Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

S0313 Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Radiation Therapy Followed By Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Stage I or Stage II Non-Hodgkin's Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00070018
First received: October 3, 2003
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. 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 chemotherapy with radiation therapy and monoclonal antibody therapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy and monoclonal antibody therapy works in treating patients with stage I or stage II non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: Cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Radiation: radiation therapy
Biological: Yttrium-90 ibritumomab tiuxetan
Biological: Indium-111 ibritumomab tiuxetan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of CHOP Plus Involved Field Radiotherapy Followed by Yttrium-90 Ibritumomab Tiuxetan for Stages I, IE, and Non-Bulky Stages II and IIE, CD20 Positive, High-Risk Localized, Aggressive Histologies of Non-Hodgkin Lymphoma, Phase II

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: at 6 weeks after treatment, then every 6 months for 2 years, then annually thereafter ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of progression or symptomatic deterioration. Progression is defined as one or more of the following must occur. Unequivocal progression of disease in the opinion of the treating physician (an explanation must be provided). Appearance of a new lesion/site. Death due to disease without documented progression or symptomatic deterioration. Symptomatic deterioration is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.


Enrollment: 46
Study Start Date: February 2004
Estimated Study Completion Date: November 2018
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CHOP + RT + Zevalin
Patients first receive 3 cycles (21 days each) of CHOP, consisting of: cyclophosphamide 750 mg/m^2 on day 1, doxorubicin 50 mg/m^2 on day 1, vincristine 1.4 mg/m^2 on day 1, and prednisone 100 mg on days 1-5. Patients receive 4000-5000 cGy of radiation therapy in 25 fractions, starting 3 weeks after completion of CHOP. 3-6 weeks after completing RT, patients receive Zevalin, which consists of: rituximab 250 mg/m^2 on days 1 and 7, 8 or 9; In-111 ibritumomab tiuxetan 5 mCi within 4 hours after rituximab on day 1; and Y-90 ibritumomab tiuxetan 0.4 mCi/kg within 4 hours after rituximab on day 7, 8 or 9.
Biological: rituximab
250 mg/m^2, as part of Zevalin regimen
Drug: Cyclophosphamide
750 mg/m^2
Drug: doxorubicin hydrochloride
50 mg/m^2
Drug: prednisone
100 mg
Drug: vincristine sulfate
1.4 mg/m^2
Radiation: radiation therapy
4000-5000 cGy total
Biological: Yttrium-90 ibritumomab tiuxetan
0.4 mCi/kg
Biological: Indium-111 ibritumomab tiuxetan
5 mCi

Detailed Description:

OBJECTIVES:

  • Determine the 2-year progression-free survival of patients with aggressive high-risk stage I or IE or non-bulky stage II or IIE CD20-positive non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone and radiotherapy followed by rituximab and yttrium Y 90 ibritumomab tiuxetan.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

  • Chemotherapy: Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 1-2 hours, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
  • Radiotherapy: Beginning 3 weeks after the completion of CHOP chemotherapy, patients undergo radiotherapy once daily 5 days a week for 4-5 weeks.
  • Monoclonal antibody therapy: Beginning 3-6 weeks after the completion of radiotherapy, patients receive rituximab IV followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients then undergo whole body imaging. If ibritumomab tiuxetan biodistribution is acceptable, patients receive rituximab IV and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7, 8, OR 9.

Patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 15 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes:

    • Diffuse large B-cell
    • Mantle cell
    • High-grade B-cell, Burkitt's, or Burkitt-like
    • Anaplastic large cell (B-cell phenotype only)
  • Stage I, IE, or non-bulky* stage II or IIE disease by Ann Arbor classification

    • Patients who have bulky stage II or IIE disease are ineligible even if, after resection, the measurements are less than 10.0 cm NOTE: *Non-bulky disease defined as any tumor measuring less than 10.0 cm or occupying less than 1/3 of the chest diameter
  • CD20-expressing disease by flow cytometry or immunoperoxidase staining
  • Aggressive lymphomas must have at least 1 of the following adverse prognostic factors:

    • Non-bulky stage II or IIE disease
    • At least 60 years of age
    • Zubrod performance status of 2
    • Lactic dehydrogenase greater than upper limit of normal
  • All disease must be encompassable in a single radiation port (including any site of resected disease) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Not specified

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No medical contraindication to study chemotherapy, rituximab, or ibritumomab tiuxetan
  • No known AIDS syndrome or HIV-associated complex

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior monoclonal antibody therapy

Chemotherapy

  • No prior chemotherapy for lymphoma

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics
  • No prior radiotherapy for lymphoma
  • No concurrent intensity-modulated radiotherapy
  • Planned involved-field radiotherapy must not encompass more than 25% of active bone marrow space

Surgery

  • See Disease Characteristics

Other

  • Concurrent participation in SWOG-8947 or SWOG-8819 allowed
  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: NCT00070018

  Show 48 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Thomas P. Miller, MD University of Arizona
Study Chair: Oliver W. Press, MD, PhD Fred Hutchinson Cancer Research Center
Study Chair: Baldassarre D. Stea, MD, PhD University of Arizona
Study Chair: Louis S. Constine, MD James P. Wilmot Cancer Center
  More Information

Additional Information:
Publications:
Miller TP, Unger JM, Spier C, et al.: Effect of adding ibritumomab tiuxetan (Zevalin) radioimmunotherapy consolidation to three cycles of CHOP plus involved-field radiotherapy for limited-stage aggressive diffuse B-cell lymphoma (SWOG 0313). [Abstract] Blood 112 (11): A-3598, 2008.

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00070018     History of Changes
Other Study ID Numbers: CDR0000329864, U10CA032102, S0313
Study First Received: October 3, 2003
Results First Received: March 5, 2012
Last Updated: January 17, 2014
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
stage I mantle cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult Burkitt lymphoma
anaplastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies, Monoclonal
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Prednisone
Rituximab
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on November 20, 2014