Ignite Creation Date:
2024-05-05 @ 11:19 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002757
Status:
COMPLETED
Last Update Posted:
2014-07-24
First Post:
1999-11-01
Brief Title:
TITLELess Intensive Therapy for Children With Non-Hodgkins Lymphoma
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
FAB LMB 96 -- Treatment of Mature B-CELL LymphomaLeukemia A SFOP LMB 96CCG 5961UKCCSG NHL 9600 Cooperative Study
Status:
COMPLETED
Status Verified Date:
2014-07
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 Less intensive therapy may attain in the same results as intensive therapy in children with non-Hodgkins lymphoma
PURPOSE Randomized phase III trial to study the effectiveness of less intensive therapy for children who have non-Hodgkins lymphoma
PURPOSE Randomized phase III trial to study the effectiveness of less intensive therapy for children who have non-Hodgkins lymphoma
Detailed Description:
OBJECTIVES
Confirm the previously found excellent survival for low-risk patients Group A with B-cell lymphomaleukemia treated with the LMB 89 regimen
Verify that good event-free survival is retained in intermediate-risk patients Group B when the dose of cyclophosphamide CTX or the number of CTX-containing regimens is reduced
Verify that good event-free survival is retained in high-risk patients Group C despite reduction in doses during consolidation therapy and a reduced number of maintenance courses and for patients with CNS involvement additional intravenous and intrathecal methotrexate in place of cranial irradiation
Monitor survival and event-free survival of all patients registered prior to the first chemotherapy course
Compare the survival and event-free survival of Group C patients with CNS involvement against results from those treated on the LMB 89 study
Compare event-free survival and survival of patients with large cell and Burkitts and Burkitts-like lymphoma
Monitor the long-term toxicity in patients treated on this study including fertility cardiotoxicity and secondary malignancy
Characterize further the biology of childhood small non-cleaved cell lymphoma with respect to drug resistance ie topoisomerase II and MDR activity viral association ie Epstein-Barr virus human immunodeficiency virus human herpesvirus 6 and specific breakpoint translocations ie IgH and C-myc per companion study CCG-B944
Characterize further the biology of childhood mature B-cell lymphoma per UKCCSG studies
OUTLINE This is a randomized study Patients are stratified according to participating group UKCCSG vs SFOP vs CCG histology large cell vs small non-cleaved cell risk group Group A vs Group B vs Group C Stage III Group B patients are further stratified according to Murphy stage stages III vs III vs IIIIV and by LDH less than twice normal vs twice normal or higher Group C patients are further stratified based on presence of CNS disease yes vs no
Patients with resected stage I and resected abdominal-only stage II disease are treated on the Group A Regimen Patients with unresected stage III stage III or CNS-negative stage IV disease with fewer than 25 blasts in bone marrow are treated on the Group B Regimen Patients with 25 or more blasts in bone marrow or with CNS involvement ie L3 blasts in CSF cranial nerve palsy clinical spinal cord compression isolated intracerebral mass or parameningeal cranial or spinal extension are treated on the Group C Regimen
The following acronyms are used
ARA-C Cytarabine NSC-63878
CF Leucovorin calcium NSC-3590
COP CTXVCRPRED or PRDL
COPAD CTXVCRPRED or PRDLDOX
COPADM CTXVCRPRED or PRDLDOXMTX
CTX Cyclophosphamide NSC-26271
CYM ARA- CMTX
CYVE ARA-CVP-16
DOX Doxorubicin NSC-123127
G-CSF Granulocyte Colony-Stimulating Factor Amgen NSC-614629
HC Hydrocortisone NSC-10483
HD High Dose
MTX Methotrexate NSC-740
PRDL Prednisolone NSC-9900
PRED Prednisone NSC-10023
