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

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00070018
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 46
• Locations: 48
• Arm: 1
• Duration (Months): 131.2
• Patients Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	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

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 Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Jan 8, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [at 6 weeks after treatment, then every 6 months for 2 years, then annually thereafter]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Alaska Regional Hospital Cancer Center	Anchorage	Alaska	United States	99508
2	Providence Cancer Center	Anchorage	Alaska	United States	99508
3	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
4	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
5	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
6	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
7	Edward Hospital Cancer Center	Naperville	Illinois	United States	60540
8	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
9	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
10	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
11	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
12	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
13	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
14	Southwest Medical Center	Liberal	Kansas	United States	67901
15	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
16	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
17	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
18	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
19	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
20	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
21	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
22	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
23	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
24	CCOP - Wichita	Wichita	Kansas	United States	67214
25	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
26	Wesley Medical Center	Wichita	Kansas	United States	67214
27	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
28	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
29	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
30	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
31	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
32	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
33	Hackley Hospital	Muskegon	Michigan	United States	49442
34	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan	United States	48075
35	Munson Medical Center	Traverse City	Michigan	United States	49684
36	Metro Health Hospital	Wyoming	Michigan	United States	49519
37	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
38	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
39	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
40	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
41	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
42	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
43	CCOP - Greenville	Greenville	South Carolina	United States	29615
44	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
45	Group Health Central Hospital	Seattle	Washington	United States	98112
46	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
47	Polyclinic First Hill	Seattle	Washington	United States	98122
48	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Thomas P. Miller, MD, University of Arizona
• Study Chair: Oliver W. Press, MD, PhD, Fred Hutchinson Cancer Center
• Study Chair: Baldassarre D. Stea, MD, PhD, University of Arizona
• Study Chair: Louis S. Constine, MD, James P. Wilmot Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00070018
• Other Study ID Numbers: CDR0000329864; U10CA032102; S0313
• First Posted: Oct 7, 2003
• Last Update Posted: Jan 11, 2022
• Last Verified: Dec 1, 2021

• 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; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	CHOP + RT + Zevalin
Arm/Group Description	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.
Period Title: Overall Study
STARTED	46
Eligible	46
Eligible and Began Protocol Therapy	46
COMPLETED	42
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	CHOP + RT + Zevalin
Arm/Group Description	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.
Overall Participants	46
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61.2
Sex: Female, Male (Count of Participants)
Female	16 34.8%
Male	30 65.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 6.5%
Not Hispanic or Latino	38 82.6%
Unknown or Not Reported	5 10.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 6.5%
White	42 91.3%
More than one race	1 2.2%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CHOP + RT + Zevalin
Arm/Group Description	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.
Measure Participants	46
Number (95% Confidence Interval) [percentage of participants]	89 193.5%

Adverse Events

Time Frame	After each cycle of CHOP, after RT, and 3 months after Zevalin therapy for a maximum of 10 months
Arm/Group Title	CHOP + RT + Zevalin
Arm/Group Description	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.
All Cause Mortality
	CHOP + RT + Zevalin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CHOP + RT + Zevalin
	Affected / at Risk (%)	# Events
Total	0/46 (0%)
Other (Not Including Serious) Adverse Events
	CHOP + RT + Zevalin
	Affected / at Risk (%)	# Events
Total	44/46 (95.7%)
Blood and lymphatic system disorders
Febrile neutropenia	4/46 (8.7%)
Hemoglobin	28/46 (60.9%)
Gastrointestinal disorders
Constipation	16/46 (34.8%)
Diarrhea	9/46 (19.6%)
Dry mouth/salivary gland (xerostomia)	10/46 (21.7%)
Dysphagia (difficulty swallowing)	6/46 (13%)
Esophagitis	3/46 (6.5%)
Heartburn/dyspepsia	5/46 (10.9%)
Mucositis/stomatitis (clinical exam) - Oral cavity	5/46 (10.9%)
Mucositis/stomatitis (functional/symptomatic) - Oral cavity	8/46 (17.4%)
Nausea	21/46 (45.7%)
Pain - Oral cavity	4/46 (8.7%)
Vomiting	11/46 (23.9%)
General disorders
Edema: limb	3/46 (6.5%)
Fatigue (asthenia, lethargy, malaise)	33/46 (71.7%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC lt1.0 x 10e9/L)	4/46 (8.7%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	3/46 (6.5%)
Injury, poisoning and procedural complications
Rash: dermatitis associated with radiation - Radiation	16/46 (34.8%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	6/46 (13%)
AST, SGOT (serum glutamic oxaloacetic transaminase)	8/46 (17.4%)
Bilirubin (hyperbilirubinemia)	3/46 (6.5%)
Creatinine	3/46 (6.5%)
Leukocytes (total WBC)	29/46 (63%)
Lymphopenia	19/46 (41.3%)
Neutrophils/granulocytes (ANC/AGC)	27/46 (58.7%)
Platelets	25/46 (54.3%)
Weight loss	8/46 (17.4%)
Metabolism and nutrition disorders
Anorexia	7/46 (15.2%)
Dehydration	4/46 (8.7%)
Glucose, serum-high (hyperglycemia)	12/46 (26.1%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	5/46 (10.9%)
Pain - Bone	3/46 (6.5%)
Pain - Muscle	5/46 (10.9%)
Nervous system disorders
Dizziness	5/46 (10.9%)
Neuropathy: sensory	14/46 (30.4%)
Pain - Head/headache	6/46 (13%)
Taste alteration (dysgeusia)	3/46 (6.5%)
Psychiatric disorders
Mood alteration - depression	3/46 (6.5%)
Respiratory, thoracic and mediastinal disorders
Cough	4/46 (8.7%)
Dyspnea (shortness of breath)	3/46 (6.5%)
Mucositis/stomatitis (clinical exam) - Pharynx	3/46 (6.5%)
Mucositis/stomatitis (functional/symptomatic) - Pharynx	5/46 (10.9%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	4/46 (8.7%)
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other (Specify)	4/46 (8.7%)
Hair loss/Alopecia (scalp or body)	24/46 (52.2%)
Rash/desquamation	8/46 (17.4%)
Vascular disorders
Hypotension	3/46 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.