Combination Chemotherapy and Rituximab in Treating Patients With Primary Mediastinal Diffuse Large B-Cell Lymphoma

NCT ID: NCT00689845

Last Updated: 2009-07-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving rituximab together with one of five different combination chemotherapy regimens may kill more cancer cells.

PURPOSE: This clinical trial is studying giving rituximab together with combination chemotherapy to see how well it works in treating patients with primary mediastinal diffuse large B-cell lymphoma.

Detailed Description

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OBJECTIVES:

Primary

* To systematically analyze the phenotype and molecular characteristics in patients with primary mediastinal diffuse large B-cell lymphoma.
* To determine the PET response rate following chemoimmunotherapy in these patients.

Secondary

* To obtain data, on a nonrandomized basis, regarding the outcomes of treatment using different chemoimmunotherapy regimens and using or omitting mediastinal radiotherapy, depending upon the practice of the participating institutions.
* To analyze progression-free and overall survival in patients treated with these regimens.

OUTLINE: This is a multicenter study.

Patients receive any one of the following standard chemoimmunotherapy regimens.

* Cohort 1 (R-CHOP-21): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
* Cohort 2 (R-CHOP-14): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, oral prednisolone on days 1-5, and filgrastim (G-CSF) subcutaneously (SC) on days 5-12. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
* Cohort 3 (R-MACOP-B): Patients receive rituximab IV on days 1, 22, 43, 64, 85, and 106; cyclophosphamide IV and doxorubicin hydrochloride IV on days 1, 15, 29, 43, 57, and 71; methotrexate IV on days 8, 36, and 64; vincristine IV on days 8, 22, 36, 50 ,64, and 78; bleomycin IV on days 22, 50, and 78; and oral prednisolone on days 1-84, followed by a taper.
* Cohort 4 (R-VACOP-B): Patients receive rituximab IV on days 1, 22, 43, 64, 85, and 106; cyclophosphamide IV on days 1, 29, and 57; doxorubicin hydrochloride IV on days 1, 15, 29, 43, 57, and 71; etoposide phosphate IV on days 15, 16, 43, 44, 71, and 72; vincristine IV and bleomycin IV on days 8, 22, 36, 50, 64, and 78; and oral prednisolone on days 1-84, followed by a taper.
* Cohort 5 (R-ACVBP): Patients receive rituximab IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1; vindesine IV and bleomycin IV on days 1 and 5; oral prednisone on days 1-5; methotrexate intrathecally on day 2; and G-CSF SC on days 6-13 for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of 4 courses of R-ACVBP, patients receive consolidation therapy comprising high-dose methotrexate IV, rituximab IV, ifosfamide IV, etoposide phosphate IV, and cytarabine SC according to protocol GELA LNH03-2B.

Patients with an International Prognostic Index score of 4 or greater or disease in close proximity to the spinal cord or cerebral meninges may receive prophylactic treatment to the CNS according to local protocol.

Beginning 8 weeks after completion of chemoimmunotherapy, patients undergo radiotherapy to the original tumor volume according to local protocol.

Fresh or fixed tissue from prior biopsy is obtained if possible. Samples are analyzed for CD3, CD20, CD30, CD15, CD10, Bcl-6, Bcl-2, MAL protein (if available), and Ki-67 via immunohistochemistry.

After completion of study treatment, patients are followed periodically.

Conditions

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Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Primary Study Purpose

TREATMENT

Study Groups

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Cohort 1

Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1. Patients also receive oral prednisolone on days 1-5. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

given IV

cyclophosphamide

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

prednisolone

Intervention Type DRUG

Given orally

vincristine sulfate

Intervention Type DRUG

Given IV

Cohort 2

Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, oral prednisolone on days 1-5, and filgrastim (G-CSF) subcutaneously (SC) on days 5-12. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Given subcutaneously

rituximab

Intervention Type BIOLOGICAL

given IV

cyclophosphamide

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

prednisolone

Intervention Type DRUG

Given orally

vincristine sulfate

Intervention Type DRUG

Given IV

Cohort 3

Patients receive rituximab IV on days 1, 22, 43, 64, 85, and 106; cyclophosphamide IV and doxorubicin hydrochloride IV on days 1, 15, 29, 43, 57, and 71; methotrexate IV on days 8, 36, and 64; vincristine IV on days 8, 22, 36, 50 ,64, and 78; bleomycin IV on days 22, 50, and 78; and oral prednisolone on days 1-84, followed by a taper.

