Intensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma

This study has been terminated.
(closed due to slow accrual)
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Information provided by (Responsible Party):
Ann S. LaCasce, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00126191
First received: August 2, 2005
Last updated: April 17, 2013
Last verified: April 2013
  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 2

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:
  • Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt [ Time Frame: 3 years ] [ Designated as safety issue: No ]

    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 [ Time Frame: Until disease progression up to 120 months ] [ Designated as safety issue: No ]
    Participants are followed after completion of protocol therapy until disease progression to determine disease free survival.


Enrollment: 10
Study Start Date: July 2005
Study Completion Date: June 2011
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Rituxan
Drug: Cyclophosphamide
Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A)
Other Name: Cytoxan
Drug: Doxorubicin
Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)
Other Name: Adriamycin, Rubex
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 Name: Oncovin, vincristine sulfate
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 Name: Rheumatrex, Trexall
Drug: Leucovorin
Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A)
Other Name: Folinic acid
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 Name: Cytosar, Tarabine PFS
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 Name: Rituxan
Drug: Cyclophosphamide
Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A)
Other Name: Cytoxan
Drug: Doxorubicin
Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)
Other Name: Adriamycin, Rubex
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 Name: Oncovin, vincristine sulfate
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 Name: Rheumatrex, Trexall
Drug: Leucovorin
Low Risk/High Risk: Given on days 11, 12 and 13 of a 14-day cycle for 3 cycles (regimen A)
Other Name: Folinic acid
Drug: Ifosfamide
High Risk: After Regimen A, Ifosomide given on days 1-5 of a 5 day cycle
Other Name: Ifex
Drug: Etoposide
High Risk: After Regimen A, etoposide given days 1-5 of a 5-day cycle
Other Name: Vepesid
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 Name: Cytosar, Tarabine PFS
Drug: Mesna
High Risk: After regimen A, mesna is given on days 1-5 of a 5-day cycle
Other Name: Mesnex

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 S. LaCasce, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00126191     History of Changes
Other Study ID Numbers: 04-336
Study First Received: August 2, 2005
Results First Received: November 30, 2012
Last Updated: April 17, 2013
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 April 17, 2014