Ignite Creation Date:
2024-05-05 @ 11:29 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00057811
Status:
COMPLETED
Last Update Posted:
2014-09-19
First Post:
2003-04-07
Brief Title:
Rituximab Rasburicase and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Advanced B-Cell Leukemia or Lymphoma
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
A Pilot Study To Determine The Toxicity Of The Addition Of Rituximab To The Induction And Consolidation Phases And The Addition Of Rasburicase To The Reduction Phase In Children With Newly Diagnosed Advanced B-Cell LeukemiaLymphoma Treated With LMBFAB Therapy
Status:
COMPLETED
Status Verified Date:
2014-09
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:
Phase II trial to study the effectiveness of combining rituximab and rasburicase with combination chemotherapy in treating young patients who have newly diagnosed advanced B-cell leukemia or lymphoma Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die Combining more than one drug with rituximab may kill more cancer cells Chemoprotective drugs such as rasburicase may protect kidney cells from the side effects of chemotherapy
Detailed Description:
OBJECTIVES
I Determine the toxicity of the addition of rituximab to induction chemotherapy comprising vincristine methylprednisolone methotrexate leucovorin calcium cyclophosphamide and doxorubicin COPADM COMRAP and to consolidation chemotherapy in children with newly diagnosed FAB prognostic group B or group C leukemia or lymphoma treated with LMBFAB therapy
II Determine the toxicity of the addition of rasburicase to the reduction phase comprising cyclophosphamide vincristine prednisone or methylprednisolone methotrexate and leucovorin calcium COP-R in these patients
III Determine the incidence of tumor lysis syndrome renal complications and the use of assisted renal support ie dialysis or hemofiltration during the COP-R reduction phase and the first induction phase of COPADM or COMRAP in these patients
IV Determine the response rate of patients treated with COMRAP incorporated into LMBFAB therapy
V Assess minimal residual disease in patients before and during COMRAP therapy incorporated into LMBFAB therapy
OUTLINE This is a multicenter study Patients are stratified according to FAB prognostic group B vs C and treated by group classification
FAB GROUP B
TREATMENT I first 6 patients
REDUCTION THERAPY Patients receive the COP-R regimen comprising cyclophosphamide IV over 15 minutes vincristine IV and methotrexate and hydrocortisone intrathecally IT on day 0 rasburicase IV over 30 minutes every 12 hours on days 0 and 1 and then once daily on days 2-4 patients exhibiting hyperuricemia and clinical suspicion of B-cell non-Hodgkins lymphoma or B-cell acute lymphocytic leukemia also receive rasburicase on days -3 -2 and -1 leucovorin calcium IV or orally every 12 hours on days 1 and 3 and prednisone PRED or methylprednisolone MePRDL IV or orally on days 0-6 Patients too critical to proceed may receive another course of reduction therapy
NOTE Patients with G6PD deficiency do not receive rasburicase during reduction therapy
INDUCTION THERAPY Patients with less than 20 tumor reduction follow the group C induction phase described below Patients with at least 20 tumor reduction receive 1 course of the COPADM regimen vincristine IV and methotrexate IV over 4 hours on day 0 PRED or MePRDL IV or orally on days 0-7 leucovorin calcium IV or orally every 6 hours for 12 doses on days 1-3 doxorubicin IV over 30-60 minutes on day 1 cyclophosphamide IV over 15 minutes every 12 hours on days 1-3 methotrexate IT and hydrocortisone IT on days 1 and 5 and filgrastim G-CSF subcutaneously SC beginning on day 6 and continuing until blood counts recover
Patients receive the second part of induction therapy when peripheral blood counts have recovered but no fewer than 16 days after the first part of induction therapy Patients receive 1 course of the COMRAP regimen comprising rituximab IV on days -2 and 0 with COPADM as in the first part of induction therapy
CONSOLIDATION THERAPY Patients receive the CYM-RM regimen comprising rituximab IV and methotrexate IV over 4 hours on day 0 leucovorin calcium IV or orally every 6 hours for 12 doses on days 1-3 cytarabine IV over 24 hours daily on days 1-5 hydrocortisone IT on days 1 and 6 methotrexate IT on day 1 and cytarabine IT on day 6
After full recovery from consolidation therapy patients with any residual masses undergo surgical excision or biopsy Patients with histology positive for tumor even if completely resected proceed to Group C consolidation therapy described below Patients with histology negative for tumor proceed to Group B maintenance therapy
MAINTENANCE THERAPY Patients receive the COPADM regimen comprising vincristine IV and methotrexate IV over 4 hours on day 0 PRED or MePRDL IV or orally on days 0-7 doxorubicin IV over 30-60 minutes and cyclophosphamide IV over 30 minutes on days 1 and 2 methotrexate IT and hydrocortisone IT on day 1 and leucovorin calcium IV or orally every 6 hours on days 1-3 12 doses
TREATMENT II 44 patients
REDUCTION THERAPY Patients receive the COP-R regimen as in treatment I
INDUCTION THERAPY Patients receive 2 courses of the COMRAP regimen as in the second induction of treatment I
CONSOLIDATION THERAPY Patients receive the CYM-RM regimen as in treatment I
MAINTENANCE THERAPY Patients receive the COPADM regimen as in treatment I
FAB GROUP C
TREATMENT I first 3 patients
REDUCTION THERAPY Patients receive the COP-R regimen as in group B treatment I with the addition of triple intrathecal therapy TIT comprising methotrexate hydrocortisone and cytarabine on days 0 2 and 4
INDUCTION THERAPY Patients receive 2 courses of the COPADM regimen as in group B treatment I with the addition of TIT on days 1 3 and 5 Patients in group C who have biopsy-proven disease after induction therapy are off protocol therapy and treated at the discretion of the investigator
CONSOLIDATION THERAPY
CNS-POSITIVE DISEASE Patients receive 2 courses of the CYVE-RM regimen comprising rituximab IV and methotrexate and hydrocortisone IT on day 0 cytarabine IV over 12 hours on days 0-4 high-dose cytarabine IV over 3 hours and etoposide IV over 2 hours on days 1-4 and G-CSF SC on days 6-20 During the first course patients also receive HD-MTX IV over 4 hours on day 17 TIT on day 18 and leucovorin calcium IV or orally every 6 hours on days 18-21 12 doses
CNS-NEGATIVE DISEASE Patients receive the CYVE-RM regimen without intrathecal therapy HD-MTX or leucovorin calcium
After full recovery from consolidation therapy patients with any residual masses undergo surgical excision or biopsy Patients who do not achieve complete remission after consolidation therapy are considered treatment failures
MAINTENANCE THERAPY each course lasts 28 days
COURSE M1 Patients receive vincristine IV and high-dose methotrexate IV over 4 hours on day 0 PRED or MePRDL IV or orally on days 0-7 doxorubicin IV over 30-60 minutes and TIT on day 1 cyclophosphamide IV over 30 minutes on days 1 and 2 and leucovorin calcium IV or orally every 6 hours on days 1-4 12 doses
COURSE M2 Patients receive etoposide IV over 90 minutes on days 0-2 and cytarabine SC every 12 hours on days 0-4
COURSE M3 Patients receive vincristine IV on day 0 cyclophosphamide IV over 30 minutes on days 0 and 1 PRED or MePRDL IV or orally twice daily on days 0-7 and doxorubicin IV over 30-60 minutes on day 0 after first dose of cyclophosphamide
COURSE M4 Patients receive etoposide and cytarabine as in course M2
TREATMENT II 37 patients
REDUCTION THERAPY Patients receive 2 courses of the COP-R regimen as in group C treatment I
INDUCTION THERAPY Patients receive the COMRAP regimen comprising rituximab IV vincristine IV and HD-MTX IV over 4 hours on day 0 PRED or MePRDL IV or orally on days 0-7 leucovorin calcium IV or orally and cyclophosphamide IV over 15 minutes on days 1-3 doxorubicin IV over 30-60 minutes on day 1 TIT on days 1 3 and 5 and G-CSF SC on days 6-20