TIT Triple Intrathecal Chemotherapy IT MTXIT HCIT ARA-C
VCR Vincristine NSC-67574
VP-16 Etoposide NSC-141540
Group A Regimen Low-Risk Patients
Induction Patients receive COPAD VCR IV on days 1 and 6 oral PRED or IV twice daily on days 1-5 then tapered over 3 days CTX IV over 15 minutes every 12 hours on days 1-3 and DOX IV over 6 hours on day 1 starting after the first CTX dose G-CSF SC is administered until hematopoietic recovery beginning on day 7 Patients receive a second course beginning on day 21
Group B Regimen Intermediate-Risk Patients
Induction 1 Patients receive CTX IV over 15 minutes on day 1 VCR IV on day 1 and oral PRED on days 1-7 and MTX IT and HC IT on day 1 Patients with responding disease proceed with COPADM Patients with no response proceed to treatment on arm I of the Group C Regimen
COPADM 1 Patients receive VCR IV on day 8 oral PRED twice daily on days 8-12 then tapered over 3 days MTX IV over 3 hours on day 8 oral CF every 6 hours for 12 doses beginning 24 hours after start of MTX CTX IV over 15 minutes every 12 hours on days 9-11 and DOX IV over 6 hours on day 9 beginning after the first CTX dose G-CSF is administered as in the Group A Regimen MTX IT and HC IT are given on days 9 and 13
Group B patients are randomized to 1 of 4 treatments following recovery and disease assessment
Arm I
Induction 2 begins no sooner than 16 days after start of COPADM 1 Patients receive COPADM 2 according to the same schedule as in COPADM 1 in Induction 1 except CTX is increased G-CSF is administered as in the Group A Regimen Patients receive MTX IT and HC IT on days 2 and 6
Consolidation Patients receive CYM MTX IV over 3 hours on day 1 oral CF every 6 hours for a maximum of 12 doses beginning 24 hours after the start of MTX and ARA-C IV over 24 hours on days 2-6 Patients receive TIT MTX IT on day 2 HC IT on days 2 and 7 and ARA-C IT on day 7
Response is assessed upon recovery with resection of residual masses If histology is negative patients proceed to a second course of CYM If histology is positive patients proceed to CYVE on arm I of the Group C Regimen
Maintenance Patients receive COPADM 3 as in COPADM 1 in Induction 1 except CTX IV is administered over 30 minutes on days 2 and 3 and MTX IT and HC IT are administered on day 2
Arm II
Induction 2 Patients receive COPADM 2 as in arm I of the Group B Regimen G-CSF is administered as in the Group A Regimen MTX IT and HC IT are administered as in Induction 1
Consolidation Patients receive CYM TIT and response assessment as in arm I of the Group B Regimen
Maintenance Patients receive no maintenance therapy
Arm III
Induction 2 Patients receive COPADM 2 as in COPADM 1 in Induction 1 G-CSF is administered as in the Group A Regimen Patients receive MTX IT and HC IT as in Induction 1
Consolidation Patients receive CYM TIT and response assessment as in arm I of the Group B Regimen
Maintenance Patients receive COPADM 3 as in arm I of the Group B Regimen Patients receive MTX IT and HC IT on day 2
Arm IV
Induction 2 Patients receive COPADM 2 as in COPADM 1 in Induction 1 G-CSF is administered as in the Group A Regimen Patients receive MTX IT and HC IT as in Induction 1
Consolidation Patients receive CYM TIT and response assessment as in arm I of the Group B Regimen
Maintenance Patients receive no maintenance therapy
Group C Regimen High-Risk Patients
Induction Patients receive COP as in Induction 1 of the Group B Regimen TIT on days 1 3 and 5 and oral CF every 12 hours on days 2 and 4 Tumor response is evaluated on day 7 and treatment decisions are made as in Induction 1 of the Group B Regimen Patients receive COPADM 1 as in COPADM 1 in Induction 1 of the Group B Regimen except HD MTX IV is given over 4 hours on day 1 G-CSF is administered as in the Group A Regimen TIT is given on days 2 4 and 6 Patients receive COPADM 2 as in COPADM 2 in arm I of the Group B Regimen Induction 2 except HD MTX IV is given over 4 hours on day 1 G-CSF is administered as in the Group A Regimen Patients receive TIT on days 2 4 and 6
