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

NCT00689845 | Unknown

• 5 other identifiers: CDR0000588011USCTU-IELSG-26-RHM-CAN0546EU-20818EudraCT 2006-005794-22USCTU-07/Q1704/68
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 8

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.

Conditions

Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Complete response rate on PET scanning at the completion of chemoimmunotherapy

Secondary Outcomes (3)

• Progression-free survival

• Death

• Survival time

Study Arms (5)

Cohort 1

EXPERIMENTAL

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; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisolone; Drug: vincristine sulfate

Cohort 2

EXPERIMENTAL

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; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisolone; Drug: vincristine sulfate

Cohort 3

EXPERIMENTAL

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; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: methotrexate; Drug: prednisolone; Drug: vincristine sulfate

Cohort 4

EXPERIMENTAL

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; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide phosphate; Drug: prednisolone; Drug: vincristine sulfate

Cohort 5

EXPERIMENTAL

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; Biological: filgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: cytarabine; Drug: doxorubicin hydrochloride; Drug: etoposide phosphate; Drug: ifosfamide; Drug: methotrexate; Drug: prednisone; Drug: vindesine

Interventions

bleomycin sulfate BIOLOGICAL

Given IV

Cohort 3; Cohort 4; Cohort 5

filgrastim BIOLOGICAL

Given subcutaneously

Cohort 2; Cohort 5

rituximab BIOLOGICAL

given IV

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

cyclophosphamide DRUG

Given IV

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

cytarabine DRUG

Given subcutaneously

Cohort 5

doxorubicin hydrochloride DRUG

Given IV

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

etoposide phosphate DRUG

Given IV

Cohort 4; Cohort 5

ifosfamide DRUG

Given IV

Cohort 5

methotrexate DRUG

Given IV

Cohort 3; Cohort 5

prednisolone DRUG

Given orally

Cohort 1; Cohort 2; Cohort 3; Cohort 4

prednisone DRUG

Given orally

Cohort 5

vincristine sulfate DRUG

Given IV

Cohort 1; Cohort 2; Cohort 3; Cohort 4

vindesine DRUG

Given IV

Cohort 5

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead

Study Sites (8)

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

RECRUITING

St. George's Hospital

London, England, SW17 0QT, United Kingdom

RECRUITING

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

RECRUITING

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, HA6 2RN, United Kingdom

RECRUITING

Cancer Research Centre at Weston Park Hospital

Sheffield, England, S1O 2SJ, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

RECRUITING

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

RECRUITING

Saint Bartholomew's Hospital

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Bleomycin; Filgrastim; Rituximab; Cyclophosphamide; Cytarabine; Doxorubicin; etoposide phosphate; Ifosfamide; Methotrexate; Prednisolone; Prednisone; Vincristine; Vindesine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Oxazines; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Peter Johnson, MD

  University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 3, 2008
• First Posted: June 4, 2008
• Study Start: June 1, 2007
• Last Updated: July 8, 2009

Record last verified: 2009-07

Locations

GB (8)