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Intensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma

Primary Purpose

Burkitt Lymphoma, Non-Hodgkins Lymphoma, Atypical Burkitt Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine
Methotrexate
Leucovorin
Ifosfamide
Etoposide
Cytarabine
Mesna
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Burkitt Lymphoma focused on measuring Burkitt Lymphoma, atypical Burkitt lymphoma, Non-Hodgkin's Lymphoma, rituximab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Dana-Farber Cancer Institute
  • Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Low Risk

High Risk

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Disease Free Survival
Participants are followed after completion of protocol therapy until disease progression to determine disease free survival.

Full Information

First Posted
August 2, 2005
Last Updated
April 17, 2013
Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00126191
Brief Title
Intensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma
Official Title
Phase II Study of Intensive Chemotherapy and Rituximab in Burkitt Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Terminated
Why Stopped
closed due to slow accrual
Study Start Date
July 2005 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Brigham and Women's Hospital

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Burkitt Lymphoma, Non-Hodgkins Lymphoma, Atypical Burkitt Lymphoma
Keywords
Burkitt Lymphoma, atypical Burkitt lymphoma, Non-Hodgkin's Lymphoma, rituximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low Risk
Arm Type
Experimental
Arm Description
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.
Arm Title
High Risk
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A)
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin, Rubex
Intervention Description
Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovin, vincristine sulfate
Intervention Description
Low Risk/High Risk: Given intravenously on day 1 and day 10 of a 14-day cycle for 3 cycles (regimen A)
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Rheumatrex, Trexall
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Folinic acid
Intervention Description
Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A)
Intervention Type
Drug
Intervention Name(s)
Ifosfamide
Other Intervention Name(s)
Ifex
Intervention Description
High Risk: After Regimen A, Ifosomide given on days 1-5 of a 5 day cycle
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Vepesid
Intervention Description
High Risk: After Regimen A, etoposide given days 1-5 of a 5-day cycle
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Cytosar, Tarabine PFS
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Mesnex
Intervention Description
High Risk: After regimen A, mesna is given on days 1-5 of a 5-day cycle
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann S. La Casce, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Intensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma

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