Group Type EXPERIMENTAL

bleomycin sulfate

Intervention Type BIOLOGICAL

Given IV

rituximab

Intervention Type BIOLOGICAL

given IV

cyclophosphamide

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

methotrexate

Intervention Type DRUG

Given IV

prednisolone

Intervention Type DRUG

Given orally

vincristine sulfate

Intervention Type DRUG

Given IV

Cohort 4

Patients receive rituximab IV on days 1, 22, 43, 64, 85, and 106; cyclophosphamide IV on days 1, 29, and 57; doxorubicin hydrochloride IV on days 1, 15, 29, 43, 57, and 71; etoposide phosphate IV on days 15, 16, 43, 44, 71, and 72; vincristine IV and bleomycin IV on days 8, 22, 36, 50, 64, and 78; and oral prednisolone on days 1-84, followed by a taper.

Group Type EXPERIMENTAL

bleomycin sulfate

Intervention Type BIOLOGICAL

Given IV

rituximab

Intervention Type BIOLOGICAL

given IV

cyclophosphamide

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

etoposide phosphate

Intervention Type DRUG

Given IV

prednisolone

Intervention Type DRUG

Given orally

vincristine sulfate

Intervention Type DRUG

Given IV

Cohort 5

Patients receive rituximab IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1; vindesine IV and bleomycin IV on days 1 and 5; oral prednisone on days 1-5; methotrexate intrathecally on day 2; and G-CSF SC on days 6-13 for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of 4 courses of R-ACVBP, patients receive consolidation therapy comprising high-dose methotrexate IV, rituximab IV, ifosfamide IV, etoposide phosphate IV, and cytarabine SC according to protocol GELA LNH03-2B.

Group Type EXPERIMENTAL

bleomycin sulfate

Intervention Type BIOLOGICAL

Given IV

filgrastim

Intervention Type BIOLOGICAL

Given subcutaneously

rituximab

Intervention Type BIOLOGICAL

given IV

cyclophosphamide

Intervention Type DRUG

Given IV

cytarabine

Intervention Type DRUG

Given subcutaneously

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

etoposide phosphate

Intervention Type DRUG

Given IV

ifosfamide

Intervention Type DRUG

Given IV

methotrexate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given orally

vindesine

Intervention Type DRUG

Given IV

Interventions

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bleomycin sulfate

Given IV

Intervention Type BIOLOGICAL

filgrastim

Given subcutaneously

Intervention Type BIOLOGICAL

rituximab

given IV

Intervention Type BIOLOGICAL

cyclophosphamide

Given IV

Intervention Type DRUG

cytarabine

Given subcutaneously

Intervention Type DRUG

doxorubicin hydrochloride

Given IV

Intervention Type DRUG

etoposide phosphate

Given IV

Intervention Type DRUG

ifosfamide

Given IV

Intervention Type DRUG

methotrexate

Given IV

Intervention Type DRUG

prednisolone

Given orally

Intervention Type DRUG

prednisone

Given orally

Intervention Type DRUG

vincristine sulfate

Given IV

Intervention Type DRUG

vindesine

Given IV

Intervention Type DRUG

Eligibility Criteria

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Exclusion Criteria

* No known HIV infection
* No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Able and willing to give informed consent and to undergo staging, including PET scanning

PRIOR CONCURRENT THERAPY:

* No prior treatment for lymphoma
* Prior corticosteroids for up to 1 week allowed for the relief of local compressive symptoms
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role lead

Principal Investigators

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Peter Johnson, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Southampton NHS Foundation Trust

Locations

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Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Site Status RECRUITING

St. George's Hospital

London, England, United Kingdom

Site Status RECRUITING

Christie Hospital

Manchester, England, United Kingdom

Site Status RECRUITING

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, United Kingdom

Site Status RECRUITING

Cancer Research Centre at Weston Park Hospital

Sheffield, England, United Kingdom

Site Status RECRUITING

Southampton General Hospital

Southampton, England, United Kingdom

Site Status RECRUITING

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status RECRUITING

Saint Bartholomew's Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Facility Contacts

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Contact Person

Role: primary

44-113-206-6400

Contact Person

Role: primary

44-208-725-2425

Contact Person

Role: primary

44-845-226-3000

Contact Person

Role: primary

44-1923-826-111

Contact Person

Role: primary

44-114-226-5007

Contact Person

Role: primary

44-238-079-6186

Contact Person

Role: primary

44-208-661-3279

Contact Person

Role: primary

44-207-796-3979

Other Identifiers

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USCTU-IELSG-26-RHM-CAN0546

Identifier Type: -

Identifier Source: secondary_id

EU-20818

Identifier Type: -

Identifier Source: secondary_id

EudraCT 2006-005794-22

Identifier Type: -

Identifier Source: secondary_id

USCTU-07/Q1704/68

Identifier Type: -

Identifier Source: secondary_id

CDR0000588011

Identifier Type: -

Identifier Source: org_study_id

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