Patients are randomized to 1 of 2 treatment arms upon recovery and disease assessment
Arm I
Consolidation Patients receive CYVE ARA-C IV on days 1-5 and VP-16 IV over 2 hours on days 2-5 G-CSF is administered as in the Group A Regimen For patients with CNS disease MTX IT and HC IT on day 1 6 hours prior to initiation of ARA-C HD MTX IV over 4 hours about day 18 oral CF every 6 hours for a maximum of 12 doses beginning 24 hours after starting MTX and TIT prior to beginning CF
Response is assessed upon recovery with resection of residual masses Patients with a complete response receive a second course of CYVE no HD MTXCF beginning 1 week after HD MTX
Maintenance 28 days between courses
Course 1 Patients receive COPADM as in arm I Maintenance in the Group B Regimen except HD MTX is administered as in Group C Induction and TIT is given on day 2 replacing MTX IT and HC
Course 2 Patients receive CYVE ARA-C IV every 12 hours on days 1-5 and VP-16 IV over 90 minutes on days 1-3
Course 3 Patients receive COPAD as in Group B Induction 1 except CTX IV is administered over 30 minutes on days 1 and 2
Course 4 Patients receive treatment identical to Course 2
Arm II
Consolidation Patients receive Mini-CYVE ARA-C IV on days 1-5 and VP-16 IV over 1 hour on days 2-5 G-CSF is administered as in the Group A Regimen For patients with CNS disease MTX IT and HC IT as in arm I in the Group C Regimen and HD MTX CF and TIT as in arm I in the Group C Regimen
Response is assessed upon recovery with resection of residual masses Patients with a complete response receive a second course of CYVE no HD MTX and CF beginning 1 week after HD MTX
Maintenance Patients receive COPADM and TIT as in arm I of the Group C Regimen in Course 1 for 1 course only
Patients are followed every 3 months for 6 months every 6 months for 25 years and then annually thereafter
PROJECTED ACCRUAL A total of 900 patients will be accrued for this study within 5 years Yearly accrual is expected to be 20 Group A patients 115 Group B patients and 45 Group C patients
Confirm the previously found excellent survival for low-risk patients Group A with B-cell lymphomaleukemia treated with the LMB 89 regimen
Verify that good event-free survival is retained in intermediate-risk patients Group B when the dose of cyclophosphamide CTX or the number of CTX-containing regimens is reduced
Verify that good event-free survival is retained in high-risk patients Group C despite reduction in doses during consolidation therapy and a reduced number of maintenance courses and for patients with CNS involvement additional intravenous and intrathecal methotrexate in place of cranial irradiation
Monitor survival and event-free survival of all patients registered prior to the first chemotherapy course
Compare the survival and event-free survival of Group C patients with CNS involvement against results from those treated on the LMB 89 study
Compare event-free survival and survival of patients with large cell and Burkitts and Burkitts-like lymphoma
Monitor the long-term toxicity in patients treated on this study including fertility cardiotoxicity and secondary malignancy
Characterize further the biology of childhood small non-cleaved cell lymphoma with respect to drug resistance ie topoisomerase II and MDR activity viral association ie Epstein-Barr virus human immunodeficiency virus human herpesvirus 6 and specific breakpoint translocations ie IgH and C-myc per companion study CCG-B944
Characterize further the biology of childhood mature B-cell lymphoma per UKCCSG studies
