comprising MTX ARA-C and dexamethasone DM is also administered on day 1 of week 17 First reinduction therapy Patients receive oral PRDL three times a day on days 1-7 and VCR IV and doxorubicin DOX IV over 30 minutes on day 1 of weeks 21-24 and TIT on day 1 of week 21 Second reinduction therapy Patients receive CTX IV and TIT on day 1 of week 25 and ARA-C IV over 1 hour on days 3-6 and oral thioguanine TG on days 1-7 of weeks 25 and 26 Second consolidation therapy Patients receive oral MP daily and oral MTX weekly during weeks 29-32 34-38 40-44 46-50 and 52 high-dose MTX CF rescue and ASP as in first consolidation therapy during weeks 33 and 45 and VM-26 ARA-C and TIT as in first consolidation therapy during weeks 39 and 51 Group 2 T-cell ALL with or without mediastinal involvement First induction therapy Patients receive treatment as in first induction therapy on group 1 Patients with residual tumor greater than 2 cm after first induction therapy also undergo mediastinal radiotherapy 5 days a weeks for 24-27 weeks concurrently with prophylactic cranial irradiation Second induction therapy Patients receive treatment as in second induction therapy on group 1 First consolidation therapy Patients receive high-dose ARA-C IV over 3 hours every 12 hours on days 1-4 and mitoxantrone DHAD IV over 30 minutes on days 3-5 during week 13 and high-dose MTX CF rescue ASP and MP as in first consolidation therapy on group 1 during week 17 First reinduction therapy Patients receive treatment as in first reinduction therapy on group 1 Second reinduction therapy Patients receive treatment as in second reinduction therapy on group 1 Second consolidation therapy Patients receive MP and MTX as in second consolidation therapy on group 1 CTX IV ARA-C IV continuously and TIT on day 1 during weeks 33 and 45 and VM-26 ARA-C and TIT as in first consolidation therapy on group 1 during weeks 39 and 51 Group 3 high-risk ALL First induction therapy Patients receive treatment as in first induction therapy on group 1 Second induction therapy Patients receive CNS-effective chemotherapy comprising high-dose ARA-C every 12 hours on days 1-4 and DHAD IV over 30 minutes on days 3-5 during week 6 First consolidation therapy Patients receive high-dose MTX CF rescue and ASP as in first consolidation therapy on group 1 and CTX ARA-C and TIT as in second consolidation therapy on group 2 during week 17 First reinduction therapy Patients receive treatment as in first reinduction therapy on group 1 Second reinduction therapy Patients receive treatment as in second reinduction therapy on group 1 Second consolidation therapy Patients receive MP and MTX as in second consolidation therapy on group 1 treatment as in second induction therapy on group 3 during week 33 high-dose MTX CF rescue ASP and MP as in first consolidation therapy on group 1 during week 39 CTX ARA-C and TIT as in second consolidation therapy on group 2 during week 45 and VM-26 ARA-C and TIT as in first consolidation therapy on group 1 during week 51 Groups 1-3 Patients who are age 15 to 50 achieve first CR and have a suitable donor undergo allogeneic bone marrow transplantation Patients who are under age 40 undergo bone marrow transplantation from a matched unrelated donor Patients who have Philadelphia chromosomebcr-abl positive disease and no suitable donor undergo purged autologous peripheral blood stem cell transplantation instead of reinduction therapy during first CR CNS therapy Patients with CNS disease at entry receive TIT 2 or 3 times weekly beginning immediately upon diagnosis and continuing until 5 doses after blasts are cleared from the CSF Patients on group 1 and 2 undergo irradiation of the entire neuraxis 5 days a week for 27-32 weeks during second induction therapy Maintenance therapy After completion of 1 year of treatment on group 1 2 or 3 patients are randomized to 1 of 2 treatment arms Arm I Patients receive MP daily and MTX weekly on odd-numbered months between months 13-30 CTX ARA-C and TIT as in second consolidation therapy on group 2 during months 14 20 and 26 VM-26 ARA-C and TIT as in first consolidation therapy on group 1 during months 16 22 and 28 and high-dose MTX CF rescue and ASP as in first consolidation therapy on group 1 during months 18 24 and 30 Arm II Patients receive MP plus MTX as in second consolidation