Intensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma - Full Text View

Sponsor:	Dana-Farber Cancer Institute
Collaborators:	Beth Israel Deaconess Medical Center Brigham and Women's Hospital
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00126191

Purpose

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	Intervention	Phase
Burkitt Lymphoma Non-Hodgkins Lymphoma Atypical Burkitt Lymphoma	Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Methotrexate Drug: Leucovorin Drug: Ifosfamide Drug: Etoposide Drug: Cytarabine Drug: Mesna	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Study of Intensive Chemotherapy and Rituximab in Burkitt Lymphoma

Resource links provided by NLM:

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

To evaluate the response rates in adults with Burkitt/atypical Burkitt [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the disease-free survival of adults with Burkitt/atypical Burkitt [ Time Frame: 4 years ] [ Designated as safety issue: No ]
To assess the safety of the treatment [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	July 2005
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Low Risk Regimen A	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 Drug: Cyclophosphamide Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A) Drug: Doxorubicin Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A) Drug: Vincristine Low Risk/High Risk: Given intravenously on day 1 and day 10 of a 14-day cycle for 3 cycles (regimen A) 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 Drug: Leucovorin Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A) 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
Experimental: High Risk Regimen A followed by Regimen B	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 Drug: Cyclophosphamide Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A) Drug: Doxorubicin Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A) Drug: Vincristine Low Risk/High Risk: Given intravenously on day 1 and day 10 of a 14-day cycle for 3 cycles (regimen A) 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 Drug: Leucovorin Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A) Drug: Ifosfamide High Risk: After Regimen A, Ifosomide given on days 1-5 of a 5 day cycle Drug: Etoposide High Risk: After Regimen A, etoposide given days 1-5 of a 5-day cycle 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 Drug: Mesna High Risk: After regimen A, mesna is given on days 1-5 of a 5-day cycle

Arms

Assigned Interventions

Experimental: Low Risk

Regimen A

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

Drug: Cyclophosphamide

Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A)

Drug: Doxorubicin

Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)

Drug: Vincristine

Low Risk/High Risk: Given intravenously on day 1 and day 10 of a 14-day cycle for 3 cycles (regimen A)

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

Drug: Leucovorin

Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A)

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

Experimental: High Risk

Regimen A followed by Regimen B

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

Drug: Cyclophosphamide

Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A)

Drug: Doxorubicin

Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)

Drug: Vincristine

Low Risk/High Risk: Given intravenously on day 1 and day 10 of a 14-day cycle for 3 cycles (regimen A)

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

Drug: Leucovorin

Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A)

Drug: Ifosfamide

High Risk: After Regimen A, Ifosomide given on days 1-5 of a 5 day cycle

Drug: Etoposide

High Risk: After Regimen A, etoposide given days 1-5 of a 5-day cycle

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

Drug: Mesna

High Risk: After regimen A, mesna is given on days 1-5 of a 5-day cycle

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00126191

Locations

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
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

More Information

No publications provided

Responsible Party:	Ann LaCasce, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00126191 History of Changes
Other Study ID Numbers:	04-336
Study First Received:	August 2, 2005
Last Updated:	October 2, 2009
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

Burkitt Lymphoma
atypical Burkitt lymphoma
Non-Hodgkin's Lymphoma
rituximab

Additional relevant MeSH terms:

Burkitt Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms
Lymphoma, B-Cell
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders

Immune System Diseases
Mesna
Levoleucovorin
Cyclophosphamide
Cytarabine
Methotrexate
Rituximab
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Doxorubicin
Etoposide
Vincristine
Leucovorin
Protective Agents

ClinicalTrials.gov processed this record on February 09, 2012