Rituximab, Combination Chemotherapy, and 90-Yttrium Ibritumomab Tiuxetan for Patients With Stage I or II Non-Hodgkin's Lymphoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00088881
• Collaborator: (none)
• Enrollment: 62
• Location: 1
• Arm: 1
• Duration (Months): 74.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving rituximab together with combination chemotherapy and 90-Yttrium 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 90-Yttrium 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 or Disease	Intervention/Treatment	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; Drug: vincristine; Radiation: indium In 111 ibritumomab tiuxetan; Radiation: radiation therapy; Procedure: positron emission tomography	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the complete response rate (CR) and functional CR rate 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 R-CHOP followed by 90-Yttrium -Zevalin™.

SECONDARY OBJECTIVES:

1. To evaluate the time to treatment failure, duration of response, and overall survival in these patients who receive therapy with R-CHOP followed by 90-Yttrium -Zevalin™.

2. 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:

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

OUTLINE:

R-CHOP (rituximab, prednisone, cyclophosphamide, doxorubicin,vincristine): 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.

Radioimmunotherapy: Beginning no more than 9 weeks after the reevaluation (or 12 weeks after the last dose of R-CHOP), 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 90-Yttrium 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone): Patients receive R-CHOP every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response after 2 courses receive 2 additional courses. Patients achieving a partial response, uncertain CR, or stable disease receive 4 additional courses. Patients with progressive disease go off study. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, 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. Radiation therapy: Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy.

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; Given IV; Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF ; Drug: vincristine; Given IV; Other Names: leurocristine sulfate VCR Vincasar PFS ; Radiation: indium In 111 ibritumomab tiuxetan; Given IV; Other Names: 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

Outcome Measures

Primary Outcome Measures

1. Complete Response (CR) +Complete Response/Uncertain (CRu) in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™. [Assessed after 2 cycles of R-CHOP, after completion of R-CHOP, and at Week 12 After 90-Yttrium Zevalin]

   Response was assessed based upon the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma (Cheson, 1999). CR is defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related B-symptoms if present prior to therapy, as well as normalization (normal limits of institutional labs) of those biochemical abnormalities (e.g., LDH) definitely attributed to NHL. CRu is defined as meeting the criteria of CR except one or more of the followings: A residual dominant node (or extra-nodal mass) that is currently > 1.5 cm in greatest diameter that has decreased by > 75% from baseline in the product of its diameters. Individual dominant nodes (or extra-nodal masses) that were previously confluent must have decreased by > 75% in SPD compared with the size of the original mass. Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia).

2. Functional CR in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™. [Assessed after 2 cycles of R-CHOP, after completion of R-CHOP, and at Week 12 After 90-Yttrium Zevalin]

   Patients will be considered a functional CR if they meet the criteria for a CR, or if they meet the criteria for a CRu or partial response (PR) by CT and are PET negative. Please see primary outcome #1 for the definition of CR and CRu. PR is defined as: A decrease of >50% in the SPD (sum of products of the diameters) of the six largest (or less) dominant nodes or extra-nodal masses. No increase in the size of the liver or the spleen. No unequivocal progression in any non-measurable or non-dominant site. Splenic and hepatic nodules must regress by >50% in SPD (sum of the products of the diameters). Bone marrow assessment is not relevant for determination of a PR because it is assessable and not measurable disease. No new sites of disease.

Secondary Outcome Measures

1. 3-year Time to Treatment Failure (TTF) Rate [Assessed every 3 months for one year; every 4 months for the second year; then every 6 months for 3 years; then annually to 10 years from patient entry.]

   Time to treatment failure (TTF) is defined as the time from step 1 registration to disease progression or death. TTF is censored at last documented progression free for cases without progression. The 3-year TTF rate is defined as the probability of patients remaining free from treatment failure at 3 years.

2. 3-year Overall Survival (OS) Rate [Assessed every 3 months for 2 years, then every 6 months for 3 years; then annually to 10 years from patient entry.]

   Overall survival (OS) is defined as the time from step 1 registration to death of any cause. OS is censored at the date last known alive for cases that are alive. The 3-year OS rate is defined as the probability of patients remaining alive at 3 years.

Eligibility Criteria

Criteria

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

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 Lactate Dehydrogenase (LDH) above institutional upper limit of normal

• Eastern Cooperative Oncology Group (ECOG) performance status = 2

• Eastern Cooperative Oncology Group (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 left ventricular ejection fraction (LVEF) of > 45%

• Patients must be tested for hepatitis B (HBV) 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

Exclusion Criteria:

• Prior chemotherapy, radiation therapy, radioimmunotherapy, or immunotherapy; a short course (=< 14 days prior to registration) of corticosteroids is allowed

• Evidence of other malignancy:

• Prior chemotherapy or prior radiation therapy for other malignancies

• 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

• 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

• Known central nervous system (CNS) lymphoma, testicular lymphoma, or vitreous lymphoma

• Known HIV infection. The safety of Zevalin™ in this population has not been tested at this time

• Serious coexisting medical condition or active infection which would compromise the ability to deliver standard R-CHOP chemotherapy

• Evidence of myelodysplasia on bone marrow aspiration and biopsy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Eastern Cooperative Oncology Group	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Thomas Witzig, Eastern Cooperative Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00088881
• Other Study ID Numbers: NCI-2012-02957; E3402; U10CA021115
• First Posted: Aug 5, 2004
• Last Update Posted: May 25, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Waldenstrom Macroglobulinemia; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	R-CHOP: Patients receive R-CHOP 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. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, 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.
Period Title: Step 1 - R-CHOP
STARTED	62
Eligible and Treated	53
COMPLETED	48
NOT COMPLETED	14
Period Title: Step 1 - R-CHOP
STARTED	56
Eligible and Treated	48
COMPLETED	45
NOT COMPLETED	11
Period Title: Step 1 - R-CHOP
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	R-CHOP: Patients receive R-CHOP 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. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, 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.
Overall Participants	53
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	21 39.6%
Male	32 60.4%

Outcome Measures

1. Primary Outcome

Title	Complete Response (CR) +Complete Response/Uncertain (CRu) in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™.
Description	Response was assessed based upon the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma (Cheson, 1999). CR is defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related B-symptoms if present prior to therapy, as well as normalization (normal limits of institutional labs) of those biochemical abnormalities (e.g., LDH) definitely attributed to NHL. CRu is defined as meeting the criteria of CR except one or more of the followings: A residual dominant node (or extra-nodal mass) that is currently > 1.5 cm in greatest diameter that has decreased by > 75% from baseline in the product of its diameters. Individual dominant nodes (or extra-nodal masses) that were previously confluent must have decreased by > 75% in SPD compared with the size of the original mass. Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia).
Time Frame	Assessed after 2 cycles of R-CHOP, after completion of R-CHOP, and at Week 12 After 90-Yttrium Zevalin

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Treatment
Arm/Group Description	R-CHOP: Patients receive R-CHOP 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. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, 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.
Measure Participants	53
Number (95% Confidence Interval) [proportion of participants]	0.87 1.6%

2. Primary Outcome

Title	Functional CR in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™.
Description	Patients will be considered a functional CR if they meet the criteria for a CR, or if they meet the criteria for a CRu or partial response (PR) by CT and are PET negative. Please see primary outcome #1 for the definition of CR and CRu. PR is defined as: A decrease of >50% in the SPD (sum of products of the diameters) of the six largest (or less) dominant nodes or extra-nodal masses. No increase in the size of the liver or the spleen. No unequivocal progression in any non-measurable or non-dominant site. Splenic and hepatic nodules must regress by >50% in SPD (sum of the products of the diameters). Bone marrow assessment is not relevant for determination of a PR because it is assessable and not measurable disease. No new sites of disease.
Time Frame	Assessed after 2 cycles of R-CHOP, after completion of R-CHOP, and at Week 12 After 90-Yttrium Zevalin

Outcome Measure Data

Analysis Population Description

Eligible and treated patients.

Arm/Group Title	Treatment
Arm/Group Description	R-CHOP: Patients receive R-CHOP 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. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, 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.
Measure Participants	53
Number (95% Confidence Interval) [proportion of participants]	0.89 1.7%

3. Secondary Outcome

Title	3-year Time to Treatment Failure (TTF) Rate
Description	Time to treatment failure (TTF) is defined as the time from step 1 registration to disease progression or death. TTF is censored at last documented progression free for cases without progression. The 3-year TTF rate is defined as the probability of patients remaining free from treatment failure at 3 years.
Time Frame	Assessed every 3 months for one year; every 4 months for the second year; then every 6 months for 3 years; then annually to 10 years from patient entry.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Treatment
Arm/Group Description	R-CHOP: Patients receive R-CHOP 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. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, 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.
Measure Participants	53
Number (95% Confidence Interval) [probability]	0.92

4. Secondary Outcome

Title	3-year Overall Survival (OS) Rate
Description	Overall survival (OS) is defined as the time from step 1 registration to death of any cause. OS is censored at the date last known alive for cases that are alive. The 3-year OS rate is defined as the probability of patients remaining alive at 3 years.
Time Frame	Assessed every 3 months for 2 years, then every 6 months for 3 years; then annually to 10 years from patient entry.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Treatment
Arm/Group Description	R-CHOP: Patients receive R-CHOP 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. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, 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.
Measure Participants	53
Number (95% Confidence Interval) [probability]	0.98

Adverse Events

Time Frame	Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
Arm/Group Title	Step 1 - R-CHOP		Step 2 - Zevalin™ Radioimmunotherapy		Step 3 - Radiation Therapy
Arm/Group Description	Patients receive R-CHOP 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.		Beginning no more than 9 weeks after the last course of R-CHOP, 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.		Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy.
All Cause Mortality
	Step 1 - R-CHOP		Step 2 - Zevalin™ Radioimmunotherapy		Step 3 - Radiation Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Step 1 - R-CHOP		Step 2 - Zevalin™ Radioimmunotherapy		Step 3 - Radiation Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/62 (71%)		46/56 (82.1%)		0/1 (0%)
Blood and lymphatic system disorders
Anemia	5/62 (8.1%)		3/56 (5.4%)		0/1 (0%)
Febrile neutropenia	10/62 (16.1%)		0/56 (0%)		0/1 (0%)
Cardiac disorders
Heart block Stokes-Adams syndrome	0/62 (0%)		0/56 (0%)		0/1 (0%)
Gastrointestinal disorders
Diarrhea w/o prior colostomy	1/62 (1.6%)		1/56 (1.8%)		0/1 (0%)
Dyspepsia	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Muco/stomatitis by exam, oral cavity	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Muco/stomatitis (symptom) oral cavity	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Nausea	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Vomiting	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
General disorders
Fatigue	7/62 (11.3%)		0/56 (0%)		0/1 (0%)
Face, pain	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Immune system disorders
Allergic reaction	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Infections and infestations
Infection w/ gr3-4 neut, lung	2/62 (3.2%)		0/56 (0%)		0/1 (0%)
Infection w/ gr3-4 neut, skin	0/62 (0%)		1/56 (1.8%)		0/1 (0%)
Infection w/ gr3-4 neut, blood	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Investigations
CD4 decreased	0/62 (0%)		1/56 (1.8%)		0/1 (0%)
Leukocytes decreased	22/62 (35.5%)		20/56 (35.7%)		0/1 (0%)
Lymphopenia	26/62 (41.9%)		34/56 (60.7%)		0/1 (0%)
Neutrophils decreased	27/62 (43.5%)		29/56 (51.8%)		0/1 (0%)
Platelets decreased	5/62 (8.1%)		26/56 (46.4%)		0/1 (0%)
Creatinine increased	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Anorexia	4/62 (6.5%)		0/56 (0%)		0/1 (0%)
Dehydration	2/62 (3.2%)		1/56 (1.8%)		0/1 (0%)
Acidosis	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Hypocalcemia	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Hyperglycemia	6/62 (9.7%)		0/56 (0%)		0/1 (0%)
Hypoglycemia	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Hypomagnesemia	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Hypophosphatemia	2/62 (3.2%)		0/56 (0%)		0/1 (0%)
