Ignite Creation Date:
2024-05-05 @ 10:01 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002744
Status:
COMPLETED
Last Update Posted:
2017-02-09
First Post:
1999-11-01
Brief Title:
Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
Randomized Comparisons of Oral Mercaptopurine vs Oral Thioguanine and IT Methotrexate vs ITT for Standard Risk Acute Lymphoblastic Leukemia
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 Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die Combining more than one drug and giving them in different ways may kill more cancer cells It is not yet known which regimen of combination chemotherapy is more effective for acute lymphoblastic leukemia
PURPOSE Randomized phase III trial to compare different regimens of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia
PURPOSE Randomized phase III trial to compare different regimens of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia
Detailed Description:
OBJECTIVES I Identify response related factors predictive of relapse among children with previously untreated standard risk acute lymphoblastic leukemia ALL II Determine the prognostic significance of residual leukemic blasts at specific times during induction therapy M3 marrow status greater than 25 blasts at day 7 M2 status 5-25 blasts at day 14 and residual circulating leukemic blasts at days 7 and 14 III Determine the prognostic significance of residual leukemic burden as measured by fluorescence activated cell sortingleukemic progenitor cell assay on marrow aspirates acquired at the end of induction therapy at the beginning of maintenance therapy and at the completion of all therapy in patients with B precursor ALL IV Determine the prognostic significance of residual t119 detected in marrow aspirates by PCR-based analyses of the fusion transcript E2A-PBX1 at the end of induction therapy at the beginning of maintenance therapy and at the completion of all therapy V Examine the interrelationships among these response-related prognostic factors and their correlation with ploidy karyotype and immunophenotype VI Determine in a randomized study whether substitution of oral thioguanine TG for oral mercaptopurine MP during consolidation interim maintenance and maintenance therapy improves event-free survival for patients with standard-risk ALL VII Study and compare the cellular pharmacokinetics of oral MP and oral TG during interim maintenance and maintenance therapy in selected patients VIII Compare the concentrations of MP and TG red blood cell metabolites ie nucleotides nucleosides free bases and methylated metabolites during interim maintenance and maintenance therapy and determine whether low levels of metabolites predict relapse in selected patients IX Determine the activities of thiopurine methyltransferase and hypoxanthine guanine phosphoribosyl transferase several times during interim maintenance and maintenance treatment and compare the activities between the two thiopurine treatment groups in selected patients X Compare the incidence of central nervous system CNS relapse and event-free survival in patients receiving intrathecal methotrexate MTX vs triple intrathecal chemotherapy MTXcytarabinehydrocortisone for presymptomatic CNS treatment XI Determine whether cerebrospinal fluid CSF terminal deoxynucleotidyl transferase TdT positivity predicts for CNS or marrow relapse by measuring TdT activity on CSF cytospins in cases with low white blood cell count less than 5 cells per cubic millimeter and suspected or questionable blasts during maintenance therapy XII Determine event-free survival in patients with standard-risk ALL and M3 marrow at day 14 when treated with intensive therapy designed for higher-risk ALL
OUTLINE This is a randomized study Patients are stratified according to participating institution The following acronyms are used ARA-C Cytarabine NSC-63878 ASP Asparaginase E coli NSC-109229 CTX Cyclophosphamide NSC-26271 DM Dexamethasone NSC-34521 DNR Daunorubicin NSC-82151 DOX Doxorubicin NSC-123127 HC Hydrocortisone NSC-10483 MP Mercaptopurine NSC-755 MTX Methotrexate NSC-740 PEG-ASP Pegaspargase NSC-624239 PRED Prednisone NSC-10023 TG Thioguanine NSC-752 TIT Triple Intrathecal Therapy IT MTXIT ARA-CIT HC VCR Vincristine NSC-67574 Induction All patients receive oral PRED on days 0-27 VCR IV on days 0 7 14 and 21 and ASP IM 3 times a week for 3 weeks beginning on day 2-4 ARA-C IT is administered on day 0 and MTX IT is administered on days 7 and 28 days 7 14 21 and 28 if CNS disease at diagnosis Following Induction patients who achieve remission are randomly assigned to 1 of 4 treatment arms Arm I Consolidation begins day 28 of Induction PRED is tapered from Induction over 10 days Patients receive VCR IV on day 0 oral MP on days 1-27 and MTX IT on days 7 14 and 21 only day 7 if CNS disease at diagnosis Interim Maintenance 1 begins day 28 of Consolidation Patients receive oral PRED on days 0-4 and 28-32 VCR IV days 0 and 28 oral MTX on days 0 7 14 21 28 35 42 and 49 and oral MP on days 0-49 Delayed Intensification 1 begins day 56 of Interim Maintenance 1 Patients receive oral DM on days 0-6 and 14-20 VCR IV on days 0 7 and 14 DOX IV over 15-120 min on days 0 7 and 14 ASP IM twice a week for 2 weeks beginning day 2-4 CTX IV over 20-30 min on day 28 oral TG on days 28-41 ARA-C IV or SC on days 29-32 and 36-39 and MTX IT on days 0 28 and 35 Interim Maintenance 2 begins day 56 of Delayed Intensification 1 Patients receive PREDVCRMTXMP as in Interim Maintenance 1 Delayed Intensification 2 begins day 56 of Interim Maintenance 2 Patients receive DMVCRDOXASP CTXTGARA-C and MTX IT as in Delayed Intensification 1 Maintenance begins day 56 of Delayed Intensification 2 Patients receive oral PRED on days 0-4 28-32 and 56-60 VCR IV on days 0 28 and 56 oral MP on days 0-83 oral MTX on days 7 14 21 28 35 42 49 56 63 70 and 77 omitted during wk of IT therapy and MTX IT on day 0 Treatment continues every 84 days for 2 years girls or 3 years boys from the beginning of Interim Maintenance 1 Arm II Patients receive treatment as in arm I except TIT is TIT substituted for MTX IT Arm III Patients receive treatment as in arm I with oral TG substituted for oral MTX in Consolidation Interim Maintenance 1 and 2 and Maintenance If secondary veno-occlusive disease occurs MP is substituted for TG during Maintenance Arm IV Patients receive treatment as in arm III with TIT substituted for MTX IT If secondary veno-occlusive disease occurs MP is substituted for TG during Maintenance Patients with M3 marrow after 2 weeks or M2 marrow after 4 weeks of Induction or with Philadelphia chromosome t922q34q11 t411q21q23 or hypodiploidy proceed to the following more intensive treatment regimen for further therapy Induction begins day 14 to day 19 of initial Induction Patients receive oral PRED on days 14-27 VCR IV on days 14 and 21 day 14 dose omitted if day 14 dose from original Induction already given DNR IV continuously on days 14-16 48 hours total ASP IM three times a week for 9 total doses including those received on original Induction MTX IT on days 28 and 35 days 21 28 and 35 if CNS disease at diagnosis Patients with M1M2 bone marrow after day 35 proceed to Consolidation Consolidation begins day 28 or 35 of Induction in this regimen depending on timing of entry on this regimen PRED is tapered from Induction over 10 days Patients receive CTX IV 20-30 minutes on days 0 and 28 oral MP on days 0-13 and 28-41 ARA-C IV or SC on days 1-4 8-11 29-32 and 36-39 VCR IV on days 14 21 42 and 49 PEG-ASP IM on days 14 and 42 and MTX IT on days 7 14 and 21 only day 7 if CNS disease at diagnosis Patients with M1 or M2 marrow and no extramedullary leukemia after day 63 proceed to Interim Maintenance 1 Interim Maintenance 1 begins day 63 of Consolidation Patients receive VCR IV on days 0 10 20 30 and 40 MTX IV on days 0 10 20 30 and 40 and PEG-ASP IM on days 1 and 21 Patients with M1 bone marrow after day 56 proceed to Delayed Intensification I Delayed Intensification 1 begins day 56 of Interim Maintenance 1 Patients receive oral DM on days 0-6 and 14-20 VCR IV on days 0 7 14 42 and 49 DOX IV over 15-120 minutes on days 0 7 and 14 PEG-ASP IM on days 3 and 42 CTX IV over 20-30 minutes on day 28 oral TG on days 28-41 ARA-C IV or SC on days 29-32 and 36-39 and MTX IT on days 28 and 35 Interim Maintenance 2 begins day 56 of Delayed Intensification 1 Patients receive VCRMTXPEG-ASP as in Interim Maintenance 1 and MTX IT on days 0 20 and 40 Delayed Intensification 2 begins day 56 of Interim Maintenance 2 Patients receive DMVCRDOXPEG-ASP CTXTGARA-C and MTX IT as in Delayed Intensification 1 Maintenance begins day 56 of Delayed Intensification 2 Patients receive PREDVCRMPMTX and MTX IT as in arm I Maintenance Patients with CNS or testicular involvement at diagnosis receive appropriate radiotherapy concurrent with Consolidation Radiotherapy begins within 4 days of initiation of Consolidation Craniospinal irradiation is given 5 days a week Testicular irradiation is given to both testes 5 days a week over 2-3 weeks Patients are followed every 6-8 weeks during year 1 every 3 months during year 2 every 6 months during year 3 and then annually thereafter
PROJECTED ACCRUAL A total of 1970 patients will be accrued for this study within 35 years
OUTLINE This is a randomized study Patients are stratified according to participating institution The following acronyms are used ARA-C Cytarabine NSC-63878 ASP Asparaginase E coli NSC-109229 CTX Cyclophosphamide NSC-26271 DM Dexamethasone NSC-34521 DNR Daunorubicin NSC-82151 DOX Doxorubicin NSC-123127 HC Hydrocortisone NSC-10483 MP Mercaptopurine NSC-755 MTX Methotrexate NSC-740 PEG-ASP Pegaspargase NSC-624239 PRED Prednisone NSC-10023 TG Thioguanine NSC-752 TIT Triple Intrathecal Therapy IT MTXIT ARA-CIT HC VCR Vincristine NSC-67574 Induction All patients receive oral PRED on days 0-27 VCR IV on days 0 7 14 and 21 and ASP IM 3 times a week for 3 weeks beginning on day 2-4 ARA-C IT is administered on day 0 and MTX IT is administered on days 7 and 28 days 7 14 21 and 28 if CNS disease at diagnosis Following Induction patients who achieve remission are randomly assigned to 1 of 4 treatment arms Arm I Consolidation begins day 28 of Induction PRED is tapered from Induction over 10 days Patients receive VCR IV on day 0 oral MP on days 1-27 and MTX IT on days 7 14 and 21 only day 7 if CNS disease at diagnosis Interim Maintenance 1 begins day 28 of Consolidation Patients receive oral PRED on days 0-4 and 28-32 VCR IV days 0 and 28 oral MTX on days 0 7 14 21 28 35 42 and 49 and oral MP on days 0-49 Delayed Intensification 1 begins day 56 of Interim Maintenance 1 Patients receive oral DM on days 0-6 and 14-20 VCR IV on days 0 7 and 14 DOX IV over 15-120 min on days 0 7 and 14 ASP IM twice a week for 2 weeks beginning day 2-4 CTX IV over 20-30 min on day 28 oral TG on days 28-41 ARA-C IV or SC on days 29-32 and 36-39 and MTX IT on days 0 28 and 35 Interim Maintenance 2 begins day 56 of Delayed Intensification 1 Patients receive PREDVCRMTXMP as in Interim Maintenance 1 Delayed Intensification 2 begins day 56 of Interim Maintenance 2 Patients receive DMVCRDOXASP CTXTGARA-C and MTX IT as in Delayed Intensification 1 Maintenance begins day 56 of Delayed