Ignite Creation Date:
2024-05-05 @ 10:05 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00003728
Status:
UNKNOWN
Last Update Posted:
2011-01-21
First Post:
1999-11-01
Brief Title:
Combination Chemotherapy Plus Steroid Therapy in Treating Children With Acute Lymphoblastic Leukemia or Lymphoblastic Non-Hodgkins Lymphoma
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
The Value of Dexamethasone Versus Prednisolone During Induction and Maintenance Therapy of Prolonged Versus Conventional Duration of L-Asparaginase Therapy During Consolidation and Late Intensification and of Corticosteroid VCR Pulses During Maintenance in Acute Lymphoblastic Leukemia and Lymphoblastic Non-Hodgkin Lymphoma of Childhood
Status:
UNKNOWN
Status Verified Date:
2009-06
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 tumor cells from dividing so they stop growing or die Combining more than one drug may kill more tumor cells It is not yet known which regimen of combination chemotherapy plus steroid therapy is more effective for acute lymphoblastic leukemia or lymphoblastic non-Hodgkins lymphoma
PURPOSE Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy plus steroid therapy in treating children who have acute lymphoblastic leukemia or lymphoblastic non-Hodgkins lymphoma
PURPOSE Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy plus steroid therapy in treating children who have acute lymphoblastic leukemia or lymphoblastic non-Hodgkins lymphoma
Detailed Description:
OBJECTIVES
Compare the value of dexamethasone DM vs prednisolone PRDL administered during induction therapy in terms of event-free and overall survival in children with acute lymphoblastic leukemia ALL or lymphoblastic non-Hodgkins lymphoma LNHL
Assess the value of increasing the number of administrations of asparaginase during consolidation and late intensification therapy in terms of disease-free and overall survival in children without very high-risk VHR features
Compare the response rate in children treated with prephase therapy comprising DM vs PRDL and intrathecal methotrexate
Compare the incidence and grade of toxic effects of these treatment regimens in these children
Compare the long-term effects of these treatment regimens on growth and pubertal development neurocognitive cardiac and endocrine function and incidence of aseptic bone necrosis in these children
Evaluate the proportion of children with VHR disease when defined according to extended VHR criteria and assess the prognostic importance of the new VHR features cytogenetics and minimal-residual disease
Compare the feasibility of the VHR chemotherapy protocol in patients treated with DM vs PRDL
OUTLINE This is a randomized multicenter study Patients are stratified for prephase therapy according to center disease acute lymphoblastic leukemia ALL vs non-Hodgkins lymphoma NHL WBC for ALL patients less than 10000mm3 vs 10000mm3 to less than 100000mm3 vs greater than 100000mm3 stage for NHL patients I or II vs III or IV and whether prephase already started yes vs no Patients are stratified for protocol II therapy according to center risk group very low risk VLR vs average risk 1 AR1 vs average risk 2 AR2 and treatment arm at first randomization
Prephase Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive oral prednisolone PRDL twice daily or methylprednisolone IV over 1 hour every 12 hours on days 1-7
Arm II Patients receive dexamethasone DM orally twice daily or IV over 1 hour every 12 hours on days 1-7
Patients in both arms also receive methotrexate MTX intrathecally IT on day 1
Protocol IA days 8-35
VLR patients Patients receive either oral PRDL or oral DM depending on earlier randomization on days 8-28 vincristine VCR IV on days 8 15 22 and 29 daunorubicin DNR IV over 1-4 hours on days 8 and 15 MTX IT on days 12 and 25 and asparaginase ASP IV over 1 hour or intramuscularly IM on days 12 15 18 22 25 29 32 and 35
AR1 patients Patients receive PRDL or DM VCR and ASP in the same manner as VLR patients Patients also receive DNR IV over 1-4 hours on days 8 15 22 and 29 and triple intrathecal therapy TIT comprising MTX cytarabine ARA-C and hydrocortisone on days 12 and 25
AR2 and very high-risk VHR patientsPatients receive PRDL or DM VCR and ASP in the same manner as VLR patients and high-dose MTX HD-MTX IV over 24 hours on day 8 cyclophosphamide CTX IV over 1 hour on day 9 DNR IV over 1-4 hours on days 15 22 and 29 and TIT on days 12 and 25
Patients with VLR AR1 or AR2 disease after protocol IA proceed to protocol IB interval therapy and then protocol II Patients with VHR disease after protocol IA proceed to the VHR patient protocol
Protocol IB for VLR AR1 or AR2 patients Patients with precursor B-cell ALL must be in complete remission CR and patients with NHL must be in CR or good partial remission
VLR patients Patients receive oral mercaptopurine MP on days 36-63 ARA-C IV on days 38-41 45-48 52-55 and 59-62 and MTX IT on days 38 and 52
AR1 and AR2 patients Patients receive oral MP and ARA-C in the same manner as VLR patients CTX IV over 1 hour on days 36 and 63 and TIT on days 38 and 52
VLR AR1 and AR2 patients are also randomized to 1 of 2 treatment arms
Arm I Patients receive ASP IV or IM on days 38 41 45 48 52 55 59 and 62
Arm II Patients receive no ASP
Interval therapy for VLR AR1 or AR2 patients begins 14 days after completion of protocol I Patients receive oral MP daily on days 1-56 HD-MTX IV over 24 hours on days 8 22 36 and 50 leucovorin calcium CF or levofolinic acid orally or IV beginning 36 hours after initiation of MTX infusion and repeating every 6 hours until hour 72 or until serum MTX level is adequate and TIT on days 9 23 37 and 51
Protocol II reinduction therapy IIA and reconsolidation therapy IIB
VLR patients Patients receive oral DM twice daily on days 1-21 VCR IV on days 8 15 22 and 29 doxorubicin DOX IV over 1-4 hours on days 8 and 15 ARA-C IV on days 38-41 and 45-48 oral thioguanine TG once daily on days 36-49 and MTX IT on day 38
AR patients Patients receive DM VCR ARA-C and TG in the same manner as VLR patients DOX IV over 1-4 hours on days 8 15 22 and 29 CTX IV over 30-60 minutes on day 36 and TIT on day 38
VLR and AR patients are also randomized to 1 of 2 treatment arms
Arm I Patients receive short-term ASP IV over 1 hour or IM on days 8 11 15 and 18
Arm II Patients receive long-term ASP IV over 1 hour or IM on days 8 11 15 18 22 25 29 and 32
Maintenance therapy for VLR and AR patients begins 14 days after completion of protocol II
VLR patients Patients receive oral MP once daily and oral MTX once weekly for a total of 74 weeks
AR1 patients Patients receive oral MP once daily on days 1-70 oral MTX on days 1 8 15 29 36 43 50 57 and 64 and TIT on day 22 Treatment repeats every 10 weeks for 6 courses
AR2 patients Patients receive MP and oral MTX as for AR1 patients HD-MTX IV over 24 hours on day 22 CF as in interval therapy on days 23 and 24 and TIT and ASP on day 23
After course 6 AR1 and AR2 patients receive further maintenance therapy comprising oral MP once daily and oral MTX once a week
VHR patient protocol recommended treatment Patients with VHR disease after protocol IA receive reinforced consolidation protocol IB and VANDA regimens
Protocol IB Patients receive oral DM twice daily on days 36-40 and 50-54 oral MP daily on days 36-40 VCR IV on days 36 and 41 HD-MTX IV over 24 hours on days 36 and 50 TIT on days 37 and 51 ARA-C IV over 3 hours every 12 hours on day 40 ASP IV over 1 hour or IM on days 41 43 45 55 57 and 59 oral TG once daily on days 50-54 vindesine DAVA IV on day 50 DNR IV over 1-4 hours on day 54 and CTX IV over 1 hour on days 52 and 53 Patients who achieve CR after protocol IB proceed to VANDA regimen
VANDA regimen Patients receive oral DM twice daily on days 1-5 ARA-C IV over 3 hours every 12 hours on days 1 and 2 mitoxantrone IV over 1 hour on days 3 and 4 etoposide VP-16 IV over 1 hour on days 3-5 TIT on day 5 and ASP IV or IM on days 7 9 11 and 13
After protocol IB and VANDA VHR patients who are eligible for stem cell transplantation SCT and have an HLA-compatible familial donor undergo transplantation Patients who are ineligible for SCT receive interval therapy followed by 2 sequences of blocks R1 R2 and R3 2 courses of each block for a total of 6 courses and then maintenance therapy for a total treatment duration of 2 years
Interval therapy Patients receive oral MP once daily on days 1-42 HD-MTX IV over 24 hours on days 8 22 and 36 CF as in interval therapy described above and TIT on days 9 23 and 37
Blocks R1 R2 and R3 this sequential regimen is repeated once
R1 Patients receive oral DM twice daily and oral MP once daily on days 1-5 VCR IV on days 1 and 6 HD-MTX IV over 24 hours on day 1 CF as in interval therapy on days 1 and 2 TIT on day 2 ARA-C IV over 3 hours every 12 hours on day 5 and ASP IV over 1 hour or IM on day 6
