Doxorubicin Hydrochloride Liposome and Rituximab With Combination Chemotherapy in Treating Patients With Newly Diagnosed Burkitt's Lymphoma or Burkitt-Like Lymphoma
- Conditions
- Lymphoma
- Interventions
- Drug: Regimen ADrug: Regimen B
- Registration Number
- NCT00392990
- Lead Sponsor
- Northwestern University
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Giving rituximab together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving doxorubicin hydrochloride liposome and rituximab together with combination chemotherapy works in treating patients with newly diagnosed Burkitt's lymphoma or Burkitt-like lymphoma.
- Detailed Description
OBJECTIVES:
Primary
* Determine the overall response rate (complete remission, complete remission undetermined, and partial remission) in HIV-negative or HIV-positive patients with newly diagnosed Burkitt's or Burkitt-like lymphoma treated with doxorubicin hydrochloride liposome and rituximab as part of the Magrath regimen.
Secondary
* Determine the complete remission rate in patients treated with this regimen.
* Determine progression-free and overall survival at 2 years in patients treated with this regimen.
* Determine the safety of adding rituximab to the standard Magrath regimen in these patients.
* Determine the safety of using doxorubicin hydrochloride liposome in place of doxorubicin hydrochloride in these patients.
* Determine correlative levels of rituximab and doxorubicin hydrochloride liposome in cerebrospinal fluid and peripheral blood.
OUTLINE: This is a multicenter study. Patients are stratified according to risk category (low risk vs high risk). Patients are assigned to 1 of 2 treatment regimens according to stratum.
* Regimen A (low-risk disease with no CNS involvement): Patients receive R-CODOX-M chemotherapy comprising rituximab IV over 2-4 hours on days 0 and 8; doxorubicin hydrochloride liposome IV over 30 minutes on day 1; vincristine IV on days 1 and 8; cyclophosphamide IV over 1 hour on days 1-5; and high-dose methotrexate (MTX) IV over 24 hours on day 10. Patients also receive leucovorin calcium IV beginning 36 hours after the start of MTX infusion and continuing every 6 hours until blood levels of MTX are safe. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily on days 4-8 in courses 1 and 3 and on days 6 and 7 in course 2. Beginning on day 12, daily G-CSF dosing resumes until blood counts recover. Patients receive CNS prophylaxis comprising cytarabine intrathecally (IT) on day 1 and MTX IT on day 3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
* Regimen B (high-risk disease with or without CNS involvement): Patients receive R-CODOX-M chemotherapy with leucovorin calcium and G-CSF support as in regimen A for courses 1 and 3 and R-IVAC chemotherapy with leucovorin calcium and G-CSF support (as below) for courses 2 and 4. R-IVAC chemotherapy comprises high-dose ifosfamide IV over 3 hours and etoposide IV over 1 hour on days 1-5; cytarabine IV over 3 hours twice daily on days 2 and 3; and rituximab IV over 2-4 hours on day 0 and on day 6 or 7. Patients also receive leucovorin calcium orally every 6 hours on day 6 and G-CSF SC once daily beginning on day 6 or 7 and continuing until blood counts recover. Patients without CNS involvement receive CNS prophylaxis comprising cytarabine IT on days 1 and 3 and MTX IT on day 15 in courses 1 and 3 and MTX IT alone on day 5 in courses 2 and 4. Patients with proven CNS involvement at diagnosis receive cytarabine IT on days 1, 3, and 5 in course 1, on days 7 and 9 in course 2, and on days 1 and 3 in course 3. These patients also receive MTX IT on days 15 and 17 in course 1, on day 5 in courses 2 and 4, and on day 15 in course 3. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
The first 10 patients enrolled on the study undergo cerebrospinal fluid and blood collection during courses 1 and 3 for correlative biological marker and pharmacological studies.
After completion of study treatment, patients are followed at 30 days and then periodically for up to 3 years.
PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Alternating doxil/Magrath regimen & rituximab/Magrath regimen Regimen A Patients are stratified between high risk and low risk disease status. Low risk patients receive 3 cycles of rituximab (500 mg/m2) R-CODOX-M chemotherapy IV over 2-4 hours with intrathecal chemotherapy (Regimen A). High risk patients receive 1 cycle of R-CODOX-M chemotherapy IV followed by R-IVAC chemotherapy over 30 minutes(Regimen B); regimens A and B are then repeated. Alternating doxil/Magrath regimen & rituximab/Magrath regimen Regimen B Patients are stratified between high risk and low risk disease status. Low risk patients receive 3 cycles of rituximab (500 mg/m2) R-CODOX-M chemotherapy IV over 2-4 hours with intrathecal chemotherapy (Regimen A). High risk patients receive 1 cycle of R-CODOX-M chemotherapy IV followed by R-IVAC chemotherapy over 30 minutes(Regimen B); regimens A and B are then repeated.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen After two cycles of treatment and at completion of treatment (4 cycles for high risk and 3 cycles for low risk) up to approximately 20 weeks. Response Rate is defined as combined number of patients with Complete Remission (CR) Complete Remission undetermined (Cru) and Partial Remission (PR) for patients with Burkitt's and Burkitt-like Lymphoma/Leukemia. Response will be measured by CT scans following treatment completion and assessed using Response Criteria for Non-Hodgkin's Lymphoma where:
CR=complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms.
CRu=same as above but allowing for 75% decrease in lymph node masses and indeterminate or normal bone marrow.
PR=50% decrease in SPD of the six largest dominant nodes or nodal masses with no increase in size or other nodes, liver, spleen and no new sites of disease.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen At 2 years from treatment initiation Median follow up 34 months (range 15-45) Overall Survival (OS) of patients with Burkitt's and Burkitt-like Lymphoma/Leukemia treated with modified Magrath regimen. OS is defined from the first dose of study drug to the time of death for any reason.
Safety of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen (Addition of Rituximab, Subsitution of Adriamycin for Doxil and Using Lower Dose of Methotrexate) After each cycle or monthly (whichever is less frequent), 30 days post last dose. Treatment duration was at a median of 13 weeks (range 11-20) for high-risk patients and 10 weeks (range 9-12) for low-risk patients. Adverse events (AE) graded as either 3 or 4 and determined to be at least possibly related to study treatment will be collected in patients Burkitt's and Burkitt-like Lymphoma/Leukemia treated with modified Magrath regimen to assess the safety and toxicity profile of the addition of rituximab, subsitution of adriamycin for doxil and lower dose of methotrexate. AEs will be assessed as follows at the following time points: At the end of each cycle or monthly whichever is less frequent and 30 days post last dose of study treatment for a maximum of 3 cycles for regimen A and 4 cycles for regimen B and up to 12 months.
In general AEs will be assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v 3.0). In general adverse events (AEs) will be graded according to the following:
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AEProgression Free Survival (PFS) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen At 2 years from treatment initiation. Median follow up 34 months (range 15-45) Progression Free Survival (PFS) will be defined from the first dose of study drug to the first documentation of progressive disease or death for any reason. Patients that are lost to follow-up before progression will be censored at the point of last documentation of not experiencing the event.
Trial Locations
- Locations (8)
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Advocate Lutheran General Cancer Care Center
🇺🇸Park Ridge, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States
John H. Stroger Cook County Hospital
🇺🇸Chicago, Illinois, United States
The Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States