Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00016302
Status:
COMPLETED
Last Update Posted:
2013-01-16
First Post:
2001-05-06
Brief Title:
Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
The Use of Modified BFM - Compound 506U78 Nelarabine NSC 686673 IND 52611 in an Intensive Chemotherapy Regimen for the Treatment of T-Cell Leukemia
Status:
COMPLETED
Status Verified Date:
2013-01
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:
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die Combining more than one drug may kill more cancer cells This phase II trial is studying several different combination chemotherapy regimens to see how well they work in treating patients with newly diagnosed acute lymphoblastic leukemia
Detailed Description:
PRIMARY OBJECTIVES
I Determine the feasibility of the addition of nelarabine to modified multiagent Berlin-Frankfurt-Muenster-86 chemotherapy in patients with newly diagnosed T-cell acute lymphoblastic leukemia
SECONDARY OBJECTIVES
I Determine the pharmacokinetics and intracellular pharmacology of nelarabine in these patients
OUTLINE This is a pilot multicenter study
Prednisone Response Pre-Induction All patients receive oral prednisone three times daily on days -7 to -1 and methotrexate intrathecally IT on day -7 of week 0 Good prednisone responders proceed to induction on regimen A Poor prednisone responders proceed to induction on regimen C
NOTE Patients who have received cytarabine IT within the week prior to study entry receive methotrexate IT on day -6
Regimen A good prednisone responders closed as of 22703
Induction weeks 1-5 Patients receive vincristine IV on days 1 8 and 15 oral prednisone three times daily on days 1-14 daunorubicin IV over 15 minutes on days 1 8 15 and 22 asparaginase intramuscularly IM on days 12 15 18 22 24 27 30 and 33 and methotrexate IT on day 1
If bone marrow is M1 week 6 of induction therapy begins on day 36 or when peripheral blood counts recover If bone marrow is M2 patients begin week 6 of induction therapy immediately If bone marrow is M3 treatment discontinues Those patients with minimal residual disease MRD on day 36 proceed to regimen B
Induction weeks 6-9 Patients receive cyclophosphamide IV over 1 hour on days 36 and 63 cytarabine IV over 72 hours on days 38-40 45-47 52-54 and 59-61 oral mercaptopurine daily on days 36-63 and methotrexate IT on days 45 and 59
Consolidation weeks 10-19 Patients receive oral mercaptopurine on days 64-119 methotrexate IV over 24 hours and leucovorin calcium IV or orally as tolerated on days 71 85 99 and 113 and methotrexate IT on days 71 85 99 and 113 Patients begin methotrexate once blood counts recover and only if bone marrow is M1
Reinduction weeks 20-29 Patients receive oral dexamethasone three times daily on days 134-154 vincristine IV on days 141 and 148 doxorubicin IV over 15 minutes on days 134 141 148 and 155 and asparaginase IM on days 141 144 148 151 154 and 157 Beginning on day 169 or when blood counts recover patients receive cyclophosphamide IV on day 169 cytarabine IV over 72 hours on days 171-173 and 178-180 oral thioguanine daily on days 169-182 and methotrexate IT on days 171 and 178 Patients also receive cranial irradiation for up to 10 days beginning on day 189
Maintenance weeks 30-101 Patients receive vincristine IV once oral prednisone three times daily for 5 days oral mercaptopurine daily and oral methotrexate weekly Treatment repeats every 8 weeks for 9 courses
Regimen B patients with MRD on day 36 of regimen A closed as of 22703
Induction weeks 1-9 Patients receive treatment as in induction of regimen A
Consolidation weeks 10-19 Patients receive treatment as in consolidation on regimen A
Reinduction weeks 20-29 Patients receive treatment as in reinduction on regimen A and nelarabine IV on days 162-166