therapy on group 1 continuously and TIT every 2 months during months 13-30 Group 4 B-cell ALL Pretreatment Patients who are age 50 and under receive CTX IV over 1 hour and oral PRDL 3 times a day on days 1-5 Patients who are over age 50 receive CTX IV and oral DM on days 1 3 and 5 Treatment Patients receive alternating therapy on blocks A and B Block A therapy consists of VCR IV MTX IV continuously and CF rescue on day 1 ifosfamide IV over 1 hour and oral DM on days 1-5 VM-26 IV over 1 hour and ARA-C IV over 1 hour every 12 hours on days 4 and 5 and TIT on days 1 and 5 Block B therapy consists of VCR IV MTX IV continuously and CF rescue on day 1 CTX IV over 1 hour and oral DM on days 1-5 DOX IV over 15 minutes on days 4 and 5 and TIT on days 1 and 5 Blocks A and B continue every 3 weeks for a total of 6 courses Patients who have not achieved CR after 3 courses or who develop disease progression at any time may optionally receive vindesine ARA-C etoposide and DM Patients with CNS disease undergo craniospinal irradiation after 2 courses of systemic chemotherapy block A and B therapy Patients receive TIT 2-3 times weekly until CSF is clear after block A therapy only if response is unsatisfactory
PROJECTED ACCRUAL Approximately 700 patients will be accrued for this study within 4 years
OUTLINE This is a randomized multicenter study Patients are assigned to 1 of 4 treatment groups based on disease status Patients in groups 1-3 with a large leukemic cell mass in particular those with a WBC greater than 25000mm3 andor marked organomegaly receive preinduction therapy comprising oral prednisolone PRDL 3 times a day on days 1-7 and vincristine VCR IV on day 1 Group 1 low-risk acute lymphocytic leukemia ALL First induction therapy Patients receive oral PRDL 3 times a day on days 1-7 of weeks 1-4 asparaginase ASP IV over 30 minutes on days 1-7 of weeks 3 and 4 VCR IV and daunorubicin IV over 30 minutes on day 1 of weeks 1-4 and methotrexate MTX IT on day 1 of week 1 Patients who achieve complete remission CR after first induction therapy proceed to first consolidation therapy on group 1 Second induction therapy Patients receive oral cyclophosphamide CTX IV on day 1 of weeks 5 7 and 9 cytarabine ARA-C IV over 1 hour or subcutaneously on days 3-6 and MTX IT on day 3 of weeks 5-8 and oral mercaptopurine MP on days 1-7 of weeks 5-8 and day 1 of week 9 Patients who achieve CR during second induction therapy undergo prophylactic cranial irradiation 5 days a week for 24 weeks Patients who achieve CR after second induction therapy proceed to group 3 First consolidation therapy Patients receive high-dose MTX IV continuously with leucovorin calcium CF rescue on day 1 ASP IV over 1 hour on day 2 and oral MP on days 1-5 of weeks 13 and 15 and teniposide VM-26 IV over 1 hour and ARA-C IV over 1 hour on days 1-5 of week 17 Triple intrathecal therapy TIT comprising MTX ARA-C and dexamethasone DM is also administered on day 1 of week 17 First reinduction therapy Patients receive oral PRDL three times a day on days 1-7 and VCR IV and doxorubicin DOX IV over 30 minutes on day 1 of weeks 21-24 and TIT on day 1 of week 21 Second reinduction therapy Patients receive CTX IV and TIT on day 1 of week 25 and ARA-C IV over 1 hour on days 3-6 and oral thioguanine TG on days 1-7 of weeks 25 and 26 Second consolidation therapy Patients receive oral MP daily and oral MTX weekly during weeks 29-32 34-38 40-44 46-50 and 52 high-dose MTX CF rescue and ASP as in first consolidation therapy during weeks 33 and 45 and VM-26 ARA-C and TIT as in first consolidation therapy during weeks 39 and 51 Group 2 T-cell ALL with or without mediastinal involvement First induction therapy Patients receive treatment as in first induction therapy on group 1 Patients with residual tumor greater than 2 cm after first induction therapy also undergo mediastinal radiotherapy 5 days a weeks for 24-27 weeks concurrently with prophylactic cranial irradiation Second induction therapy Patients receive treatment as in second induction therapy on group 1 First consolidation therapy Patients receive high-dose ARA-C IV over 3 hours every 12 hours on days 1-4 and mitoxantrone DHAD IV over 30 minutes on days 3-5 during week 13 and high-dose MTX CF rescue ASP and MP as in first consolidation therapy on group 1 during week 17 First