OUTLINE This is a randomized study Patients are stratified according to participating group UKCCSG vs SFOP vs CCG histology large cell vs small non-cleaved cell risk group Group A vs Group B vs Group C Stage III Group B patients are further stratified according to Murphy stage stages III vs III vs IIIIV and by LDH less than twice normal vs twice normal or higher Group C patients are further stratified based on presence of CNS disease yes vs no
Patients with resected stage I and resected abdominal-only stage II disease are treated on the Group A Regimen Patients with unresected stage III stage III or CNS-negative stage IV disease with fewer than 25 blasts in bone marrow are treated on the Group B Regimen Patients with 25 or more blasts in bone marrow or with CNS involvement ie L3 blasts in CSF cranial nerve palsy clinical spinal cord compression isolated intracerebral mass or parameningeal cranial or spinal extension are treated on the Group C Regimen
The following acronyms are used
ARA-C Cytarabine NSC-63878
CF Leucovorin calcium NSC-3590
COP CTXVCRPRED or PRDL
COPAD CTXVCRPRED or PRDLDOX
COPADM CTXVCRPRED or PRDLDOXMTX
CTX Cyclophosphamide NSC-26271
CYM ARA- CMTX
CYVE ARA-CVP-16
DOX Doxorubicin NSC-123127
G-CSF Granulocyte Colony-Stimulating Factor Amgen NSC-614629
HC Hydrocortisone NSC-10483
HD High Dose
MTX Methotrexate NSC-740
PRDL Prednisolone NSC-9900
PRED Prednisone NSC-10023
TIT Triple Intrathecal Chemotherapy IT MTXIT HCIT ARA-C
VCR Vincristine NSC-67574
VP-16 Etoposide NSC-141540
Group A Regimen Low-Risk Patients
Induction Patients receive COPAD VCR IV on days 1 and 6 oral PRED or IV twice daily on days 1-5 then tapered over 3 days CTX IV over 15 minutes every 12 hours on days 1-3 and DOX IV over 6 hours on day 1 starting after the first CTX dose G-CSF SC is administered until hematopoietic recovery beginning on day 7 Patients receive a second course beginning on day 21
Group B Regimen Intermediate-Risk Patients
Induction 1 Patients receive CTX IV over 15 minutes on day 1 VCR IV on day 1 and oral PRED on days 1-7 and MTX IT and HC IT on day 1 Patients with responding disease proceed with COPADM Patients with no response proceed to treatment on arm I of the Group C Regimen
COPADM 1 Patients receive VCR IV on day 8 oral PRED twice daily on days 8-12 then tapered over 3 days MTX IV over 3 hours on day 8 oral CF every 6 hours for 12 doses beginning 24 hours after start of MTX CTX IV over 15 minutes every 12 hours on days 9-11 and DOX IV over 6 hours on day 9 beginning after the first CTX dose G-CSF is administered as in the Group A Regimen MTX IT and HC IT are given on days 9 and 13
Group B patients are randomized to 1 of 4 treatments following recovery and disease assessment
Arm I
Induction 2 begins no sooner than 16 days after start of COPADM 1 Patients receive COPADM 2 according to the same schedule as in COPADM 1 in Induction 1 except CTX is increased G-CSF is administered as in the Group A Regimen Patients receive MTX IT and HC IT on days 2 and 6
Consolidation Patients receive CYM MTX IV over 3 hours on day 1 oral CF every 6 hours for a maximum of 12 doses beginning 24 hours after the start of MTX and ARA-C IV over 24 hours on days 2-6 Patients receive TIT MTX IT on day 2 HC IT on days 2 and 7 and ARA-C IT on day 7
Response is assessed upon recovery with resection of residual masses If histology is negative patients proceed to a second course of CYM If histology is positive patients proceed to CYVE on arm I of the Group C Regimen
Maintenance Patients receive COPADM 3 as in COPADM 1 in Induction 1 except CTX IV is administered over 30 minutes on days 2 and 3 and MTX IT and HC IT are administered on day 2
Arm II
Induction 2 Patients receive COPADM 2 as in arm I of the Group B Regimen G-CSF is administered as in the Group A Regimen MTX IT and HC IT are administered as in Induction 1
Consolidation Patients receive CYM TIT and response assessment as in arm I of the Group B Regimen