Maintenance weeks 30-101 Patients receive oral mercaptopurine daily on days 1-28 and 36-56 oral methotrexate weekly and nelarabine IV on days 29-33 Treatment repeats every 8 weeks for 4 courses Beginning on week 62 patients receive vincristine IV once oral prednisone three times daily for 5 days oral mercaptopurine daily and oral methotrexate weekly Treatment repeats every 8 weeks for 5 courses
Regimen C poor prednisone responders from stage 1 of study and all patients entered during stage 2 of study closed as of 22703
Induction weeks 1-5 Patients receive treatment as in induction weeks 1-5 on regimen A and nelarabine IV over 1 hour on days 29-33
If bone marrow is M1 patients begin week 6 of induction therapy on day 36 or when peripheral blood counts recover If bone marrow is M2 patients begin week 6 of induction therapy immediately If bone marrow is M3 treatment discontinues
Induction weeks 6-9 Patients receive treatment as in induction weeks 6-9 on regimen A
Consolidation weeks 10-19 Patients receive treatment as in consolidation on regimen A
Reinduction weeks 20-29 Patients receive treatment as in reinduction on regimen B
Maintenance weeks 30-101 Patients receive treatment as in maintenance on regimen B
Regimen D effective 52004
Induction weeks 1-5 Patients receive vincristine IV on days 1 8 and 15 oral prednisone 3 times a day on days 1-14 daunorubicin IV over 15 minutes on days 1 8 15 and 22 nelarabine IV over 1 hour on days 29-33 asparaginase IM on days 12 15 18 22 24 27 30 and 33 and methotrexate IT on day 1
If bone marrow is M1 week 6 of induction therapy begins on day 36 or when peripheral blood counts recover If bone marrow is M2 patients begin week 6 of induction therapy immediately If bone marrow is M3 treatment discontinues
Induction weeks 6-9 Patients receive cyclophosphamide IV over 1 hour on days 36 and 50 cytarabine IV or SC on days 36-39 43-46 50-53 and 57-60 oral mercaptopurine once daily on days 36-63 and methotrexate IT on days 43 and 57
Patients who are poor responders to prednisone in induction therapy proceed to regimen F Patients who are good responders to prednisone but have MRD after induction therapy proceed to regimen E Patients who are good responders to prednisone and have no MRD after induction therapy continue therapy on regimen D
Consolidation weeks 10-19 Patients must have M1 marrow to proceed Patients receive oral mercaptopurine on days 70-126 methotrexate IV over 24 hours on days 77 84 91 and 98 leucovorin calcium IV or orally every 6 hours on days 78-79 85-86 92-93 and 99-100 and methotrexate IT on days 77 84 91 and 98
Reinduction weeks 20-29 Patients 13 years old receive dexamethasone 3 times daily on days 140-161 Patients 13 years old receive oral dexamethasone on days 140-146 and 155-161 nelarabine IV on days 169-173 vincristine IV over 15 minutes on days 140 147 and 153 pegaspargase IM on day 143 cyclophosphamide IV on day 176 cytarabine IV or SC on days 176-179 and 183-186 oral thioguanine on days 176-189 and methotrexate IT on days 176 and 183 Patients with CNS disease undergo craniocervical radiotherapy beginning on day 196 and continuing for 7-10 days
Maintenance weeks 30-61 Patients receive oral mercaptopurine on days 1-28 and 36-56 oral methotrexate on days 1 8 15 22 36 43 and 50 and nelarabine IV on days 29-33 Treatment repeats every 8 weeks for 4 courses
Maintenance weeks 62-101 Patients receive vincristine IV on day 1 oral dexamethasone twice daily on days 1-5 oral mercaptopurine on days 1-56 and oral methotrexate on days 1 8 15 22 29 36 43 and 50 Treatment repeats every 8 weeks for 5 courses
Regimen E good responders to induction prednisone but with MRD effective 52004 Patients receive consolidation therapy reinduction therapy and maintenance therapy as in regimen D but nelarabine is administered at a higher dose
Regimen F poor responders to induction prednisone effective 52004 Patients receive nelarabine at a higher dose during induction therapy Patients receive consolidation therapy reinduction therapy and maintenance therapy as in regimen E
Patients are followed monthly for 1 year every 2 months for 1 year every 4 months for 1 year every 6 months for 1 year and then annually thereafter
PROJECTED ACCRUAL A total of 100 patients 30 for regimens A B and C 70 for regimens D E and F will be accrued for this study within 9-29 months
I Determine the feasibility of the addition of nelarabine to modified multiagent Berlin-Frankfurt-Muenster-86 chemotherapy in patients with newly diagnosed T-cell acute lymphoblastic leukemia
SECONDARY OBJECTIVES
I Determine the pharmacokinetics and intracellular pharmacology of nelarabine in these patients
OUTLINE This is a pilot multicenter study
Prednisone Response Pre-Induction All patients receive oral prednisone three times daily on days -7 to -1 and methotrexate intrathecally IT on day -7 of week 0 Good prednisone responders proceed to induction on regimen A Poor prednisone responders proceed to induction on regimen C
NOTE Patients who have received cytarabine IT within the week prior to study entry receive methotrexate IT on day -6
Regimen A good prednisone responders closed as of 22703
Induction weeks 1-5 Patients receive vincristine IV on days 1 8 and 15 oral prednisone three times daily on days 1-14 daunorubicin IV over 15 minutes on days 1 8 15 and 22 asparaginase intramuscularly IM on days 12 15 18 22 24 27 30 and 33 and methotrexate IT on day 1
If bone marrow is M1 week 6 of induction therapy begins on day 36 or when peripheral blood counts recover If bone marrow is M2 patients begin week 6 of induction therapy immediately If bone marrow is M3 treatment discontinues Those patients with minimal residual disease MRD on day 36 proceed to regimen B
Induction weeks 6-9 Patients receive cyclophosphamide IV over 1 hour on days 36 and 63 cytarabine IV over 72 hours on days 38-40 45-47 52-54 and 59-61 oral mercaptopurine daily on days 36-63 and methotrexate IT on days 45 and 59
Consolidation weeks 10-19 Patients receive oral mercaptopurine on days 64-119 methotrexate IV over 24 hours and leucovorin calcium IV or orally as tolerated on days 71 85 99 and 113 and methotrexate IT on days 71 85 99 and 113 Patients begin methotrexate once blood counts recover and only if bone marrow is M1
Reinduction weeks 20-29 Patients receive oral dexamethasone three times daily on days 134-154 vincristine IV on days 141 and 148 doxorubicin IV over 15 minutes on days 134 141 148 and 155 and asparaginase IM on days 141 144 148 151 154 and 157 Beginning on day 169 or when blood counts recover patients receive cyclophosphamide IV on day 169 cytarabine IV over 72 hours on days 171-173 and 178-180 oral thioguanine daily on days 169-182 and methotrexate IT on days 171 and 178 Patients also receive cranial irradiation for up to 10 days beginning on day 189
Maintenance weeks 30-101 Patients receive vincristine IV once oral prednisone three times daily for 5 days oral mercaptopurine daily and oral methotrexate weekly Treatment repeats every 8 weeks for 9 courses
Regimen B patients with MRD on day 36 of regimen A closed as of 22703
Induction weeks 1-9 Patients receive treatment as in induction of regimen A
Consolidation weeks 10-19 Patients receive treatment as in consolidation on regimen A
Reinduction weeks 20-29 Patients receive treatment as in reinduction on regimen A and nelarabine IV on days 162-166
Maintenance weeks 30-101 Patients receive oral mercaptopurine daily on days 1-28 and 36-56 oral methotrexate weekly and nelarabine IV on days 29-33 Treatment repeats every 8 weeks for 4 courses Beginning on week 62 patients receive vincristine IV once oral prednisone three times daily for 5 days oral mercaptopurine daily and oral methotrexate weekly Treatment repeats every 8 weeks for 5 courses
Regimen C poor prednisone responders from stage 1 of study and all patients entered during stage 2 of study closed as of 22703
Induction weeks 1-5 Patients receive treatment as in induction weeks 1-5 on regimen A and nelarabine IV over 1 hour on days 29-33
If bone marrow is M1 patients begin week 6 of induction therapy on day 36 or when peripheral blood counts recover If bone marrow is M2 patients begin week 6 of induction therapy immediately If bone marrow is M3 treatment discontinues
Induction weeks 6-9 Patients receive treatment as in induction weeks 6-9 on regimen A
Consolidation weeks 10-19 Patients receive treatment as in consolidation on regimen A
Reinduction weeks 20-29 Patients receive treatment as in reinduction on regimen B
Maintenance weeks 30-101 Patients receive treatment as in maintenance on regimen B
Regimen D effective 52004
Induction weeks 1-5 Patients receive vincristine IV on days 1 8 and 15 oral prednisone 3 times a day on days 1-14 daunorubicin IV over 15 minutes on days 1 8 15 and 22 nelarabine IV over 1 hour on days 29-33 asparaginase IM on days 12 15 18 22 24 27 30 and 33 and methotrexate IT on day 1
If bone marrow is M1 week 6 of induction therapy begins on day 36 or when peripheral blood counts recover If bone marrow is M2 patients begin week 6 of induction therapy immediately If bone marrow is M3 treatment discontinues
Induction weeks 6-9 Patients receive cyclophosphamide IV over 1 hour on days 36 and 50 cytarabine IV or SC on days 36-39 43-46 50-53 and 57-60 oral mercaptopurine once daily on days 36-63 and methotrexate IT on days 43 and 57
Patients who are poor responders to prednisone in induction therapy proceed to regimen F Patients who are good responders to prednisone but have MRD after induction therapy proceed to regimen E Patients who are good responders to prednisone and have no MRD after induction therapy continue therapy on regimen D
Consolidation weeks 10-19 Patients must have M1 marrow to proceed Patients receive oral mercaptopurine on days 70-126 methotrexate IV over 24 hours on days 77 84 91 and 98 leucovorin calcium IV or orally every 6 hours on days 78-79 85-86 92-93 and 99-100 and methotrexate IT on days 77 84 91 and 98
Reinduction weeks 20-29 Patients 13 years old receive dexamethasone 3 times daily on days 140-161 Patients 13 years old receive oral dexamethasone on days 140-146 and 155-161 nelarabine IV on days 169-173 vincristine IV over 15 minutes on days 140 147 and 153 pegaspargase IM on day 143 cyclophosphamide IV on day 176 cytarabine IV or SC on days 176-179 and 183-186 oral thioguanine on days 176-189 and methotrexate IT on days 176 and 183 Patients with CNS disease undergo craniocervical radiotherapy beginning on day 196 and continuing for 7-10 days
Maintenance weeks 30-61 Patients receive oral mercaptopurine on days 1-28 and 36-56 oral methotrexate on days 1 8 15 22 36 43 and 50 and nelarabine IV on days 29-33 Treatment repeats every 8 weeks for 4 courses
Maintenance weeks 62-101 Patients receive vincristine IV on day 1 oral dexamethasone twice daily on days 1-5 oral mercaptopurine on days 1-56 and oral methotrexate on days 1 8 15 22 29 36 43 and 50 Treatment repeats every 8 weeks for 5 courses
Regimen E good responders to induction prednisone but with MRD effective 52004 Patients receive consolidation therapy reinduction therapy and maintenance therapy as in regimen D but nelarabine is administered at a higher dose
Regimen F poor responders to induction prednisone effective 52004 Patients receive nelarabine at a higher dose during induction therapy Patients receive consolidation therapy reinduction therapy and maintenance therapy as in regimen E
Patients are followed monthly for 1 year every 2 months for 1 year every 4 months for 1 year every 6 months for 1 year and then annually thereafter
PROJECTED ACCRUAL A total of 100 patients 30 for regimens A B and C 70 for regimens D E and F will be accrued for this study within 9-29 months
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 |
|---|---|---|---|
| CDR0000068620 | REGISTRY | PDQ Physician Data Query | httpsreporternihgovquickSearchU10CA098543 |
| COG-AALL00P2 | None | None | None |
| U10CA098543 | NIH | None | None |