Ignite Creation Date:
2024-05-05 @ 5:08 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00392834
Status:
COMPLETED
Last Update Posted:
2018-06-06
First Post:
2006-10-25
Brief Title:
Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed HIV-Associated Burkitts Lymphoma
Sponsor:
AIDS Malignancy Consortium
Organization:
AIDS Malignancy Consortium
Study Overview
Official Title:
Prospective Phase II Study of a High Dose Short Course Regimen R-CODOX-MIVAC Including CNS Penetration and Intensive IT Prophylaxis in HIV-Associated Burkitts and Atypical Burkitts Lymphoma
Status:
COMPLETED
Status Verified Date:
2018-05
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:
RATIONALE Monoclonal antibodies such as rituximab 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 Drugs used in chemotherapy work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing Giving rituximab together with combination chemotherapy may kill more cancer cells
PURPOSE This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with newly diagnosed HIV-associated Burkitts lymphoma
PURPOSE This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with newly diagnosed HIV-associated Burkitts lymphoma
Detailed Description:
OBJECTIVES
Primary
Determine the efficacy of rituximab cyclophosphamide vincristine doxorubicin hydrochloride and high-dose methotrexate R-CODOX-M alone or alternating with rituximab and ifosfamide etoposide phosphate and high-dose cytarabine IVAC and intrathecal CNS prophylaxis in patients with newly diagnosed previously untreated HIV-associated Burkitts lymphoma or atypical Burkitts lymphoma
Determine the safety of this regimen in these patients
Secondary
Evaluate downstream effectors of apoptosis as mechanisms of chemotherapy resistance and prognosis and perform exploratory analysis of their relationship to treatment effect
Evaluate multi-drug resistance gene expression as a mechanism of chemotherapy resistance and prognosis and perform exploratory analysis of their relationship to treatment effect
Confirm the use of flow cytometry in the identification of occult leptomeningeal disease and determine whether abnormal flow cytometry is predictive when CNS cytology is negative for malignant cells
Determine the biologic and prognostic significance of Epstein-Barr virus EBV-positive Burkitts lymphoma in the highly active antiretroviral therapy era and perform exploratory analysis of their relationship to treatment effect
Compare genotyping in patients with HIV-associated Burkitts lymphoma with that of patients who are HIV-negative and determine whether they are uniform in their genetic profile or whether some cases are more like diffuse large B-cell lymphoma
Determine if EBV detection in cerebrospinal fluid at diagnosis is predictive of leptomeningeal disease
OUTLINE This is a prospective multicenter study Patients are stratified according to risk category low-risk vs high-risk Patients with low-risk disease receive 3 courses of R-CODOX-M chemotherapy as described below Patients with high-risk disease receive 4 alternating courses of R-CODOX-MIVAC chemotherapy as described below in an ABAB sequence Courses repeat every 21-28 days in the absence of disease progression or unacceptable toxicity
NOTE In patients presenting with anasarca pleural effusion or ascites methotrexate can pool causing difficulties with clearance in this case treatment may be given in a reverse sequence BABA
Regimen A R-CODOX-M chemotherapy Patients receive rituximab IV and doxorubicin hydrochloride IV over 15 minutes on day 1 cyclophosphamide IV over 30-60 minutes on days 1 and 2 pegfilgrastim subcutaneously SC on day 3 vincristine IV on days 1 and 8 high-dose methotrexate IV over 2-4 hours on day 15 and leucovorin calcium IV beginning 24 hours after the start of methotrexate and continuing every 6 hours until the methotrexate level is less than 50 nmolL Patients receive CNS prophylaxis comprising methotrexate intrathecally IT cytarabine IT and hydrocortisone IT on day 1 Patients with high-risk disease receive an additional dose of cytarabine IT on day 3 Patients also receive filgrastim G-CSF SC once daily on days 3-9 Once the methotrexate levels drops below 50 nmolL patients resume G-CSF SC once daily beginning on approximately day 18 and continuing until blood counts recover
Regimen B rituximab and IVAC chemotherapy Patients receive rituximab IV on day 1 ifosfamide IV continuously and etoposide IV continuously over 24 hours on days 1-5 and high-dose cytarabine IV over 1-3 hours twice daily on days 1-2 Patients receive CNS prophylaxis comprising methotrexate IT and hydrocortisone IT on day 5 Patients also receive pegfilgrastim SC once 24-48 hours after completion of chemotherapy OR G-CSF SC beginning on day 6 and continuing until blood counts recover
Patients with CNS involvement leptomeningeal andor intraparenchymal at diagnosis do not receive CNS prophylaxis as above Instead these patients receive a combination of sequential liposomal cytarabine and methotrexate IT or via an Ommaya reservoir on day 1 and then every 14 days as tolerated until completion of systemic chemotherapy
NOTE Rituximab may be given up to 3 days before a chemotherapy course and anytime during the course for 3 low-risk disease or 4 high-risk disease total doses