CONSOLIDATION THERAPY CNS-positive disease Patients receive the CYVE-RM regimen plus HD-MTX as in group C treatment I Patients then receive CYVE-RM for a second course
CNS-NEGATIVE DISEASE Patients receive CYVE-RM regimen as in group C treatment I
MAINTENANCE THERAPY Patients receive maintenance therapy as in group C treatment I
Patients are followed every 3-6 months for 1 year and then every 6 months for up to 5 years
I Determine the toxicity of the addition of rituximab to induction chemotherapy comprising vincristine methylprednisolone methotrexate leucovorin calcium cyclophosphamide and doxorubicin COPADM COMRAP and to consolidation chemotherapy in children with newly diagnosed FAB prognostic group B or group C leukemia or lymphoma treated with LMBFAB therapy
II Determine the toxicity of the addition of rasburicase to the reduction phase comprising cyclophosphamide vincristine prednisone or methylprednisolone methotrexate and leucovorin calcium COP-R in these patients
III Determine the incidence of tumor lysis syndrome renal complications and the use of assisted renal support ie dialysis or hemofiltration during the COP-R reduction phase and the first induction phase of COPADM or COMRAP in these patients
IV Determine the response rate of patients treated with COMRAP incorporated into LMBFAB therapy
V Assess minimal residual disease in patients before and during COMRAP therapy incorporated into LMBFAB therapy
OUTLINE This is a multicenter study Patients are stratified according to FAB prognostic group B vs C and treated by group classification
FAB GROUP B
TREATMENT I first 6 patients
REDUCTION THERAPY Patients receive the COP-R regimen comprising cyclophosphamide IV over 15 minutes vincristine IV and methotrexate and hydrocortisone intrathecally IT on day 0 rasburicase IV over 30 minutes every 12 hours on days 0 and 1 and then once daily on days 2-4 patients exhibiting hyperuricemia and clinical suspicion of B-cell non-Hodgkins lymphoma or B-cell acute lymphocytic leukemia also receive rasburicase on days -3 -2 and -1 leucovorin calcium IV or orally every 12 hours on days 1 and 3 and prednisone PRED or methylprednisolone MePRDL IV or orally on days 0-6 Patients too critical to proceed may receive another course of reduction therapy
NOTE Patients with G6PD deficiency do not receive rasburicase during reduction therapy
INDUCTION THERAPY Patients with less than 20 tumor reduction follow the group C induction phase described below Patients with at least 20 tumor reduction receive 1 course of the COPADM regimen vincristine IV and methotrexate IV over 4 hours on day 0 PRED or MePRDL IV or orally on days 0-7 leucovorin calcium IV or orally every 6 hours for 12 doses on days 1-3 doxorubicin IV over 30-60 minutes on day 1 cyclophosphamide IV over 15 minutes every 12 hours on days 1-3 methotrexate IT and hydrocortisone IT on days 1 and 5 and filgrastim G-CSF subcutaneously SC beginning on day 6 and continuing until blood counts recover
Patients receive the second part of induction therapy when peripheral blood counts have recovered but no fewer than 16 days after the first part of induction therapy Patients receive 1 course of the COMRAP regimen comprising rituximab IV on days -2 and 0 with COPADM as in the first part of induction therapy
CONSOLIDATION THERAPY Patients receive the CYM-RM regimen comprising rituximab IV and methotrexate IV over 4 hours on day 0 leucovorin calcium IV or orally every 6 hours for 12 doses on days 1-3 cytarabine IV over 24 hours daily on days 1-5 hydrocortisone IT on days 1 and 6 methotrexate IT on day 1 and cytarabine IT on day 6
After full recovery from consolidation therapy patients with any residual masses undergo surgical excision or biopsy Patients with histology positive for tumor even if completely resected proceed to Group C consolidation therapy described below Patients with histology negative for tumor proceed to Group B maintenance therapy
MAINTENANCE THERAPY Patients receive the COPADM regimen comprising vincristine IV and methotrexate IV over 4 hours on day 0 PRED or MePRDL IV or orally on days 0-7 doxorubicin IV over 30-60 minutes and cyclophosphamide IV over 30 minutes on days 1 and 2 methotrexate IT and hydrocortisone IT on day 1 and leucovorin calcium IV or orally every 6 hours on days 1-3 12 doses
TREATMENT II 44 patients
REDUCTION THERAPY Patients receive the COP-R regimen as in treatment I
INDUCTION THERAPY Patients receive 2 courses of the COMRAP regimen as in the second induction of treatment I
CONSOLIDATION THERAPY Patients receive the CYM-RM regimen as in treatment I
MAINTENANCE THERAPY Patients receive the COPADM regimen as in treatment I
FAB GROUP C
TREATMENT I first 3 patients
REDUCTION THERAPY Patients receive the COP-R regimen as in group B treatment I with the addition of triple intrathecal therapy TIT comprising methotrexate hydrocortisone and cytarabine on days 0 2 and 4
INDUCTION THERAPY Patients receive 2 courses of the COPADM regimen as in group B treatment I with the addition of TIT on days 1 3 and 5 Patients in group C who have biopsy-proven disease after induction therapy are off protocol therapy and treated at the discretion of the investigator
CONSOLIDATION THERAPY
CNS-POSITIVE DISEASE Patients receive 2 courses of the CYVE-RM regimen comprising rituximab IV and methotrexate and hydrocortisone IT on day 0 cytarabine IV over 12 hours on days 0-4 high-dose cytarabine IV over 3 hours and etoposide IV over 2 hours on days 1-4 and G-CSF SC on days 6-20 During the first course patients also receive HD-MTX IV over 4 hours on day 17 TIT on day 18 and leucovorin calcium IV or orally every 6 hours on days 18-21 12 doses
CNS-NEGATIVE DISEASE Patients receive the CYVE-RM regimen without intrathecal therapy HD-MTX or leucovorin calcium
After full recovery from consolidation therapy patients with any residual masses undergo surgical excision or biopsy Patients who do not achieve complete remission after consolidation therapy are considered treatment failures
MAINTENANCE THERAPY each course lasts 28 days
COURSE M1 Patients receive vincristine IV and high-dose methotrexate IV over 4 hours on day 0 PRED or MePRDL IV or orally on days 0-7 doxorubicin IV over 30-60 minutes and TIT on day 1 cyclophosphamide IV over 30 minutes on days 1 and 2 and leucovorin calcium IV or orally every 6 hours on days 1-4 12 doses
COURSE M2 Patients receive etoposide IV over 90 minutes on days 0-2 and cytarabine SC every 12 hours on days 0-4
COURSE M3 Patients receive vincristine IV on day 0 cyclophosphamide IV over 30 minutes on days 0 and 1 PRED or MePRDL IV or orally twice daily on days 0-7 and doxorubicin IV over 30-60 minutes on day 0 after first dose of cyclophosphamide
COURSE M4 Patients receive etoposide and cytarabine as in course M2
TREATMENT II 37 patients
REDUCTION THERAPY Patients receive 2 courses of the COP-R regimen as in group C treatment I
INDUCTION THERAPY Patients receive the COMRAP regimen comprising rituximab IV vincristine IV and HD-MTX IV over 4 hours on day 0 PRED or MePRDL IV or orally on days 0-7 leucovorin calcium IV or orally and cyclophosphamide IV over 15 minutes on days 1-3 doxorubicin IV over 30-60 minutes on day 1 TIT on days 1 3 and 5 and G-CSF SC on days 6-20
CONSOLIDATION THERAPY CNS-positive disease Patients receive the CYVE-RM regimen plus HD-MTX as in group C treatment I Patients then receive CYVE-RM for a second course
CNS-NEGATIVE DISEASE Patients receive CYVE-RM regimen as in group C treatment I
MAINTENANCE THERAPY Patients receive maintenance therapy as in group C treatment I
Patients are followed every 3-6 months for 1 year and then every 6 months for up to 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 |
|---|---|---|---|
| U10CA098543 | NIH | Clinical Trialsgov | httpsreporternihgovquickSearchU10CA098543 |
| NCI-2009-00405 | REGISTRY | None | None |
| COG-ANHL01P1 | OTHER | None | None |
| CDR0000271941 | OTHER | None | None |