R2 Patients receive DM HD-MTX CF TIT and ASP as in block R1 and oral TG once daily on days 1-5 DAVA IV on day 1 CTX IV over 1 hour on days 3 and 4 and DNR IV over 1-4 hours on day 5
R3 Patients receive DM and ASP as in block R1 and ARA-C IV over 3 hours every 12 hours on days 1 and 2 VP-16 IV over 1 hour on days 3-5 and TIT on day 5
Maintenance therapy begins 14 days after the second course of block R3 and ends 2 years after initiation of study therapy Patients receive treatment as in maintenance therapy for AR1 patients Treatment repeats every 10 weeks for 5 courses
Patients are followed every 3 months for 5 years and then annually thereafter
PROJECTED ACCRUAL A total of 1400-1500 patients will be accrued for this study within 55 years
Compare the value of dexamethasone DM vs prednisolone PRDL administered during induction therapy in terms of event-free and overall survival in children with acute lymphoblastic leukemia ALL or lymphoblastic non-Hodgkins lymphoma LNHL
Assess the value of increasing the number of administrations of asparaginase during consolidation and late intensification therapy in terms of disease-free and overall survival in children without very high-risk VHR features
Compare the response rate in children treated with prephase therapy comprising DM vs PRDL and intrathecal methotrexate
Compare the incidence and grade of toxic effects of these treatment regimens in these children
Compare the long-term effects of these treatment regimens on growth and pubertal development neurocognitive cardiac and endocrine function and incidence of aseptic bone necrosis in these children
Evaluate the proportion of children with VHR disease when defined according to extended VHR criteria and assess the prognostic importance of the new VHR features cytogenetics and minimal-residual disease
Compare the feasibility of the VHR chemotherapy protocol in patients treated with DM vs PRDL
OUTLINE This is a randomized multicenter study Patients are stratified for prephase therapy according to center disease acute lymphoblastic leukemia ALL vs non-Hodgkins lymphoma NHL WBC for ALL patients less than 10000mm3 vs 10000mm3 to less than 100000mm3 vs greater than 100000mm3 stage for NHL patients I or II vs III or IV and whether prephase already started yes vs no Patients are stratified for protocol II therapy according to center risk group very low risk VLR vs average risk 1 AR1 vs average risk 2 AR2 and treatment arm at first randomization
Prephase Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive oral prednisolone PRDL twice daily or methylprednisolone IV over 1 hour every 12 hours on days 1-7
Arm II Patients receive dexamethasone DM orally twice daily or IV over 1 hour every 12 hours on days 1-7
Patients in both arms also receive methotrexate MTX intrathecally IT on day 1
Protocol IA days 8-35
VLR patients Patients receive either oral PRDL or oral DM depending on earlier randomization on days 8-28 vincristine VCR IV on days 8 15 22 and 29 daunorubicin DNR IV over 1-4 hours on days 8 and 15 MTX IT on days 12 and 25 and asparaginase ASP IV over 1 hour or intramuscularly IM on days 12 15 18 22 25 29 32 and 35
AR1 patients Patients receive PRDL or DM VCR and ASP in the same manner as VLR patients Patients also receive DNR IV over 1-4 hours on days 8 15 22 and 29 and triple intrathecal therapy TIT comprising MTX cytarabine ARA-C and hydrocortisone on days 12 and 25
AR2 and very high-risk VHR patientsPatients receive PRDL or DM VCR and ASP in the same manner as VLR patients and high-dose MTX HD-MTX IV over 24 hours on day 8 cyclophosphamide CTX IV over 1 hour on day 9 DNR IV over 1-4 hours on days 15 22 and 29 and TIT on days 12 and 25
Patients with VLR AR1 or AR2 disease after protocol IA proceed to protocol IB interval therapy and then protocol II Patients with VHR disease after protocol IA proceed to the VHR patient protocol
Protocol IB for VLR AR1 or AR2 patients Patients with precursor B-cell ALL must be in complete remission CR and patients with NHL must be in CR or good partial remission
VLR patients Patients receive oral mercaptopurine MP on days 36-63 ARA-C IV on days 38-41 45-48 52-55 and 59-62 and MTX IT on days 38 and 52
AR1 and AR2 patients Patients receive oral MP and ARA-C in the same manner as VLR patients CTX IV over 1 hour on days 36 and 63 and TIT on days 38 and 52
VLR AR1 and AR2 patients are also randomized to 1 of 2 treatment arms
Arm I Patients receive ASP IV or IM on days 38 41 45 48 52 55 59 and 62
Arm II Patients receive no ASP
Interval therapy for VLR AR1 or AR2 patients begins 14 days after completion of protocol I Patients receive oral MP daily on days 1-56 HD-MTX IV over 24 hours on days 8 22 36 and 50 leucovorin calcium CF or levofolinic acid orally or IV beginning 36 hours after initiation of MTX infusion and repeating every 6 hours until hour 72 or until serum MTX level is adequate and TIT on days 9 23 37 and 51
Protocol II reinduction therapy IIA and reconsolidation therapy IIB
VLR patients Patients receive oral DM twice daily on days 1-21 VCR IV on days 8 15 22 and 29 doxorubicin DOX IV over 1-4 hours on days 8 and 15 ARA-C IV on days 38-41 and 45-48 oral thioguanine TG once daily on days 36-49 and MTX IT on day 38
AR patients Patients receive DM VCR ARA-C and TG in the same manner as VLR patients DOX IV over 1-4 hours on days 8 15 22 and 29 CTX IV over 30-60 minutes on day 36 and TIT on day 38
VLR and AR patients are also randomized to 1 of 2 treatment arms
Arm I Patients receive short-term ASP IV over 1 hour or IM on days 8 11 15 and 18
Arm II Patients receive long-term ASP IV over 1 hour or IM on days 8 11 15 18 22 25 29 and 32
Maintenance therapy for VLR and AR patients begins 14 days after completion of protocol II
VLR patients Patients receive oral MP once daily and oral MTX once weekly for a total of 74 weeks
AR1 patients Patients receive oral MP once daily on days 1-70 oral MTX on days 1 8 15 29 36 43 50 57 and 64 and TIT on day 22 Treatment repeats every 10 weeks for 6 courses
AR2 patients Patients receive MP and oral MTX as for AR1 patients HD-MTX IV over 24 hours on day 22 CF as in interval therapy on days 23 and 24 and TIT and ASP on day 23
After course 6 AR1 and AR2 patients receive further maintenance therapy comprising oral MP once daily and oral MTX once a week
VHR patient protocol recommended treatment Patients with VHR disease after protocol IA receive reinforced consolidation protocol IB and VANDA regimens
Protocol IB Patients receive oral DM twice daily on days 36-40 and 50-54 oral MP daily on days 36-40 VCR IV on days 36 and 41 HD-MTX IV over 24 hours on days 36 and 50 TIT on days 37 and 51 ARA-C IV over 3 hours every 12 hours on day 40 ASP IV over 1 hour or IM on days 41 43 45 55 57 and 59 oral TG once daily on days 50-54 vindesine DAVA IV on day 50 DNR IV over 1-4 hours on day 54 and CTX IV over 1 hour on days 52 and 53 Patients who achieve CR after protocol IB proceed to VANDA regimen
VANDA regimen Patients receive oral DM twice daily on days 1-5 ARA-C IV over 3 hours every 12 hours on days 1 and 2 mitoxantrone IV over 1 hour on days 3 and 4 etoposide VP-16 IV over 1 hour on days 3-5 TIT on day 5 and ASP IV or IM on days 7 9 11 and 13
After protocol IB and VANDA VHR patients who are eligible for stem cell transplantation SCT and have an HLA-compatible familial donor undergo transplantation Patients who are ineligible for SCT receive interval therapy followed by 2 sequences of blocks R1 R2 and R3 2 courses of each block for a total of 6 courses and then maintenance therapy for a total treatment duration of 2 years
Interval therapy Patients receive oral MP once daily on days 1-42 HD-MTX IV over 24 hours on days 8 22 and 36 CF as in interval therapy described above and TIT on days 9 23 and 37
Blocks R1 R2 and R3 this sequential regimen is repeated once
R1 Patients receive oral DM twice daily and oral MP once daily on days 1-5 VCR IV on days 1 and 6 HD-MTX IV over 24 hours on day 1 CF as in interval therapy on days 1 and 2 TIT on day 2 ARA-C IV over 3 hours every 12 hours on day 5 and ASP IV over 1 hour or IM on day 6
R2 Patients receive DM HD-MTX CF TIT and ASP as in block R1 and oral TG once daily on days 1-5 DAVA IV on day 1 CTX IV over 1 hour on days 3 and 4 and DNR IV over 1-4 hours on day 5
R3 Patients receive DM and ASP as in block R1 and ARA-C IV over 3 hours every 12 hours on days 1 and 2 VP-16 IV over 1 hour on days 3-5 and TIT on day 5
Maintenance therapy begins 14 days after the second course of block R3 and ends 2 years after initiation of study therapy Patients receive treatment as in maintenance therapy for AR1 patients Treatment repeats every 10 weeks for 5 courses
Patients are followed every 3 months for 5 years and then annually thereafter
PROJECTED ACCRUAL A total of 1400-1500 patients will be accrued for this study within 55 years
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EORTC-58951 | None | None | None |