Patients undergo blood and cerebrospinal fluid collection and tumor biopsies periodically during study treatment for correlative studies of prognostic biomarkers predictive of survival eg c-flip protein expression p53 mutations by immunohistochemistry IHC multidrug resistance gene expression by IHC and Epstein-Barr virus in tumor DNA or cerebrospinal fluid by polymerase chain reaction genotyping of Burkitts lymphoma and flow cytometry as a tool by staining for detecting occult positivity of leptomeningeal disease in Burkitts lymphoma
After completion of study treatment patients are followed every 4 months for at least 2 years
PROJECTED ACCRUAL A total of 34 patients will be accrued for this study
Primary
Determine the efficacy of rituximab cyclophosphamide vincristine doxorubicin hydrochloride and high-dose methotrexate R-CODOX-M alone or alternating with rituximab and ifosfamide etoposide phosphate and high-dose cytarabine IVAC and intrathecal CNS prophylaxis in patients with newly diagnosed previously untreated HIV-associated Burkitts lymphoma or atypical Burkitts lymphoma
Determine the safety of this regimen in these patients
Secondary
Evaluate downstream effectors of apoptosis as mechanisms of chemotherapy resistance and prognosis and perform exploratory analysis of their relationship to treatment effect
Evaluate multi-drug resistance gene expression as a mechanism of chemotherapy resistance and prognosis and perform exploratory analysis of their relationship to treatment effect
Confirm the use of flow cytometry in the identification of occult leptomeningeal disease and determine whether abnormal flow cytometry is predictive when CNS cytology is negative for malignant cells
Determine the biologic and prognostic significance of Epstein-Barr virus EBV-positive Burkitts lymphoma in the highly active antiretroviral therapy era and perform exploratory analysis of their relationship to treatment effect
Compare genotyping in patients with HIV-associated Burkitts lymphoma with that of patients who are HIV-negative and determine whether they are uniform in their genetic profile or whether some cases are more like diffuse large B-cell lymphoma
Determine if EBV detection in cerebrospinal fluid at diagnosis is predictive of leptomeningeal disease
OUTLINE This is a prospective multicenter study Patients are stratified according to risk category low-risk vs high-risk Patients with low-risk disease receive 3 courses of R-CODOX-M chemotherapy as described below Patients with high-risk disease receive 4 alternating courses of R-CODOX-MIVAC chemotherapy as described below in an ABAB sequence Courses repeat every 21-28 days in the absence of disease progression or unacceptable toxicity
NOTE In patients presenting with anasarca pleural effusion or ascites methotrexate can pool causing difficulties with clearance in this case treatment may be given in a reverse sequence BABA
Regimen A R-CODOX-M chemotherapy Patients receive rituximab IV and doxorubicin hydrochloride IV over 15 minutes on day 1 cyclophosphamide IV over 30-60 minutes on days 1 and 2 pegfilgrastim subcutaneously SC on day 3 vincristine IV on days 1 and 8 high-dose methotrexate IV over 2-4 hours on day 15 and leucovorin calcium IV beginning 24 hours after the start of methotrexate and continuing every 6 hours until the methotrexate level is less than 50 nmolL Patients receive CNS prophylaxis comprising methotrexate intrathecally IT cytarabine IT and hydrocortisone IT on day 1 Patients with high-risk disease receive an additional dose of cytarabine IT on day 3 Patients also receive filgrastim G-CSF SC once daily on days 3-9 Once the methotrexate levels drops below 50 nmolL patients resume G-CSF SC once daily beginning on approximately day 18 and continuing until blood counts recover
Regimen B rituximab and IVAC chemotherapy Patients receive rituximab IV on day 1 ifosfamide IV continuously and etoposide IV continuously over 24 hours on days 1-5 and high-dose cytarabine IV over 1-3 hours twice daily on days 1-2 Patients receive CNS prophylaxis comprising methotrexate IT and hydrocortisone IT on day 5 Patients also receive pegfilgrastim SC once 24-48 hours after completion of chemotherapy OR G-CSF SC beginning on day 6 and continuing until blood counts recover
Patients with CNS involvement leptomeningeal andor intraparenchymal at diagnosis do not receive CNS prophylaxis as above Instead these patients receive a combination of sequential liposomal cytarabine and methotrexate IT or via an Ommaya reservoir on day 1 and then every 14 days as tolerated until completion of systemic chemotherapy
NOTE Rituximab may be given up to 3 days before a chemotherapy course and anytime during the course for 3 low-risk disease or 4 high-risk disease total doses
Patients undergo blood and cerebrospinal fluid collection and tumor biopsies periodically during study treatment for correlative studies of prognostic biomarkers predictive of survival eg c-flip protein expression p53 mutations by immunohistochemistry IHC multidrug resistance gene expression by IHC and Epstein-Barr virus in tumor DNA or cerebrospinal fluid by polymerase chain reaction genotyping of Burkitts lymphoma and flow cytometry as a tool by staining for detecting occult positivity of leptomeningeal disease in Burkitts lymphoma
After completion of study treatment patients are followed every 4 months for at least 2 years
PROJECTED ACCRUAL A total of 34 patients will be accrued for this study
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 |
|---|---|---|---|
| CDR0000510918 | OTHER | NCI | httpsreporternihgovquickSearchU01CA070019 |
| U01CA070019 | NIH | None | None |