Ignite Creation Date:
2024-05-05 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00137111
Status:
COMPLETED
Last Update Posted:
2020-09-11
First Post:
2005-08-25
Brief Title:
Therapy for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Status:
COMPLETED
Status Verified Date:
2020-09
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 primary objective is to estimate the overall event-free survival of children at least one year of age at diagnosis who are treated with risk-directed therapy and to monitor the molecular remission induction rate
Detailed Description:
These are the following secondary objectives
To determine if CNS irradiation can be safely omitted in the context of the systemic therapy used in the protocol
To identify whether prolonged 24 hour intravenous infusions of HDMTX produce greater methotrexate polyglutamate MTXPG accumulation than short 4 hour infusions 42 hours after 1 gmm2 of HDMTX stratified for lineage T- vs B-lineage and ploidy hyperdiploid vs non-hyperdiploid B-lineage
To determine whether prolonged 24 hour intravenous infusions of HDMTX produce greater antileukemic effects than short 4 hour infusions based on the inhibition of de novo purine synthesis in bone marrow blasts and the decrease in circulating blasts during the 4 day window prior to initiation of conventional remission induction therapy
MRD
Other exploratory objectives
Details of Treatment Plan
Treatment will consist of three main phases Remission Induction Consolidation and Continuation Treatment with an Upfront HDMTX Window for research purposes will be optional
All patients will receive IT therapy on day 1 dose is age dependent
Upfront High-Dose Methotrexate Window
HDMTX 1 gm2 as a 4 hour infusion versus as a 24 hour infusion Leucovorin rescue will be given
Remission Induction
Prednisone 40 mgm2day PO Days 5 - 32 Vincristine 15 mgm2week IV Days 5 12 19 26 Daunorubicin 25 mgm2week IV Days 5 12 L-asparaginase 10000 Unitm2dose IM Days 6 8 10 12 14 16 19 21 23 Cyclophosphamide 1000 mgm2dose IV Day 26 Cytarabine 75 mgm2dose IV Days 27-30 34-37 6-Mercaptopurine 60 mgm2dose PO Days 26-39 Imatinib 40 mgm2 bid for Ph positive patients starting Day 22 of induction Intrathecal therapy will be administered on day 1 and 19 dose age dependent Patients with high risk of CNS relapse will receive additional IT treatments on days 8 and 26
Consolidation Treatment
High dose methotrexate targeted dose depending on risk status days 1 15 29 and 43 and mercaptopurine 50 mgm2day days 1-56
Reintensification treatment for patients with high risk disease
Patients with high risk disease will be offered the option of hematopoietic stem cell transplant HSCT and may receive an additional 1-2 cycles of reintensification treatment prior to maximize the anti-leukemic kill before transplant
Dexamethasone 20 mgm2 PO days 1-3 Cytarabine 2 gm2 IV x 4 doses days 3-5 Etoposide 100 mgm2 IV x 5 doses days 3-5 L-asparaginase 25000 Unitsm2 IM day 6 Intrathecal treatment Day 5
Continuation Treatment lasts 120 weeks for girls and 146 weeks for boys
Treatment will depend on risk classification low versus standard versus high risk
Treatment weeks 1 to 20
Week StandardHigh Risk Low Risk
1 DEX DOX VCR 6MP ASP 6MP DEX VCR
2 6MP ASP 6MP MTX
3 6MP ASP 6MP MTX
4 DEX DOX VCR 6MP ASP 6MP DEX VCR
5 6MP ASP 6MP MTX
6 6MP ASP 6MP MTX
7 Reinduction I Reinduction I
8 Reinduction I Reinduction I
9 Reinduction I Reinduction I
10 6MP ASP 6MP MTX
11 DOX VCR 6MP ASP 6MP MTX
12 6MP ASP 6MP MTX
13 6MP ASP 6MP MTX
14 DEX DOX VCR 6MP ASP 6MP DEX VCR
15 6MP ASP 6MP MTX
16 6MP ASP 6MP MTX
17 Reinduction II Reinduction II
18 Reinduction II Reinduction II
19 Reinduction II Reinduction II
20 No chemotherapy 6MP MTX
Dexamethasone 12 mgm2 stdhigh risk or 8 mgm2 low risk PO daily tid x 5 days Days 1-5 Doxorubicin 30 mgm2 IV Day 1 Vincristine 20 mgm2 IV push max 2 mg Day 1 Mercaptopurine 50 mgm2 PO daily x 7 days stdhigh risk Days 1-7 75 mgm2 PO daily x 7 days low risk Days 1-7 L-asparaginase 25000 Unitm2 IM Day 1 Methotrexate 40 mgm2 IV or IM Day 1
Reinduction I and II
This phase of treatment will be started at weeks 7 and 17 after bone marrow examination confirms complete remission Reinduction treatment will be given twice weeks 7 to 9 and weeks 17 to 19 for all patients
