Ignite Creation Date:
2024-05-05 @ 11:56 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00187122
Status:
COMPLETED
Last Update Posted:
2008-04-23
First Post:
2005-09-13
Brief Title:
Treatment for Patients With Stage III or IV Non-Hodgkin Lymphoma
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
Treatment for Newly Diagnosed Patients With Stage IIIIV Non-Hodgkin Lymphoma-Study XIII A Therapeutic Pilot Study
Status:
COMPLETED
Status Verified Date:
2008-04
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:
The main purpose of this study is to determine if it is feasible to administer an intensified multi-agent chemotherapy regimen for children with stage III and IV non-Hodgkin lymphoma and to find out what the toxicities are
Detailed Description:
The overall objective of this research study is to determine the toxicity and feasibility of administration of an intensified multi-agent chemotherapy regimen for children with stages III and IV non-Hodgkin lymphoma NHL lymphoblastic histiotype The planned pilot therapy includes major modifications of our best previous treatments for patients with T-cell acute lymphoblastic leukemia ALL that may improve the disease-free survival of these children and adolescents Ultimately it is intended to propose this therapy for further evaluation in the setting of a patient population large enough to evaluate its efficacy
Secondary objectives are
To determine the toxicity of high-dose methotrexate HDMTX given prior to the inductionconsolidation phase of therapy and of repeated induction treatment weeks 16-21 in patients with advanced stage NHL lymphoblastic histiotype
To determine the toxicity and feasibility of administration of continuation therapy which include additional drug pairs not used in the St Jude Total XI-ALL study
To estimate the complete response CR rate and event-free survival EFS in children with stage IIIIV lymphoblastic NHL after treatment with this intensified multiagent chemotherapy Pooling of data from this study with that gained from treatment of patients with T-ALL on the Total XIII and XIII B studies with appropriate stratification will facilitate this aim
To compare plasma and cerebrospinal fluid concentrations of VP-16 after 1 hour of administration The data obtained here will be pooled for analysis with that from Total XIII and Total XIII B studies
To assess serially whether the frequency of specific HPRT mutations in are related to cumulative dose of etoposide or plasma AUC of etoposide etoposide catechol or both
To assess the degree of bone marrow infiltration at the time of diagnosis and serially during remission using and comparing morphologic immunologic and molecular methods In the absence of morphologically detected tumor cells we will estimate the frequency of minimal residual disease MRD during remission using immunologic and molecular methods The data obtained here will be pooled for analysis with that obtained from T-cell ALL cases treated on Total XIII and Total XIII B ALL studies
Because similar studies are being conducted for patients with T-ALL on the Total XIII and Total XIII B ALL studies we will pool data from the present study with that from T-cell ALL cases treated on Total XIII and Total XIII B ALL studies and correlate detection of lymphoblasts in bone marrow or cerebrospinal fluid CSF with subsequent clinical course complete remission duration
To evaluate the sensitivity of neoplastic cells at diagnosis to anticancer drugs This evaluation will be limited to patients with bone marrow involvement or viable tumor samples at diagnosis Information obtained from this aim will complement that obtained from patients with T-ALL in the Total XIII and Total XIII B ALL studies
Details of Treatment Plan
Pre-Induction Chemotherapy
Methotrexate 200 mgm2hr IV push then 800 mgm2 IV over 24 hours
Induction
Induction Chemotherapy uses several chemotherapy drugs to kill cancer cells in the body and lasts 6 to 8 weeks
Prednisone 40 mgm2day PO days 1-29 Vincristine 15 mgm2week IV days 1 8 15 22 Daunomycin 25 mgm2week IV days 1 8 L-asparaginase 10000 Unitsm2 IM days 2 4 6 and 8 Etoposide 300 mgm2 IV Days 22 25 29 Cytarabine 300 mgm2 IV Days 22 25 29 For infants less than 12 months of age Vincristine dosage is 005 mgkgdose CNS Therapy
All patients will receive triple IT therapy on days 1 22 and 43 Patients with known CNS disease will receive additional IT treatments until 2 consecutive CSF studies are normal Children with cranial nerve palsies will receive local irradiation to the base of the skull
Consolidation
HDMTX 2 gm2 days 44 and 51 Mercaptopurine 75 mgm2 PO daily for 14 days ITMHA will be given into spinal fluid IT the day before first HDMTX dose
Continuation
Continuation Continuation therapy lasts 120 weeks The following drugs will be given in different two-drug combinations during this treatment
Weeks
1 VP-16 Cyclo 2 6-MP MTX 3 MTX Ara-C 4 Dex VCR 5 VP-16 Cyclo 6 6-MP HDMTX 7 VP-16 Ara-C 8 Dex VCR 9 VP-16 Cyclo 10 6-MP MTX 11 MTX Ara-C 12 Dex VCR 13 VP-16 Cyclo 14 6-MP HDMTX 15 VP-16 Ara-C
IT MHA MTX hydrocortisone Ara-C dose age dependent given one day before HDMTX IT MHA every 4 weeks for patients with CNS 2 or 3 status Reinduction therapy same as initial induction treatment except that only one dose of VP-16ara-C will be given on day 22 will be given from weeks 16 to 21
