Intensive Chemotherapy and Rituximab in the Treatment of Burkitt Lymphoma

NCT00126191 | Terminated Phase 2 Results DMC

• 1 other identifier: 04-336
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Burkitt Lymphoma; Non-Hodgkins Lymphoma; Atypical Burkitt Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Secondary Outcomes (1)

• Disease Free Survival

  Until disease progression up to 120 months

Study Arms (2)

Low Risk

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Methotrexate; Drug: Leucovorin; Drug: Cytarabine

High Risk

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Methotrexate; Drug: Leucovorin; Drug: Ifosfamide; Drug: Etoposide; Drug: Cytarabine; Drug: Mesna

Interventions

Rituximab DRUG

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

Also known as: Rituxan

High Risk; Low Risk

Cyclophosphamide DRUG

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

Also known as: Cytoxan

High Risk; Low Risk

Doxorubicin DRUG

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

Also known as: Adriamycin, Rubex

High Risk; Low Risk

Vincristine DRUG

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

Also known as: Oncovin, vincristine sulfate

High Risk; Low Risk

Methotrexate DRUG

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

Also known as: Rheumatrex, Trexall

High Risk; Low Risk

Leucovorin DRUG

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

Also known as: Folinic acid

High Risk; Low Risk

Ifosfamide DRUG

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

Also known as: Ifex

High Risk

Etoposide DRUG

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

Also known as: Vepesid

High Risk

Cytarabine DRUG

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

Also known as: Cytosar, Tarabine PFS

High Risk; Low Risk

Mesna DRUG

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

Also known as: Mesnex

High Risk

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Beth Israel Deaconess Medical Center: collaborator
• Brigham and Women's Hospital: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, Non-Hodgkin

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Methotrexate; Leucovorin; Ifosfamide; Etoposide; Cytarabine; Mesna

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Aminopterin; Pterins; Pteridines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes; Oxazines; Heterocyclic Compounds, 1-Ring; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Ann LaCasce, MD
• Organization: DFCI

ALACASCE@PARTNERS.ORG

617-632-5959

Study Officials

• Ann S. La Casce, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: August 2, 2005
• First Posted: August 3, 2005
• Study Start: July 1, 2005
• Primary Completion: December 1, 2009
• Study Completion: June 1, 2011
• Last Updated: May 23, 2013
• Results First Posted: May 23, 2013

Record last verified: 2013-04

Locations

US (2)