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

Sponsor

University Hospital Southampton NHS Foundation Trust (Other)

Overall Status

Unknown status

CT.gov ID

NCT00689845

Collaborator

(none)

120

Enrollment

Locations

Arms

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: bleomycin sulfate Biological: filgrastim Biological: rituximab Drug: cyclophosphamide Drug: cytarabine Drug: doxorubicin hydrochloride Drug: etoposide phosphate Drug: ifosfamide Drug: methotrexate Drug: prednisolone Drug: prednisone Drug: vincristine sulfate Drug: vindesine	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Primary Purpose:

Treatment

Official Title:

A Clinico-Pathologic Study of Primary Mediastinal B-Cell Lymphoma (IELSG 26)

Study Start Date :

Jun 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: rituximab given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: prednisolone Given orally Drug: vincristine sulfate Given IV
Experimental: 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.	Biological: filgrastim Given subcutaneously Biological: rituximab given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: prednisolone Given orally Drug: vincristine sulfate Given IV
Experimental: 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.	Biological: bleomycin sulfate Given IV Biological: rituximab given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: methotrexate Given IV Drug: prednisolone Given orally Drug: vincristine sulfate Given IV
Experimental: 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.	Biological: bleomycin sulfate Given IV Biological: rituximab given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide phosphate Given IV Drug: prednisolone Given orally Drug: vincristine sulfate Given IV
Experimental: 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.	Biological: bleomycin sulfate Given IV Biological: filgrastim Given subcutaneously Biological: rituximab given IV Drug: cyclophosphamide Given IV Drug: cytarabine Given subcutaneously Drug: doxorubicin hydrochloride Given IV Drug: etoposide phosphate Given IV Drug: ifosfamide Given IV Drug: methotrexate Given IV Drug: prednisone Given orally Drug: vindesine Given IV

Outcome Measures

Primary Outcome Measures

Complete response rate on PET scanning at the completion of chemoimmunotherapy []

Secondary Outcome Measures

Progression-free survival []
Death []
Survival time []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed primary mediastinal diffuse large B-cell lymphoma
CD20-positive disease
Any stage of disease
Must have a dominant mass within the anterior mediastinum

PATIENT CHARACTERISTICS:

ANC ≥ 1.5 x 10^9/L (unless due to lymphoma)
Platelets ≥ 100 x 10^9/L (unless due to lymphoma)
WBC ≥ 3.0 x 10^9/L (unless due to lymphoma)
Serum creatinine ≤ 2 times upper limit of normal (ULN) (unless due to lymphoma)
AST/ALT ≤ 2.5 times ULN (unless due to lymphoma)
Total bilirubin ≤ 2.5 times ULN (unless due to lymphoma)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Must be fit to receive chemotherapy with curative intent
No evidence of clinically significant cardiac disease* within the past 12 months, including any of the following:
Symptomatic ventricular arrhythmias
Congestive heart failure
Myocardial infarction NOTE: * Cardiac compromise due to local extension of lymphoma will not be an exclusion criterion in the absence of other cardiac disease.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
2	St. George's Hospital	London	England	United Kingdom	SW17 0QT
3	Christie Hospital	Manchester	England	United Kingdom	M20 4BX
4	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England	United Kingdom	HA6 2RN
5	Cancer Research Centre at Weston Park Hospital	Sheffield	England	United Kingdom	S1O 2SJ
6	Southampton General Hospital	Southampton	England	United Kingdom	SO16 6YD
7	Royal Marsden - Surrey	Sutton	England	United Kingdom	SM2 5PT
8	Saint Bartholomew's Hospital	London		United Kingdom