Atypical Burkitt Lymphoma, Burkitt Lymphoma, Non-Hodgkins Lymphoma
Conditions
Keywords
Burkitt Lymphoma, atypical Burkitt lymphoma, Non-Hodgkin's Lymphoma, rituximab
Brief summary
The purpose of this study is to learn more about how well a chemotherapy regime including rituximab works in treating patients with Burkitt or atypical Burkitt lymphoma.
Detailed description
* Patients will be placed into one of two groups, low risk and high risk. Low risk disease is defined as one area of disease measuring less than 10cm and a normal blood test called LDH (lactate hydrogenase). Patients not fitting the low risk criteria are considered high risk. * If the patient has low risk disease their treatment cycle consist of three cycles of A. * If the patient has high risk disease they will receive Cycle A followed by cycle B which will then repeat. * Cycle A consists of the drugs: rituximab, cyclophosphamide, oncovin, doxorubicin and methotrexate (R-CODOX-M). The treatment cycle is approximately 14 days. A spinal tap is performed on day 1 and day 3 of the cycle and the patient will be hospitalized until between day 11 and day 13. After the patient's blood counts return to normal(usually around day 21),the next round of treatment will occur. * Cycle B consists of the drugs: rituximab, ifosfamide, VP-16 and ara-c (IVAC). The treatment cycle is approximately 5 days. A spinal tap is performed on day 4 and once blood counts return to normal the patient will start cycle A again. * After the patient has finished the treatments, they will be re-evaluated with CT scans and PET scans to determine whether or not they are in remission. Every three months for two years, blood tests and CT and PET scans will be performed. Follow up after that will be every 6 months for two years.
Interventions
DRUGRituximab
Low Risk: Intravenously on Day 3 of the first cycle (One cycle is 14 days) then day 1 for next 2 cycles (Regimen A) High Risk: Regimen A followed by a 5-day cycle where rituximan is given on day 1
DRUGCyclophosphamide
Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A)
DRUGDoxorubicin
Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)
DRUGVincristine
Low Risk/High Risk: Given intravenously on day 1 and day 10 of a 14-day cycle for 3 cycles (regimen A)
DRUGMethotrexate
Low Risk: Given on day 10 of a 14-day cycle for 3 cycles (regimen A) High Risk: Regimen A followed by methotrexate on day 3 and day 5 of a 5-day cycle
DRUGLeucovorin
Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A)
DRUGIfosfamide
High Risk: After Regimen A, Ifosomide given on days 1-5 of a 5 day cycle
DRUGEtoposide
High Risk: After Regimen A, etoposide given days 1-5 of a 5-day cycle
DRUGCytarabine
Low Risk: Given on days 1, 3, 5 and 10 of a 14-day cycle for 3 cycles (regimen A) High Risk: After regimen A, cytarabine given on days 1 and 2 of a 5-day cycle
DRUGMesna
High Risk: After regimen A, mesna is given on days 1-5 of a 5-day cycle
Sponsors
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented Burkitt or atypical Burkitt according to World Health Organization (WHO) criteria. * Pathology must be reviewed at the Brigham and Women's Hospital (BWH). * Measurable or evaluable disease: Disease reproducibly measurable in two perpendicular dimensions on exam, computed tomography (CT), radiograph, or magnetic resonance imaging (MRI). Disease present on bone marrow biopsy will be considered as evaluable disease. * The following may not be used as the sole site of measurable or evaluable disease: \*ascites, \*pleural effusion, \*bone lesion or \*central nervous system (CNS) disease. * Age \> 18 * Laboratory data (within 2 weeks of study registration): * ANC \> 1500/ul; * platelet \> 100,000/ul; * creatinine \< 1.5 X normal; * creatinine clearance \> 60 ml/min; * bilirubin \< 1.5 X normal; * AST and ALT \< 2.5 X normal; * alkaline phosphates \< 3 X normal; * HIV negative; * cardiac ejection fraction \> 50%.
Exclusion criteria
* Previous chemotherapy or radiation therapy. Steroids of less than 72 hours duration for impending oncologic emergency are allowed. * Uncontrolled bacterial, fungal, or viral infection. * Concomitant malignancy excluding carcinoma in situ of the cervix and basal cell carcinoma of the skin. * Serious comorbid disease. Clinically significant pulmonary symptomatology. In patients with a history of symptomatic pulmonary disease, pulmonary function tests (PFTs) should document an forced expiratory volume at 1 second (FeV1), forced vital capacity (FVC), and total lung capacity (TLC) of \> 60% predicted and carbon monoxide diffusing capacity of the lung (DLCO) of \> 50% predicted. No clinically significant cardiac symptomatology. The cardiac ejection fraction must be \> 50%. * Pregnancy. All males and females with reproductive potential must consent to use an effective form of contraception while on study. * Major surgery within the previous 2 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt | 3 years | Complete Response (CR): Disappearance of all measurable or evaluable disease confirmed. Partial Response (PR): Reduction of 50% or greater in the sum of the products of the perpendicular diameters of all measurable. Of 8 High Risk participants, 7 met the primary response outcome. 1 High Risk participant did not meet protocol defined primary outcome response and died two months following enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival | Until disease progression up to 120 months | Participants are followed after completion of protocol therapy until disease progression to determine disease free survival. |
Countries
United States
Participant flow
Recruitment details
This BL protocl was IRB approved 01/18/05, activated 7/18/05. Participants were identified either in the outpatient clinic at DFCI or while admitted to our partner inpatient hospital, Brigham & Women's Hospital. The study was closed to accrual 6/2/08 due to slow accrual.
Pre-assignment details
Participants with previous chemotherapy or radiation, uncontrolled infection, concomitant malignancy (some exclusions), serious comorbid disease, pregnancy, and HIV+ were excluded. Subjects stratified according to risk: Single focus disease \<10cm and normal LGH=low risk, all others high risk.
Participants by arm
| Arm | Count |
|---|---|
| Low Risk Regimen A. Single focus of disease less than 10 cm in greatest dimension and a normal LDH. Participants at low risk received three cycles of Regimen A (AAA). | 2 |
| High Risk Regimen A followed by Regimen B. Cycles A and B will then be repeated (ABAB). | 8 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | High Risk | Low Risk | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 1 Participants | 9 Participants |
| Region of Enrollment United States | 8 participants | 2 participants | 10 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 2 | 0 / 8 |
| serious Total, serious adverse events | 1 / 2 | 2 / 8 |
Outcome results
Primary
Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt
Complete Response (CR): Disappearance of all measurable or evaluable disease confirmed. Partial Response (PR): Reduction of 50% or greater in the sum of the products of the perpendicular diameters of all measurable. Of 8 High Risk participants, 7 met the primary response outcome. 1 High Risk participant did not meet protocol defined primary outcome response and died two months following enrollment.
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Risk | Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt | 2 participants |
| High Risk | Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt | 7 participants |
Secondary
Disease Free Survival
Participants are followed after completion of protocol therapy until disease progression to determine disease free survival.
Time frame: Until disease progression up to 120 months
Population: One low-risk participant was lost to follow-up after 48 months of disease free survival.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low Risk | Disease Free Survival | 84 Months |
| High Risk | Disease Free Survival | 52 Months |