Intensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
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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".
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If the patient has "low risk" disease their treatment cycle consist of three cycles of
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If the patient has "high risk" disease they will receive Cycle A followed by cycle B which will then repeat.
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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.
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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.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Low Risk Low-risk patients receive 3 cycles of regimen A. Regimen A: Rituximab (375 mg/m^2) on Days 1 and 3. Cyclophosphamide (800 mg/m^2) on days 1 and 2. Vincristine (1.4 mg/m^2) on days 1 and 10. Doxorubicin (50 mg/m^2) on Day 1. Methotrexate (3000 mg/m^2) on Day 10. Intrathecal Cytarabine (50mg) will be given on Day 1 and intrathecal methotrexate (12mg) will be given on Days 1 and 10. Leucovorin on days 11 and 12. Rituximab is given on Days 1 and 3 in cycle 1, and on Day 1 of all other cycles. |
Drug: Rituximab
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
Other Names:
Drug: Cyclophosphamide
Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
Drug: Doxorubicin
Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
Drug: Vincristine
Low Risk/High Risk: Given intravenously on day 1 and day 10 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
Drug: Methotrexate
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
Other Names:
Drug: Leucovorin
Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
Drug: Cytarabine
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
Other Names:
|
| Experimental: High Risk High-risk patients receive 4 alternating cycles of regimens A and B (A-B-A-B). Regimen A (as described earlier). Regimen B: Rituximab (375mg/m^2) on Day 1. Ifosfamide (1500mg/m^2) on Days 1-5. Mesna (275 mg/m^2) on Days 1-5. Etoposide (60mg/mg^2) on Days 1-5. Cytarabine (2 gm/m^2) twice a day on Days 1 and 2. Intrathecal methotrexate (12mg) on Day 5, and intrathecal methotrexate (50mg) on Day 3 (also on Day 1 for patients with central nervous system involvement). |
Drug: Rituximab
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
Other Names:
Drug: Cyclophosphamide
Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
Drug: Doxorubicin
Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
Drug: Vincristine
Low Risk/High Risk: Given intravenously on day 1 and day 10 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
Drug: Methotrexate
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
Other Names:
Drug: Leucovorin
Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
Drug: Ifosfamide
High Risk: After Regimen A, Ifosomide given on days 1-5 of a 5 day cycle
Other Names:
Drug: Etoposide
High Risk: After Regimen A, etoposide given days 1-5 of a 5-day cycle
Other Names:
Drug: Cytarabine
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
Other Names:
Drug: Mesna
High Risk: After regimen A, mesna is given on days 1-5 of a 5-day cycle
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically documented Burkitt or atypical Burkitt according to World Health Organization (WHO) criteria.
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Pathology must be reviewed at the Brigham and Women's Hospital (BWH).
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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.
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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.
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Age > 18
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Laboratory data (within 2 weeks of study registration):
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ANC > 1500/ul;
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platelet > 100,000/ul;
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creatinine < 1.5 X normal;
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creatinine clearance > 60 ml/min;
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bilirubin < 1.5 X normal;
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AST and ALT < 2.5 X normal;
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alkaline phosphates < 3 X normal;
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HIV negative;
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cardiac ejection fraction > 50%.
Exclusion Criteria:
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Previous chemotherapy or radiation therapy. Steroids of less than 72 hours duration for impending oncologic emergency are allowed.
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Uncontrolled bacterial, fungal, or viral infection.
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Concomitant malignancy excluding carcinoma in situ of the cervix and basal cell carcinoma of the skin.
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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%.
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Pregnancy. All males and females with reproductive potential must consent to use an effective form of contraception while on study.
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Major surgery within the previous 2 weeks.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 2 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- Dana-Farber Cancer Institute
- Beth Israel Deaconess Medical Center
- Brigham and Women's Hospital
Investigators
- Principal Investigator: Ann S. La Casce, MD, Dana-Farber Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 04-336
Study Results
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 Detail | 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. |
| Arm/Group Title | Low Risk | High Risk |
|---|---|---|
| Arm/Group Description | 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). | Regimen A followed by Regimen B. Cycles A and B will then be repeated (ABAB). |
| Period Title: Overall Study | ||
| STARTED | 2 | 8 |
| COMPLETED | 2 | 6 |
| NOT COMPLETED | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | Low Risk | High Risk | Total |
|---|---|---|---|
| Arm/Group Description | 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). | Regimen A followed by Regimen B. Cycles A and B will then be repeated (ABAB). | Total of all reporting groups |
| Overall Participants | 2 | 8 | 10 |
| Age (Count of Participants) | |||
| <=18 years |
1
50%
|
0
0%
|
1
10%
|
| Between 18 and 65 years |
1
50%
|
8
100%
|
9
90%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (Count of Participants) | |||
| <=18 years |
1
50%
|
0
0%
|
1
10%
|
| Between 18 and 65 years |
1
50%
|
8
100%
|
9
90%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
1
12.5%
|
1
10%
|
| Male |
2
100%
|
7
87.5%
|
9
90%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
2
100%
|
8
100%
|
10
100%
|
Outcome Measures
| Title | Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Low Risk | High Risk |
|---|---|---|
| Arm/Group Description | 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). | Regimen A followed by Regimen B. Cycles A and B will then be repeated (ABAB). |
| Measure Participants | 2 | 8 |
| Number [participants] |
2
100%
|
7
87.5%
|
| Title | Disease Free Survival |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| One low-risk participant was lost to follow-up after 48 months of disease free survival. |
| Arm/Group Title | Low Risk | High Risk |
|---|---|---|
| Arm/Group Description | 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). | Regimen A followed by Regimen B. Cycles A and B will then be repeated (ABAB). |
| Measure Participants | 1 | 8 |
| Mean (Full Range) [Months] |
84
|
52
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | Grade 4 hematologic toxicities were not considered to be serious adverse events in this Burkitts Lymphoma study. Hospitalization without accompanying SAE did not constitute SAE for this study. | |||
| Arm/Group Title | Low Risk | High Risk | ||
| Arm/Group Description | 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). | Regimen A followed by Regimen B. Cycles A and B will then be repeated (ABAB). | ||
All Cause Mortality |
||||
| Low Risk | High Risk | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Low Risk | High Risk | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/2 (50%) | 2/8 (25%) | ||
| Endocrine disorders | ||||
| Hyperuricemia | 1/2 (50%) | 1 | 1/8 (12.5%) | 1 |
| General disorders | ||||
| Fatigue | 1/2 (50%) | 1 | 1/8 (12.5%) | 1 |
| Metabolism and nutrition disorders | ||||
| Bilirubin | 1/2 (50%) | 1 | 1/8 (12.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Low Risk | High Risk | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | 0/8 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Ann LaCasce, MD |
|---|---|
| Organization | DFCI |
| Phone | 617-632-5959 |
| ALACASCE@PARTNERS.ORG |
- 04-336