Reinduction I for StandardHigh Risk ALL
Dexamethasone 8 mgm2day PO tid Days 1-8 15 21 Vincristine 15 mgm2week IV max 2 mg Days 1 8 15 Doxorubicin 30 mgm2 Days 1 8 L-asparaginase 25000 Unitm2 IM Days 1 8 15 Intrathecal chemotherapy dose age dependent Day 1
Reinduction II for StandardHigh Risk ALL
Dexamethasone 8 mgm2day PO tid Days 1-8 15-21 Vincristine 15 mgm2week IV max 2 mg Days 1 8 15 L-asparaginase 25000 Unitm2 weekly IM Days 1 8 17 Intrathecal chemotherapy dose age dependent Day 1 High-dose cytarabine 2 gmm2 IV q 12 Days 15 16
Reinduction I and II for Low Risk ALL Dexamethasone 8 mgm2day PO tid Days 1-8 15-21 Vincristine 15 mgm2week IV max 2 mg Days 1 8 15 L-asparaginase 10000 Unitm2thrice weekly IM Days 2 4 6 8 10 12 15 17 19 Doxorubicin 30 mgm2week IV Day 1 Intrathecal chemotherapy dose age dependent on Day 1
Treatment Weeks 21 to end of therapy Week StandardHigh Risk Low Risk
21 6MP MTX 6MP MTX
22 6MP MTX 6MP MTX
23 Cyclo Ara-C 6MP MTX
24 DEX VCR 6MP DEX VCR
25 6MP MTX 6MP MTX
26 6MP MTX 6MP MTX
27 Cyclo Ara-C 6MP MTX
28 DEX VCR 6MP DEX VCR
Mercaptopurine 75 mgm2 PO daily x 7 days Days 1-7 Methotrexate 40 mgm2 IV or IM Day 1 Cyclophosphamide 300 mgm2 IV Day 1 Cytarabine 300 mgm2 IV Day 1 Dexamethasone 12 mgm2 stdhigh risk or 8 mgm2 low risk PO daily tid x 5 Day 1-5 Vincristine 20 mgm2 IV push max 2 mg Day 1
The same treatment weeks 21-28 will be repeated for a total of 6 times until week 68 After week 68 all patients will receive daily 6MP and weekly MTX with pulses of dexamethasone and vincristine every 4 weeks until week 100 after which only 6MP and methotrexate will be given Intrathecal treatment will be given every 8 weeks only to patients at high risk of CNS relapse after week 48 and will be discontinued after week 96 Continuation therapy will be discontinued after 120 weeks in girls and after 146 weeks in boys
Patients who meet the criteria of high-risk ALL are candidates for allogeneic hematopoietic stem cell transplantation However if the option is declined by the patients or guardians or the procedure is deemed unsuitable by the attending physician and the principal investigator the patient will remain on study and continue to receive chemotherapy
To determine if CNS irradiation can be safely omitted in the context of the systemic therapy used in the protocol
To identify whether prolonged 24 hour intravenous infusions of HDMTX produce greater methotrexate polyglutamate MTXPG accumulation than short 4 hour infusions 42 hours after 1 gmm2 of HDMTX stratified for lineage T- vs B-lineage and ploidy hyperdiploid vs non-hyperdiploid B-lineage
To determine whether prolonged 24 hour intravenous infusions of HDMTX produce greater antileukemic effects than short 4 hour infusions based on the inhibition of de novo purine synthesis in bone marrow blasts and the decrease in circulating blasts during the 4 day window prior to initiation of conventional remission induction therapy
MRD
Other exploratory objectives
Details of Treatment Plan
Treatment will consist of three main phases Remission Induction Consolidation and Continuation Treatment with an Upfront HDMTX Window for research purposes will be optional
All patients will receive IT therapy on day 1 dose is age dependent
Upfront High-Dose Methotrexate Window
HDMTX 1 gm2 as a 4 hour infusion versus as a 24 hour infusion Leucovorin rescue will be given
Remission Induction
Prednisone 40 mgm2day PO Days 5 - 32 Vincristine 15 mgm2week IV Days 5 12 19 26 Daunorubicin 25 mgm2week IV Days 5 12 L-asparaginase 10000 Unitm2dose IM Days 6 8 10 12 14 16 19 21 23 Cyclophosphamide 1000 mgm2dose IV Day 26 Cytarabine 75 mgm2dose IV Days 27-30 34-37 6-Mercaptopurine 60 mgm2dose PO Days 26-39 Imatinib 40 mgm2 bid for Ph positive patients starting Day 22 of induction Intrathecal therapy will be administered on day 1 and 19 dose age dependent Patients with high risk of CNS relapse will receive additional IT treatments on days 8 and 26
Consolidation Treatment
High dose methotrexate targeted dose depending on risk status days 1 15 29 and 43 and mercaptopurine 50 mgm2day days 1-56
Reintensification treatment for patients with high risk disease
