Ignite Creation Date:
2024-05-05 @ 11:56 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00187057
Status:
COMPLETED
Last Update Posted:
2015-08-27
First Post:
2005-09-12
Brief Title:
Study for Treatment of Cancer in Children With Ataxia-telangiectasia
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
Pilot Study I for Treatment of Cancer in Children With Ataxia-Telangiectasia
Status:
COMPLETED
Status Verified Date:
2013-08
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:
This is a pilotfeasibility study designed to investigate the feasibility of treating children with Ataxia-Telangiectasia A-T and cancer with regimens nearly as intense as non-A-T patients with cancer would receive
Detailed Description:
Approximately 10-30 of A-T patients will develop a malignancy during their lifetime The vast majority of these cancers are of lymphoid origin There is no consensus regarding the optimal strategy for treating children with A-T who develop hematopoietic malignancies Historically many of these children have been treated with therapy that is much less intensive than the conventional approach for non-A-T patients with similar malignancies during the corresponding treatment era Although these less intensive approaches may have stemmed from perceptions that these children would not tolerate intensive therapy there is in fact no data to suggest that these children cannot tolerate intensive therapy However it is clear that children with A-T require a modification in certain components of intensive therapy
To provide children with A-T and either ALL or malignant lymphoma the best chance for a cure we propose to use modern therapeutic strategies with minimal modifications which address the unique toxicity profile encountered in treating children with A-T
Secondary objectives include
To clinically and biologically characterize the malignancies occurring in children with A-T usually malignant lymphoma or ALL This will include in vitro drug sensitivity screening
To study chemotherapy-induced DNA damage in children with A-T
Detailed Description of Treatment Plan
Acute Lymphoblastic Leukemia ALL Low Risk
Induction
Prednisone 40 mgm2day PO days 1-28
Vinblastine 6 mgm2dose IV day 8
Vincristine 15 mgm2dose days 1 15
Daunomycin 20 mgm2week IV days 115
Asparaginase 10000 Um2dose IM days 2 4 6 8 10 12
VP-16 225 mgm2dose Days 22 25 29
Ara-C 300 mgm2dose Days 22 25 29
All patients will receive CNS therapy with triple intrathecal therapy on days 1 22 and 43 of induction treatment dose age adjusted
Consolidation
Methotrexate 2 mgm2 IV day 43 and 50 and mercaptopurine 75 mgm2 days 43-56
Continuation therapy 120 weeks
Week
1 6-MP MTX
2 6-MP MTX
3 6-MP MTX
4 Dex VCR
5 6-MP MTX
6 6-MP MTX
7 6-MP HDMTX
8 Dex VCR
9 6-MP MTX
10 6-MP MTX
11 6-MP MTX
12 Dex VCR
13 6-MP MTX
14 6-MP MTX
15 6-MP HDMTX
This sequence will be repeated through week 52 after which 6-MP MTX will be given weekly to complete 120 weeks IT MHA MTX hydrocortisone Ara-C on weeks 1 2 7 and 15 and then every 4-8 weeks depending on CNS status
Dosages Schedules and Routes
6-MP 75 mgm2 PO daily x 7
MTX 40 mgm2 IM or IV q every week
Dex 6 mgm2 PO in 3 divided doses daily x 7
VCR 15 mgm2 IV max 20 mg
HDMTX 2 gm2 IV over 2 hours every 8 weeks
Reinduction
Reinduction therapy weeks 16-21 Reinduction therapy same as initial induction treatment minus dose 2 and 3 of VP16 ara-C and minus day 22 intrathecal therapy will be given after bone marrow examination on week 15 confirms complete remission
Acute Lymphoblastic Leukemia ALL - High Risk
Induction
Prednisone 40 mgm2day PO divided in 3 doses days 1-28
Vinblastine 6 mgm2dose IV day 8
Vincristine 15 mgm2dose days 1 15
Daunomycin 20 mgm2week IV days 1 15