Intensification 2 Patients receive oral PRED on days 0-4 28-32 and 56-60 VCR IV on days 0 28 and 56 oral MP on days 0-83 oral MTX on days 7 14 21 28 35 42 49 56 63 70 and 77 omitted during wk of IT therapy and MTX IT on day 0 Treatment continues every 84 days for 2 years girls or 3 years boys from the beginning of Interim Maintenance 1 Arm II Patients receive treatment as in arm I except TIT is TIT substituted for MTX IT Arm III Patients receive treatment as in arm I with oral TG substituted for oral MTX in Consolidation Interim Maintenance 1 and 2 and Maintenance If secondary veno-occlusive disease occurs MP is substituted for TG during Maintenance Arm IV Patients receive treatment as in arm III with TIT substituted for MTX IT If secondary veno-occlusive disease occurs MP is substituted for TG during Maintenance Patients with M3 marrow after 2 weeks or M2 marrow after 4 weeks of Induction or with Philadelphia chromosome t922q34q11 t411q21q23 or hypodiploidy proceed to the following more intensive treatment regimen for further therapy Induction begins day 14 to day 19 of initial Induction Patients receive oral PRED on days 14-27 VCR IV on days 14 and 21 day 14 dose omitted if day 14 dose from original Induction already given DNR IV continuously on days 14-16 48 hours total ASP IM three times a week for 9 total doses including those received on original Induction MTX IT on days 28 and 35 days 21 28 and 35 if CNS disease at diagnosis Patients with M1M2 bone marrow after day 35 proceed to Consolidation Consolidation begins day 28 or 35 of Induction in this regimen depending on timing of entry on this regimen PRED is tapered from Induction over 10 days Patients receive CTX IV 20-30 minutes on days 0 and 28 oral MP on days 0-13 and 28-41 ARA-C IV or SC on days 1-4 8-11 29-32 and 36-39 VCR IV on days 14 21 42 and 49 PEG-ASP IM on days 14 and 42 and MTX IT on days 7 14 and 21 only day 7 if CNS disease at diagnosis Patients with M1 or M2 marrow and no extramedullary leukemia after day 63 proceed to Interim Maintenance 1 Interim Maintenance 1 begins day 63 of Consolidation Patients receive VCR IV on days 0 10 20 30 and 40 MTX IV on days 0 10 20 30 and 40 and PEG-ASP IM on days 1 and 21 Patients with M1 bone marrow after day 56 proceed to Delayed Intensification I Delayed Intensification 1 begins day 56 of Interim Maintenance 1 Patients receive oral DM on days 0-6 and 14-20 VCR IV on days 0 7 14 42 and 49 DOX IV over 15-120 minutes on days 0 7 and 14 PEG-ASP IM on days 3 and 42 CTX IV over 20-30 minutes on day 28 oral TG on days 28-41 ARA-C IV or SC on days 29-32 and 36-39 and MTX IT on days 28 and 35 Interim Maintenance 2 begins day 56 of Delayed Intensification 1 Patients receive VCRMTXPEG-ASP as in Interim Maintenance 1 and MTX IT on days 0 20 and 40 Delayed Intensification 2 begins day 56 of Interim Maintenance 2 Patients receive DMVCRDOXPEG-ASP CTXTGARA-C and MTX IT as in Delayed Intensification 1 Maintenance begins day 56 of Delayed Intensification 2 Patients receive PREDVCRMPMTX and MTX IT as in arm I Maintenance Patients with CNS or testicular involvement at diagnosis receive appropriate radiotherapy concurrent with Consolidation Radiotherapy begins within 4 days of initiation of Consolidation Craniospinal irradiation is given 5 days a week Testicular irradiation is given to both testes 5 days a week over 2-3 weeks Patients are followed every 6-8 weeks during year 1 every 3 months during year 2 every 6 months during year 3 and then annually thereafter
PROJECTED ACCRUAL A total of 1970 patients will be accrued for this study within 35 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 |
|---|---|---|---|
| CDR0000064665 | OTHER | Clinical Trialsgov | None |
| CCG-1952 | None | None | None |