Ignite Creation Date:
2025-12-24 @ 6:39 PM
Ignite Modification Date:
2025-12-25 @ 4:09 PM
Study NCT ID:
NCT00187057
Status:
COMPLETED
Last Update Posted:
2015-08-27
First Post:
2005-09-12
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Study for Treatment of Cancer in Children With Ataxia-telangiectasia
Sponsor:
St. Jude Children's Research Hospital
Organization:
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 pilot/feasibility 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 mg/m2/day PO days 1-28
Vinblastine 6 mg/m2/dose IV day 8
Vincristine 1.5 mg/m2/dose days 1, 15
Daunomycin 20 mg/m2/week IV days 1,15
Asparaginase 10,000 U/m2/dose IM days 2, 4, 6, 8, 10, 12
VP-16 225 mg/m2/dose Days 22, 25, 29
Ara-C 300 mg/m2/dose 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 mg/m2 IV day 43 and 50 and mercaptopurine 75 mg/m2 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 mg/m2 PO; daily x 7
MTX 40 mg/m2 IM or IV; q (every) week;
Dex 6 mg/m2 PO; in 3 divided doses daily x 7
VCR 1.5 mg/m2 IV (max. 2.0 mg)
HDMTX 2 g/m2 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 mg/m2/day PO) divided in 3 doses days 1-28
Vinblastine 6 mg/m2/dose IV day 8
Vincristine 1.5 mg/m2/dose days 1, 15
Daunomycin 20 mg/m2/week IV days 1, 15
Asparaginase 10,000 U/m2/dose IM days 2, 4, 6, 8, 10, 12, (15, 17, 19)
VP16 225 mg/m2/dose days 22, 25, 29
Ara-C 300 mg/m2/dose days 22,25,29
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 (i.e., days 29 and 36).
Consolidation:
HDMTX 2 mg/m2 IV day 43 and 50
6 MP 75 mg/m2 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 6MP/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 and risk status.
Dosages, Schedules and Routes:
VP 16 225 mg/m2 IV once a week
Cyclophosphamide 300 mg/m2 IV (with MESNA) once a week in addition to the 6 hour IV hydration
6-MP 75 mg/m2 PO; daily x 7
MTX 40 mg/m2 IM or IV once a week
Ara-C 300 mg/m2 IV push; once a week
Dex 8 mg/m2/day PO; in 3 divided doses daily x 7
VCR 1.5 mg/m2 IV push (max. 2.0 mg)
HDMTX 2 g/m2 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 mg/m2/day (divided every 12 hour) IV (with MESNA) Day 1, 2, 3
Vincristine 2.0 mg/m2 IV Day 1
Vinblastine 6 mg/m2 IV Day 6
Prednisone 60 mg/m2/day (bid) PO Day 1-5
Adriamycin 50 mg/m2 (over 6 hrs) IV Day 1
G-CSF 5 mcg/kg/day until count recovery.
Group B
COP Induction:
Cyclophosphamide 300 mg/m2 IV (divided every 12 hours) IV (with MESNA) Day 1
Vincristine 1.0 mg/m2 IV Day 1
Prednisone 60 mg/m2/day (divided bid) PO days 1-7
CNS Therapy Intrathecal Day 1 - dose age adjusted
COPAD-M3 Induction x 2 cycles:
Vinblastine 6 mg/m2 IV Day 1
HD MTX 3 mg/m2 IV over 3 hours Day 1 with leucovorin rescue
CNS Therapy intrathecal each age adjusted Day 2, 6
Cyclophosphamide 500 mg/m2/day (second course 1 mg/m2/day) IV (with MESNA) Day 2, 3, 4
Adriamycin 50 mg/m2 IV Day 2
Prednisone 60 mg/m2 (divided bid) PO Day 1-5
G-CSF 5 mcg/kg/day until count recovery
CYM Consolidation x 2 cycles:
HD MTX 3 mg/m2 IV over 3 hours Day 1 with leucovorin rescue
Ara-C 100 mg/m2/day CI/IV (x 5 days) Day 2-6
CNS Therapy intrathecal each age adjusted Day 2 and 7
Maintenance:
Prednisone 60 mg/m2/day (divided bid) PO Day 1-5
HDMTX 3 mg/m2 IV over 3 hours Day 1 with leucovorin rescue
CNS Therapy intrathecal each age adjusted Day 2
Cyclophosphamide 500 mg/m2/day IV (with MESNA) Day 2, 3
Adriamycin 50 mg/m2 IV Day 3
Vincristine 2 mg/m2 IV Day 1
G-CSF 5 mcg/kg/day until count recovery
* Limited Stage Non-Hodgkins Lymphoma
Induction:
Vincristine 2 mg/m2 IV days 1, 22 (maximum dose 2 mg)
Vinblastine 6 mg/m2 IV, day 8
Prednisone 40 mg/m2/day in 3 divided doses x 28 days
Adriamycin 30 mg/m2/day IV over one hour days 1 and 22
Cyclophosphamide 750 mg/m2/day 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 mg/m2 by IV
Cyclophosphamide 750 mg/m2
Prednisone 40 mg/m2 in 3 divided doses x 5 days
Vincristine 2.0 mg/m2 (max. 2.0 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 induction/consolidation.
* Hodgkins Disease
Participants with favorable disease will receive VAMP chemotherapy:
VAMP chemotherapy doses and schedule:
Vinblastine 6 mg/m2, IV day 1, 15 (maximum dosage: 10 mg)
Adriamycin 25 mg/m2, IV day 1, 15
Methotrexate 20 mg/m2, IV day 1, 15
Prednisone 40 mg/m2 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 mg/m2 IV day 1, 15
Adriamycin 25 mg/m2 IV day 1,15
Methotrexate 20 mg/m2 IV day 1, 15
Prednisone 40 mg/m2 (divided into 3 daily doses) PO day 1-14
COP chemotherapy doses (cycles 2, 4, 6, 8)
Cyclophosphamide 600 mg/m2 IV (with MESNA) day 1, 8
Vincristine 1.4 mg/m2 IV day 1,8 (max dose 2 mg)
Procarbazine 100 mg/m2 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 mg/m2/day PO days 1-28
Vinblastine 6 mg/m2/dose IV day 8
Vincristine 1.5 mg/m2/dose days 1, 15
Daunomycin 20 mg/m2/week IV days 1,15
Asparaginase 10,000 U/m2/dose IM days 2, 4, 6, 8, 10, 12
VP-16 225 mg/m2/dose Days 22, 25, 29
Ara-C 300 mg/m2/dose 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 mg/m2 IV day 43 and 50 and mercaptopurine 75 mg/m2 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 mg/m2 PO; daily x 7
MTX 40 mg/m2 IM or IV; q (every) week;
Dex 6 mg/m2 PO; in 3 divided doses daily x 7
VCR 1.5 mg/m2 IV (max. 2.0 mg)
HDMTX 2 g/m2 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 mg/m2/day PO) divided in 3 doses days 1-28
Vinblastine 6 mg/m2/dose IV day 8
Vincristine 1.5 mg/m2/dose days 1, 15
Daunomycin 20 mg/m2/week IV days 1, 15
Asparaginase 10,000 U/m2/dose IM days 2, 4, 6, 8, 10, 12, (15, 17, 19)
VP16 225 mg/m2/dose days 22, 25, 29
Ara-C 300 mg/m2/dose days 22,25,29
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 (i.e., days 29 and 36).
Consolidation:
HDMTX 2 mg/m2 IV day 43 and 50
6 MP 75 mg/m2 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 6MP/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 and risk status.
Dosages, Schedules and Routes:
VP 16 225 mg/m2 IV once a week
Cyclophosphamide 300 mg/m2 IV (with MESNA) once a week in addition to the 6 hour IV hydration
6-MP 75 mg/m2 PO; daily x 7
MTX 40 mg/m2 IM or IV once a week
Ara-C 300 mg/m2 IV push; once a week
Dex 8 mg/m2/day PO; in 3 divided doses daily x 7
VCR 1.5 mg/m2 IV push (max. 2.0 mg)
HDMTX 2 g/m2 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 mg/m2/day (divided every 12 hour) IV (with MESNA) Day 1, 2, 3
Vincristine 2.0 mg/m2 IV Day 1
Vinblastine 6 mg/m2 IV Day 6
Prednisone 60 mg/m2/day (bid) PO Day 1-5
Adriamycin 50 mg/m2 (over 6 hrs) IV Day 1
G-CSF 5 mcg/kg/day until count recovery.
Group B
COP Induction:
Cyclophosphamide 300 mg/m2 IV (divided every 12 hours) IV (with MESNA) Day 1
Vincristine 1.0 mg/m2 IV Day 1
Prednisone 60 mg/m2/day (divided bid) PO days 1-7
CNS Therapy Intrathecal Day 1 - dose age adjusted
COPAD-M3 Induction x 2 cycles:
Vinblastine 6 mg/m2 IV Day 1
HD MTX 3 mg/m2 IV over 3 hours Day 1 with leucovorin rescue
CNS Therapy intrathecal each age adjusted Day 2, 6
Cyclophosphamide 500 mg/m2/day (second course 1 mg/m2/day) IV (with MESNA) Day 2, 3, 4
Adriamycin 50 mg/m2 IV Day 2
Prednisone 60 mg/m2 (divided bid) PO Day 1-5
G-CSF 5 mcg/kg/day until count recovery
CYM Consolidation x 2 cycles:
HD MTX 3 mg/m2 IV over 3 hours Day 1 with leucovorin rescue
Ara-C 100 mg/m2/day CI/IV (x 5 days) Day 2-6
CNS Therapy intrathecal each age adjusted Day 2 and 7
Maintenance:
Prednisone 60 mg/m2/day (divided bid) PO Day 1-5
HDMTX 3 mg/m2 IV over 3 hours Day 1 with leucovorin rescue
CNS Therapy intrathecal each age adjusted Day 2
Cyclophosphamide 500 mg/m2/day IV (with MESNA) Day 2, 3
Adriamycin 50 mg/m2 IV Day 3
Vincristine 2 mg/m2 IV Day 1
G-CSF 5 mcg/kg/day until count recovery
* Limited Stage Non-Hodgkins Lymphoma
Induction:
Vincristine 2 mg/m2 IV days 1, 22 (maximum dose 2 mg)
Vinblastine 6 mg/m2 IV, day 8
Prednisone 40 mg/m2/day in 3 divided doses x 28 days
Adriamycin 30 mg/m2/day IV over one hour days 1 and 22
Cyclophosphamide 750 mg/m2/day 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 mg/m2 by IV
Cyclophosphamide 750 mg/m2
Prednisone 40 mg/m2 in 3 divided doses x 5 days
Vincristine 2.0 mg/m2 (max. 2.0 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 induction/consolidation.
* Hodgkins Disease
Participants with favorable disease will receive VAMP chemotherapy:
VAMP chemotherapy doses and schedule:
Vinblastine 6 mg/m2, IV day 1, 15 (maximum dosage: 10 mg)
Adriamycin 25 mg/m2, IV day 1, 15
Methotrexate 20 mg/m2, IV day 1, 15
Prednisone 40 mg/m2 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 mg/m2 IV day 1, 15
Adriamycin 25 mg/m2 IV day 1,15
Methotrexate 20 mg/m2 IV day 1, 15
Prednisone 40 mg/m2 (divided into 3 daily doses) PO day 1-14
COP chemotherapy doses (cycles 2, 4, 6, 8)
Cyclophosphamide 600 mg/m2 IV (with MESNA) day 1, 8
Vincristine 1.4 mg/m2 IV day 1,8 (max dose 2 mg)
Procarbazine 100 mg/m2 PO day 1-14
(NO RADIATION THERAPY)
Study Oversight
Has Oversight DMC:
False
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?: