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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Cancer Center
    • Anchorage, Alaska, United States, 99508
      • Alaska Regional Hospital Cancer Center
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
  • Idaho
    • Boise, Idaho, United States, 83712
      • Mountain States Tumor Institute at St. Luke's Regional Medical Center
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Naperville, Illinois, United States, 60540
      • Edward Hospital Cancer Center
    • Springfield, Illinois, United States, 62781-0001
      • Regional Cancer Center at Memorial Medical Center
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Cancer Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67208
      • Associates in Womens Health, PA - North Review
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Michigan
    • Battle Creek, Michigan, United States, 49017
      • Battle Creek Health System Cancer Care Center
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Butterworth Hospital at Spectrum Health
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Health Care
    • Muskegon, Michigan, United States, 49442
      • Hackley Hospital
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield Campus
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Independence, Ohio, United States, 44131
      • Community Oncology Group at Cleveland Clinic Cancer Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic - Wooster
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
  • Washington
    • Seattle, Washington, United States, 98104
      • Minor and James Medical, PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	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.	at 6 weeks after treatment, then every 6 months for 2 years, then annually thereafter

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Oliver W. Press, MD, PhD, Fred Hutchinson Cancer Center; Study Chair: Thomas P. Miller, MD, University of Arizona; Study Chair: Baldassarre D. Stea, MD, PhD, University of Arizona; Study Chair: Louis S. Constine, MD, James P. Wilmot Cancer Center

Publications and helpful links

General 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.
• Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. doi: 10.1182/blood-2014-06-584623. Epub 2014 Nov 13.

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): January 8, 2015

Study Registration Dates

• First Submitted: October 3, 2003
• First Submitted That Met QC Criteria: October 6, 2003
• First Posted (Estimate): October 7, 2003

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: anaplastic large cell lymphoma; contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult Burkitt lymphoma; stage I mantle cell lymphoma; stage I adult Burkitt lymphoma; contiguous stage II adult Burkitt lymphoma; contiguous stage II adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Liposomal doxorubicin; Antibodies, Monoclonal; Vincristine
• Other Study ID Numbers: CDR0000329864; U10CA032102 (U.S. NIH Grant/Contract); S0313 (Other Identifier: SWOG)