Conditions: Lymphoma
Keywords: contiguous stage II grade 1 follicular lymphoma contiguous stage II grade 2 follicular lymphoma contiguous stage II grade 3 follicular lymphoma noncontiguous stage II grade 1 follicular lymphoma noncontiguous stage II grade 2 follicular lymphoma noncontiguous stage II grade 3 follicular lymphoma stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 87
Healthy volunteers: no

Brief summary:
RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving a radiolabeled monoclonal antibody together with rituximab and combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects of giving iodine I 131 tositumomab together with rituximab and combination chemotherapy and to see how well it works in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.

Detailed description:
OBJECTIVES:

* To evaluate the response rate in patients with previously untreated stage II-IV follicular non-Hodgkin lymphoma treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) in combination with iodine I 131 tositumomab.
* To evaluate the toxicity of this regimen in these patients.
* To estimate the 3-year progression-free survival rate in patients treated with this regimen.
* To estimate the 5-year progression-free and overall survival rate in patients treated with this regimen.
* To assess the safety profile of this regimen in these patients.

OUTLINE: This is a multicenter study.

* Induction therapy: Patients receive R-CHOP\* comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with at least stable disease then proceed to consolidation therapy.

NOTE: \*Patients receive R-CHOP in courses 1-4 and CHOP alone in courses 5 and 6.

* Consolidation therapy: Within 12 weeks after completion of induction therapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo whole body gamma camera scans over a 1-week period to determine the rate of total body clearance of radioactivity and the therapeutic dose of iodine I 131 tositumomab. Within 7-14 days after the dosimetric dose, patients receive tositumomab IV over 1 hour followed by a therapeutic dose of iodine I 131 tositumomab IV over 20 minutes. Patients with at least stable disease then proceed to maintenance therapy.
* Maintenance therapy: Beginning approximately 1 year after study entry and no more than 28 days after restaging, patients receive rituximab IV every 3 months for up to 4 years (16 courses) in the absence of disease progression or unacceptable toxicity.

After completion of maintenance therapy, patients are followed annually for up to 7 years. Patients who do not complete maintenance therapy are followed every 6 months for 2 years and then annually for up to 7 years.

Arms:
arm 1: Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 Cycles

Patients are restaged by CT scan. Unlabeled tositumomab antibody 450 mg IV within 12 after Cycle 6 of CHOP. Dosimetric dose 35 mg IV after infusion of unlabeled tositumomab antibody. Unlabeled tositumomab antibody 450 mg IV 7-14 days after dosimetric dose. Therapeutic dose 35 mg IV after infusion of unlabeled tositumomab antibody.

Rituximab 375 mg/m2 IV q 3 months x 4 years beginning 1 year after registration.

Interventions: intervention 1: rituximab intervention 2: tositumomab intervention 3: cyclophosphamide intervention 4: doxorubicin intervention 5: prednisone intervention 6: vincristine intervention 7: tositumomab
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None

Protocol document:
Prot_SAP_ICF_000.pdf: 
 
 
 
 
 
PRIVILEGED COMMUNICATION 
 
S0801 
FOR INVESTIGATIONAL USE ONLY 
 
Sent for IRB review December 1, 2008 
Revised 11/5/10 
Activation Date April 1, 2009 
Revised 8/20/12 
Revised 1/15/16 
 
SOUTHWEST ONCOLOGY GROUP 
 
A PHASE II STUDY OF IODINE-131-LABELED TOSITUMOMAB IN COMBINATION WITH 
CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE, PREDNISONE AND RITUXIMAB THERAPY 
FOR PATIENTS WITH ADVANCED STAGE FOLLICULAR NON-HODGKIN’S LYMPHOMA 
 
 
Page 
   
SCHEMA ......................................................................................................................... 
2 
  1.0 
OBJECTIVES .................................................................................................................. 
3 
  2.0 
BACKGROUND .............................................................................................................. 
3 
  3.0 
DRUG INFORMATION ................................................................................................... 
6 
  4.0 
STAGING CRITERIA ...................................................................................................... 20 
  5.0 
ELIGIBILITY CRITERIA .................................................................................................. 21 
  6.0 
STRATIFICATION FACTORS ........................................................................................ 23 
  7.0 
TREATMENT PLAN ........................................................................................................ 23 
  8.0 
TOXICITIES TO BE MONITORED AND DOSAGE MODIFICATIONS .......................... 30 
  9.0 
STUDY CALENDAR ....................................................................................................... 34 
10.0 
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS .................................. 35 
11.0 
STATISTICAL CONSIDERATIONS ................................................................................ 37 
12.0 
DISCIPLINE REVIEW ..................................................................................................... 37 
13.0 
REGISTRATION GUIDELINES ...................................................................................... 38 
14.0 
DATA SUBMISSION SCHEDULE .................................................................................. 40 
15.0 
SPECIAL INSTRUCTIONS ............................................................................................. 42 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS ..................................................... 44 
17.0 
BIBLIOGRAPHY ............................................................................................................. 47 
18.0 
MASTER FORMS SET ................................................................................................... 48 
19.0 
APPENDIX …………………………………………………………………………………….  89 
PARTICIPANTS: ALL SOUTHWEST ONCOLOGY GROUP MEMBER, CCOP AND AFFILIATE 
MEDICAL ONCOLOGISTS AND PATHOLOGISTS 
 
STUDY COORDINATORS: 
AGENTS: 
Principal Investigator 
Paul M. Barr, M.D. (Medical Oncology) 
Cyclophosphamide (Cytoxan®) (NSC-26271) 
University of Rochester 
Doxorubicin (NSC-123127) 
James P. Wilmot Cancer Center 
Iodine-131-labeled Murine Monoclonal  
601 Elmwood Avenue, Box 704 
Tositumomab Antibody (NSC-715813) 
Rochester, NY 14642 
Prednisone (NSC-10023) 
Phone:  585/273-3258 
Rituximab Chimeric Monoclonal anti-CD20  
E-mail:  paul_barr@urmc.rochester.edu 
Antibody (IDEC-C2B8) (NSC-687451) 
 
Vincristine (Oncovin) (NSC-67574) 
Jonathan W. Friedberg, M.D. (Medical Oncology) 
James P. Wilmot Cancer Center  
BIOSTATISTICIANS: 
University of Rochester 
 
601 Elmwood Avenue, Box 704 
Michael LeBlanc, Ph.D. (Biostatistics) 
Rochester, NY 14642 
Hongli Li, M.S. (Biostatistics) 
Phone:  585/273-4150 
Southwest Oncology Group Statistical Center 
Fax:  585/276-0337 
Fred Hutchinson Cancer Research Center 
E-mail:  Jonathan_Friedberg@urmc.rochester.edu 
1100 Fairview Avenue North, M3-C102 
 
P.O. Box 19024 
Oliver W. Press, M.D. (Medical Oncology) 
Seattle, WA 98109-1024 
Fred Hutchinson Cancer Research Center 
Phone:  206/667-4623 
1100 Fairview Avenue North, D3-190 
Fax:  206/667-4408 
Seattle, WA 98109 
Email:  mleblanc@fhcrc.org 
Phone:  206/667-1872 
Email:  hongli@fhcrc.org 
Fax:  206/667-1874 
Email:  press@u.washington.edu 
 
 
mb 
(Version Date:  01/15/16) 


 
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Page 1a 
 
Revised 1/15/16 
 
 
 
STUDY COORDINATORS (contd): 
 
Lisa M. Rimsza, M.D. (Pathology) 
 
Arizona Cancer Center 
 
1501 N. Campbell Avenue, Room 5208, Box 245043 
Tucson, AZ 85724-5043 
 
Phone:  520/626-8396 
 
Fax:  520/626-6081 
E-mail:  lrimsza@email.arizona.edu 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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SCHEMA 
 
 
 
 
                 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  * 
 
 
  * 
    * 
Study           1          22             43 
     64 
        85            106 
134 
135 
142  
226 365 
Day 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Restaging 
Rituximab #1 
Rituximab #2 
Rituximab #3 
Rituximab #4 
CHOP #1 
CHOP #2 
CHOP #3 
CHOP #4 
CHOP #5 
CHOP #6 
Dosimetric Tositumomab 
Therapeutic Tositumomab 
Begin  
Rituximab 
Maintenance 


 
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1.0 
OBJECTIVES 
 
1.1   
To evaluate response rate and toxicity in patients with advanced stage follicular NHL 
treated with R-CHOP + I-131 tositumomab with rituximab maintenance. 
 
1.2 
To estimate the 3-year progression-free survival rate for patients with advanced stage 
follicular NHL treated with R-CHOP + I-131 tositumomab with rituximab maintenance. 
 
1.3 
To estimate the 5-year progression-free and overall survival rate for this regimen. 
 
1.4 
To assess the safety profile of rituximab maintenance following the R-CHOP + I-131 
tositumomab regimen. 
 
1.5 
To bank serum and tissue specimens for future correlative studies. 
 
 
2.0 
BACKGROUND 
 
Introduction:  Follicular NHL 
 
Non-Hodgkin’s lymphoma is the fifth most common cancer in the U.S., and is significantly 
increasing in incidence.  The National Cancer Institute estimates that over 60,000 new cases of 
NHL will be diagnosed in the U.S. this year, and the second most common histology is follicular 
lymphoma.  (1)  More than 90% of all cases of NHL are of B-cell derivation.   
 
Historically, advanced stage follicular lymphoma has been considered an incurable disease with 
standard therapeutic approaches.  Significant improvements in overall survival have been 
reported recently when monoclonal antibodies directed against CD20 have been included in 
treatment programs.  Sequential trials conducted since 1980 in the Southwest Oncology Group 
have demonstrated significant improvements in both failure-free and overall survival in the most 
recent therapeutic era (S9800 and S9911).  (2)  Thus, the most important advance in the 
treatment of follicular lymphoma over the past 30 years has been the incorporation of monoclonal 
antibodies into the therapeutic regimens. 
 
Monoclonal Antibody Therapy 
 
RITUXAN® (Rituximab, BiogenIdec, Cambridge, MA, and Genentech Inc., South San Francisco, 
CA) is a chimeric anti-CD20 monoclonal antibody with murine variable regions and human IgG 
kappa constant regions.  A pivotal trial of rituximab, 375 mg/m2/week x 4 weeks, in 166 patients 
with relapsed or refractory follicular or low-grade lymphoma, showed overall response rate of 
48%, with 6% complete responses.  (3)  Adverse events were brief in this trial and usually related 
to the initial infusion although subsequent studies have documented rare occurrences of hepatitis 
B reactivation with fulminant hepatitis, hepatic failure, or death.  Only one patient developed an 
anti-chimeric antibody response.  This promising response rate, along with in vitro data that 
suggests a chemo-sensitizing effect of the antibody, led to interest in combining rituximab with 
chemotherapy in indolent histologies.  The majority of patients received rituximab in combination 
with chemotherapy in subsequent trials. 
 
The choice of a chemotherapy regimen for such a study is controversial, since no regimen has 
demonstrated clear superiority over any other.  Although a strong case can be made for using 
chlorambucil or CVP as the "standard" regimen for indolent NHL, CHOP was chosen for this trial 
for several compelling reasons.  First, the use of a moderately aggressive regimen such as 
CHOP is considered most likely to produce a state of minimal tumor burden, which is considered 
the ideal setting for immunotherapies.  (Antibody molecules are large proteins which penetrate 
large tumor masses poorly.  Furthermore, theoretical models suggest that the maximal crossfire 
from radiolabeled antibodies occurs when cell clusters are less than 1 mm in diameter).  Second, 
other adjuvant immunotherapies such as interferon-alpha have been shown to produce an  
 


 
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advantage in terms of progression-free or overall survival only in studies using aggressive 
chemotherapy regimens such as CHOP and not when combined with regimens such as 
chlorambucil or CVP.  Finally, randomized studies suggest that combining rituximab with CHOP 
chemotherapy has significant benefit in follicular lymphoma.  (4)  The addition of rituximab to 
CHOP clearly provides for improved response rates and prolonged PFS compared to CHOP 
alone.  However, in follow-up it does not appear that R-CHOP is curative, thus further 
improvements are needed in therapy of follicular lymphoma. 
 
Clinical Studies with Radioimmunoconjugates  
 
An alternative approach to enhance the efficacy of anti-CD20 antibodies involves conjugating 
them to cytotoxic radionuclides, which can then be selectively targeted to B lymphoid tumors.  
Study RIT-I-000 was the initial Phase I/II, open-label study of non-myeloablative doses of 
Iodine-131 tositumomab antibody for the treatment of patients with B-cell NHL of all histologic 
types.  (5)  Fifty-nine patients were enrolled.  Twenty-eight patients had low-grade NHL, 14 had 
transformed low-grade NHL, 15 had intermediate-grade NHL, and 2 had high-grade NHL.  
Patients received 1 - 3 dosimetric doses followed by a therapeutic dose.  The dosimetric dose(s) 
involved the IV administration of 5 mCi of Iodine-131 tositumomab antibody to determine the rate 
of whole body clearance so that a whole body radiation dose (cGy) could be calculated.  Each 
dosimetric dose was preceded by 0, 95, or 475 mg of unlabeled antibody.  Therapeutic dose-
escalation was initiated at 25 cGy and adjusted in 10 cGy increments until the maximum tolerated 
dose (MTD) was reached.  Fifty-three of the 59 patients received a therapeutic dose.  The MTD 
was 75 cGy for patients who had not undergone BMT.  A response was observed in 42/59 (71%) 
patients and a complete response (CR) was observed in 20/59 (34%) patients.  The median 
duration of response was 271 days (95% confidence interval: 140 - 394 days) and median 
duration of CR was 566 days (95% confidence interval: 385 days to upper limit not reached).  
The dose-limiting toxicity was hematologic; three patients developed a platelet count < 10,000 
cells/mm3 and two patients had an ANC < 100 cells/mm3.  The most prevalent non-hematologic 
toxicities were transient, mild to moderate fever, nausea, asthenia, and chills.  Nine of 59 (15%) 
patients developed human anti-murine antibodies (HAMA). 
 
Study RIT-II-001 was a Phase II, multicenter, open-label study of non-myeloablative doses of 
Iodine-131 tositumomab antibody for the treatment of patients with low-grade B-cell lymphomas 
and transformed low-grade lymphomas.   (6)  Thirty-seven patients had low-grade NHL and 10 
had transformed low-grade NHL.  The median time from diagnosis was 41 months, the median 
number of prior therapies was 4, 91% had Stage III or IV disease, 44% had bulky disease, 44% 
had an elevated LDH.  Patients received 1 dosimetric dose followed by a therapeutic dose.  The 
dosimetric dose involved the IV administration of 450 mg of unlabeled antibody and 35 mg (5 
mCi) of Iodine-131 tositumomab antibody to determine the rate of whole body clearance so that 
whole body radiation dose (cGy) could be calculated.  The therapeutic dose involved IV 
administration of 450 mg of unlabeled antibody and 35 mg of Iodine-131 tositumomab antibody 
with radioactive Iodine-131 titrated to deliver 75 cGy.  A response was observed in 27/47 (57%) 
patients and a complete response (CR) was observed in 14/47 (30%) patients.  A response was 
observed in 6/10 (60%) patients and a CR was observed in 5/10 (50%) patients with transformed 
low-grade NHL.  The dose-limiting toxicity was hematologic; 5 patients developed a platelet count 
< 10,000 cells/mm3 and, mild to moderate asthenia, nausea and fever.  Only 1 of 46 (2%) 
patients developed HAMA following treatment as assessed by centralized validated HAMA 
assay.   
 
A Phase III randomized study compared yttrium-90 ibritumomab tiuxetan radioimmunotherapy 
(another radioimmunoconjugate) with rituximab in 143 patients with relapsed or refractory low-
grade, follicular, or transformed CD20 (+) NHL.  (7)  The overall response rate was 80% for the 
yttrium-90 ibritumomab tiuxetan group versus 56% for the rituximab group, which reached 
statistical significance.  Complete response rates were 30% and 16% in the yttrium-90 
ibritumomab tiuxetan and rituximab groups, respectively.  However, there was no statistically 
significant benefit in response duration or survival between the two groups.  This is the first 
randomized, controlled trial demonstrating unequivocally that a radiolabeled antibody produces  
 


 
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higher overall and complete response rates than the corresponding unlabeled antibody.  Whether 
the higher response rates with radiolabeled antibodies will translate into longer overall survival 
will require longer follow-up.  
 