Asparaginase 10000 Um2dose IM days 2 4 6 8 10 12 15 17 19
VP16 225 mgm2dose days 22 25 29
Ara-C 300 mgm2dose days 222529
All patients will receive triple IT therapy on days 1 22 and 43 of induction with additional IT therapy on days 8 and 15 if CNS leukemia CNS 2 or CNS 3 is present at diagnosis If required for patients with CNS 2 and 3 at diagnosis IT therapy will continue until 2 consecutive CSF studies are normal ie days 29 and 36
Consolidation
HDMTX 2 mgm2 IV day 43 and 50
6 MP 75 mgm2 PO days 43-56
Continuation Therapy 120 weeks
Week
1 Dex VCR
2 VP-16 CTX
3 6-MP MTX
4 MTX Ara-C
5 Dex VCR
6 VP-16 CTX
7 6-MP HDMTX
8 6-MP MTX
9 Dex VCR
10 VP-16 CTX
11 6-MP MTX
12 MTX Ara-C
13 Dex VCR
14 VP-16 CTX
15 6-MP HDMTX
These sequences will be repeated through week 52 after which 6MPMTX will be given weekly to complete 120 weeks
IT MHA MTX hydrocortisone Ara-C on weeks 1 2 7 and 15 and then every 4-8 weeks depending on CNS status and risk status
Dosages Schedules and Routes
VP 16 225 mgm2 IV once a week
Cyclophosphamide 300 mgm2 IV with MESNA once a week in addition to the 6 hour IV hydration
6-MP 75 mgm2 PO daily x 7
MTX 40 mgm2 IM or IV once a week
Ara-C 300 mgm2 IV push once a week
Dex 8 mgm2day PO in 3 divided doses daily x 7
VCR 15 mgm2 IV push max 20 mg
HDMTX 2 gm2 IV over 2 hours every 8 weeks x 7
B-Cell Non-Hodgkins Lymphoma
Overview - the chemotherapy regimen used varies with grouping based on extent of disease
Group A
Induction COPAD x 2 cycles
Cyclophosphamide 500 mgm2day divided every 12 hour IV with MESNA Day 1 2 3
Vincristine 20 mgm2 IV Day 1
Vinblastine 6 mgm2 IV Day 6
Prednisone 60 mgm2day bid PO Day 1-5
Adriamycin 50 mgm2 over 6 hrs IV Day 1
G-CSF 5 mcgkgday until count recovery
Group B
COP Induction
Cyclophosphamide 300 mgm2 IV divided every 12 hours IV with MESNA Day 1
Vincristine 10 mgm2 IV Day 1
Prednisone 60 mgm2day divided bid PO days 1-7
CNS Therapy Intrathecal Day 1 - dose age adjusted
COPAD-M3 Induction x 2 cycles
Vinblastine 6 mgm2 IV Day 1
HD MTX 3 mgm2 IV over 3 hours Day 1 with leucovorin rescue
CNS Therapy intrathecal each age adjusted Day 2 6
Cyclophosphamide 500 mgm2day second course 1 mgm2day IV with MESNA Day 2 3 4
Adriamycin 50 mgm2 IV Day 2
Prednisone 60 mgm2 divided bid PO Day 1-5
G-CSF 5 mcgkgday until count recovery
CYM Consolidation x 2 cycles
HD MTX 3 mgm2 IV over 3 hours Day 1 with leucovorin rescue
Ara-C 100 mgm2day CIIV x 5 days Day 2-6
CNS Therapy intrathecal each age adjusted Day 2 and 7
Maintenance
Prednisone 60 mgm2day divided bid PO Day 1-5
HDMTX 3 mgm2 IV over 3 hours Day 1 with leucovorin rescue
CNS Therapy intrathecal each age adjusted Day 2
Cyclophosphamide 500 mgm2day IV with MESNA Day 2 3
Adriamycin 50 mgm2 IV Day 3
Vincristine 2 mgm2 IV Day 1
G-CSF 5 mcgkgday until count recovery
Limited Stage Non-Hodgkins Lymphoma
Induction
Vincristine 2 mgm2 IV days 1 22 maximum dose 2 mg
Vinblastine 6 mgm2 IV day 8
Prednisone 40 mgm2day in 3 divided doses x 28 days
Adriamycin 30 mgm2day IV over one hour days 1 and 22
Cyclophosphamide 750 mgm2day IV days 1 and 22
Triple IT chemotherapy for participants with head and neck primary tumors on days 1 8 22 Each dose age adjusted
Consolidation - start day 43
Adriamycin 30 mgm2 by IV
Cyclophosphamide 750 mgm2
Prednisone 40 mgm2 in 3 divided doses x 5 days
Vincristine 20 mgm2 max 20 mg by IV
Triple IT chemotherapy for head and neck primaries on days 43 and 64
Maintenance
Maintenance chemotherapy will be administered only to patients with lymphoblastic lymphoma and will consist of 24 weeks of chemotherapy with oral daily 6-MP and weekly oral methotrexate and TIT every 6 weeks for patients with head and neck primaries after inductionconsolidation
Hodgkins Disease
Participants with favorable disease will receive VAMP chemotherapy