Dosages Schedules and Routes VP-16 300 mgm2 IV over 1 hour once a week Cyclophosphamide 300 mgm2 IV push once a week Mercaptopurine 6-MP 75 mgm2 PO daily x 7 Methotrexate MTX 40 mgm2 IM or IV once a week only IM after CNS radiation Cytarabine Ara-C 300 mgM2 IV push once a week Dexamethasone Dex 8 mgm2 PO in 3 divided doses daily x 7 Vincristine VCR 15 mgm2 IV once a week max 2 mg L-Asparaginase L-ASP 10000 Um2 IM every 4 weeks x 9 HDMTX 2 gm2 IV over 2 hours every 8 weeks x 7 same leucovorin rescue as used in consolidation phase
Secondary objectives are
To determine the toxicity of high-dose methotrexate HDMTX given prior to the inductionconsolidation phase of therapy and of repeated induction treatment weeks 16-21 in patients with advanced stage NHL lymphoblastic histiotype
To determine the toxicity and feasibility of administration of continuation therapy which include additional drug pairs not used in the St Jude Total XI-ALL study
To estimate the complete response CR rate and event-free survival EFS in children with stage IIIIV lymphoblastic NHL after treatment with this intensified multiagent chemotherapy Pooling of data from this study with that gained from treatment of patients with T-ALL on the Total XIII and XIII B studies with appropriate stratification will facilitate this aim
To compare plasma and cerebrospinal fluid concentrations of VP-16 after 1 hour of administration The data obtained here will be pooled for analysis with that from Total XIII and Total XIII B studies
To assess serially whether the frequency of specific HPRT mutations in are related to cumulative dose of etoposide or plasma AUC of etoposide etoposide catechol or both
To assess the degree of bone marrow infiltration at the time of diagnosis and serially during remission using and comparing morphologic immunologic and molecular methods In the absence of morphologically detected tumor cells we will estimate the frequency of minimal residual disease MRD during remission using immunologic and molecular methods The data obtained here will be pooled for analysis with that obtained from T-cell ALL cases treated on Total XIII and Total XIII B ALL studies
Because similar studies are being conducted for patients with T-ALL on the Total XIII and Total XIII B ALL studies we will pool data from the present study with that from T-cell ALL cases treated on Total XIII and Total XIII B ALL studies and correlate detection of lymphoblasts in bone marrow or cerebrospinal fluid CSF with subsequent clinical course complete remission duration
To evaluate the sensitivity of neoplastic cells at diagnosis to anticancer drugs This evaluation will be limited to patients with bone marrow involvement or viable tumor samples at diagnosis Information obtained from this aim will complement that obtained from patients with T-ALL in the Total XIII and Total XIII B ALL studies
Details of Treatment Plan
Pre-Induction Chemotherapy
Methotrexate 200 mgm2hr IV push then 800 mgm2 IV over 24 hours
Induction
Induction Chemotherapy uses several chemotherapy drugs to kill cancer cells in the body and lasts 6 to 8 weeks
Prednisone 40 mgm2day PO days 1-29 Vincristine 15 mgm2week IV days 1 8 15 22 Daunomycin 25 mgm2week IV days 1 8 L-asparaginase 10000 Unitsm2 IM days 2 4 6 and 8 Etoposide 300 mgm2 IV Days 22 25 29 Cytarabine 300 mgm2 IV Days 22 25 29 For infants less than 12 months of age Vincristine dosage is 005 mgkgdose CNS Therapy
All patients will receive triple IT therapy on days 1 22 and 43 Patients with known CNS disease will receive additional IT treatments until 2 consecutive CSF studies are normal Children with cranial nerve palsies will receive local irradiation to the base of the skull
Consolidation
HDMTX 2 gm2 days 44 and 51 Mercaptopurine 75 mgm2 PO daily for 14 days ITMHA will be given into spinal fluid IT the day before first HDMTX dose
Continuation
Continuation Continuation therapy lasts 120 weeks The following drugs will be given in different two-drug combinations during this treatment
Weeks
1 VP-16 Cyclo 2 6-MP MTX 3 MTX Ara-C 4 Dex VCR 5 VP-16 Cyclo 6 6-MP HDMTX 7 VP-16 Ara-C 8 Dex VCR 9 VP-16 Cyclo 10 6-MP MTX 11 MTX Ara-C 12 Dex VCR 13 VP-16 Cyclo 14 6-MP HDMTX 15 VP-16 Ara-C
IT MHA MTX hydrocortisone Ara-C dose age dependent given one day before HDMTX IT MHA every 4 weeks for patients with CNS 2 or 3 status Reinduction therapy same as initial induction treatment except that only one dose of VP-16ara-C will be given on day 22 will be given from weeks 16 to 21
Dosages Schedules and Routes VP-16 300 mgm2 IV over 1 hour once a week Cyclophosphamide 300 mgm2 IV push once a week Mercaptopurine 6-MP 75 mgm2 PO daily x 7 Methotrexate MTX 40 mgm2 IM or IV once a week only IM after CNS radiation Cytarabine Ara-C 300 mgM2 IV push once a week Dexamethasone Dex 8 mgm2 PO in 3 divided doses daily x 7 Vincristine VCR 15 mgm2 IV once a week max 2 mg L-Asparaginase L-ASP 10000 Um2 IM every 4 weeks x 9 HDMTX 2 gm2 IV over 2 hours every 8 weeks x 7 same leucovorin rescue as used in consolidation phase
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