As with rituximab, there is considerable interest in combining these radioimmunoconjugates with 
conventional chemotherapy as definitive treatment for de novo disease.  Concurrent 
administration of cytotoxic chemotherapy and radioimmunoconjugates is not possible because 
both produce myelosuppression.  S9911 was a Phase II pilot study (n=90) in indolent lymphoma 
studying the feasibility and toxicity of CHOP followed by the I-131 tositumomab regimen in 
previously untreated patients with follicular NHL.  (8)  The overall response rate to the entire 
treatment regimen (chemotherapy + iodine-131 tositumomab) was 90%, including 67% complete 
remissions.  Importantly, this trial demonstrated the safety of this regimen in a group of patients 
with a median age of patients of 50 years, and a range of 23 to 84 years.  The two-year 
progression free survival was estimated to be 81%, which is better than observed historically with 
CHOP alone, or CHOP with rituximab, in patients with follicular NHL.  
 
In S9911, 2% of patients were not able to receive iodine-131 tositumomab because of 
inadequate response to chemotherapy.  Additionally, most of the responses after chemotherapy 
were partial responses.  Since that trial was conducted, several randomized trials have 
demonstrated superior response rates, and improved CR rates, when rituximab is added to the 
chemotherapy regimen.  Thus, we hypothesize that administering rituximab with CHOP 
chemotherapy, prior to iodine-131 tositumomab, will result in better tumor responses prior to 
iodine-131 tositumomab consolidation likely leading to an improved therapeutic outcome.   
 
There is now growing experience giving CD20 targeted radioimmunotherapy after a rituximab 
regimen.  Preliminary results of a British multicenter Phase II trial to evaluate the efficacy and 
safety of 90Y ibritumomab tiuxetan in elderly pts with histologically confirmed first relapsed or 
primary refractory DLBCL not appropriate for autologous stem cell transplantation included 28 
patients who had previously been treated with rituximab containing chemotherapy programs.  
Thirty-seven percent of these 28 patients were refractory to CHOP-rituximab, and the overall 
response rate was 19% for this group.  There was no suggestion of increased toxicities despite 
receiving radioimmunotherapy within 6 weeks of CHOP-rituximab.  (9)  S0433 is an ongoing 
Phase II trial in patients with diffuse large B-cell lymphoma evaluating the safety and efficacy of 
R-CHOP followed by Iodine-131 tositumomab.  Twenty-nine patients have been enrolled thus far, 
without evidence of increased toxicities following Iodine-131 tositumomab therapy.  Finally, 
preliminary results of a trial utilizing ibritumomab tiuxetan consolidation following standard 
chemotherapy in patients with newly diagnosed follicular lymphoma suggest a benefit to 
radioimmunotherapy consolidation. (10) 
 
Several randomized studies support the role of “maintenance” rituximab (given on a schedule) in 
improving failure-free survival, and potentially overall survival, following chemotherapy in the de 
novo setting, and rituximab-chemotherapy combination treatment in the relapsed setting.  S0801 
hypothesizes that rituximab maintenance will prolong failure-free survival after R-CHOP + iodine-
131 tositumomab therapy.  Rituximab maintenance after chemotherapy alone provides significant 
benefit as far as progression-free survival; and borderline overall survival benefit.  There are two 
studies that suggest a benefit to rituximab maintenance after R-chemotherapy in the relapsed 
setting.  Forstpointner randomized patients to rituximab maintenance vs. observation following R-
FCM chemotherapy. (11)  The response duration was significantly prolonged by R-maintenance 
after R-FCM.  Van Oers and colleagues initially randomized patients with relapsed follicular 
lymphoma to CHOP vs. R-CHOP, and then performed a secondary randomization in responding 
patients to rituximab maintenance vs. observation. (12)  Improved PFS was found utilizing 
maintenance therapy both after induction with CHOP and R-CHOP.  Rituximab maintenance also 
improved overall survival from second randomization: 85% at 3 years versus 77% with 
observation.  The survival benefit is only of borderline significance in patients who were treated 
with R-CHOP.   
 


 
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Current protocol 
 
Therefore, this trial will build upon the promising results observed in S9911, and upon the 
aforementioned randomized trials, in a rational, incremental way.  Treatment will be in three 
parts: induction with CHOP and rituximab therapy; consolidation with iodine-131 tositumomab, 
and maintenance with rituximab.  It is hoped this strategy will further improve overall survival for 
patients with follicular NHL.   
 
As we have demonstrated safety in our pilot study, S9911, and ongoing S0433, I-131-
tositumomab will be given sequentially approximately four weeks after the last cycle of CHOP 
chemotherapy.  We will omit rituximab from the last two cycles of CHOP chemotherapy as we 
have demonstrated safety of that regimen in S0433. 
 
Patients known to be HIV-positive are not eligible for this study because the severally depressed 
immune system and poor bone marrow reserve found in HIV-infected patients, as well as the 
possibility of premature death, would compromise study objectives.   
 
Inclusion of Women and Minorities 
 
This study was designed to include women and minorities, but was not designed to measure 
differences of intervention effects. 
 
 
3.0 
DRUG INFORMATION  
 
3.1 
Cyclophosphamide (Cytoxan®) (NSC-26271) 
 
a. 
DESCRIPTION 
 
2-[bis (2-chloroethyl) amino] tetrahydro-2H-1, 3,2-oxazaphosphorine 2-oxide 
monohydrate.  Cyclophosphamide is biotransformed principally in the liver to 
active alkylating metabolites, which cross-link to tumor cell DNA. 
 
b. 
TOXICOLOGY  
 
Human Toxicology:  Toxicity from cyclophosphamide includes bone marrow 
suppression which usually occurs 10 to 12 days after administration, nausea, 
vomiting, anorexia, abdominal discomfort, diarrhea, stomatitis, hemorrhagic 
colitis, jaundice, reversible alopecia, hemorrhagic cystitis which can frequently be 
prevented with increased hydration, hematuria, ureteritis, tubular necrosis, 
fibrosis of the bladder, cardiac toxicity which may potentiate doxorubicin-induced 
cardiotoxicity, rare anaphylactic reaction, skin rash, hyperpigmentation of the 
skin and nails, interstitial pulmonary fibrosis, and cross sensitivity with other 
alkylating agents.  Treatment with cyclophosphamide may cause significant 
suppression of the immune system.  With the combination therapy the most 
frequent adverse event observed to date is neutropenia.  Prophylactic G-CSF for 
subsequent cycles has been necessary.  Dose reductions have been necessary 
for neutropenia and mucositis.  For further details, refer to Section 2.0, 
Background. 
 
Second malignancies, most frequently of the urinary bladder and hematologic 
systems, have been reported when cyclophosphamide is used alone or with 
other anti-neoplastic drugs.  It may occur several years after treatment has been 
discontinued.  Increased myelosuppression may be seen with chronic 
administration of high doses of phenobarbital.  Cyclophosphamide inhibits 
cholinesterase activity and potentiates effect of succinylcholine chloride.  If 
patient requires general anesthesia within 10 days after cyclophosphamide 
administration, the anesthesiologist should be alerted.  Adrenal insufficiency may 
be worsened with cyclophosphamide.  The occurrence of acute leukemia has  
 


 
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been reported rarely in patients treated with anthracycline/alkylator combination 
chemotherapy.  The occurrence of acute leukemia has been reported in patients 
treated with anthracycline/alkylator combination chemotherapy. 
 
For prescribing information and a comprehensive list of adverse events 
associated with cyclophosphamide, refer to the drug package insert. 
 
c. 
PHARMACOLOGY 
 
Pharmacokinetics:  Cyclophosphamide is activated principally in the liver by a 
mixed function microsomal oxidase system.  PO administration is well absorbed, 
with bioavailability greater than 75%.  Five to twenty-five percent of unchanged 
drug is excreted in the urine.  Several active and inactive metabolites have been 
identified with variable plasma protein binding.  There appears to be no evidence 
of clinical toxicity in patients with renal failure, although elevated levels of 
metabolites have been observed. 
 
Formulation:  Cyclophosphamide is supplied in 100 mg, 200 mg, 500 mg, 1 gram 
and 2 gram vials as a white powder.  The drug should be reconstituted with 
Sterile Water for Injection, USP, and may be diluted in either normal saline or 
D5W.   
 
Storage and Stability:  Although the reconstituted cyclophosphamide is stable for 
six days under refrigeration, it contains no preservatives and therefore should be 
used within 6 hours. 
 
Administration:  The drug should be diluted in about 150 cc of normal saline or 
D5W and infused IV.  An added dose of IV fluids may help prevent bladder 
toxicity. 
 
Supplier:  This drug is commercially available for purchase by the third party.  
This drug will not be supplied by the NCI. 
 
3.2 
Doxorubicin (NSC-123127) 
 
a. 
DESCRIPTION 
 
Mechanism of Action:  Doxorubicin is a cytotoxic anthracycline antibiotic different 
from daunorubicin by the presence of a hydroxyl group in the C-14 position.  
Doxorubicin is produced by fermentation from S. Peucetius var. caesius.  Its 
mechanism of action is thought to be the binding of nucleic acids, preventing 
DNA and possibly RNA synthesis. 
 
b. 
TOXICOLOGY 
 
Human Toxicology:  Studies with doxorubicin have shown that the major toxic 
effects of this drug are alopecia, which is often total but always reversible; 
nausea and vomiting, which develops shortly after drug administration, 
occasionally persisting for 2 - 3 days; fever on the day of administration; and 
phlebitis at the site of the drug's injection.  Extravasation of the drug will lead to 
soft tissue necrosis.  Phlebosclerosis, cellulitis, vesication and erythematous 
streaking have also been seen.  Mucositis may be seen 5 - 10 days after 
administration.  Ulceration and necrosis of the colon, particularly the cecum, with 
bleeding and severe infection have been reported with concomitant 
administration of cytarabine.  Anorexia and diarrhea have also been observed.  
Hyperpigmentation of nail beds and dermal creases, onycholysis and recall of 
skin reaction from prior radiotherapy may occur.  Cardiac toxicity manifested as 
cute left ventricular failure, congestive heart failure, arrhythmia or severe 


 
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cardiomyopathy has been reported, but appears to occur predominantly in 
patients who receive total doses in excess of 550 mg/m2. Myelosuppression, 
predominantly neutropenia, is common with nadir occurring approximately two 
weeks after a single injection; lesser degrees of anemia and thrombocytopenia 
have been reported.  Rapid recovery of the blood counts approximately two and 
a half weeks after a single injection generally permits an every three week 
schedule.  Patients with obstructive liver disease have more severe 
myelosuppression due to impaired drug excretion.  Thus, patients with hepatic 
dysfunction may need to have reduced dosage or to be excluded from therapy.  
Renal excretion of doxorubicin is minimal, but enough to color the urine red; thus 
impaired renal function does not appear to increase the toxicity of doxorubicin.  
Other side effects include fever, chills, facial flushing, itching, anaphylaxis, 
conjunctivitis and lacrimation.  The occurrence of acute leukemia has been 
reported rarely in patients treated with anthracycline/alkylator combination 
chemotherapy. 
 
c. 
PHARMACOLOGY 
 
Pharmacokinetics:  Intravenous administration is followed by a rapid plasma 
clearance with significant tissue binding.  Urinary excretion is negligible; biliary 
excretion accounts for 40 to 50% of the administered dose being recovered in 
the bile or the feces in 7 days.  The drug does not cross the blood-brain barrier. 
 
Formulation:  Doxorubicin is supplied in 10, 20 and 50 mg single-use vials, and 
150 mg multidose vials as a red-orange, lyophilized powder, which has a storage 
stability of at least two years - see expiration date on vial.  Doxorubicin should be 
reconstituted with 5, 10, 25 and 75 ml respectively, of Sodium Chloride Injection, 
USP (0.9%) to give a final concentration of 2 mg/mL. 
 
Storage and Stability:  The reconstituted doxorubicin is stable for 24 hours at 
room temperature and 48 hours under refrigeration (2-8°C).  It should be 
protected from exposure to sunlight.  Discard any unused solution from the vials.  
Bacteriostatic diluents with preservatives are NOT recommended as they might 
possibly worsen the reaction to extravasated drug. 
 
Administration:  Doxorubicin may be further diluted in 5% dextrose or sodium 
chloride injection and should be administered slowly into tubing of a freely 
flowing intravenous infusion with great care taken to avoid extravasation. 
 
Supplier:  This drug is commercially available for purchase by the third party.  
This drug will not be supplied by the NCI. 
 
3.3 
Iodine-131-labeled Murine Monoclonal Tositumomab Antibody (NSC-715813) 
 
a. 
DESCRIPTION   
 
Tositumomab Antibody/Iodine-131 Tositumomab Antibody  
 
Tositumomab Antibody is an IgG2a Kappa (murine) monoclonal antibody that 
binds to the CD20 antigen on the surface of the normal and malignant human B 
cells to induce apoptosis and mediate antibody-dependent cellular cytotoxicity.  
Iodine-131 tositumomab Antibody is the radionuclide-labeled monoclonal 
antibody that can recognize tumor-associated antigens to selectively target 
radioactivity to tumor cells.  By using isotopes emitting beta particles to label this 
antibody, the radiation emitted from the radiolabeled antibody bound to a tumor 
cell also kills neighboring cells because the path length of beta particles can 
extend over several cell diameters.  This crossfire of beta particles can destroy 
antigen-positive and -negative tumor cells, as well as untargeted antigen-positive 


 
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tumor cells within a tumor.  Iodine-131 tositumomab Antibody, used in 
conjunction with Tositumomab Antibody, is a radioimmunotherapeutic agent 
being studied for the treatment of non-Hodgkin's lymphoma and other CD20-
expressing B-cell malignancies.   
 
b. 
TOXICOLOGY 
 
Human Toxicology:  Unlabeled tositumomab antibody and Iodine-131 
tositumomab antibody infusions are approved by the FDA in non-myeloablative 
doses for the treatment of non-Hodgkin’s lymphoma.  The infusions are 
accompanied by few or no adverse experiences in most patients.  The most 
frequent non-hematologic adverse experience reported was a transient mild to 
moderate flu-like syndrome consisting of fever (39%), and chills (19%). Other 
adverse experiences commonly reported include nausea (39%), asthenia (36%), 
headache (23%), rash (18%), anorexia (16%), infection (16%), pain (16%), 
myalgia (16%), arthralgia (14%), pruritus (14%), abdominal pain (13%), vomiting 
(13%), pharyngitis (11%), diarrhea (10%), and increased cough (10%).  The 
concomitant administration of SSKI or other oral iodine product may contribute to 
the nausea and other gastrointestinal adverse experiences. Only 3% and 4% of 
patients experienced an adverse experience which required an adjustment to the 
rate of infusion during the administration of the dosimetric and therapeutic doses, 
respectively.   
 
Bone marrow suppression is the dose-limiting toxicity and a total body dose of 75 
cGy was determined to be the maximum tolerated dose for a non-myeloablative 
regimen in patients previously treated with chemotherapy.  An absolute 
neutrophil count (ANC) of < 100 cells/mm3 has occurred in 3% of patients, and an 
ANC of < 1,000 cells/mm3 has occurred in 47% of patients.  A platelet count of < 
10,000 cells/mm3 has occurred in 5% of patients, and a platelet count of < 50,000 
cells/mm3 has occurred in 37% of patients.  A hemoglobin of < 6.5 g/dL has 
occurred in 4% of patients, and a hemoglobin of < 8.0 g/dL has occurred in 12% 
of patients.  A white blood cell count of < 2,000 cells/mm3 has occurred in 41% of 
patients.  The median nadirs were 62,000 cells/mm3 for platelet count, 1,000 
cells/mm3 for ANC, and 11.1 gm/dL for hemoglobin.  Blood count nadirs (which 
occur approximately 4 to 6 weeks after therapy) were higher and the time to 
recovery shorter in patients who were less heavily pretreated.  The need for 
hematologic supportive care, which included transfusions and colony stimulating 
factors and were used at the discretion of the investigators, ranged from 0% in 
previously untreated patients to 24% in patients having received 4 or more prior 
therapies and was 18% overall.  The frequency of HAMA-positivity was related to 
the extent of prior therapy; 38% in previously untreated patients versus 4% in 
previously treated patients (≥ 1 prior therapies).  Thyroid function has been 
followed long-term and elevated thyroid stimulating hormone has been noted in 5 
out of 106 (4%) of patients.  Four of these patients have been started on oral 
thyroid supplementation, although clinical hypothyroidism has not been 
diagnosed.  No significant changes in serum immunoglobulins have occurred 
post-treatment.  Four patients developed a myelodysplastic syndrome or acute 
myelocytic leukemia in long-term follow-up.   
 
c. 
PHARMACOLOGY 
 
Pharmacokinetics:  After IV administration, a two compartmental model best fit 
the data with a median terminal half-life of 70.4 hours.  The mean clearance was 
97.9 ± 109.2 mL/hr (mean ± standard deviation).  Dose-dependent 
pharmacokinetics were observed with a larger area under the curve (AUC),  
 


 
S0801 
 
Page 10 
 
 
 
 
slower clearance, longer terminal half-life, and smaller volume of distribution at 
steady state observed with increasing predose levels of tositumomab antibody.  
The route of excretion was renal with 65 ± 13% of the injected dose recovered in 
the urine over the initial 5 day time period.  The mean total body effective half-
lives were 65.2 ± 12.5 and 65.8 ± 12.9 hours by sodium iodide probe counts and 
gamma camera counts, respectively.  Organ doses were modest and below 
normal tissue tolerances.  The mean splenic dose was 399 ± 215 cGy/75 cGy 
total body dose (TBD).  The kidney received 630 ± 201 cGy/75 cGy TBD.  The 
cGy doses to other normal tissues from a 75 cGy whole body dose were quite 
modest, with the liver and the lungs receiving an average dose of 256  ± 80 cGy 
and 182 ± 58 cGy, respectively.  The mean bladder wall dose was 202 ± 49 
cGy/75 cGy TBD, the mean bone marrow dose was 103 ± 15 cGy/75 cGy TBD, 
and the mean blood dose was 369 ± 97 cGy/75 cGy TBD.   
 
Formulation:  Tositumomab Antibody and Iodine-131 Tositumomab Antibody: 
 
Tositumomab antibody is a murine anti-human B-cell monoclonal antibody of the 
IgG2a subclass.  As formulated, tositumomab antibody is a sterile, clear, 
colorless liquid supplied in a 3 mL or 20 mL glass vial stoppered with a gray 
silicone-coated butyl rubber stopper and capped with an aluminum crimp seal.  
Each single-use 3 mL vial contains not less than 2.5 mL of solution; each single-
use 20 mL vial contains not less than 16.1 mL of solution.  The formulation or 
each single-use vial is: 
 
Protein concentration 14.0 ± 0.7 mg/mL  
 
Potassium phosphate:  10  mM, pH 7.2 ± 0.2  
 
Sodium Chloride:  145  mM 
 
Maltose:  10% 
 
Iodine-131 Tositumomab Antibody: 
 
The Iodine-131 tositumomab antibody is a sterile, colorless liquid in a glass vial 
stoppered with a gray silicone-coated butyl rubber stopper and capped with an 
aluminum crimp seal.  Each vial is intended for single-use only. 
 
The dosimetric vial contains not less than 1.4 mL of solution in a 10 mL vial 
consisting of: 
 
Protein concentration 1.1 - 2.5 mg/mL  
 
Calibrated activity:  8 - 12 mCi 
 
Povidone:  5.5% 
 
Ascorbic Acid:  0.1% 
 
Potassium phosphate:  12.5 mM, pH 6.8 - 7.2 
 
Sodium Chloride:  0.9% 
 
Maltose:  1 - 2%  
 
OR, the dosimetric vial may contain not less than 20 mL of solution in a 30 mL 
vial consisting of: 


 
S0801 
 
Page 11 
 
 
 
 
Protein concentration 0.10 - 0.25 mg/mL  
 
Calibrated activity:  12 - 18 mCi 
 
Povidone:  5.5% 
 
Ascorbic Acid:  0.1% 
 
Potassium phosphate:  12.5 mM, pH 6.5 - 7.2 
 
Sodium Chloride:  0.9% 
 
Maltose:  1 - 2%  
 
The therapeutic vial contains not less than 20 mL solution in a 30 mL vial 
consisting of: 
 
Protein concentration:  1.1 - 2.5 mg/mL 
 
Calibrated activity:  112 - 168 mCi 
 
Povidone:  5.5% 
 
Ascorbic Acid:  0.1% 
 
Potassium Phosphate:  12.5 mM, pH 6.5 - 7.5 
 
Sodium Chloride:  0.9% 
 
Maltose:  1 - 2% 
 
Storage and Stability: 
 
Tositumomab:  Non-radioactive anti-tositumomab will be shipped overnight as 
needed to the study site.  Anti-B1 must be stored at 2 - 8°C in a secure area until 
it is needed for use.  The vials are single-use as they do not contain preservative. 
 
I-131-Tositumomab:  The lead pot containing Iodine-131 Tositumomab must be 
stored in a freezer until it is thawed for administration to the patient.  See the 
section on Thawing for Administration in the User’s Instructions for complete 
instructions on the procedure for thawing the vials.  Allow approximately 20 
minutes for thawing of the 10 ml dosimetric vial and approximately 60 minutes for 
thawing of the 30 ml dosimetric or therapeutic vial. The thawed vial may be 
refrigerated at 2 - 8°C for up to 6 hours.  The product must be administered to 
the patient within 72 hours of the calibration date and time specified on the 
product label. 
 
Administration:  See Section 7.5c for detailed administration instructions for both 
unlabeled and I-131-labeled tositumomab. 
 
Supplier:  GlaxoSmithKline, will supply tositumomab antibody and I-131- 
tositumomab antibody free of charge for this study.  Any questions regarding 
tositumomab antibody or Iodine-131 tositumomab antibody may be directed to 
the Service Center at (toll free) 877/423-9927. 
 


 
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Revised 1/12/10 
 
 
 
 
Drug Ordering:  Unlabeled tositumomab antibody and I-131 tositumomab 
antibody (dosimetric and therapeutic) will be ordered by completing one form, the 
Study Drug Order Form for S0801 found on the members section of the 
Southwest Oncology Group website  
(https://swog.org/Members/ClinicalTrials/GetSecuredFile.asp?Document=MISC2
-0801.pdf) and faxing it to GlaxoSmithKline Clinical Research Department (fax 
number 877/279-1512).  The Study Drug Order Form must be faxed to 
GlaxoSmithKline by Wednesday, 4:00 p.m. Eastern Time (EST) prior to the 
treatment week.  The product will be shipped frozen on dry ice and will be sent to 
the site using priority overnight delivery.  Upon receipt, immediately follow the 
section on Procedure for Opening in the User’s Instructions.  For questions 
related to radiolabeled antibody ordering, call the Service Center at (toll free) 
877/423-9927. 
 
NOTE:  Institutions must be approved by GlaxoSmithKline and receive an 
on-site training session prior to administering I-131 labeled tositumomab 
antibody.  (See Section 15.1 for specific instructions.) 
 
Drug Returns:  Unused I-131 tositumomab antibody must be decayed at the site 
according to institutional policy.  Unused non-radiolabeled tositumomab antibody 
must be returned.  Contact the Service Center (toll free:  1-877-423-9927) for 
instructions.  Used empty vials (from both radiolabeled and non-radiolabeled 
antibody) should be disposed of at the site according to institutional policies. 
 
3.4 
Prednisone (NSC-10023) 
 
a. 
DESCRIPTION 
 
Prednisone is a glucocorticoid rapidly absorbed from the GI tract. 
 
b. 
TOXICOLOGY 
 
Human Toxicology:  Possible adverse effects associated with the use of 
prednisone are:  fluid and electrolyte disturbances, congestive heart failure in 
susceptible persons, hypertension, euphoria, personality changes, insomnia, 
mood swings, depression, exacerbation of infection (e.g., tuberculosis), 
exacerbation or symptoms of diabetes, psychosis, muscle weakness, 
osteoporosis, vertebral compression fractures, pancreatitis, esophagitis, peptic 
ulcer, dermatologic disturbances, convulsions, vertigo and headache, endocrine 
abnormalities, ophthalmic changes, and metabolic changes.  Some patients have 
experienced itching and other allergic, anaphylactic or other hypersensitivity 
reactions.  Withdrawal from prolonged therapy may result in symptoms including 
fever, myalgia and arthralgia.  Phenytoin phenobarbitol and ephedrine enhance 
metabolic clearance of corticosteroids. 
 
Corticosteroids should be used cautiously in patients with hypothyroidism, 
cirrhosis, ocular herpes simplex, existing emotional instability or psychotic 
tendencies, 
nonspecific 
ulcerative 
colitis, 
diverticulitis, 
fresh 
intestinal 
anastomoses, peptic ulcer, renal insufficiency, hypertension, osteoporosis and 
myasthenia gravis.  Immunization procedures (especially smallpox vaccination) 
should not be undertaken in patients on corticosteroids. 
 
c. 
PHARMACOLOGY 
 
Pharmacokinetics:  Natural and synthetic glucocorticoids are readily and 
completely absorbed from the GI tract.  Prednisone is very slightly soluble in 
water.  Glucocorticoids have salt-retaining properties.  The anti-inflammatory 
property of this drug is its ability to modify the body's immune system.  On the 
other hand, glucocorticoids suppress the body's response to viral as well as 
bacterial infections.   


 
S0801 
 
Page 13 
 
 
 
 
Formulation:  Prednisone is available in 2.5 mg, 5 mg, 10 mg, 20 mg and 50 mg 
tablets. 
 
Storage and Stability:  Prednisone should be stored at room temperature. 
 
Administration:  Prednisone is administered orally. 
 
Supplier:  Prednisone is commercially available and should be purchased by 
third party.  Prednisone will not be supplied by the NCI. 
 
3.5 
Rituximab Chimeric Monoclonal anti-CD20 Antibody (IDEC-C2B8) (NSC-687451) 
 
a. 
DESCRIPTION   
 
Rituximab is a mouse/human chimeric monoclonal antibody consisting of human 
IgG1 heavy and kappa light chain constant regions with murine variable regions 
from the murine IgG1 kappa anti-human CD20 monoclonal antibody rituximab.  
The rituximab antibody is produced by a Chinese hamster ovary transfectoma.   
 
b. 
TOXICOLOGY 
 
Human Toxicology: Single doses of up to 500 mg/m2 and weekly x 4 doses of 
375 mg/m2 have been administered without dose limiting toxicity.  Adverse 
events are most common during the initial antibody infusion and usually consist 
of Grade I, or 2 fever (73%), asthenia (16%) chills (38%) nausea (19%), vomiting 
(11%), rash (14%) and tumor site pain (3%).  Grade 1 or 2 hypotension (8%) 
may be treated with IV fluids.  Hematologic toxicity is usually mild and reversible.  
Transient decreases in the WBC or platelet count have been observed - 
especially in patients with high levels of circulating tumor cells or bone marrow 
involvement.  Two patients have had late-onset Grade 4 neutropenia at four and 
ten months that was attributed to an unknown cause, were transient and 
resolved.  Infections (Grade 1 and 2) have not been related to dose level.  
Symptoms are generally associated with the initial antibody infusions and 
diminish in frequency with each successive infusion.   
 
Severe Infusion and Hypersensitivity Reactions:  Rituximab has caused severe 
infusion reactions.  In some cases, these reactions were fatal.  An infusion-
related symptom complex consisting of fever and chills/rigors has occurred in the 
majority of patients during the first rituximab infusion.  Signs and symptoms of 
severe infusion reactions may include urticaria, hypotension, angioedema, 
hypoxia, or bronchospasm.  The most severe manifestations and sequelae 
include pulmonary infiltrates, acute respiratory distress syndrome, myocardial 
infarction, ventricular fibrillation, cardiogenic shock, and anaphylactic and 
anaphylactoid events.  These reactions generally occurred within 30 minutes to 2 
hours of beginning the first infusion, and resolved with slowing or interruption of 
the rituximab infusion and with supportive care (including, but not limited to IV 
saline, diphenhydramine, and acetaminophen). 
 
Tumor Lysis Syndrome:  Rituximab rapidly decreases benign and malignant 
CD20 positive cells.  Tumor lysis syndrome has been reported to occur within 12 
to 24 hours after the first rituximab infusion in patients with high numbers of 
circulating malignant lymphocytes.  Patients with high tumor burden (bulky 
lesions) may also be at risk.  Patients at risk for developing tumor lysis syndrome 
should be followed closely and appropriate laboratory monitoring performed. 
 


 
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Hepatitis B Reactivation with Related Fulminant Hepatitis and Other Viral 
Infections:  Hepatitis B virus (HBV) reactivation with fulminant hepatitis, hepatic 
failure, and death has been reported in some patients with hematologic 
malignancies treated with rituximab.  The majority of patients received rituximab 
in combination with chemotherapy.  The median time to the diagnosis of hepatitis 
was approximately 4 months after the initiation of rituximab and approximately 
one month after the last dose. 
 
Persons at high risk of HBV infection should be screened before initiation of 
rituximab.  Carriers of hepatitis B should be closely monitored for clinical and 
laboratory signs of active HBV infection and for signs of hepatitis during and for 
up to several months following rituximab therapy.  In patients who develop viral 
hepatitis, rituximab and any concomitant chemotherapy should be discontinued 
and appropriate treatment including antiviral therapy initiated.  There are 
insufficient data regarding the safety of resuming rituximab therapy in patients 
who develop hepatitis subsequent to HBV reactivation.   
 
The following additional serious viral infections, either new, reactivated or 
exacerbated, have been identified in clinical studies or postmarketing reports.  
The majority of patients received rituximab in combination with chemotherapy or 
as part of a hematopoietic stem cell transplant.  These viral infections included 
JC virus (progressive multifocal leukoencephalopathy [PML]), cytomegalovirus, 
herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and 
hepatitis C.  In some cases, the viral infections occurred up to one year following 
discontinuation of rituximab and have resulted in death.   
 
Severe Mucocutaneous Reactions:  Mucocutaneous reactions, some with fatal 
outcome, have been reported in patients treated with rituximab.  These reports 
included paraneoplastic pemphigus (an uncommon disorder which is a 
manifestation of the patient's underlying malignancy), Stevens-Johnson 
syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal 
necrolysis.  The onset of the reaction in the reported cases has varied from 1-13 
weeks following rituximab exposure.  Patients experiencing a severe 
mucocutaneous reaction should not receive any further infusions and seek 
prompt medical evaluation.  Skin biopsy may help to distinguish among different 
mucocutaneous reactions and guide subsequent treatment.  The safety of 
readministration of rituximab to patients with any of these mucocutaneous 
reactions has not been determined.  
 
Bowel Obstruction and Perforation:  Abdominal pain, bowel obstruction and 
perforation, in some cases leading to death, were observed in patients receiving 
rituximab in combination with chemotherapy for DLBCL.  In post-marketing 
reports, which include both patients with low-grade or follicular NHL and DLBCL, 
the mean time to onset of symptoms was 6 days (range 1-77) in patients with 
documented gastrointestinal perforation.  Complaints of abdominal pain, 
especially early in the course of treatment, should prompt a thorough diagnostic 
evaluation and appropriate treatment.   
 
Cardiovascular:  The incidence of serious cardiovascular events in the double-
blind clinical trial for rheumatoid arthritis (RA) patients was 1.7% and 1.3% in 
rituximab and placebo groups, respectively.  Three cardiovascular deaths 
occurred during the double-blind period of the RA studies, including all rituximab 
regimens (3/759 = 0.4%) as compared to none in the placebo group (0/389).   
 
Since patients with RA are at increased risk for cardiovascular events compared 
to the general population, patients with RA should be monitored throughout the 
infusion and rituximab should be discontinued in the event of a serious or life-
threatening cardiac event.   


Revised 6/3/10 
S0801 
Revised 3/28/14 
Page 15 
 
 
 
 
Rituximab infusions should be discontinued in the event of serious or life-
threatening cardiac arrhythmias.  Patients who develop clinically significant 
arrhythmias should undergo cardiac monitoring during and after subsequent 
infusions of rituximab.  Patients with pre-existing cardiac conditions including 
arrhythmias and angina have had recurrences of these events during rituximab 
therapy and should be monitored throughout the infusion and immediate post-
infusion period.  
 
Renal:  Rituximab administration has been associated with severe renal toxicity 
including acute renal failure requiring dialysis and in some cases, has led to a 
fatal outcome in hematologic malignancy patients.  Renal toxicity has occurred in 
patients with high numbers of circulating malignant cells (> 25,000/mm3) or high 
tumor burden who experience tumor lysis syndrome and in patients with NHL 
administered concomitant cisplatin therapy during clinical trials.  The combination 
of cisplatin and rituximab is not an approved treatment regimen.  If this 
combination is used in clinical trials extreme caution should be exercised; 
patients should be monitored closely for signs of renal failure.  Discontinuation of 
rituximab should be considered for those with rising serum creatinine or oliguria.   
 
Immunization:  The safety of immunization with live viral vaccines following 
rituximab therapy has not been studied and vaccination with live virus vaccines is 
not recommended.  The ability to generate a primary or anamnestic humoral 
response to vaccination is currently being studied.  For patients with NHL, the 
benefits of primary and/or booster vaccinations should be weighed against the 
risks of delay in initiation of rituximab therapy.   
 
Carcinogenesis, Impairment of Fertility, Pregnancy, and Nursing:  No long-term 
animal studies have been performed to establish the carcinogenic potential of 
rituximab.  Studies also have not been completed to assess mutagenic potential 
of rituximab, or to determine potential effects on fertility in males or females.  
Individuals of childbearing potential should use effective contraceptive methods 
during treatment and for up to 12 months following rituximab therapy.   
 
It is not known whether rituximab is excreted in human milk.  Because human 
IgG is excreted in human milk and the potential for absorption and 
immunosuppression in the infant is unknown, women should be advised to 
discontinue nursing until circulating drug levels are no longer detectable.   
 
Comprehensive Adverse Events and Potential Risks list (CAEPR) For 
Rituximab (NSC 687451) 
 
The Comprehensive Adverse Event and Potential Risks list (CAEPR) provides a 
single list of reported and/or potential adverse events (AE) associated with an 
agent using a uniform presentation of events by body system. In addition to the 
comprehensive list, a subset, the Agent Specific Adverse Event List (ASAEL), 
appears in a separate column and is identified with bold and italicized text. This 
subset of AEs (ASAEL) contains events that are considered 'expected' for 
expedited reporting purposes only. Refer to the 'CTEP, NCI Guidelines: Adverse 
Event Reporting Requirements'  
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adverse_events.h
tm for further clarification. Frequency is provided based on 986 patients. Below is 
the CAEPR for Rituximab. 


Revised 6/3/10 
S0801 
Revised 3/28/14 
Page 16 
 
 
 
 
Version 2.1, March 19, 20101 
 
 
 Adverse Events with Possible  
 Relationship to Rituximab 
 (CTCAE 4.0 Term) 
[n= 986] 
 
 
 
 EXPECTED AEs 
FOR CTEP-AERS 
REPORTING  
Agent Specific 
Adverse Event List
(ASAEL) 
 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious 
(<3%) 
 
Expected 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
  
 
Anemia 
 
 Anemia 
 
Blood and lymphatic 
system disorders - 
Other (Hyperviscosity: 
Waldenstrom’s) 
 
 Blood and lymphatic 
system disorders - 
Other 
(Hyperviscosity: 
Waldenstrom’s) 
 
Febrile neutropenia 
 
 Febrile neutropenia
CARDIAC DISORDERS  
  
 
Myocardial infarction 
 
 Myocardial 
infarction 
 
Sinus tachycardia 
 
 Sinus tachycardia 
 
Supraventricular 
tachycardia 
 
 Supraventricular 
tachycardia 
GASTROINTESTINAL DISORDERS  
  
 
Abdominal pain 
 
 Abdominal pain 
 
Diarrhea 
 
 Diarrhea 
 
Nausea 
 
 Nausea 
 
Vomiting 
 
 Vomiting 
GENERAL DISORDERS AND ADMINISTRATION SITE 
CONDITIONS 
  
Chills 
 
 
 Chills 
 
Edema limbs 
 
  
 
Fatigue 
 
 Fatigue 
Fever 
 
 
 Fever 
Infusion related 
reaction 
 
 
 Infusion related 
reaction 
 
Pain 
 
  
IMMUNE SYSTEM DISORDERS 
  
 
Allergic reaction 
 
 Allergic reaction 
 
 
Anaphylaxis 
  
 
Serum sickness 
 
 Serum sickness 
INFECTIONS AND INFESTATIONS 
  
 
Infection2
 
 Infection2
 
Infections and 
infestations - Other 
(Activation of Hepatitis 
B, C, CMV, parvovirus 
B19, JC virus, varicella 
zoster, herpes simplex, 
West Nile virus) 
 
 Infections and 
infestations - Other 
(Activation of 
Hepatitis B, C, CMV, 
parvovirus B19, JC 
virus, varicella 
zoster, herpes 
simplex, West Nile 
virus) 
 
Infections and 
infestations - Other 
(Infection in HIV Positive 
Patients) 
 
  


Revised 6/3/10 
S0801 
 
Page 17 
 
 
 
 
INVESTIGATIONS 
  
Lymphocyte count 
decreased 
 
 
 Lymphocyte count 
decreased 
 
Neutrophil count 
decreased 
 
 Neutrophil count 
decreased 
 
Platelet count 
decreased 
 
 Platelet count 
decreased 
 
White blood cell 
decreased 
 
 White blood cell 
decreased 
METABOLISM AND NUTRITION DISORDERS  
  
 
Hyperglycemia 
 
  
 
Hypocalcemia 
 
 Hypocalcemia 
 
Hypokalemia 
 
  
 
 
Tumor lysis 
syndrome 
 Tumor lysis 
syndrome 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS   
 
Arthralgia 
 
 Arthralgia 
 
Back pain 
 
  
 
Myalgia 
 
 Myalgia 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL 
CYSTS AND POLYPS) 
  
 
Tumor pain 
 
 Tumor pain 
NERVOUS SYSTEM DISORDERS 
  
 
Dizziness 
 
 Dizziness 
 
Headache 
 
 Headache 
 
Lethargy 
 
  
 
 
Nervous system 
disorders - Other 
(progressive 
multifocal 
leukoencepha-
lopathy) 
  
 
Seizure 
 
 Seizure 
RENAL AND URINARY DISORDERS 
  
 
Acute kidney injury 
 
  
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
  
 
 
Adult respiratory 
distress syndrome 
  
 
Allergic rhinitis 
 
  
 
Bronchospasm 
 
 Bronchospasm 
 
Cough 
 
 Cough 
 
Dyspnea 
 
 Dyspnea 
 
Hypoxia 
 
 Hypoxia 
 
Pneumonitis 
 
 Pneumonitis 
 
Sore throat 
 
  
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
  
 
 
Erythema 
multiforme 
 Erythema 
multiforme 
 
Hyperhidrosis 
 
 Hyperhidrosis 
 
Pruritus 
 
 Pruritus 
 
Rash maculo-papular 
 
 Rash maculo-
papular 
 
Skin and subcutaneous 
tissue disorders - Other 
(angioedema) 
 
  
 
 


Revised 6/3/10 
S0801 
 
Page 18 
 
 
 
 
 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS (contd.) 
  
 
 
Stevens-Johnson 
syndrome 
 Stevens-Johnson 
syndrome 
 
 
Toxic epidermal 
necrolysis 
 Toxic epidermal 
necrolysis 
 
Urticaria 
 
 Urticaria 
VASCULAR DISORDERS 
  
 
Flushing 
 
 Flushing 
 
Hypertension 
 
 Hypertension 
 
Hypotension 
 
 Hypotension 
1 This table will be updated as the toxicity profile of the agent is revised.  
Updates will be distributed to all Principal Investigators at the time of revision.  
The current version can be obtained by contacting PIO@CTEP.NCI.NIH.GOV.  
Your name, the name of the investigator, the protocol and the agent should be 
included in the e-mail. 
2 Infection includes all 75 sites of infection under the INFECTIONS AND 
INFESTATIONS SOC. 
3 Gastrointestinal 
obstruction 
includes 
Colonic 
obstruction, 
Duodenal 
obstruction, Esophageal obstruction, Ileal obstruction, Jejunal obstruction, 
Obstruction gastric, Rectal obstruction, and Small intestinal obstruction under 
the GASTROINTESTINAL DISORDERS SOC. 
4 Gastrointestinal perforation includes Colonic perforation, Duodenal perforation, 
Esophageal perforation, Gastric perforation, Ileal perforation, Jejunal 
perforation, Rectal perforation, and Small intestinal perforation under the 
GASTROINTESTINAL DISORDERS SOC. 
 
Also reported on rituximab trials but with the relationship to rituximab still 
undetermined: 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Bone marrow hypocellular; 
Hemolysis 
CARDIAC DISORDERS - Atrial fibrillation; Atrial flutter; Cardiac disorders - Other 
(cyanosis); Left ventricular systolic dysfunction; Sinus bradycardia; Ventricular 
fibrillation 
 
EYE DISORDERS - Conjunctivitis; Eye disorders - Other (ocular edema); Uveitis; 
Watering eyes 
GASTROINTESTINAL DISORDERS - Constipation; Dyspepsia; Dysphagia; 
Gastrointestinal obstruction3; Gastrointestinal perforation4; Mucositis oral 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Flu like 
symptoms; Non-cardiac chest pain 
INFECTIONS AND INFESTATIONS - Infections and infestations - Other 
(Opportunistic infection associated with >=Grade 2 Lymphopenia) 
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - Fracture 
INVESTIGATIONS 
- 
Alkaline 
phosphatase 
increased; 
Aspartate 
aminotransferase increased; Blood bilirubin increased; Cardiac troponin I 
increased; Cardiac troponin T increased; Creatinine increased; Investigations - 
Other (hyperphosphatemia); Investigations - Other (LDH increased); Weight loss 
METABOLISM AND NUTRITION DISORDERS - Anorexia; Hypercalcemia; 
Hyperkalemia; 
Hypermagnesemia; 
Hypernatremia; 
Hyperuricemia; 
Hypoglycemia; Hypomagnesemia; Hyponatremia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Arthritis 
NERVOUS SYSTEM DISORDERS - Nervous system disorders - Other (Cranial 
Neuropathy NOS); Peripheral motor neuropathy; Peripheral sensory neuropathy; 
Pyramidal tract syndrome; Reversible posterior leukoencephalopathy syndrome; 
Syncope 


Revised 6/3/10 
S0801 
 
Page 18a 
 
 
 
 
PSYCHIATRIC DISORDERS - Agitation; Anxiety; Depression; Insomnia 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Epistaxis; 
Pharyngolaryngeal pain; Pleural effusion; Pulmonary edema; Respiratory, 
thoracic and mediastinal disorders - Other (bronchiolitis obliterans) 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Alopecia; Skin and 
subcutaneous tissue disorders - Other (paraneoplastic pemphigus) 
VASCULAR DISORDERS - Phlebitis; Thromboembolic event; Vasculitis 
 
Note: Rituximab in combination with other agents could cause an exacerbation 
of any adverse event currently known to be caused by the other agent, or the 
combination may result in events never previously associated with either agent. 
 
c. 
PHARMACOLOGY 
 
Pharmacokinetics:  In prior studies patients treated at the 375 mg/m2 dose levels 
exhibited detectable antibody concentrations throughout the treatment period.  
Most patients exhibited increasing pre-infusion antibody concentrations with each 
subsequent infusion.  In nine patients, the T1/2 following the first antibody infusion 
was 59.8 hours (11.1 - 104.6 hr) with a Cmax of 271 mcg/mL.  Following the fourth 
antibody infusion when circulating B cells had been depleted and antigenic sites 
coated, the T 1/2 was 174 hr (26.4 - 442.3 hr) and Cmax 496.7 mcg/mL.   
 
Formulation:  Rituximab antibody will be provided in 100 mg (10 mL) and 500 mg 
(50 mL) pharmaceutical grade vials at a concentration of 10 mg of protein per mL 
(actual concentration should be noted on the product label).   
 
Storage and Stability:  Rituximab should be stored at 2 - 8°C.  Do not freeze or 
store at room temperature.  The product is a protein- HANDLE GENTLY AND 
AVOID FOAMING.  The avoidance of foaming during product handling, 
preparation and administration is important, as foaming may lead to the de-
naturing of the product proteins.   


 
S0801 
 
Page 19 
 
 
 
 
Administration:  The total amount of rituximab needed for a patient's initial four 
infusions (induction therapy) will be determined AT STUDY ENTRY.  For 
subsequent maintenance rituximab, the dose should be recalculated at the 
beginning of each cycle. 
 
Prepare the rituximab infusion solution as follows: 
 
1. 
If a delay in administration of the infusion occurs after the product is 
prepared, the properly identified container may be kept refrigerated at 2 - 
8°C for up to six hours.   
 
2. 
Use sterile, non-pyrogenic, disposable containers, syringes, needles, 
stopcocks and transfer tubing, etc. 
 
3. 
Transfer of the rituximab from the glass vial should be made by using a 
suitable sterile graduated syringe and large gauge needle. 
 
4. 
Transfer the appropriate amount of rituximab from the graduated syringe, 
into a partially filled IV pack containing sterile, pyrogen-free 0.9% sodium 
chloride solution, USP (saline solution).  The final concentration of 
rituximab in saline solution should be a maximum of 1 mg/ml.  Mix by 
inverting the bag gently.  DO NOT USE A VACUUM APPARATUS to 
transfer the product from the syringe to the plastic bag. 
 
5. 
Place an IV administration set into the outflow port of the bag containing 
the infusion solution. 
 
6. 
NOTE:  DO NOT USE evacuated glass containers which require vented 
administration sets because this causes foaming as air bubbles pass 
through the solution. 
 
The administration of rituximab will be accomplished by slow IV infusion.  
CAUTION: DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS.  
IV pumps such as the IMED 960 may be used with the rituximab infusion.  DO 
NOT INFUSE CONCOMITANTLY with another IV solution or IV medications.  
Prime the line with the rituximab solution such that approximately 30 mL are 
delivered.  This will saturate the filter and tubing. 
 
Supplier:  This drug is commercially available for purchase by the third party.  
This drug will not be supplied by the NCI. 
 
3.6 
Vincristine (Oncovin) (NSC-67574) 
 
a. 
DESCRIPTION 
 
Chemistry:  Vincristine is one of the so-called vinca-alkaloids and is extracted 
from the plant cantharanthus roseus (vinca rosea). 
 
Biochemistry:  This drug appears to produce the arrest of mitosis in animal cells 
by interfering with microtubule function. 
 
b. 
TOXICOLOGY 
 
Human Toxicology:  The primary toxic effects of vincristine are neurological with 
paresthesia, weakness, muscle wasting, motor difficulties including difficulty 
walking and slapping gait, loss of deep tendon reflexes, sensory loss, neuritic 
pain, paralytic ileus, bladder atony, and constipation.  Rarely, it produces 
myelosuppression.  Other side effects may include alopecia, allergic reactions,   
 


 
S0801 
 
Page 20 
 
 
 
 
(including rare anaphylaxis, rash and edema), jaw pain, hypertension, 
hypotension, nausea, vomiting, diarrhea, fever, headache, oral ulceration, optic 
atrophy with blindness, ptosis, diplopia and photophobia.  The occurrence of 
acute 
leukemia 
has 
been 
reported 
rarely 
in 
patients 
treated 
with 
anthracycline/alkylator combination chemotherapy. 
 
c. 
PHARMACOLOGY 
 
Pharmacokinetics:  After IV administration, a triphasic serum decay pattern 
follows with half-lives of 5 minutes, 2 - 3 hours, and 85 hours.  The range of 
terminal half-life is 19 - 155 hours.  Excretion is 80% in the feces and 10 - 20 % 
in the urine. 
 
The liver is the major excretory organ in humans and animals, and biliary 
obstruction causes increased toxicity in man. 
 
Formulation:  1 mg/1 mL, 2 mg/2 mL, and 5 mg/5 mL vials containing solution.  It 
is also available in 1 mg/mL and 2 mg/2 mL disposable syringes. 
 
Storage and Stability:  It should be stored under refrigeration.  Vincristine is 
available with and without preservatives so the time-frame for use once the vial 
has been entered varies.  The intact vials have a labeled expiration date.  Protect 
from light.  Parenteral drug products should be inspected visually for particulate 
matter and discoloration prior to administration. 
Administration:  Vincristine should be administered intravenously through a 
freely-running IV.  If it extravasates, it produces a severe local reaction with skin 
slough.  FATAL IF GIVEN INTRATHECALLY, FOR INTRAVENOUS USE 
ONLY. 
 
Supplier:  Vincristine is commercially available, and should be purchased through 
a third party.  This drug will NOT be supplied by the NCI. 
  
4.0 
STAGING CRITERIA  
 
4.1 
The Ann Arbor staging criteria will be used.  Stage is based on extent of disease at the 
time of diagnosis.  Bulky disease determination is made after surgical resection, if 
applicable. 
 
4.2 
Ann Arbor Classification (AJCC Manual for Staging of Cancer, 6th ed., 2002) 
 
 
STAGE II 
Involvement of two or more lymph node regions on the same side of the 
diaphragm (II) or localized involvement of an extralymphatic organ or site 
and its associated regional lymph nodes (IIE). 
 
STAGE III 
Involvement of lymph node regions on both sides of the diaphragm (III), 
which may be accompanied by localized involvement of an associated 
extralymphatic organ or site (IIIE) or spleen (IIIS) or both (IIISE). 
 
STAGE IV 
Diffuse or disseminated involvement of one or more extra lymphatic 
organs with or without associated lymph node involvement, or isolated 
extralymphatic organ involvement with distant (non-regional) nodal 
involvement). 
 
A = Asymptomatic 
 
B = Unexplained fever (38°C), night sweats, unexplained weight loss > 10% of body 
weight over the previous six months 
 
 
4.3 
"Bulky" is defined as a mediastinal mass > 1/3 of the maximum chest diameter (i.e., 
internal dimension of the thoracic cavity measured at its widest point per radiograph) or 
any other mass ≥ 10 cm in maximum diameter. 


 
S0801 
 
Page 21 
 
Revised 1/12/10 
 
 
 
 
5.0 
ELIGIBILITY CRITERIA 
 
Each of the criteria in the following section must be met in order for a patient to be considered eligible for 
registration.  Use the spaces provided to confirm a patient's eligibility.  For each criterion requiring test 
results and dates, please record this information on the S0801 Prestudy Form (Form #62797) and submit 
to the Data Operations Center in Seattle (see Section 14.0).  Any potential eligibility issues should be 
addressed to the Data Operations Center in Seattle at 206/652-2267 prior to registration.   
 
In calculating days of tests and measurements, the day a test or measurement is done is considered Day 
0.  Therefore, if a test is done on a Monday, the Monday four weeks later would be considered Day 28.  
This allows for efficient patient scheduling without exceeding the guidelines.  If Day 28 or 42 falls on a 
weekend or holiday, the limit may be extended to the next working day.   
 
The registering institution must have submitted the S0801 Site Contact Information Form (Appendix 19.4) 
and a copy of their radioactive materials license to GlaxoSmithKline and been approved by 
GlaxoSmithKline for this study.  (The approval process is required only for the FIRST patient registered to 
this study by any one institution.)  Institutions previously approved by GlaxoSmithKline (formerly Corixa) 
for the Southwest Oncology Group study S0433 or S0016, need not repeat the approval process; 
however, they must still submit the completed form and license to GlaxoSmithKline. 
 
SWOG Patient No.   
 
 
Patient's Initials (L, F, M)   
 
 
 
 5.1 
All patients must have previously untreated Stage III, IV, or bulky Stage II follicular B-cell 
non-Hodgkin’s lymphoma (Grade 1, Grade 2 or Grade 3), which is positive for CD20.  A 
pathology report providing confirmation of CD20 expression must be submitted per 
Section 14.4.  Diffuse large cell component must be less than 25% of the biopsy. 
 
 
 5.2 
Pathology Review:  Adequate sections and a paraffin block or at least 10 unstained 
sections from the original diagnostic specimen must be available for submission for 
review by the lymphoma pathology group as outlined in Section 12.0.  An adequate 
biopsy requires sufficient tissue to establish the architecture and a WHO histologic 
subtype with certainty.  Thus, core biopsies, especially multiple core biopsies MAY be 
adequate; whereas, needle aspirations or cytologies are not adequate.  With patient's 
consent, any left over tissue not consumed by testing will be retained for future studies. 
 
 
 5.3 
All patients must have bidimensionally measurable disease (defined in Section 10.1a) 
documented within 28 days prior to registration.  Patients with non-measurable disease 
(defined in Section 10.1b) in addition to measurable disease must have all non-
measurable disease assessed with 42 days prior to registration. 
 
 
 5.4 
Patients must have a unilateral or bilateral bone marrow aspirate and biopsy performed 
within 42 days prior to registration.  However, if the most recent biopsy was positive and 
was performed more than 42 days but within 6 months prior to registration, the procedure 
does NOT need to be repeated. 
 
 
 5.5 
Patients must have a CT scan of the chest and abdomen/pelvis performed within 28 days 
prior to registration.  PET/CT is allowed if CT is of diagnostic quality and contrast 
enhanced. 
 
 
 5.6 
Patients are encouraged to participate in the central lymphoma repository tissue 
procurement protocol, SWOG-8819, and the serum procurement protocol, SWOG-8947, 
as outlined in Section 15.0.  With the patient's consent, specimens should be submitted 
as specified in SWOG-8819 and SWOG-8947 and Section 9.0 of this protocol.  
 
 
 5.7 
Patients must be ≥ age 18. 


 
S0801 
 
Page 22 
 
 
 
 
SWOG Patient No.   
 
 
Patient's Initials (L, F, M)   
 
 
 
 5.8 
Patients must not have clinical evidence of central nervous system involvement by 
lymphoma.  Any laboratory or radiographic tests performed to assess CNS involvement 
must be negative within 42 days of registration. 
 
 
 5.9 
Patients must not have received prior chemotherapy, radiation, or antibody therapy for 
lymphoma. 
 
 
 5.10 
All patients must have a Zubrod performance status of 0 - 2 (see Section 10.4). 
 
 
 5.11 
Serum LDH and hemoglobin must be measured within 28 days prior to registration. 
 
 
 5.12 
Patients must have a cardiac ejection fraction ≥ 45% by MUGA scan or an ECHO with no 
significant abnormalities within 42 days prior to registration. 
 
 
 5.13 
Patients known to be HIV positive, or who have a history of solid organ transplantation 
are ineligible due to concern over immunosuppression associated with B-cell depletion.  
Patients at high risk of Hepatitis B virus (HBV) infection are eligible, but should be 
screened before initiation of rituximab (See Section 2.0 for justification). 
 
 
 5.14 
Patients requiring continuous supplemental oxygen therapy are ineligible. 
 
 
 5.15 
No other prior malignancy is allowed except for the following: adequately treated basal 
cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II 
cancer from which the patient is currently in complete remission, or any other cancer 
from which the patient has been disease-free for 5 years. 
 
 
 5.16 
Pregnant or nursing women may not participate.  Women or men of reproductive 
potential must have agreed to use an effective contraceptive method from the time of 
registration to 12 months after completion of rituximab maintenance.  (For justification, 
see Sections 2.0 and 3.0.) 
 
 
 5.17 
All patients must be informed of the investigational nature of this study and must sign and 
give written informed consent in accordance with institutional and federal guidelines. 
 
 
 5.18 
At the time of patient registration, the treating institution's name and ID number must be 
provided to the Data Operations Center in Seattle in order to ensure that the current 
(within 365 days) date of institutional review board approval for this study has been 
entered into the data base. 
 
SECOND REGISTRATION: 
 
 
 5.19 
Patients must have completed R-CHOP+ I-131 tositumomab therapy and have stable 
disease or better documented within 28 days prior to registering to Step 2, rituximab 
maintenance therapy. 
 
 
 5.20 
Patients must be planning to begin rituximab maintenance therapy approximately 7 
months after receiving therapeutic I-131 tositumomab treatment.   


 
S0801 
 
Page 23 
 
Revised 9/24/10 
 
 
 
 
6.0 
STRATIFICATION FACTORS 
 
Stratification factors are not applicable to this study. 
 
 
7.0 
TREATMENT PLAN   
 
For treatment or dose modification related questions, please contact Dr. Friedberg at 585/273-
4150, or Dr. Press at 206/667-1872.  For dosing principles or questions, please consult the 
Southwest Oncology Group Policy #38 "Dosing Principles for Patients on Clinical Trials" at 
http://swog.org (then click on "Policies and Manuals" under the "Visitors" menu and choose Policy 
38). 
 
7.1 
Good Medical Practice 
 
The following pre-study tests must be obtained within 28 days prior to registration in 
accordance with good medical practice.  Results of these tests do not determine eligibility 
and minor deviations would be acceptable if they do not impact on patient safety in the 
clinical judgment of the treating physician.  The Study Coordinator must be contacted if 
there are significant deviations in the values of these tests.  If an individual test is 
considered to be unnecessary, the rationale for not conducting the test must be 
documented in the medical record. 
 
a. 
Platelets > 100,000 cells/mcL; ANC > 1,000 cells/mcL 
 
b. 
Bilirubin ≤ 2 x ULN (unless from Gilbert's syndrome or NHL) 
 
c. 
Creatinine ≤ 2 x ULN 
 
d.   
It is suggested that Beta 2 microglobulin, urinalysis, uric acid, transaminases, 
and a Hepatitis B virus (HBV) screening be performed as baseline prestudy tests 
to assess potential treatment-related toxicities.  These tests are not required for 
eligibility. 
 
e. 
PET scans:  The role of PET imaging in follicular lymphoma is controversial, and 
is only required for Day 226 restaging for this study.  PET/CT scans should not 
replace CT scans required by the protocol.  There is no role for routine PET 
imaging during subsequent restaging procedures. 
 
7.2 
Concomitant Medications: 
 
a. 
To prevent tumor lysis syndrome in patients with bulky tumors, oral or IV fluid 
intake in excess of 2 L daily is encouraged during therapy.  In addition, the 
routine administration of allopurinol (300 mg/day) is recommended prior to and 
during the first cycle of chemotherapy. 
 
b. 
Growth factors, including G-CSF, GM-CSF, and Neulasta are also permitted at 
the discretion of the treating physician (see Section 8.5). 
 
c. 
The use of routine acetominophen 500 - 1,000 mg p.o. and diphenhydramine 25 
mg p.o. or I.V. as premedications is REQUIRED prior to antibody therapy unless 
medically contraindicated.  Diphenhydramine, epinephrine and hydrocortisone 
need to be available during rituximab and tositumomab infusions. 
 
d. 
Prophylactic antibiotic therapy to prevent febrile neutropenia is at the discretion 
of the treating physician. 
 


 
S0801 
 
Page 24 
 
 
 
 
7.3 
R-CHOP 
 
Treatment with CHOP will be administered every 21 days for a maximum of 6 cycles (one 
cycle is defined as a single 21 day course of treatment).  Rituximab will be given before 
chemotherapy.  If circulating lymphocyte count exceeds 20,000 cells/mcL, rituximab 
will be omitted for the first cycle of therapy only.  During the final two cycles, 
patients will only receive CHOP chemotherapy without rituximab.  Patients with 
progressive disease at restaging (after 6 cycles) will discontinue treatment.  R-CHOP will 
be given as indicated below. 
 
AGENT 
DOSE 
ROUTE 
SCHEDULE 
REPEAT 
TREATMENT 
INTERVAL 
Cyclophosphamide 
750 mg/m2 
IV over 15 
minutes 
Day 1 
Every 21 days 
for 6 cycles 
Doxorubicin 
50 mg/m2 
Slow IV 
infusion 
Day 1 
Every 21 days 
for 6 cycles 
Vincristine 
1.4 mg/m2  
(max 2.0 mg) 
Slow IV 
infusion 
Day 1 
Every 21 days 
for 6 cycles 
Prednisone 
100 mg 
PO 
Days 1-5 
Every 21 days 
for 6 cycles 
Rituximab 
375 mg/m2 
Slow IV 
infusion 
Day 1 
Every 21 days 
for 4 cycles 
 
7.4 
Evaluation for I-131 Tositumomab Therapy 
 
Patients will be restaged 3-4 weeks after Day 1 dose of Cycle 6 of induction R-CHOP 
therapy, with CT scans of the chest, abdomen, and pelvis AND a bone marrow biopsy 
and aspiration, if initially involved with lymphoma (see Section 9.0).  The following 
conditions must be met prior to proceeding with I-131 tositumomab antibody 
treatment.  Patients who do not qualify for I-131 tositumomab antibody treatment 
upon re-evaluation will be removed from protocol treatment. 
 
a. 
The training session with GlaxoSmithKline must have been completed (see 
Section 7.5a). 
 
b.  
Patients must have stable disease or better. 
 
c. 
Patients must have no more than 25% of the intratrabecular marrow space 
involved by lymphoma in bone marrow biopsy specimens as assessed 
microscopically after completion of 6 cycles of R-CHOP chemotherapy.  Bilateral 
posterior iliac crest core biopsies are required if the percentage of intratrabecular 
space involved exceeds 10% on a unilateral biopsy.  The mean of bilateral 
biopsies must be no more than 25%.  The procedure for bilateral bone marrow 
biopsy analysis of marrow involvement is included in Appendix 19.2. 
 
d.   
Patients must have granulocytes ≥ 1,500/mcL and platelets ≥ 100,000/mcL within 
14 days of the planned dosimetric infusion.  Patients must not have active 
obstructive hydronephrosis. 
 
7.5 
Tositumomab and I-131 Tositumomab  
 
a. 
Institutions 
must 
have 
completed 
an 
on-site 
training 
session 
with 
GlaxoSmithKline representatives to review the details of drug administration and 
dosimetry prior to treating a patient with tositumomab and Iodine-131 
tositumomab.  The training session must occur prior to the dosimetric infusion of 
I-131 tositumomab, and the date of the training session must be noted on the  
 


 
S0801 
 
Page 25 
 
Revised 2/8/10 
 
 
 
 
S0801 Tositumomab Treatment Form (Form #57447).  For subsequent patients, 
the original training session date must still be noted on the S0801 Tositumomab 
Treatment Form (Form #57447). 
 
b. 
GlaxoSmithKline will contact each institution (by telephone) to provide assistance 
and arrange for training (if required, see Section 15.1).  The training session 
must be performed only for the FIRST patient registered to this study at any one 
institution.  However, retraining is available upon institutional request. 
 
c. 
Tositumomab and I-131 Tositumomab will be given as indicated below:   
 
AGENT 
DOSE 
ROUTE 
SCHEDULE 
Unlabeled Tositumomab 
Antibody** 
450 mg 
IV over 1 
hour 
Within 12 weeks after 
completion of CHOP  
(last dose of Cycle 6) 
Dosimetric Dose +ƒ 
35 mg 
IV over 20 
minutes 
After infusion of unlabeled 
tositumomab antibody 
Unlabeled Tositumomab 
Antibody** 
450 mg 
IV over 1 
hour 
Within 7-14 days after the 
dosimetric dose√ 
Therapeutic Dose +ƒ 
35 mg 
IV over 20 
minutes 
After infusion of unlabeled 
tositumomab antibody √ 
** Patients must receive tositumomab, 450 mg of unlabeled tositumomab antibody (to 
50 mL using 0.9% sodium chloride) prior to the dosimetric dose.  Seven to fourteen 
days later the unlabelled tositumomab dose is repeated followed by the therapeutic 
dose, as described in Section 7.6.  Patients must be premedicated with 
acetaminophen 650 mg po and diphenhydramine 50 mg po prior to administration of 
unlabeled tositumomab antibody. 
+  Patients must receive SSKI, Lugol's Solution or potassium iodide at least 24 
hours prior the first infusion of the dosimetric dose.  Treatment will continue 
daily until 14 days after the last infusion of the therapeutic dose (see Section 
7.6b.3). 
ƒ 
Ideally, the dosimetric infusion will be given on Day 135 and the therapeutic infusion 
on Day 142.  Due to the logistics of ordering, receiving and administering I-131-
tositumomab, a 4 week period of flexibility after Day 135 will be allowed within which 
the radiolabeled antibody therapy may be given.  However, it is recommended that 
institutions allow no more than 14 days between the dosimetric and therapeutic 
infusions of tositumomab. 
√ 
See Section 7.6c.2. 
 
7.6 
Tositumomab administration details. 
 
a. 
Preparation, Dosing, and Administration: 
 
Patients will undergo two phases of tositumomab administration.  The first phase, 
termed "dosimetric dose", involves the intravenous (IV) administration of a low-
radioactive dose (five mCi) of iodine-131 tositumomab antibody for the purpose 
of determining the rate of total body clearance of radioactivity (residence time) so 
that a total body radiation dose can be calculated (see Appendix 19.1).  The 
calculated total body radiation dose per mCi administered can then be used to 
determine how many mCi of iodine-131 conjugated with tositumomab antibody 
will be required to deliver the total body radiation dose in the second phase of the 
study, termed "therapeutic dose."  Both the dosimetric dose and the therapeutic 
dose will be immediately preceded by an infusion of 450 mg unlabeled 
tositumomab antibody (see Sections 7.6b and 7.6c). 
 


 
S0801 
 
Page 26 
 
Revised 2/8/10 
 
 
 
 
Administration of the radiolabeled tositumomab antibody will be performed by 
personnel authorized to deliver such doses of radioisotope to patients.  Special 
radiation precautions will be used during and after the administration of the 
therapeutic dose, as required by the national and/or regional regulations for the 
radiopharmaceutical industry.  Restrictions on patient contact with others will be 
set in accordance with these regulatory guidelines [Nuclear Regulatory 
Commission (NRC) and state laws].  The dosimetric and therapeutic doses may 
be given as either an outpatient or inpatient procedure depending on current 
NRC and state regulations. 
 