VAMP chemotherapy doses and schedule
Vinblastine 6 mgm2 IV day 1 15 maximum dosage 10 mg
Adriamycin 25 mgm2 IV day 1 15
Methotrexate 20 mgm2 IV day 1 15
Prednisone 40 mgm2 PO day 1-14 divided into 3 daily doses
Repeat cycle every 28 days total number of cycles 6 NO RADIATION THERAPY
Participants with unfavorable disease will receive VAMP and COP
VAMP chemotherapy doses cycles 1 3 5 7
Vinblastine 6 mgm2 IV day 1 15
Adriamycin 25 mgm2 IV day 115
Methotrexate 20 mgm2 IV day 1 15
Prednisone 40 mgm2 divided into 3 daily doses PO day 1-14
COP chemotherapy doses cycles 2 4 6 8
Cyclophosphamide 600 mgm2 IV with MESNA day 1 8
Vincristine 14 mgm2 IV day 18 max dose 2 mg
Procarbazine 100 mgm2 PO day 1-14
NO RADIATION THERAPY
To provide children with A-T and either ALL or malignant lymphoma the best chance for a cure we propose to use modern therapeutic strategies with minimal modifications which address the unique toxicity profile encountered in treating children with A-T
Secondary objectives include
To clinically and biologically characterize the malignancies occurring in children with A-T usually malignant lymphoma or ALL This will include in vitro drug sensitivity screening
To study chemotherapy-induced DNA damage in children with A-T
Detailed Description of Treatment Plan
Acute Lymphoblastic Leukemia ALL Low Risk
Induction
Prednisone 40 mgm2day PO days 1-28
Vinblastine 6 mgm2dose IV day 8
Vincristine 15 mgm2dose days 1 15
Daunomycin 20 mgm2week IV days 115
Asparaginase 10000 Um2dose IM days 2 4 6 8 10 12
VP-16 225 mgm2dose Days 22 25 29
Ara-C 300 mgm2dose Days 22 25 29
All patients will receive CNS therapy with triple intrathecal therapy on days 1 22 and 43 of induction treatment dose age adjusted
Consolidation
Methotrexate 2 mgm2 IV day 43 and 50 and mercaptopurine 75 mgm2 days 43-56
Continuation therapy 120 weeks
Week
1 6-MP MTX
2 6-MP MTX
3 6-MP MTX
4 Dex VCR
5 6-MP MTX
6 6-MP MTX
7 6-MP HDMTX
8 Dex VCR
9 6-MP MTX
10 6-MP MTX
11 6-MP MTX
12 Dex VCR
13 6-MP MTX
14 6-MP MTX
15 6-MP HDMTX
This sequence will be repeated through week 52 after which 6-MP MTX will be given weekly to complete 120 weeks IT MHA MTX hydrocortisone Ara-C on weeks 1 2 7 and 15 and then every 4-8 weeks depending on CNS status
Dosages Schedules and Routes
6-MP 75 mgm2 PO daily x 7
MTX 40 mgm2 IM or IV q every week
Dex 6 mgm2 PO in 3 divided doses daily x 7
VCR 15 mgm2 IV max 20 mg
HDMTX 2 gm2 IV over 2 hours every 8 weeks
Reinduction
Reinduction therapy weeks 16-21 Reinduction therapy same as initial induction treatment minus dose 2 and 3 of VP16 ara-C and minus day 22 intrathecal therapy will be given after bone marrow examination on week 15 confirms complete remission
Acute Lymphoblastic Leukemia ALL - High Risk
Induction
Prednisone 40 mgm2day PO divided in 3 doses days 1-28
Vinblastine 6 mgm2dose IV day 8
Vincristine 15 mgm2dose days 1 15
Daunomycin 20 mgm2week IV days 1 15
Asparaginase 10000 Um2dose IM days 2 4 6 8 10 12 15 17 19
VP16 225 mgm2dose days 22 25 29
Ara-C 300 mgm2dose days 222529
All patients will receive triple IT therapy on days 1 22 and 43 of induction with additional IT therapy on days 8 and 15 if CNS leukemia CNS 2 or CNS 3 is present at diagnosis If required for patients with CNS 2 and 3 at diagnosis IT therapy will continue until 2 consecutive CSF studies are normal ie days 29 and 36
Consolidation
HDMTX 2 mgm2 IV day 43 and 50
6 MP 75 mgm2 PO days 43-56
Continuation Therapy 120 weeks
Week
1 Dex VCR
2 VP-16 CTX
3 6-MP MTX
4 MTX Ara-C
5 Dex VCR
6 VP-16 CTX
7 6-MP HDMTX
8 6-MP MTX
9 Dex VCR
10 VP-16 CTX
11 6-MP MTX
12 MTX Ara-C
13 Dex VCR
14 VP-16 CTX
15 6-MP HDMTX
These sequences will be repeated through week 52 after which 6MPMTX will be given weekly to complete 120 weeks
IT MHA MTX hydrocortisone Ara-C on weeks 1 2 7 and 15 and then every 4-8 weeks depending on CNS status and risk status
Dosages Schedules and Routes
VP 16 225 mgm2 IV once a week
Cyclophosphamide 300 mgm2 IV with MESNA once a week in addition to the 6 hour IV hydration
6-MP 75 mgm2 PO daily x 7
MTX 40 mgm2 IM or IV once a week
Ara-C 300 mgm2 IV push once a week
Dex 8 mgm2day PO in 3 divided doses daily x 7
VCR 15 mgm2 IV push max 20 mg
HDMTX 2 gm2 IV over 2 hours every 8 weeks x 7
B-Cell Non-Hodgkins Lymphoma
Overview - the chemotherapy regimen used varies with grouping based on extent of disease
Group A
Induction COPAD x 2 cycles
Cyclophosphamide 500 mgm2day divided every 12 hour IV with MESNA Day 1 2 3
Vincristine 20 mgm2 IV Day 1
Vinblastine 6 mgm2 IV Day 6
Prednisone 60 mgm2day bid PO Day 1-5
Adriamycin 50 mgm2 over 6 hrs IV Day 1
G-CSF 5 mcgkgday until count recovery
Group B
COP Induction
Cyclophosphamide 300 mgm2 IV divided every 12 hours IV with MESNA Day 1
Vincristine 10 mgm2 IV Day 1
Prednisone 60 mgm2day divided bid PO days 1-7
CNS Therapy Intrathecal Day 1 - dose age adjusted
COPAD-M3 Induction x 2 cycles
Vinblastine 6 mgm2 IV Day 1
HD MTX 3 mgm2 IV over 3 hours Day 1 with leucovorin rescue
CNS Therapy intrathecal each age adjusted Day 2 6
Cyclophosphamide 500 mgm2day second course 1 mgm2day IV with MESNA Day 2 3 4
Adriamycin 50 mgm2 IV Day 2
Prednisone 60 mgm2 divided bid PO Day 1-5
G-CSF 5 mcgkgday until count recovery
CYM Consolidation x 2 cycles
HD MTX 3 mgm2 IV over 3 hours Day 1 with leucovorin rescue
Ara-C 100 mgm2day CIIV x 5 days Day 2-6
CNS Therapy intrathecal each age adjusted Day 2 and 7
Maintenance
Prednisone 60 mgm2day divided bid PO Day 1-5
HDMTX 3 mgm2 IV over 3 hours Day 1 with leucovorin rescue
CNS Therapy intrathecal each age adjusted Day 2
Cyclophosphamide 500 mgm2day IV with MESNA Day 2 3
Adriamycin 50 mgm2 IV Day 3
Vincristine 2 mgm2 IV Day 1
G-CSF 5 mcgkgday until count recovery
Limited Stage Non-Hodgkins Lymphoma
Induction
Vincristine 2 mgm2 IV days 1 22 maximum dose 2 mg
Vinblastine 6 mgm2 IV day 8
Prednisone 40 mgm2day in 3 divided doses x 28 days
Adriamycin 30 mgm2day IV over one hour days 1 and 22
Cyclophosphamide 750 mgm2day IV days 1 and 22
Triple IT chemotherapy for participants with head and neck primary tumors on days 1 8 22 Each dose age adjusted
Consolidation - start day 43
Adriamycin 30 mgm2 by IV
Cyclophosphamide 750 mgm2
Prednisone 40 mgm2 in 3 divided doses x 5 days
Vincristine 20 mgm2 max 20 mg by IV
Triple IT chemotherapy for head and neck primaries on days 43 and 64
Maintenance
Maintenance chemotherapy will be administered only to patients with lymphoblastic lymphoma and will consist of 24 weeks of chemotherapy with oral daily 6-MP and weekly oral methotrexate and TIT every 6 weeks for patients with head and neck primaries after inductionconsolidation
Hodgkins Disease
Participants with favorable disease will receive VAMP chemotherapy
VAMP chemotherapy doses and schedule
Vinblastine 6 mgm2 IV day 1 15 maximum dosage 10 mg
Adriamycin 25 mgm2 IV day 1 15
Methotrexate 20 mgm2 IV day 1 15
Prednisone 40 mgm2 PO day 1-14 divided into 3 daily doses
Repeat cycle every 28 days total number of cycles 6 NO RADIATION THERAPY
Participants with unfavorable disease will receive VAMP and COP
VAMP chemotherapy doses cycles 1 3 5 7
Vinblastine 6 mgm2 IV day 1 15
Adriamycin 25 mgm2 IV day 115
Methotrexate 20 mgm2 IV day 1 15
Prednisone 40 mgm2 divided into 3 daily doses PO day 1-14
COP chemotherapy doses cycles 2 4 6 8
Cyclophosphamide 600 mgm2 IV with MESNA day 1 8
Vincristine 14 mgm2 IV day 18 max dose 2 mg
Procarbazine 100 mgm2 PO day 1-14
NO RADIATION THERAPY
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