Intensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma

April 17, 2013 updated by: Ann S. LaCasce, MD, Dana-Farber Cancer Institute

Phase II Study of Intensive Chemotherapy and Rituximab in Burkitt Lymphoma

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • 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 Names:
  • Cytoxan
Drug: Doxorubicin
Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Cytoxan
Drug: Doxorubicin
Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Cytosar, Tarabine PFS
Drug: Ifosfamide
High Risk: After Regimen A, Ifosomide given on days 1-5 of a 5 day cycle
Other Names:
  • Ifex
Drug: Etoposide
High Risk: After Regimen A, etoposide given days 1-5 of a 5-day cycle
Other Names:
  • Vepesid
Drug: Mesna
High Risk: After regimen A, mesna is given on days 1-5 of a 5-day cycle
Other Names:
  • Mesnex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt
Time Frame: 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.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival
Time Frame: Until disease progression up to 120 months
Participants are followed after completion of protocol therapy until disease progression to determine disease free survival.
Until disease progression up to 120 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

Beth Israel Deaconess Medical Center
Brigham and Women's Hospital

Investigators

  • Principal Investigator: Ann S. La Casce, MD, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2005

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

August 2, 2005

First Submitted That Met QC Criteria

August 2, 2005

First Posted (Estimate)

August 3, 2005

Study Record Updates

Last Update Posted (Estimate)

May 23, 2013

Last Update Submitted That Met QC Criteria

April 17, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 04-336

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe