Clinical trial NCT00070018: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: 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
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-10-07
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Progression-free Survival
timeFrame: at 6 weeks after treatment, then every 6 months for 2 years, then annually thereafter
Secondary outcomes:
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Regional Hospital Cancer Center
state: Alaska
city: Anchorage
country: United States
facility: Providence Cancer Center
state: Alaska
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: Boise
country: United States
facility: Mountain States Tumor Institute at St. Luke's Regional Medical Center
state: Idaho
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital Cancer Center
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Topeka
country: United States
facility: Cotton-O'Neil Cancer Center
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Muskegon
country: United States
facility: Hackley Hospital
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute at Providence Hospital - Southfield Campus
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Independence
country: United States
facility: Community Oncology Group at Cleveland Clinic Cancer Center
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic - Wooster
state: Ohio
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Seattle
country: United States
facility: Minor and James Medical, PLLC
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: Polyclinic First Hill
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
Study officials:
affiliation: University of Arizona
name: Thomas P. Miller, MD
role: STUDY_CHAIR
affiliation: Fred Hutchinson Cancer Center
name: Oliver W. Press, MD, PhD
role: STUDY_CHAIR
affiliation: University of Arizona
name: Baldassarre D. Stea, MD, PhD
role: STUDY_CHAIR
affiliation: James P. Wilmot Cancer Center
name: Louis S. Constine, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.