reinduction therapy Patients receive treatment as in first reinduction therapy on group 1 Second reinduction therapy Patients receive treatment as in second reinduction therapy on group 1 Second consolidation therapy Patients receive MP and MTX as in second consolidation therapy on group 1 CTX IV ARA-C IV continuously and TIT on day 1 during weeks 33 and 45 and VM-26 ARA-C and TIT as in first consolidation therapy on group 1 during weeks 39 and 51 Group 3 high-risk ALL First induction therapy Patients receive treatment as in first induction therapy on group 1 Second induction therapy Patients receive CNS-effective chemotherapy comprising high-dose ARA-C every 12 hours on days 1-4 and DHAD IV over 30 minutes on days 3-5 during week 6 First consolidation therapy Patients receive high-dose MTX CF rescue and ASP as in first consolidation therapy on group 1 and CTX ARA-C and TIT as in second consolidation therapy on group 2 during week 17 First reinduction therapy Patients receive treatment as in first reinduction therapy on group 1 Second reinduction therapy Patients receive treatment as in second reinduction therapy on group 1 Second consolidation therapy Patients receive MP and MTX as in second consolidation therapy on group 1 treatment as in second induction therapy on group 3 during week 33 high-dose MTX CF rescue ASP and MP as in first consolidation therapy on group 1 during week 39 CTX ARA-C and TIT as in second consolidation therapy on group 2 during week 45 and VM-26 ARA-C and TIT as in first consolidation therapy on group 1 during week 51 Groups 1-3 Patients who are age 15 to 50 achieve first CR and have a suitable donor undergo allogeneic bone marrow transplantation Patients who are under age 40 undergo bone marrow transplantation from a matched unrelated donor Patients who have Philadelphia chromosomebcr-abl positive disease and no suitable donor undergo purged autologous peripheral blood stem cell transplantation instead of reinduction therapy during first CR CNS therapy Patients with CNS disease at entry receive TIT 2 or 3 times weekly beginning immediately upon diagnosis and continuing until 5 doses after blasts are cleared from the CSF Patients on group 1 and 2 undergo irradiation of the entire neuraxis 5 days a week for 27-32 weeks during second induction therapy Maintenance therapy After completion of 1 year of treatment on group 1 2 or 3 patients are randomized to 1 of 2 treatment arms Arm I Patients receive MP daily and MTX weekly on odd-numbered months between months 13-30 CTX ARA-C and TIT as in second consolidation therapy on group 2 during months 14 20 and 26 VM-26 ARA-C and TIT as in first consolidation therapy on group 1 during months 16 22 and 28 and high-dose MTX CF rescue and ASP as in first consolidation therapy on group 1 during months 18 24 and 30 Arm II Patients receive MP plus MTX as in second consolidation therapy on group 1 continuously and TIT every 2 months during months 13-30 Group 4 B-cell ALL Pretreatment Patients who are age 50 and under receive CTX IV over 1 hour and oral PRDL 3 times a day on days 1-5 Patients who are over age 50 receive CTX IV and oral DM on days 1 3 and 5 Treatment Patients receive alternating therapy on blocks A and B Block A therapy consists of VCR IV MTX IV continuously and CF rescue on day 1 ifosfamide IV over 1 hour and oral DM on days 1-5 VM-26 IV over 1 hour and ARA-C IV over 1 hour every 12 hours on days 4 and 5 and TIT on days 1 and 5 Block B therapy consists of VCR IV MTX IV continuously and CF rescue on day 1 CTX IV over 1 hour and oral DM on days 1-5 DOX IV over 15 minutes on days 4 and 5 and TIT on days 1 and 5 Blocks A and B continue every 3 weeks for a total of 6 courses Patients who have not achieved CR after 3 courses or who develop disease progression at any time may optionally receive vindesine ARA-C etoposide and DM Patients with CNS disease undergo craniospinal irradiation after 2 courses of systemic chemotherapy block A and B therapy Patients receive TIT 2-3 times weekly until CSF is clear after block A therapy only if response is unsatisfactory
PROJECTED ACCRUAL Approximately 700 patients will be accrued for this study within 4 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 |
|---|---|---|---|
| EU-93002 | None | None | None |
| GER-GMALL-ALL-0593 | None | None | None |