Maintenance Patients receive no maintenance therapy
Arm III
Induction 2 Patients receive COPADM 2 as in COPADM 1 in Induction 1 G-CSF is administered as in the Group A Regimen Patients receive MTX IT and HC IT as in Induction 1
Consolidation Patients receive CYM TIT and response assessment as in arm I of the Group B Regimen
Maintenance Patients receive COPADM 3 as in arm I of the Group B Regimen Patients receive MTX IT and HC IT on day 2
Arm IV
Induction 2 Patients receive COPADM 2 as in COPADM 1 in Induction 1 G-CSF is administered as in the Group A Regimen Patients receive MTX IT and HC IT as in Induction 1
Consolidation Patients receive CYM TIT and response assessment as in arm I of the Group B Regimen
Maintenance Patients receive no maintenance therapy
Group C Regimen High-Risk Patients
Induction Patients receive COP as in Induction 1 of the Group B Regimen TIT on days 1 3 and 5 and oral CF every 12 hours on days 2 and 4 Tumor response is evaluated on day 7 and treatment decisions are made as in Induction 1 of the Group B Regimen Patients receive COPADM 1 as in COPADM 1 in Induction 1 of the Group B Regimen except HD MTX IV is given over 4 hours on day 1 G-CSF is administered as in the Group A Regimen TIT is given on days 2 4 and 6 Patients receive COPADM 2 as in COPADM 2 in arm I of the Group B Regimen Induction 2 except HD MTX IV is given over 4 hours on day 1 G-CSF is administered as in the Group A Regimen Patients receive TIT on days 2 4 and 6
Patients are randomized to 1 of 2 treatment arms upon recovery and disease assessment
Arm I
Consolidation Patients receive CYVE ARA-C IV on days 1-5 and VP-16 IV over 2 hours on days 2-5 G-CSF is administered as in the Group A Regimen For patients with CNS disease MTX IT and HC IT on day 1 6 hours prior to initiation of ARA-C HD MTX IV over 4 hours about day 18 oral CF every 6 hours for a maximum of 12 doses beginning 24 hours after starting MTX and TIT prior to beginning CF
Response is assessed upon recovery with resection of residual masses Patients with a complete response receive a second course of CYVE no HD MTXCF beginning 1 week after HD MTX
Maintenance 28 days between courses
Course 1 Patients receive COPADM as in arm I Maintenance in the Group B Regimen except HD MTX is administered as in Group C Induction and TIT is given on day 2 replacing MTX IT and HC
Course 2 Patients receive CYVE ARA-C IV every 12 hours on days 1-5 and VP-16 IV over 90 minutes on days 1-3
Course 3 Patients receive COPAD as in Group B Induction 1 except CTX IV is administered over 30 minutes on days 1 and 2
Course 4 Patients receive treatment identical to Course 2
Arm II
Consolidation Patients receive Mini-CYVE ARA-C IV on days 1-5 and VP-16 IV over 1 hour on days 2-5 G-CSF is administered as in the Group A Regimen For patients with CNS disease MTX IT and HC IT as in arm I in the Group C Regimen and HD MTX CF and TIT as in arm I in the Group C Regimen
Response is assessed upon recovery with resection of residual masses Patients with a complete response receive a second course of CYVE no HD MTX and CF beginning 1 week after HD MTX
Maintenance Patients receive COPADM and TIT as in arm I of the Group C Regimen in Course 1 for 1 course only
Patients are followed every 3 months for 6 months every 6 months for 25 years and then annually thereafter
PROJECTED ACCRUAL A total of 900 patients will be accrued for this study within 5 years Yearly accrual is expected to be 20 Group A patients 115 Group B patients and 45 Group C patients
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 |
|---|---|---|---|
| CDR0000064702 | OTHER | Clinical Trialsgov | None |
| COG-C5961 | OTHER | None | None |
| CCG-5961 | OTHER | None | None |
| SFOP-LMB-96 | None | None | None |
| CCLG-NHL-9600 | None | None | None |
| EU-96048 | None | None | None |