Ignite Creation Date:
2024-05-05 @ 11:37 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00098839
Status:
COMPLETED
Last Update Posted:
2017-12-12
First Post:
2004-12-08
Brief Title:
Chemoimmunotherapy With Epratuzumab in Relapsed Acute Lymphoblastic Leukemia ALL
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
A Feasibility Pilot and Phase II Study Of Chemoimmunotherapy With Epratuzumab IND 12034 for Children With Relapsed CD22-Positive Acute Lymphoblastic Leukemia ALL
Status:
COMPLETED
Status Verified Date:
2017-11
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 Phase II trial is studying how well giving epratuzumab together with an established chemotherapy platform works in treating young patients with relapsed acute lymphoblastic leukemia Monoclonal antibodies such as epratuzumab can block cancer growth in different ways Some block the ability of cancer cells to grow and spread Others find cancer cells and help kill them or carry cancer-killing substances to them Chemotherapy drugs work in different ways to stop the growth of cancer cells either by killing them or by stopping them from dividing Giving monoclonal antibody therapy in combination chemotherapy may kill cancer cells more effectively
Detailed Description:
PRIMARY OBJECTIVES
I Determine the feasibility of epratuzumab administered alone and in combination with re-induction combination chemotherapy in pediatric patients with relapsed CD22-positive acute lymphoblastic leukemia
II Determine the toxic effects of this regimen in these patients
III Determine the antitumor activity of this regimen in these patients
IV To estimate the remission re-induction rate and four-month event-free survival EFS for patients with early first relapse ALL who receive epratuzumab in combination with cytotoxic thermotherapy
SECONDARY OBJECTIVES
I Determine the pharmacokinetics of epratuzumab in these patients II Determine the biologic activity of epratuzumab using measurements of minimal residual disease in these patients
III Determine the human anti-human antibody HAHA response in patients treated with this regimen
OUTLINE This is a multicenter study comprising a feasibility part A closed to accrual as of 103006 followed by a pilot part B study A Simons two stage design was initially used to evaluate the efficacy of the once weekly dosing schedule for part B patients called B1 cohort which planned to accrue a total of 112 patients with 56 to be enrolled at the first stage After completion the accrual of stage 1 ie after 56 patients were enrolled the design of part B was revised to evaluate a modified doing schedule twice weekly doing called B2 cohort using a stratified two-stage design by London and Chang 2005 where patients enrolled to B2 were stratified according to relapse first early marrow relapsed occurring 18 months from initial diagnosis vs 18-36 months from initial diagnosis
PART A CLOSED TO ACCRUAL 103006
REDUCTION THERAPY Patients receive epratuzumab IV over several hours on days -14 -10 -6 and -2 and cytarabine intrathecally IT on day -14
NOTE Patients who receive IT chemotherapy within 7 days of study entry as prior maintenance chemotherapy eg before the diagnosis of relapse did not receive this first dose of IT cytarabine
RE-INDUCTION THERAPY BLOCK 1 Patients received vincristine IV on days 1 8 15 and 22 oral prednisone two or three times daily on days 1-29 pegaspargase intramuscularly IM on days 2 9 16 and 23 dexrazoxane IV followed by doxorubicin IV over 15 minutes on day 1 methotrexate IT on days 15 and 29 for CNS-negative disease and epratuzumab IV over 1 hour on days 8 15 22 and 29 Patients with CNS-positive disease also received triple IT therapy ITT consisting of methotrexate cytarabine hydrocortisone on days -10 -6 1 and 15
RE-INDUCTION THERAPY BLOCK 2 Beginning at least 7 days after the last dose of IT chemotherapy patients received etoposide IV over 2 hours and cyclophosphamide IV over 30 minutes on days 1-5 Patients also received high-dose methotrexate IV continuously over 24 hours on day 22 Beginning 42 hours after the start of the methotrexate infusion day 24 patients received leucovorin calcium IV every 6 hours for a minimum of 3 doses Patients with CNS-negative disease also receive methotrexate IT on days 1 and 22 Patients with CNS-positive disease will receive triple IT as in re-induction therapy block 1 on days 1 and 22 Patients received filgrastim G-CSF subcutaneously SC once daily beginning on day 6 and continuing until blood counts recover
RE-INDUCTION THERAPY PART 3 Beginning at least 7 days after the last dose of IT chemotherapy patients received cytarabine IV over 3 hours twice daily on days 1 2 8 and 9 and native E Coli asparaginase IM on days 2 and 9 Patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recovered
PART B
RE-INDUCTION THERAPY BLOCK 1 Patients received vincristine prednisone pegaspargase doxorubicin cytarabine methotrexate and epratuzumab as in phase I re-induction therapy block 1 Epratuzumab was given on Days 1 8 15 and 22 before amendment 5 B1 cohort and on Days 1 4 8 11 15 18 22 and 25 after amendment 5 B2 cohort Patients with CNS-negative disease received methotrexate IT on days 1 and 22 Patients with CNS-positive disease received triple IT therapy comprising methotrexate cytarabine and hydrocortisone on days 8 15 22 and 29
RE-INDUCTION THERAPY BLOCKS 2 AND 3 Patients received re-induction therapy blocks 2 and 3 as in the part A re-induction therapy blocks 2 and 3 portion of the study
Patients are followed annually
I Determine the feasibility of epratuzumab administered alone and in combination with re-induction combination chemotherapy in pediatric patients with relapsed CD22-positive acute lymphoblastic leukemia
II Determine the toxic effects of this regimen in these patients
III Determine the antitumor activity of this regimen in these patients
IV To estimate the remission re-induction rate and four-month event-free survival EFS for patients with early first relapse ALL who receive epratuzumab in combination with cytotoxic thermotherapy
SECONDARY OBJECTIVES
I Determine the pharmacokinetics of epratuzumab in these patients II Determine the biologic activity of epratuzumab using measurements of minimal residual disease in these patients
III Determine the human anti-human antibody HAHA response in patients treated with this regimen
OUTLINE This is a multicenter study comprising a feasibility part A closed to accrual as of 103006 followed by a pilot part B study A Simons two stage design was initially used to evaluate the efficacy of the once weekly dosing schedule for part B patients called B1 cohort which planned to accrue a total of 112 patients with 56 to be enrolled at the first stage After completion the accrual of stage 1 ie after 56 patients were enrolled the design of part B was revised to evaluate a modified doing schedule twice weekly doing called B2 cohort using a stratified two-stage design by London and Chang 2005 where patients enrolled to B2 were stratified according to relapse first early marrow relapsed occurring 18 months from initial diagnosis vs 18-36 months from initial diagnosis
PART A CLOSED TO ACCRUAL 103006
REDUCTION THERAPY Patients receive epratuzumab IV over several hours on days -14 -10 -6 and -2 and cytarabine intrathecally IT on day -14
NOTE Patients who receive IT chemotherapy within 7 days of study entry as prior maintenance chemotherapy eg before the diagnosis of relapse did not receive this first dose of IT cytarabine
RE-INDUCTION THERAPY BLOCK 1 Patients received vincristine IV on days 1 8 15 and 22 oral prednisone two or three times daily on days 1-29 pegaspargase intramuscularly IM on days 2 9 16 and 23 dexrazoxane IV followed by doxorubicin IV over 15 minutes on day 1 methotrexate IT on days 15 and 29 for CNS-negative disease and epratuzumab IV over 1 hour on days 8 15 22 and 29 Patients with CNS-positive disease also received triple IT therapy ITT consisting of methotrexate cytarabine hydrocortisone on days -10 -6 1 and 15
RE-INDUCTION THERAPY BLOCK 2 Beginning at least 7 days after the last dose of IT chemotherapy patients received etoposide IV over 2 hours and cyclophosphamide IV over 30 minutes on days 1-5 Patients also received high-dose methotrexate IV continuously over 24 hours on day 22 Beginning 42 hours after the start of the methotrexate infusion day 24 patients received leucovorin calcium IV every 6 hours for a minimum of 3 doses Patients with CNS-negative disease also receive methotrexate IT on days 1 and 22 Patients with CNS-positive disease will receive triple IT as in re-induction therapy block 1 on days 1 and 22 Patients received filgrastim G-CSF subcutaneously SC once daily beginning on day 6 and continuing until blood counts recover
RE-INDUCTION THERAPY PART 3 Beginning at least 7 days after the last dose of IT chemotherapy patients received cytarabine IV over 3 hours twice daily on days 1 2 8 and 9 and native E Coli asparaginase IM on days 2 and 9 Patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recovered
PART B
RE-INDUCTION THERAPY BLOCK 1 Patients received vincristine prednisone pegaspargase doxorubicin cytarabine methotrexate and epratuzumab as in phase I re-induction therapy block 1 Epratuzumab was given on Days 1 8 15 and 22 before amendment 5 B1 cohort and on Days 1 4 8 11 15 18 22 and 25 after amendment 5 B2 cohort Patients with CNS-negative disease received methotrexate IT on days 1 and 22 Patients with CNS-positive disease received triple IT therapy comprising methotrexate cytarabine and hydrocortisone on days 8 15 22 and 29
RE-INDUCTION THERAPY BLOCKS 2 AND 3 Patients received re-induction therapy blocks 2 and 3 as in the part A re-induction therapy blocks 2 and 3 portion of the study
Patients are followed annually
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 |
|---|---|---|---|
| NCI-2011-01624 | REGISTRY | None | None |
| COG-ADVL04P2 | OTHER | None | None |
| CDR0000396777 | OTHER | None | None |
| U10CA098543 | NIH | Clinical Trialsgov | httpsreporternihgovquickSearchU10CA098543 |