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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.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00088881
First received: August 4, 2004
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: prednisone
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Radiation: indium In 111 ibritumomab tiuxetan
Radiation: radiation therapy
Procedure: positron emission tomography
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 62
Study Start Date: December 2004
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (rituximab, chemotherapy, radiotherapy)
See Detailed Description.
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

Detailed Description:

PRIMARY OBJECTIVES:

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™.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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

OUTLINE:

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.

  Eligibility

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

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
  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: NCT00088881

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas Witzig Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00088881     History of Changes
Other Study ID Numbers: NCI-2012-02957, E3402, ECOG-E3402, U10CA021115
Study First Received: August 4, 2004
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Paraproteinemias
Vascular Diseases
Antibodies, Monoclonal
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Rituximab
Vincristine
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on November 25, 2014