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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00689845
First received: June 3, 2008
Last updated: July 7, 2009
Last verified: July 2009
  Purpose

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 Intervention
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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Primary Purpose: Treatment
Official Title: A Clinico-Pathologic Study of Primary Mediastinal B-Cell Lymphoma (IELSG 26)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Complete response rate on PET scanning at the completion of chemoimmunotherapy [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]
  • Death [ Designated as safety issue: No ]
  • Survival time [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: June 2007
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00689845

Locations
United Kingdom
Leeds Cancer Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Contact Person    44-113-206-6400      
St. George's Hospital Recruiting
London, England, United Kingdom, SW17 0QT
Contact: Contact Person    44-208-725-2425    rpetteng@sghms.ac.uk   
Christie Hospital Recruiting
Manchester, England, United Kingdom, M20 4BX
Contact: Contact Person    44-845-226-3000      
Mount Vernon Cancer Centre at Mount Vernon Hospital Recruiting
Northwood, England, United Kingdom, HA6 2RN
Contact: Contact Person    44-1923-826-111      
Cancer Research Centre at Weston Park Hospital Recruiting
Sheffield, England, United Kingdom, S1O 2SJ
Contact: Contact Person    44-114-226-5007    b.w.hancock@sheffield.ac.uk   
Southampton General Hospital Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Contact Person    44-238-079-6186    johnsonp@soton.ac.uk   
Royal Marsden - Surrey Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Contact Person    44-208-661-3279    david.cunningham@rmh.nhs.uk   
Saint Bartholomew's Hospital Recruiting
London, United Kingdom
Contact: Contact Person    44-207-796-3979    silvia.montoto@cancer.org.uk   
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust.
Investigators
Principal Investigator: Peter Johnson, MD University Hospital Southampton NHS Foundation Trust.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00689845     History of Changes
Other Study ID Numbers: CDR0000588011, USCTU-IELSG-26-RHM-CAN0546, EU-20818, EudraCT 2006-005794-22, USCTU-07/Q1704/68
Study First Received: June 3, 2008
Last Updated: July 7, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Methotrexate
Cytarabine
Rituximab
Ifosfamide
Liposomal doxorubicin
Etoposide phosphate
Doxorubicin
Prednisone
Etoposide
Vincristine
Prednisolone
Methylprednisolone Hemisuccinate
Bleomycin
Vindesine
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate

ClinicalTrials.gov processed this record on September 18, 2014