Hypokalemia	2/62 (3.2%)		0/56 (0%)		0/1 (0%)
Hyponatremia	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Nervous system disorders
Neuropathy-sensory	3/62 (4.8%)		1/56 (1.8%)		0/1 (0%)
Syncope	3/62 (4.8%)		0/56 (0%)		0/1 (0%)
Neuropathic, pain	0/62 (0%)		1/56 (1.8%)		0/1 (0%)
Psychiatric disorders
Psychosis	2/62 (3.2%)		0/56 (0%)		0/1 (0%)
Renal and urinary disorders
Bladder, pain	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/62 (3.2%)		0/56 (0%)		0/1 (0%)
Pulmonary/Upper Respiratory-other	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Nail changes	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Vascular disorders
Hypotension	1/62 (1.6%)		0/56 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Step 1 - R-CHOP		Step 2 - Zevalin™ Radioimmunotherapy		Step 3 - Radiation Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/62 (100%)		55/56 (98.2%)		0/1 (0%)
Blood and lymphatic system disorders
Anemia	48/62 (77.4%)		44/56 (78.6%)		0/1 (0%)
Gastrointestinal disorders
Constipation	35/62 (56.5%)		0/56 (0%)		0/1 (0%)
Diarrhea w/o prior colostomy	16/62 (25.8%)		6/56 (10.7%)		0/1 (0%)
Dry mouth	6/62 (9.7%)		0/56 (0%)		0/1 (0%)
Dyspepsia	19/62 (30.6%)		0/56 (0%)		0/1 (0%)
Muco/stomatitis by exam, oral cavity	14/62 (22.6%)		0/56 (0%)		0/1 (0%)
Muco/stomatitis (symptom) oral cavity	17/62 (27.4%)		0/56 (0%)		0/1 (0%)
Nausea	37/62 (59.7%)		6/56 (10.7%)		0/1 (0%)
Vomiting	15/62 (24.2%)		0/56 (0%)		0/1 (0%)
Abdomen, pain	6/62 (9.7%)		0/56 (0%)		0/1 (0%)
General disorders
Fatigue	50/62 (80.6%)		32/56 (57.1%)		0/1 (0%)
Fever w/o neutropenia	0/62 (0%)		3/56 (5.4%)		0/1 (0%)
Rigors/chills	7/62 (11.3%)		0/56 (0%)		0/1 (0%)
Edema limb	6/62 (9.7%)		0/56 (0%)		0/1 (0%)
Investigations
Leukocytes decreased	39/62 (62.9%)		51/56 (91.1%)		0/1 (0%)
Lymphopenia	50/62 (80.6%)		47/56 (83.9%)		0/1 (0%)
Neutrophils decreased	28/62 (45.2%)		41/56 (73.2%)		0/1 (0%)
Platelets decreased	20/62 (32.3%)		51/56 (91.1%)		0/1 (0%)
Weight loss	11/62 (17.7%)		3/56 (5.4%)		0/1 (0%)
Alkaline phosphatase increased	13/62 (21%)		8/56 (14.3%)		0/1 (0%)
Alanine aminotransferase increased	4/62 (6.5%)		0/56 (0%)		0/1 (0%)
Aspartate aminotransferase increased	9/62 (14.5%)		4/56 (7.1%)		0/1 (0%)
Blood bilirubin increased	0/62 (0%)		3/56 (5.4%)		0/1 (0%)
Creatinine increased	4/62 (6.5%)		0/56 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Anorexia	14/62 (22.6%)		4/56 (7.1%)		0/1 (0%)
Hypocalcemia	5/62 (8.1%)		0/56 (0%)		0/1 (0%)
Hyperglycemia	44/62 (71%)		16/56 (28.6%)		0/1 (0%)
Hypokalemia	4/62 (6.5%)		0/56 (0%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Joint, pain	4/62 (6.5%)		0/56 (0%)		0/1 (0%)
Muscle, pain	9/62 (14.5%)		0/56 (0%)		0/1 (0%)
Nervous system disorders
Taste disturbance	12/62 (19.4%)		3/56 (5.4%)		0/1 (0%)
Dizziness	7/62 (11.3%)		0/56 (0%)		0/1 (0%)
Neuropathy-motor	6/62 (9.7%)		0/56 (0%)		0/1 (0%)
Neuropathy-sensory	38/62 (61.3%)		10/56 (17.9%)		0/1 (0%)
Head/headache	8/62 (12.9%)		3/56 (5.4%)		0/1 (0%)
Psychiatric disorders
Insomnia	6/62 (9.7%)		0/56 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	7/62 (11.3%)		0/56 (0%)		0/1 (0%)
Dyspnea	8/62 (12.9%)		4/56 (7.1%)		0/1 (0%)
Voice changes/dysarthria	0/62 (0%)		3/56 (5.4%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Sweating	5/62 (8.1%)		0/56 (0%)		0/1 (0%)
Alopecia	31/62 (50%)		7/56 (12.5%)		0/1 (0%)
Pruritus/itching	6/62 (9.7%)		0/56 (0%)		0/1 (0%)
Rash/desquamation	11/62 (17.7%)		0/56 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.