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Rituximab, Combination Chemotherapy, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Stage I or Stage II Non-Hodgkin's Lymphoma

This study has been terminated.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: August 4, 2004
Last updated: July 15, 2013
Last verified: July 2013

August 4, 2004
July 15, 2013
December 2004
March 2009   (final data collection date for primary outcome measure)
  • Complete response rate (CR/CRu) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Functional CR rate [ Time Frame: From the documented beginning of response to time of relapse, assessed up to 10 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00088881 on Archive Site
  • Time to treatment failure (TTF) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated by Kaplan-Meier method.
  • Overall survival (OS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated by Kaplan-Meier method.
  • Duration of response [ Time Frame: From the documented beginning of response (CR, CRu or PR) to the time of relapse, assessed up to 10 years ] [ Designated as safety issue: No ]
    Estimated by Kaplan-Meier method.
  • Toxicity as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
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Rituximab, Combination Chemotherapy, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Stage I or Stage II Non-Hodgkin's Lymphoma
A Phase II Trial of R-CHOP Followed by Zevalin Radioimmunotherapy for Patients With Previously Untreated Stages I and II CD20+ Diffuse Large Cell Non-Hodgkin's Lymphoma

This phase II trial is studying how well giving rituximab together with combination chemotherapy and yttrium Y 90 ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining a monoclonal antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more cancer cells.


I. To evaluate the complete response rate (CR) and functional CR rate (CR or Cru/PR and PET negative) in patients with previously untreated stage I (with at least 1 risk factor) or stage II CD20+ diffuse large cell lymphoma who receive therapy with RCHOP followed by 90Y -Zevalin™.


I. To evaluate the time to treatment failure, duration of response, and overall survival in these patients who receive therapy with R-CHOP followed by 90Y -Zevalin™.

II. To evaluate the toxicity of this therapy. III. To evaluate the toxicity of adding involved field radiation therapy > 12 weeks after Zevalin™ for patients with CT+/PET+ residual masses.


I. To evaluate PET scans pre -and post - R-CHOP/Zevalin™ therapy.


Monoclonal antibody (MOAB) therapy/chemotherapy: Patients receive oral prednisone once daily on days 1-5. Patients also receive rituximab IV over several hours followed by cyclophosphamide IV, doxorubicin IV, and vincristine IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) after 2 courses receive 2 additional courses. Patients achieving a partial response, uncertain CR, or stable disease receive 4 additional courses. Patients are evaluated 3 weeks after the last course of therapy. Patients with progressive disease go off study.

MOAB therapy/radioimmunotherapy: Beginning no more than 9 weeks after the last course of MOAB therapy and chemotherapy, patients receive rituximab IV on day 1 followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8.

Radiotherapy: Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually for 5 years.

Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Contiguous Stage II Adult Diffuse Large Cell Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Stage I Adult Diffuse Large Cell Lymphoma
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
  • Biological: rituximab
    Given IV
    Other Names:
    • IDEC-C2B8
    • IDEC-C2B8 monoclonal antibody
    • Mabthera
    • MOAB IDEC-C2B8
    • Rituxan
  • Drug: prednisone
    Given orally
    Other Names:
    • DeCortin
    • Deltra
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Radiation: indium In 111 ibritumomab tiuxetan
    Given IV
    Other Name: IDEC-In2B8
  • Radiation: radiation therapy
    Undergo radiotherapy
    Other Names:
    • irradiation
    • radiotherapy
    • therapy, radiation
  • Procedure: positron emission tomography
    Undergo PET scans
    Other Names:
    • FDG-PET
    • PET
    • PET scan
    • tomography, emission computed
Experimental: Treatment (rituximab, chemotherapy, radiotherapy)
See Detailed Description.
  • Biological: rituximab
  • Drug: prednisone
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: vincristine sulfate
  • Radiation: indium In 111 ibritumomab tiuxetan
  • Radiation: radiation therapy
  • Procedure: positron emission tomography
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
March 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have histologically confirmed diagnosis of diffuse large cell lymphoma
  • Patients must be stage I or II (Modified Ann Arbor staging)
  • Baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging; patients must have at least one objective measurable disease parameter (a lesion with at least 1 dimension > 1.5 cm); or if they are stage 1
  • Stage I patients must have at least one of the following risk factors:

    • Age >= 60 years
    • Bulky disease (>= 5 cm in at least one dimension)
    • Elevated LDH above institutional upper limit of normal
    • ECOG performance status = 2
  • Patients must not have had prior chemotherapy, radiation therapy, radioimmunotherapy, or immunotherapy; a short course (=< 14 days prior to registration) of corticosteroids is allowed
  • ECOG performance status 0-2
  • Absolute neutrophil count >= 1500/mm^3 (includes neutrophils and bands)
  • Platelet count >= 100,000/mm^3
  • Creatinine < 2.0 mg/dl
  • Total bilirubin < 2 mg/dl (may be up to 3.0 mg/dl if due to liver involvement by lymphoma); patients with elevated total bilirubin should have a direct bilirubin checked; if the direct bilirubin is normal there is no need for a dose reduction
  • Patients must have no evidence of other malignancy

    • No prior chemotherapy or prior radiation therapy for other malignancies
    • Not currently receiving hormone therapy or chemotherapy for another malignancy even if the treatment is being provided in the adjuvant treatment setting, i.e. with no evidence of the original other malignancy
    • Adjuvant hormonal therapy must have been discontinued > 3 months before entering this study
    • Patients are eligible if they meet the following conditions: (a) treated carcinoma-in-situ of the cervix; (b) treated squamous cell or basal cell skin cancer; or (c) any other surgically cured malignancy from which the patient has been disease free for at least 3 years
  • Female patients must not be pregnant or breast feeding, as there would be radiation exposure to the fetus or child; a negative pregnancy test is required =< 1 week prior to registration for women of childbearing potential (WOCBP)
  • Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
  • Patients must not have known CNS lymphoma, testicular lymphoma, or vitreous lymphoma
  • Patients must have no known HIV infection. The safety of Zevalin™ in this population has not been tested at this time
  • Patients must not have a serious coexisting medical condition or active infection which would compromise the ability to deliver standard R-CHOP chemotherapy
  • Patients must have LV ejection fraction of > 45%
  • No evidence of myelodysplasia on bone marrow aspiration and biopsy
  • Patients must be tested for hepatitis B surface antigen within 2 weeks of registration

    • NOTE: Patients who test positive will be allowed to participate but must be followed closely for clinical and laboratory signs of active HBV infection and for signs of hepatitis
18 Years and older
Contact information is only displayed when the study is recruiting subjects
United States
NCI-2012-02957, E3402, ECOG-E3402, U10CA021115
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Thomas Witzig Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP