Intensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma

Overview[ - collapse ][ - ]

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.
ConditionBurkitt Lymphoma
Non-Hodgkins Lymphoma
Atypical Burkitt Lymphoma
InterventionDrug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Methotrexate
Drug: Leucovorin
Drug: Ifosfamide
Drug: Etoposide
Drug: Cytarabine
Drug: Mesna
PhasePhase 2
SponsorDana-Farber Cancer Institute
Responsible PartyDana-Farber Cancer Institute
ClinicalTrials.gov IdentifierNCT00126191
First ReceivedAugust 2, 2005
Last UpdatedApril 17, 2013
Last verifiedApril 2013

Tracking Information[ + expand ][ + ]

First Received DateAugust 2, 2005
Last Updated DateApril 17, 2013
Start DateJuly 2005
Estimated Primary Completion DateJune 2011
Current Primary Outcome MeasuresResponse 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.
Current Secondary Outcome MeasuresDisease 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.

Descriptive Information[ + expand ][ + ]

Brief TitleIntensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma
Official TitlePhase II Study of Intensive Chemotherapy and Rituximab in Burkitt Lymphoma
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.
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Burkitt Lymphoma
  • Non-Hodgkins Lymphoma
  • Atypical Burkitt Lymphoma
InterventionDrug: 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:
RituxanDrug: Cyclophosphamide
Low Risk/High Risk: Intravenously on day 1 and day 2 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
CytoxanDrug: Doxorubicin
Low Risk/High Risk: Given on day 1 of a 14-day cycle for 3 cycles (regimen A)
Other Names:
Adriamycin, RubexDrug: 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 sulfateDrug: 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, TrexallDrug: 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 acidDrug: Ifosfamide
High Risk: After Regimen A, Ifosomide given on days 1-5 of a 5 day cycle
Other Names:
IfexDrug: Etoposide
High Risk: After Regimen A, etoposide given days 1-5 of a 5-day cycle
Other Names:
VepesidDrug: 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 PFSDrug: Mesna
High Risk: After regimen A, mesna is given on days 1-5 of a 5-day cycle
Other Names:
Mesnex
Study Arm (s)
  • 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.
  • 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).

Recruitment Information[ + expand ][ + ]

Recruitment StatusTerminated
Estimated Enrollment10
Estimated Completion DateJune 2011
Estimated Primary Completion DateDecember 2009
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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00126191
Other Study ID Numbers04-336
Has Data Monitoring CommitteeYes
Information Provided ByDana-Farber Cancer Institute
Study SponsorDana-Farber Cancer Institute
CollaboratorsBeth Israel Deaconess Medical Center
Brigham and Women's Hospital
Investigators Principal Investigator: Ann S. La Casce, MD Dana-Farber Cancer Institute
Verification DateApril 2013

Locations[ + expand ][ + ]

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