Patients with high risk disease will be offered the option of hematopoietic stem cell transplant HSCT and may receive an additional 1-2 cycles of reintensification treatment prior to maximize the anti-leukemic kill before transplant
Dexamethasone 20 mgm2 PO days 1-3 Cytarabine 2 gm2 IV x 4 doses days 3-5 Etoposide 100 mgm2 IV x 5 doses days 3-5 L-asparaginase 25000 Unitsm2 IM day 6 Intrathecal treatment Day 5
Continuation Treatment lasts 120 weeks for girls and 146 weeks for boys
Treatment will depend on risk classification low versus standard versus high risk
Treatment weeks 1 to 20
Week StandardHigh Risk Low Risk
1 DEX DOX VCR 6MP ASP 6MP DEX VCR
2 6MP ASP 6MP MTX
3 6MP ASP 6MP MTX
4 DEX DOX VCR 6MP ASP 6MP DEX VCR
5 6MP ASP 6MP MTX
6 6MP ASP 6MP MTX
7 Reinduction I Reinduction I
8 Reinduction I Reinduction I
9 Reinduction I Reinduction I
10 6MP ASP 6MP MTX
11 DOX VCR 6MP ASP 6MP MTX
12 6MP ASP 6MP MTX
13 6MP ASP 6MP MTX
14 DEX DOX VCR 6MP ASP 6MP DEX VCR
15 6MP ASP 6MP MTX
16 6MP ASP 6MP MTX
17 Reinduction II Reinduction II
18 Reinduction II Reinduction II
19 Reinduction II Reinduction II
20 No chemotherapy 6MP MTX
Dexamethasone 12 mgm2 stdhigh risk or 8 mgm2 low risk PO daily tid x 5 days Days 1-5 Doxorubicin 30 mgm2 IV Day 1 Vincristine 20 mgm2 IV push max 2 mg Day 1 Mercaptopurine 50 mgm2 PO daily x 7 days stdhigh risk Days 1-7 75 mgm2 PO daily x 7 days low risk Days 1-7 L-asparaginase 25000 Unitm2 IM Day 1 Methotrexate 40 mgm2 IV or IM Day 1
Reinduction I and II
This phase of treatment will be started at weeks 7 and 17 after bone marrow examination confirms complete remission Reinduction treatment will be given twice weeks 7 to 9 and weeks 17 to 19 for all patients
Reinduction I for StandardHigh Risk ALL
Dexamethasone 8 mgm2day PO tid Days 1-8 15 21 Vincristine 15 mgm2week IV max 2 mg Days 1 8 15 Doxorubicin 30 mgm2 Days 1 8 L-asparaginase 25000 Unitm2 IM Days 1 8 15 Intrathecal chemotherapy dose age dependent Day 1
Reinduction II for StandardHigh Risk ALL
Dexamethasone 8 mgm2day PO tid Days 1-8 15-21 Vincristine 15 mgm2week IV max 2 mg Days 1 8 15 L-asparaginase 25000 Unitm2 weekly IM Days 1 8 17 Intrathecal chemotherapy dose age dependent Day 1 High-dose cytarabine 2 gmm2 IV q 12 Days 15 16
Reinduction I and II for Low Risk ALL Dexamethasone 8 mgm2day PO tid Days 1-8 15-21 Vincristine 15 mgm2week IV max 2 mg Days 1 8 15 L-asparaginase 10000 Unitm2thrice weekly IM Days 2 4 6 8 10 12 15 17 19 Doxorubicin 30 mgm2week IV Day 1 Intrathecal chemotherapy dose age dependent on Day 1
Treatment Weeks 21 to end of therapy Week StandardHigh Risk Low Risk
21 6MP MTX 6MP MTX
22 6MP MTX 6MP MTX
23 Cyclo Ara-C 6MP MTX
24 DEX VCR 6MP DEX VCR
25 6MP MTX 6MP MTX
26 6MP MTX 6MP MTX
27 Cyclo Ara-C 6MP MTX
28 DEX VCR 6MP DEX VCR
Mercaptopurine 75 mgm2 PO daily x 7 days Days 1-7 Methotrexate 40 mgm2 IV or IM Day 1 Cyclophosphamide 300 mgm2 IV Day 1 Cytarabine 300 mgm2 IV Day 1 Dexamethasone 12 mgm2 stdhigh risk or 8 mgm2 low risk PO daily tid x 5 Day 1-5 Vincristine 20 mgm2 IV push max 2 mg Day 1
The same treatment weeks 21-28 will be repeated for a total of 6 times until week 68 After week 68 all patients will receive daily 6MP and weekly MTX with pulses of dexamethasone and vincristine every 4 weeks until week 100 after which only 6MP and methotrexate will be given Intrathecal treatment will be given every 8 weeks only to patients at high risk of CNS relapse after week 48 and will be discontinued after week 96 Continuation therapy will be discontinued after 120 weeks in girls and after 146 weeks in boys
Patients who meet the criteria of high-risk ALL are candidates for allogeneic hematopoietic stem cell transplantation However if the option is declined by the patients or guardians or the procedure is deemed unsuitable by the attending physician and the principal investigator the patient will remain on study and continue to receive chemotherapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
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 |
|---|---|---|---|
| R37CA036401 | NIH | None | None |
| P30CA021765 | NIH | None | None |
| F32CA141762 | NIH | None | httpsreporternihgovquickSearchF32CA141762 |