NOTE:  Unused drug must be returned as specified in Section 3.3c. 
 
b. 
Dosimetric Dose: 
 
1. 
Preparation of Unlabeled Tositumomab Antibody 
 
To prepare unlabeled tositumomab antibody for administration to 
patients, 450 mg unlabeled tositumomab antibody is sterilely-removed 
from the product vials and diluted to 50 mL using 0.9% sodium chloride 
for injection. 
 
2. 
Preparation of Dosimetric Dose (i.e., Tracer Dose) 
 
To prepare the dosimetric dose, an amount of tositumomab antibody (33 
- 34 mg) is added to the trace-labeled antibody preparation (1-2 mg of 
tositumomab antibody radiolabeled with 5 mCi of 131-Iodine) sufficient to 
result in a final amount of 35 mg of tositumomab antibody.  This latter 
preparation is then diluted to a final volume of 30 mL using 0.9% sodium 
chloride for injection. 
 
3. 
Administration of Saturated Solution Potassium Iodide (SSKI), Lugol’s 
Solution, or Potassium Iodide Tablets   
 
Patients will be treated with either saturated solution of potassium iodide 
(SSKI) four drops by mouth, three times a day, Lugol’s solution 20 drops 
by mouth, three times a day, or potassium iodide tablets 130 mg by 
mouth every day starting at least 24 hours prior to the first infusion of the 
Iodine-131 tositumomab Antibody (i.e., the dosimetric dose) and 
continuing for 14 days following the last infusion of Iodine-131 
tositumomab Antibody (i.e., therapeutic dose).  The SSKI or Lugol’s 
solution may be given with juice or cola to mask taste.  In no instance 
should a patient receive the dosimetric dose of iodine-131 
tositumomab antibody if they have not yet received at least 3 doses 
of SSKI, three doses of Lugol’s solution, or one 130 mg potassium 
iodide tablet (at least 24 hours prior to the dosimetric dose).  
Patients should be monitored for compliance with regard to SSKl, 
Lugol's solution, or potassium iodide tablets.   
 
All concomitant medications must be recorded in the comments 
section of the S0801 Tositumomab Treatment Form (Form #57447). 
 
4. 
Administration of Dosimetric Dose 
 
On Day 135, patients will receive the intravenous (IV) administration of 
450 mg unlabeled tositumomab antibody followed by the IV 
administration of the dosimetric dose (five mCi of Iodine-131 
tositumomab antibody).  The unlabeled antibody must be administered 
through an in-line filter [Abbott lab filter set with 0.22 micron filter and  
 


 
S0801 
 
Page 27 
 
 
 
 
injection site-15 inch option-lock (part 2679)].  The in-line filter may 
remain connected to or removed from the infusion line following the 
unlabeled antibody.  A new filter should not be added for the 
radiolabeled infusion.  Thirty to sixty minutes before the unlabeled 
tositumomab antibody infusion, patients will be premedicated with 
acetaminophen 650 mg by mouth and diphenhydramine 50 mg by mouth 
(unless 
the 
patient 
is 
hypersensitive 
to 
acetaminophen 
or 
diphenhydramine).  Unlabeled tositumomab antibody (see Section 
7.6b.1) will then be given as an intravenous (IV) infusion over 1 hour or 
longer depending on infusion-related adverse experiences. The 
dosimetric dose (see Section 7.6b.2) will be given as an intravenous 
infusion over 20 minutes.  At the end of the infusion of the dosimetric 
dose, the syringe or IV bag must be refilled with 0.9% sodium chloride 
and the contents infused over a period of 10 minutes.  Vital signs must 
be taken every 15 minutes during each of the tositumomab antibody 
infusions. 
 
5. 
Whole Body Dosimetry 
 
Whole body dosimetry will be performed separately for each patient as 
described in Appendix 19.1 using the worksheets provided.  For all 
patients, whole body anterior and posterior gamma camera scans will be 
obtained within one hour after the completion of the administration of the 
dosimetric dose on Day 0 (Day 135) before any urination, and then either 
on Day 2, 3, or 4 (Days 137, 138 or 139) after urination and again on 
either Day 6 or 7 (Day 141 or 142) after urination using a gamma camera 
with appropriate medium- or high-energy collimator.  The anterior and 
posterior whole body scans will be obtained at 10-30 cm/minute scan 
speed.  Anterior and posterior whole body counts, anterior and posterior 
background counts, and anterior and posterior counts of a calibrated 
standard will be obtained and recorded.  All static and whole body scan 
images for dosimetry will be retained electronically for submission upon 
request to GlaxoSmithKline or its designee. 
 
The above-determined counts will be used to calculate the activity to be 
administered to deliver 75 cGy (unless adjusted for obesity and/or 
platelet count - see below).  The mCi dose will be calculated as 
described in Appendix 19.1 and accompanying worksheets.   
 
Dose Adjustments based on weight and platelet counts:   
 
For excessively obese patients, the calculations to determine the iodine-
131 tositumomab antibody activity to administer will be performed using 
an upper limit of mass (maximum effective mass) based upon height and 
gender (see Table 1, Appendix 19.1d).  
 
The administered activity (mCi of Iodine-131 tositumomab antibody) for 
patients with platelet counts of 100,000 - 149,999 cells/µL will be 
adjusted to deliver 65 cGy, with additional adjustment of activity for 
obesity, if indicated.  Iodine I-131 antibody should not be given if 
platelets are less than 100,000 cells/mcL. 
 
The dose calibrator used for measuring the mCi of activity of Iodine-131 
tositumomab antibody to be administered to the patient must be 
appropriately calibrated. 
 


 
S0801 
 
Page 28 
 
 
 
 
The dosimetry worksheets for the first three patients at each 
clinical site must be submitted to GlaxoSmithKline by fax to 
confirm that the calculations were performed correctly (Fax:  
877/279-1512).  A dosimetry hotline will be maintained by 
GlaxoSmithKline to assist in calculation of the proper therapeutic 
dose (Service Center, toll free 877/423-9927). 
 
c. 
Therapeutic Dose: 
 
1. 
Preparation 
 
To prepare the therapeutic dose, an amount of tositumomab antibody is 
added to the radiolabeled preparation (tositumomab antibody labeled 
with enough 131 Iodine to administer the specified whole body radiation 
dose calculated for the patient from the dosimetric dose) sufficient to 
result in a final amount of 35 mg of tositumomab antibody, unless the 
amount of tositumomab antibody in the radiolabeled preparation is 
already ≥ 35 mg.  This latter preparation is then diluted to a final volume 
of 30 mL using 0.9% sodium chloride for injection.  In rare cases, greater 
than 30 mL of Iodine-131 tositumomab antibody will be required and the 
dose will then be prepared in 60 mL. 
 
2. 
Administration 
 
The therapeutic dose is to be given 7 days after the administration of the 
dosimetric dose (may be delayed but no longer than 14 days after 
dosimetric dose).  Those patients who experienced an anaphylactic 
response or serious adverse experience felt to be related to study 
drug during or following trace-labeled antibody administration will 
be removed from protocol treatment.  Patients will be premedicated 
with acetaminophen and diphenhydramine as they were prior to the 
dosimetric dose.  Patients should also still be receiving SSKl or Lugol's 
solution as described in Section 7.6b.3.  The unlabeled antibody must be 
administered through an in-line filter [Abbott Lab filter set with 0.22 
micron filter and injection site - 15 inch option-lock (part 2679)].  The in-
line filter may remain connected to or removed from the infusion line 
following the unlabeled antibody.  A new filter should not be added for 
the radiolabeled infusion.  Unlabeled tositumomab antibody will then be 
given as an intravenous (IV) infusion over 1 hour or longer depending on 
infusion-related adverse experiences.  The therapeutic dose will be given 
as an intravenous infusion over 20 minutes.  At the end of the infusion of 
the therapeutic dose, the syringe or IV bag must be refilled with 30 mL 
0.9% sodium chloride and the contents infused over a period of 10 
minutes.  Vital signs must be taken every 15 minutes during each of the 
tositumomab antibody infusions.  
 
7.7 
CNS Prophylaxis:  No CNS prophylaxis is permitted. 
 
7.8 
Allopurinol:  To prevent the rare event of tumor lysis syndrome in patients with bulky 
tumors (> 10 cm), oral or IV fluid intake in excess of 2,000 mL daily is encouraged during 
therapy for all patients on the study.  In addition, the routine administration of allopurinol 
(300 mg/day) is also recommended prior to and during the first cycle of therapy.  If rash 
occurs, allopurinol can be discontinued. 
 


 
S0801 
 
Page 29 
 
 
 
 
7.9 
Evaluation for Rituximab Maintenance Therapy:  Restaging will be repeated 12 weeks 
after completion of therapeutic tositumomab, with a PET scan, diagnostic CT scan of the 
chest, abdomen and pelvis and a bone marrow aspiration and biopsy (if initially positive).  
Patients showing evidence of disease progression as defined by Section 10.2f will be 
removed from protocol treatment (see Section 7.12). 
 
Restaging is also requested at approximately 1 year (Day 365) after initial registration in 
order to determine eligibility for rituximab maintenance therapy. 
 
7.10 
Rituximab Maintenance Therapy:  Rituximab maintenance therapy will begin 1 year (± 4 
weeks) after initial registration.  Treatment will be administered for 16 cycles, Cycles 7- 
22 (each cycle is given every 3 months).   
 
Patients will be restaged approximately 1 year after initial registration.  All patients with 
stable disease or better (as defined in Section 10.2) will receive rituximab maintenance 
therapy on the following dose/schedule.  Patients should register to rituximab 
maitenance therapy within 28 days after restaging (see Second Registration, 
Section 5.19-5.20). 
 
AGENT 
DOSE 
ROUTE 
SCHEDULE 
REPEAT TREATMENT 
INTERVAL 
Rituximab 
375 mg/m2 
Slow IV 
infusion 
Day 1 
q 3 months x 4 years 
 
7.11 
Follow-Up Assessments:  During the rituximab maintenance phase of protocol treatment, 
patients will undergo follow-up assessments once every six months.  After completion of 
rituximab maintenance, patients will undergo follow-up assessments annually thereafter 
for a maximum of seven years on protocol.  Patients who do not complete rituximab 
maintenance therapy will undergo follow-up assessments every six months for two years, 
and then annually for a maximum of seven years on protocol. 
 
7.12 
Criteria for Removal from Protocol Treatment 
 
a. 
Progression of disease or symptomatic deterioration as defined in Section 10.2f. 
 
b. 
Unacceptable toxicity, as defined in Section 8.0.  Patients who experience an 
anaphylactic response or serious adverse experience felt to be related to study 
drug during or following trace labeled antibody administration will be removed 
from protocol treatment (see Section 7.6c.2). 
 
c. 
Failure to meet criteria for I-131 antibody administration following completion of 
CHOP chemotherapy as defined in Section 7.4. 
 
d. 
Completion of protocol treatment. 
 
e. 
Delay of protocol treatment for more than 8 weeks. 
 
f. 
The patient may withdraw from the study at any time for any reason. 
 
7.13 
All reasons for discontinuation of treatment must be documented in the Off Treatment 
Notice (Form #8756). 
 
7.14 
All patients will be followed for a maximum of seven years or until death whichever 
occurs first. 
 
 


 
S0801 
 
Page 30 
 
Revised 11/5/10 
 
 
 
 
8.0 
TOXICITIES TO BE MONITORED AND DOSAGE MODIFICATIONS 
 
8.1 
Two different versions of the NCI Common Terminology Criteria for Averse Events 
(CTCAE) will be used on this study. 
 
a. 
Serious Adverse Event (SAE) reporting 
 
The CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0 
will be utilized for SAE reporting only.  The CTCAE Version 4.0 is identified and 
located at the CTEP website at  
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
All 
appropriate treatment areas should have access to a copy of the CTCAE 
Version. 
 
b. 
Routine toxicity reporting 
 
This study will utilize the CTCAE Version 3.0 for routine toxicity reporting.  A copy 
of the CTCAE Version 3.0 can be downloaded from the CTEP homepage 
(http://ctep.cancer.gov).  All appropriate treatment areas should have access to a 
copy of the CTCAE Version 3.0 
 
8.2 
CHOP Dose Modification: 
 
a. 
Hematologic Toxicity:  The CHOP regimen should be given as described in 
Section 7.0 if the granulocytes are > 1,000 cells/mcL and the platelets are > 
100,000 cells/mcL by the time the next cycle is due.  If the blood counts have not 
recovered, treatment should be delayed one week and counts repeated unless 
low peripheral counts are due to tumor.  If, after two weeks, counts have not yet 
recovered, the patient should be treated at 75% of the last dose received of 
cyclophosphamide and doxorubicin when counts have recovered to granulocytes 
> 1,000 cells/mcL and platelets > 100,000 cells/mcL. 
 
Severe infection (NCI CTC Version 3.0, Grade 3 or 4) due to chemotherapy-
related neutropenia requires a decrease in the doses of cyclophosphamide and 
doxorubicin to 75% of the last dose received.  Re-escalation is at the discretion 
of the treating physician.  Cytokines may be administered to prevent neutropenia.  
The NCI will not provide cytokines for this study. 
 
b. 
Impaired Hepatic Function:  All patients with bilirubin ≤ 2 x the institutional upper 
limit of normal will receive a full initial dose of doxorubicin and vincristine.  If the 
bilirubin rises to > 2 x the institutional upper limit of normal (but ≤ 5 x IULN), the 
doxorubicin and vincristine doses must be reduced by 50% of last dose received 
to avoid undue hepatic toxicity.   Full doses should be given once the bilirubin is 
≤ 2 x the institutional upper limit of normal.  If the bilirubin rises to > 5 x the 
institutional upper limits of normal, doxorubicin and vincristine should be 
discontinued for that cycle.  If hepatic function has not recovered to ≤ 2 x the 
institutional upper limits of normal by the time the next cycle is due, then remove 
patient from protocol treatment.  In cases of obstruction of biliary duct by tumor 
mass, a biliary drainage shunt should be placed prior to chemotherapy. 
 
Bilirubin 
Doxorubicin Dose 
Vincristine Dose 
 
≤ 2 x IULN 
100% 
100% 
 
> 2 - 5 x IULN 
50% 
50% 
 
> 5 x IULN 
0% 
0% 
 


 
S0801 
 
Page 30a 
 
Revised 11/5/10 
 
 
 
 
 
c. 
Impaired Renal Function:  All patients with serum creatinine levels ≤ 2 x the 
institutional upper limit of normal will receive full dose of all drugs.  If creatinine 
rises > 2 x the institutional upper limit of normal, the dose of cyclophosphamide 
must be reduced by 25% from last dose.  Re-escalation is at the discretion of the 
treating physician if the serum creatinine level drops to ≤ 2 x the institutional 
upper limit of normal. 
 
d. 
Hemorrhagic cystitis:  Cyclophosphamide will be discontinued and the patient 
removed from protocol treatment if Grade 3 or 4 hemorrhagic cystitis resulting 
from this drug occurs.  Adequate fluid intake is recommended during therapy. 


 
S0801 
 
Page 31 
 
 
 
 
e. 
Neuropathy:  Patients experiencing Grade 3 vincristine-neuropathy (e.g., 
obstipation, weakness) will have the dose of vincristine reduced by 50% for all 
further cycles of CHOP.  Patients experiencing Grade 4 vincristine neuropathy 
will have vincristine omitted from all future cycles of CHOP. 
 
8.3 
Rituximab Dose Antibody Modification:   
 
a. 
Patients may experience transient fever and rigors with infusion of rituximab.  If 
Grade 3 fever (or Grade 2 fever with rigors) or Grade 2 rigors are noted, the 
antibody infusion should be temporarily discontinued, the patient should be 
observed, and the severity of the side effects should be evaluated.  The patient 
should be treated according to the best available local practices and procedures.  
Following observation, when fever resolves to Grade 2 or less and rigors to 
Grade 1 or less, the infusion should be continued, initially, at 1/2 the previous 
rate.  Following the antibody infusion, the IV line should be kept open for 
medications, as needed.   
 
b. 
Hypotension, bronchospasm and angioedema have occurred as part of an 
infusion 
related 
symptom 
complex. 
 
If 
a 
Grade 
3 
or 
greater 
hypersensitivity/allergic reaction occurs, antibody infusion should be interrupted 
and may be resumed at a 50% reduction in rate when symptoms have 
completely resolved.  Treatment with diphenhydramine and acetaminophen is 
recommended; additional treatment with bronchodilators or IV saline may be 
used at the physician's discretion.   
 
c. 
Precautionary 
hospitalization 
for 
patients 
experiencing 
severe 
infusion 
symptoms, which do not resolve after discontinuation of the cycle, is 
recommended.  
 
If there are no complications, the IV line may be discontinued after one hour of 
observation.  If complications occur during the rituximab infusion, the patient 
should be observed for two hours after the completion of the infusion.  If a patient 
experiences a Grade 3 toxicity that persists until the next scheduled infusion, the 
patient must discontinue treatment until toxicities have resolved to Grade 2 or 
less.  If treatment is delayed for more than three weeks, remove the patient from 
protocol treatment. 
 
d. 
Tumor Lysis Syndrome:  Appropriate medical therapy should be provided for 
patients who develop tumor lysis syndrome.  Following treatment for and 
resolution of tumor lysis syndrome, subsequent rituximab therapy may be 
administered in conjunction with prophylactic therapy for this syndrome.  Contact 
the Study Coordinator prior to resuming treatment in these patients. 
 
e. 
Hepatitis B Reactivation with Related Fulminant Hepatitis and Other Viral 
Infections:  Carriers of hepatitis B should be closely monitored for clinical and 
laboratory signs of active HBV infection and for signs of hepatitis throughout their 
study participation.  Patients with any evidence of active hepatic disease or 
known HBV infection should be managed as clinically appropriate and should 
only receive rituximab if they have control of the infection and are adequately 
informed of the risks.  Patients who have never received vaccination for HBV, 
and have not had serologic testing for HBsAg, should be tested for surface 
antigen positivity.   
 
In patients who develop progressive multifocal leukoencephalopathy (PML), 
rituximab should be discontinued and reductions or discontinuation of 
concomitant immunosuppressive therapy and appropriate treatment, including 
antiviral therapy, should be considered.  Physicians should consider PML in any 
patients presenting with new onset neurologic manifestations, particularly in 
patients with systemic lupus erythematosus (SLE) or lymphoid malignancies.  
Consultation with a neurologist, brain MRI, and lumbar puncture should be  
 


 
S0801 
 
Page 32 
 
 
 
 
considered as clinically indicated.  There are no known interventions that can 
reliably prevent PML or adequately treat PML if it occurs.   
 
f. 
Severe Mucocutaneous Reactions:  All patients on and off rituximab therapy 
should be closely monitored for signs and symptoms suggestive of severe 
cutaneous and mucocutaneous reactions.  Should these symptoms arise, 
discontinue rituximab therapy (if applicable) and support as clinically indicated.   
 
g. 
Cardiovascular events:  Patients with rheumatoid arthritis (RA) are at increased 
risk for cardiovascular events compared to the general population.  Patients with 
RA should be monitored throughout the infusion, and rituximab should be 
discontinued in the event of a serious or life-threatening cardiac event.   
 
Patients who develop clinically significant arrhythmias should undergo cardiac 
monitoring during and after subsequent infusions of rituximab.  Patients with pre-
existing cardiac conditions, including arrhythmias and angina, that have had 
recurrences of these events during rituximab therapy should be monitored 
throughout the infusion and immediate post-infusion period.  Patients off 
rituximab therapy should be closely monitored for signs and symptoms 
suggestive of life-threatening cardiac events and supported as clinically 
indicated.   
 
h. 
Bowel obstruction and perforation:  Complaints of abdominal pain, especially 
early in the course, should prompt a thorough diagnostic evaluation and 
appropriate treatment.  If patient experiences a bowel obstruction or perforation, 
discontinue rituximab therapy.  Patients off rituximab therapy should be closely 
monitored for signs and symptoms suggestive of bowel obstruction and 
supported as clinically indicated. 
 
i. 
Renal:  Discontinuation of rituximab should be considered for those with rising 
serum creatinine or oliguria.  
 
8.4 
Iodine-131 Tositumomab Antibody Dose Modification   
 
Iodine-131 should be given as specified in Section 7.5 as long as counts have recovered 
to granulocytes ≥ 1,500 cells/mcL and platelets ≥ 100,000 cells/mcL.   
 
a. 
Dose Adjustments based on weight and platelet counts: 
 
For excessively obese patients, the calculations to determine the Iodine-131 
tositumomab antibody activity to administer will be performed using an upper 
limit of mass (maximum effective mass) based upon height and gender (see 
Table 1, Appendix 19.1d).   
 
The administered activity (mCi of Iodine-131 tositumomab antibody) for patients 
with platelet counts of 100,000 - 149,999 cells/mcL will be adjusted to deliver 65 
cGy, with additional adjustment of activity for obesity, if indicated.  Iodine-131 
antibody should not be given if platelets are less than 100,000/mcL. 
 
The dose calibrator used for measuring the mCi of activity of Iodine-131 
tositumomab antibody to be administered to the patient must be appropriately 
calibrated. 
 
b. 
Other dose adjustments: 
 
During the administration of the unlabeled tositumomab antibody, tracer, and 
therapeutic doses, emergency support for anaphylaxis is to be readily available, 
including 
a 
tray 
for 
epinephrine, 
diphenhydramine, 
hydrocortisone, 
a 
laryngoscope, and an endotracheal tube.  Although acute adverse experiences  
 


 
S0801 
 
Page 33 
 
Revised 2/8/10 
 
 
 
 
occurring during the infusion or up to 24 hours after the infusion of tositumomab 
antibody have been infrequent, based upon past experience, symptoms of fever, 
nausea, vomiting, rigors, hypotension, pruritis, tachycardia, erythematous rash, 
urticaria, mucus membrane congestion, arthralgias, and myalgias may occur.  
The patient should be treated according to physician's judgment.  However, it is 
recommended that acetaminophen 650 mg by mouth and/or diphenhydramine 
50 mg by mouth or IV be given to control these symptoms if they occur.  Severe 
rigors should also be treated at the physician's discretion but may be controlled 
by meperidine 25 - 50 mg IV.  Experience has shown that rigors generally abate 
within 30 minutes without pharmaceutical intervention.   
 
If any of these toxicities occur during antibody infusion, the rate of antibody 
infusion should be decreased as indicated below: 
 
Infusion rate adjustment 
 
Fever 
Rigors 
Mucosal 
Congestion/Edema 
% Drop in 
Systolic BP 
Infusion Rate 
Adjustment 
Grade 1  
(38.0 – 
39.0oC 
Grade 1-2  
(Mild to 
Moderate) 
Grade 1-2  
(Mild to Moderate) 
30 – 49  
Decrease by ½ 
Grade ≥ 2  
(≥ 39oC) 
Grade ≥ 3  
(Severe) 
Grade ≥ 3  
(Severe) 
≥ 50 
Stop Infusion* 
* Temporarily discontinue infusion until adverse experiences have reversed 
(generally 15 to 30 min.) and then resume infusion at 25 – 50% of initial rate. 
 
8.5 
Use of Colony Stimulating Factors (CSF) and Platelet and Red Blood Cell Transfusions 
 
Colony Stimulating Factors (CSF) should be administered only in accordance with 
published ASCO guidelines.  Use of CSF under these conditions will be at the discretion 
of the treating investigator, but must be recorded on the S0801 Induction R-CHOP 
Treatment Form (Form #23097). 
 
Platelet transfusions should be administered only in patients with Grade 3 or 4 
thrombocytopenia with obvious bleeding.  The use of platelet and red cell transfusions 
under these conditions will be at the discretion of the treating investigator, but must be 
recorded on the corresponding S0801 Treatment Summary Form(s) (Form #23097, 
57447, or 14046). 
 
8.6 
For treatment or dose modification related questions, please contact Dr. Friedberg at 
585-273-4150 or Dr. Press at 206/667-1872. 
 
8.7 
Unexpected or fatal toxicities (including suspected reactions) must be reported to the 
Operations Office, to the Study Coordinator, to the IRB and the NCI.  The procedure for 
reporting adverse reactions is outlined in Section 16.0. 
 


S0801
Page 34
Revised 9/24/10
Revised 8/20/12
9.0  STUDY CALENDAR     S0801, "A Phase II Study of Iodine-131-Labeled Tositumomab in Combination With Cyclophosphamide, Doxorubicin, Vincristine,  
                                                        Prednisone, and Rituximab Therapy for Patients with Advanced Stage Follicular Non-Hodgkin's Lymphoma"
£
Induction Therapy
Evaluation for 
     Antibody
         Ω
Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 I-131 Tositumomab
    Treatment
    Restaging
Rituxan
√
REQUIRED STUDIES
PRE
Day
Day
Day
Day
Day
Day
Day
Day
Day
Day
Day
Maintenance
Follow
STUDY
1
22
43
64
85
106
134
135
142
226
365
Cycles 7-22
Up
PHYSICAL
History & Physical Exam
X
X
X
X
X
X
X
X
X
X ∆
X
Weight & Performance Status
X
X
X
X
X ∆
X
Tumor Assessment  
X
X
X
X
X ∆
X
Toxicity Notation
X
X
X
X
X
X
X
X
X
X
X
X ∆
X
LABORATORY
CBC, Platelets & Differential 
X ß
X
X
X
X
X
X
X
X
X ∆
X
Hemoglobin
X
Serum Creatinine
X ß
X
X
X
X
X
X
X
X ∆
X
Bilirubin
X ß
X
X
X
X
X
X
X
X ∆
X
SGOT/SGPT and/or Alk Phosphatase
X ß
X
X
X ∆
X
LDH
X
X
X
X ∆
X
Thyroid Stimulating Hormone (TSH)
X
X 
X
X
X ∆
X
Beta 2 Microglobulin
X ß
Uric acid
X ß
X 
Urinalysis
X ß
X 
HBV screening
X  ß
X
Immunophenotyping (CD20)
X
Materials for pathology review # 
X 
Bone marrow asp./biopsy    
X
X*
X*
X*
GlaxoSmithKline  approval
X
GlaxoSmithKline  training session
X
RESEARCH SPECIMENS ¢   
Serum for SWOG-8947
X
Tissue for SWOG-8819
X
X-RAYS AND SCANS 
Diagnostic CT scan: Chest, Abdomen, Pelvis 
X
X
X
X
X ∆
X
PET/CT 
Xƒ
X
MUGA or 2-d ECHO
X
 
TREATMENT (See Section 7.3) π
Induction Therapy
Rituximab
X†
X
X
X
Cyclophosphamide
X
X
X
X
X
X
 
 
Doxorubicin
X
X
X
X
X
X
 
 
Vincristine
X
X
X
X
X
X
Prednisone 
X
X
X
X
X
X
Consolidation
SSKI, Lugol's, Potassium Iodide §
X §
X §
X §
Unlabeled anti-tositumomab antibody
X
X
I-131 anti-tositumomab dosimetric infusion
X
Whole Body Dosimetry ¶
X ¶
X ¶
I-131 anti-tositumomab therapeutic infusion ¥
X ¥ 
Maintenance Therapy
Rituximab (375 mg/m2 q 3 months x 4yrs)
 
X
NOTE:  Data submission forms are found in Section 18.0.  Forms submission guidelines may be found in Section 14.0.
ƒ   PET/CT is optional at baseline but required at Day 226 restaging.  There is no role for routine PET imaging during subsequent restaging procedures.
#   See Section 12.0.
Ω  Restaging must occur 12 weeks after completion of therapeutic tositumomab (approximately Day 226), as well as on Day 365 after initiation of CHOP.  The same assessments that
    were used at baseline should be used for restaging.  
√   Patients removed from protocol  treatment for any reason will be evaluated at that time by repeating CBC with platelets, LDH, creatinine, liver enzymes, 
    CT of chest, abdomen and pelvis, and all pre-treatment scans to evaluate disease.  Follow-up evaluations will include all restaging tests and will 
    occur every six months for two years then annually for a maximum of seven years on protocol.
£   Evaluation for I-131 tositumomab therapy:  Re--evaluation will occur 4-12 weeks after Day 1 dose of Cycle 6 of CHOP (see Section 7.5b).
π   Patients with progressive disease at any time will discontinue protocol treatment (see Section 10.2f).
ß   These tests are required prestudy for Good Medical Practice (see Section 7.1 for guidance on timing and interpretation of these results).
*   Repeat if initially abnormal
§   SSKI, Lugol's or Potassium Iodide will be administered at least 24 hours prior to the dosimetric dose and will continue for 14 days following the last infusion of
    radiolabeled tositumomab antibody.
¶  Three whole body scans will be done:  the first on Day 1 after the dosimetric infusion (projected to be Day 134 of the protocol treatment), the second on either  
    Day 3, 4, or 5 after the dosimetric infusion and the third on either Day 7 or 8 after the dosimetric infusion ( see Section 7.6b.5).
¥   The therapeutic dose is to be given 7 days after the administration of the dosimetric dose (may be delayed but no longer than 14 days after the dosimetric dose).
    CBC/platelets/differential should be checked weekly after the therapeutic infusion until the patient experiences a nadir and recovers from the nadir (6-8 weeks).
¢    See Section 15.0.
†   If circulating lymphocyte count exceeds 20,000 cells/mcL, rituximab will be omitted for the first cycle.
∆  Rituxan maintenance should be administered once every 3 months for 4 years beginning approximately 1 year after initiation of induction therapy.  History, physical exam, weight, 
   performance status, and toxicity notation as well as restaging labs should be performed every 6 months throughout Rituxan maintenance. CT scans should be performed every 6 months 
   for 2 years, then annually throughout Rituxan maintenance. 
  


 
S0801 
 
Page 35 
 
 
 
 
10.0 
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS 
 
10.1 
Measurability of Lesions: 
 
a. 
Measurable Disease: Lesions that can be accurately measured in two 
dimensions by CT, MRI, plain x-ray, or other conventional technique and have a 
greatest transverse diameter of 1 cm or greater; or palpable lesions with both 
diameters 2 cm or greater.  Note: PET scans are insufficient for evaluation of 
measurable disease. 
 
b. 
Non-measurable Disease: All other lesions including unidimensional lesions, 
lesions too small to be considered measurable, pleural or pericardial effusion, 
ascites, bone disease, leptomeningeal disease, lymphangitis, pulmonitis, 
abdominal masses not confirmed or followed by CT or disease documented only 
by PET imaging or indirect evidence (e.g., lab values). 
 
10.2 
Objective Disease Status: Objective status is to be recorded at each evaluation 
according to the 2007 revised Cheson et al. criteria. (13) All measurable lesions up to a 
maximum of 6 lesions (largest) should be identified as target lesions at baseline. If there 
are more than 6 measurable lesions the remaining will be identified as non-target lesions 
and included as non-measurable disease. The 6 lesions should be selected according to 
the following features: they should be from disparate regions of the body as possible and 
they should include mediastinal and retroperitoneal areas of disease if these sites have 
measurable lesions.  Measurements must be provided for target lesions, while presence 
or absence must be noted for non-target measurable and non-measurable disease. 
 
a. 
Complete Response (CR):  Complete disappearance of all measurable and 
non-measurable disease with the exception of the following.  In patients with no 
pretreatment PET scan or when the PET scan was positive before therapy, a 
post-treatment residual mass of any size is permitted as long as it is PET 
negative.  If the PET scan was negative before therapy, all nodal masses > 1.5 
cm in greatest transverse diameter (GTD) at baseline must have regressed to ≤ 
1.5 cm in GTD and all nodal masses > 1 cm and ≤ 1.5 cm in GTD and > 1 cm in 
their short axis before treatment must have regressed to ≤ 1 cm in their short 
axis.  No new lesions visible on PET scan or by any other imaging studies.  The 
spleen and/or liver, if considered enlarged at baseline based on physical 
examination or imaging study (other than PET), must have regressed in size and 
must not be palpable.  If bone marrow was positive at baseline, it must be 
negative based on biopsy and aspirate at same site.  Normalization of markers 
(e.g., LDH definitely assignable to NHL).  Tumor measurements must be 
obtained by an imaging modality other than PET.  All disease must be assessed 
using the same technique as baseline. 
 
b. 
Partial Response (PR):  Applies to patients with at least one lesion that does not 
qualify for a CR.  For patients with measurable disease, ≥ 50% decrease in sum 
of the product of the diameters (SPD) of up to six dominant lesions identified at 
baseline.  No new lesions and no increase in the size of the liver, spleen, or other 
nodes.  Splenic and hepatic nodules must have regressed by ≥ 50% in SPD.  In 
patients with no pretreatment PET scan or when the PET scan was positive 
before therapy, PET should be positive in at least one previously involved site.  
Tumor measurements must be obtained by an imaging modality other than PET.  
All disease must be assessed using the same technique as baseline.  Note: 
Patients who meet all other criteria, but have new lesions observed on PET scan 
only (i.e., not confirmed on CT or other imaging studies), are considered partial 
responders.  


 
S0801 
 
Page 36 
 
 
 
 
c. 
Stable Disease (SD):  Does not qualify for CR, PR, or Relapsed/Progressive 
Disease.  Tumor measurements must be obtained by an imaging modality other 
than PET.  All disease must be assessed using the same technique as baseline. 
 
d. 
Relapsed Disease (after CR)/Progressive Disease (after PR, SD):  At least 
50% increase in the SPD of target measurable nodal lesions over the smallest 
sum observed (over baseline if no decrease during therapy), or ≥ 50% increase 
in the GTD of any node > 1 cm in shortest axis, or ≥ 50% increase in the SPD of 
other target measurable lesions (e.g., splenic or hepatic nodules) over the 
smallest sum observed.  Appearance of any new bone marrow involvement.  
Appearance of any new lesion > 1.5 cm in longest axis, or ≥ 50% increase in 
GTD of any previously involved node with a diameter ≤ 1.0 cm in the short axis 
such that its longest axis is now > 1.5 cm.  Lymph nodes should be considered 
abnormal for relapse or progressive disease only if the long axis is > 1.5 cm, or if 
the both the long and short axes are > 1 cm.  In patients with no pretreatment 
PET scan or when the PET scan was positive before therapy, lesions should be 
PET positive.  Tumor measurements must be obtained by an imaging modality 
other than PET.  All disease must be assessed using the same technique as 
baseline.  Note: Appearance of any new lesion on PET alone (not confirmed by 
CT or other imaging modality) is NOT considered relapse/progression. 
 
10.3  
Best Response: 
 
a.  
CR: One objective status of CR documented before relapse. 
 
b.  
CRU: One objective status of CRU documented before relapse but not qualifying 
as a CR. 
 
c.  
PR: One objective status of PR documented before progression but not 
qualifying as a CR or CRU. 
 
d.  
Stable: At least one objective status of stable documented at least 6 weeks after 
registration, not qualifying as anything else above. 
 
e.  
Increasing Disease: Objective status of progression within 12 weeks of 
registration not qualifying as anything else above. 
 
f.  
Inadequate assessment, response unknown: Progression greater than 12 weeks 
after registration and no other response category applies. 
 
10.4 
Performance Status:  Patients will be graded according to the Zubrod performance 
status scale: 
 
GRADE 
SCALE 
 
0 
Fully active; able to carry on all pre-disease activities without 
restriction.   
 
1 
Restricted in physically strenuous activity but ambulatory and 
able to carry out work of a light or sedentary nature, e.g., light 
housework, office work.   
 
2 
Ambulatory and capable of all self-care but unable to carry out 
any work activities; up and about more than 50% of waking 
hours.   
 
3 
Capable of only limited self-care; confined to bed or chair more 
than 50% of waking hours.   


 
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4 
Completely disabled; cannot carry on any self-care; totally 
confined to bed or chair.   
 
10.5 
Progression-Free Survival:  From date of registration to date of first observation of 
progressive disease (as defined in 10.2f), or death due to any cause.  Patients last 
known to be alive and progression-free are censored at date of last contact. 
 
10.6 
Time to Death:  From date of registration to date of death due to any cause.  Patients 
last known to be alive and are censored at date of last contact. 
 
 
11.0 
STATISTICAL CONSIDERATIONS  
 
11.1 
We estimate the accrual rate to this protocol to be approximately 9-10 patients per 
month.  SWOG protocol S9911 used a similar combination of CHOP chemotherapy with 
iodine-131 tositumomab in patients with follicular NHL, and accrued at a rate of over 10 
patients per month.  The most recent SWOG protocol in follicular lymphoma (S0016), a 
randomized study, accrued on average 9 patients per month.   
 
11.2 
This is the primary objective of the study:  Eighty eligible patients accrued over 12 
months with 36 months of additional follow-up will be sufficient to estimate the true 3-year 
PFS within this group to within +/- 0.11.  A true 3-year PFS of 85% would be of interest, 
while further testing would not be pursued if the true 3-year PFS probability is 70% or 
lower.  An estimated 3-year PFS rate of 79% or greater will be considered evidence 
warranting further study of the regimen.  This design has a significance level of 5.3% and 
power of 95%.   
 
11.3 
Secondary endpoints include 5-year PFS, 5-year overall survival, and response.  The 
probability of response or a particular toxicity can be estimated to within at worst ± 0.11 
with 80 patients (95% confidence interval).  Any adverse event with at least a 5% 
probability will be seen at least once (98% chance).   
 
11.4 
Data and Safety Monitoring:  There is no formal data and safety monitoring committee for 
Phase II studies.  Toxicity and accrual monitoring are done routinely by the Study 
Coordinator, Study Statistician, and the Disease Committee Chair.  Endpoint monitoring 
is done by the study Statistician and Study Coordinator.  Accrual reports are generated 
weekly, and formal toxicity reports are generated every 6 months.  In addition, the 
Statistical Center, Adverse Event Coordinator at the Operations Office, and Executive 
Officer monitor toxicities on an ongoing basis. 
 
 
12.0 
DISCIPLINE REVIEW 
 
12.1 
Pathology Review: 
 
All patients registered to this study will undergo pathology review.  The purpose of this 
review is to verify the histologic diagnosis of follicular non-Hodgkin's lymphoma. 
 
12.2 
All pathology submissions for patients registered on this study by Southwest Oncology 
Group institutions and affiliates must be entered and tracked using the SWOG Online 
Specimen Tracking System.  Southwest Oncology Group members may log on to the 
Specimen Tracking System via the CRA Workbench (http://gill.crab.org/txwb/logon.asp) 
using their SWOG roster ID numbers and passwords. 
 
In the online Specimen Tracking System, laboratory ID numbers are used to identify the 
laboratories to which specimens are shipped.  The laboratory ID number for this study 
may be found listed next to the laboratory name in Section 12.3 below. 


 
S0801 
 
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ALL SPECIMENS MUST BE LOGGED VIA THIS SYSTEM.  THERE ARE NO 
EXCEPTIONS.  For any questions or problems regarding the Specimen Tracking 
System, please send an email to technicalquestion@crab.org 
 
12.3 
The following materials are to be submitted for review: 
 
a. 
One representative H&E section from each block of the original diagnostic 
specimen.  (Note:  Needle aspirates are not adequate for this submission.  
Consult with Dr. Rimsza's laboratory if adequacy of specimen is in question.) 
 
b. 
Either 12 unstained slides or a paraffin block from the representative diagnostic 
specimen.  If a block is sent, then the tissue will be conserved (no more than 12 
additional cuts will be made).  Send paraffin block on cool packs to keep the 
paraffin from melting. 
 
c. 
One copy of the pathology report. 
 
12.4 
Failure to submit a registered patient's pathology materials for pathology will make the 
patient ineligible. 
 
12.5 
Pathology materials are to be submitted within 28 days of registration to: 
 
Lab #2:  
SWOG Lymphoma Repository – University of Arizona 
Arizona Health Science Center 
Department of Pathology, Room 5211, Box 245043 
1501 North Campbell Avenue 
Tucson, AZ  85724-5043 
 
Contact: 
Yvette Frutiger/Lisa M. Rimsza, M.D. 
Phone:  
520/626-7477 
FAX: 
 
520/626-6081 
Email:  
frutiger@email.arizona.edu 
 
The materials must be identified with a "SWOG Pathology Materials" label on the 
outside of each package.  If this label is missing, the materials will not be 
reviewed, rendering the patient ineligible.  These labels will be provided by the 
Data Operations Center in Seattle.  To obtain additional labels, please call 206/652-
2267 and ask for the Pathology/RT Coordinator. 
 
12.6 
With patient's consent any left over tissue not consumed by testing will be retained for 
future studies. 
 
 
13.0 
REGISTRATION GUIDELINES 
 
13.1  
Patients must be registered prior to initiation of treatment (no more than five working 
days prior to planned start of treatment).  Second registration must also take place no 
more than 5 working days prior to planned start of rituximab maintenance therapy. 
 
13.2  
For either phone or web registration, the individual registering the patient must have 
completed the appropriate Southwest Oncology Group Registration Form. The 
completed form must be referred to during the registration but should not be submitted as 
part of the patient data. 
 
The individual registering the patient must also be prepared to provide the treating 
institution's name and ID number in order to ensure that the current (within 365 days) 
date of institutional review board approval for this study has been entered into the data 
base.  Patients will not be registered if the IRB approval date has not been provided or is 
> 365 days prior to the date of registration. 


 
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Revised 1/12/10 
 
 
 
 
13.3  
Registration procedures 
 
a. 
You may register patients from Member, CCOP and approved Affiliate 
institutions to a therapeutics study using the SWOG Registration program. To 
access the Registration program go to the SWOG Web site (http://swog.org) and 
click on the Logon link to go to the SWOG Members Area logon page 
(https://swog.org/visitors/logon.asp).  This Web program is available at any time 
except for periods listed under Down Times.  Log on as an Individual User 
using your SWOG Roster ID Number and individual web user password.  Help 
for the logon process may be found at https://swog.org/visitors/logonhelp.asp. 
After you have logged on, click on the Clinical Trials link and then the Patient 
Reg link to go to the Entry Page for the Patient Registration program. If you are a 
Registrar at an institution with Internet access you are encouraged to register this 
way.  For new users, the link to a "Starter Kit" of help files may be found by 
clicking on Starter Kit link at the logon page. 
 
To register a patient the following must be done (in order): 
 
1. 
You are entered into the Southwest Oncology Group Roster and issued 
a SWOG Roster ID Number,  
 
2. 
You are associated as an investigator or CRA/RN to the institution where 
a registration is occurring, and  
 
3. 
You are granted permission to use the Patient Registration program at 
that institution.  
 
For assistance with points 1 and 2 call the SWOG Operations Office at 210/614-
8808. For point 3 you must contact your Web User Administrator.  Each SWOG 
institution has one or more Web User Administrators who may set up Web Users 
at their institution and assign permissions and passwords to these users. For 
other password problems or problems with the Patient Registration program, 
please e-mail webreghelp@crab.org. Include your name, Roster ID Number, and 
telephone number, when the problem occurred, and exactly what you were 
doing. 
 
b.   
If the Web Reg program is not used, the registration must be done by phone. 
  
Member, Affiliate and CCOP Institutions 
 
Registration by phone of patients from member, affiliate and CCOP institutions 
must be done through the Southwest Oncology Group Data Operations Center in 
Seattle by telephoning 206/652-2267, 6:30 a.m. to 4:00 p.m. Pacific Time, 
Monday through Friday, excluding holidays. 
 
13.4  
For either method of registration, exceptions to Southwest Oncology Group registration 
policies will not be permitted. 
  
a. 
Patients must meet all eligibility requirements. 
 
b. 
Institutions must be identified as approved for registration. 
 
c. 
Registrations may not be cancelled. 
  
d. 
Late registrations (after initiation of treatment) will not be accepted. 
 
 


 
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14.0 
DATA SUBMISSION SCHEDULE 
 
14.1 
Data must be submitted according to the protocol requirements for ALL patients 
registered, whether or not assigned treatment is administered, including patients deemed 
to be ineligible.  Patients for whom documentation is inadequate to determine eligibility 
will generally be deemed ineligible. 
 
14.2 
Master forms are included in Section 18.0 and (with the exception of the sample consent 
form and the Registration Form) must be submitted to the Data Operations Center in 
Seattle.  Data from approved SWOG institutions must be submitted on-line via the Web; 
see Section 14.3a for details.  Exceptions to online data submission are patient-
completed 
(e.g. 
Quality 
of 
Life) 
forms 
and 
source 
documents 
(e.g. 
pathology/operative/lab reports). 
 
14.3 
Data Submission Procedures.   
 
a. 
Southwest Oncology Group institutions must submit data electronically via the 
Web by using the SWOG CRA Workbench.  To access the CRA Workbench, go 
to the SWOG Web site (http://swog.org) and logon to the Members Area.  After 
you have logged on, click on the CRA Workbench link to access the home page 
for CRA Workbench website.  Next, click on the Data Submission link and follow 
the instructions.  For new users, the link to a "Starter Kit" of help files may be 
found by clicking on the Starter Kit link at the Members’ logon page. 
 
To submit data via the web the following must be done (in order): 
 
1.  
You are entered into the Southwest Oncology Group Roster and issued 
a SWOG Roster ID Number, 
2.  
You are associated as an investigator or CRA/RN at the institution where 
the patient is being treated or followed, and 
3.  
Your Web User Administrator has added you as a web user and has 
given you the appropriate system permissions to submit data for that 
institution. 
 
For assistance with points 1 and 2 call the Operations Office at 210/614-8808.  
For point 3, contact your local Web User Administrator (refer to the "Who is my 
Web User Administrator?" function on the swog.org Members logon page).  For 
other 
difficulties 
with 
the 
CRA 
Workbench, 
please 
email 
technicalquestion@crab.org.   
 
b. 
If you need to submit data that are not available for online data submission, the 
only alternative is via facsimile.  Should the need for this occur, institutions may 
submit data via facsimile to 800/892-4007 or 206/342-1680 locally.  Please do 
not use cover sheet for faxed data. 
 
14.4 
WITHIN 7 DAYS OF INITIAL REGISTRATION:   
 
Submit a copy of the following: 
 
a. 
S0801 Prestudy Form (Form #62797) 
 
b. 
Lymphoma Baseline Tumor Assessment Form (Form #39601).  CT reports are 
required for the baseline CT scan. 
 
c. 
Pathology report confirming histology and CD20+ antigen expression. 
 


 
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Revised 1/12/10 
 
Revised 2/8/10 
 
 
 
 
14.5 
WITHIN 28 DAYS OF INITIAL REGISTRATION:   
 
Submit histopathologic materials (H&E stained section, and paraffin block or 12 
unstained slides) along with a copy of the pathology report to the Southwest Oncology 
Group Lymphoma Repository - University of Arizona (see Section 12.0).   
 
14.6 
AT PRESTUDY (PRIOR TO INITIATION OF TREATMENT): 
 
(Optional) Submit tissue (for SWOG-8819) and/or serum for (SWOG-8947). 
 
14.7 
AT THE END OF EACH CYCLE OF INDUCTION R-CHOP TREATMENT: 
 
Submit the S0801 Induction R-CHOP Treatment Form (Form #23097) and the S0801 
Induction Therapy Adverse Event Form (Form #33275).   
 
14.8 
WITHIN 4 – 12 WEEKS AFTER THE COMPLETION OF R-CHOP TREATMENT: 
 
 
Submit the S0801 Patient Re-Evaluation Form (Form #19777). 
 
14.9 
AFTER COMPLETION OF TOSITUMOMAB TREATMENT: 
 
Submit the S0801 Tositumomab Treatment Form (Form #57447) and the S0801 
Induction Therapy Adverse Event Form (Form #33275). 
 
14.10 
EVERY 3 MONTHS AFTER EACH DOSE OF RITUXIMAB MAINTENANCE THERAPY: 
 
Submit the S0801 Maintenance Therapy Form (Form #14046) and the S0801 
Maintenance Therapy Adverse Event Form (Form #57656)  
 
14.11 
WITHIN 14 DAYS OF DISCONTINUATION OF R-CHOP + I-131 TOSITUMOMAB 
THERAPY OR RITUXIMAB MAINTENANCE THERAPY: 
 
Submit the Off Treatment Notice (Form #28829). 
 
14.12 
THREE MONTHS AFTER OFF TREATMENT:   
 
Submit the S0801 Induction Therapy Adverse Event Form (Form #33275) (if the patient 
was on R-CHOP induction therapy) or the S0801 Maintenance Therapy Adverse Event 
Form (Form #57656) (if the patient was on rituximab maintenance therapy).   
 14.13 
WITHIN 14 DAYS OF PROGRESSION/RELAPSE: 
 
Submit copies of the S0801 Induction or Maintenance Therapy Adverse Event Form 
(Form #33275 or Form #57656) and the S0801 Treatment Form(s) (Form #23097, 
57447, or 14046) (if the patient was still on protocol treatment) and the Follow-Up Form 
(Form #64587) documenting date, site, and method for determining progression/relapse. 
 
14.14 
WITHIN 14 DAYS OF EACH DISEASE ASSESSMENT UNTIL PROGRESSION: 
 
Submit the Lymphoma Follow-Up Tumor Assessment Form (Form #27780).  CT reports 
are required for the follow-up CT scans. 
 
14.15 
AFTER PROTOCOL TREATMENT:  EVERY SIX MONTHS FOR 2 YEARS AND 
ANNUALLY THEREAFTER UNTIL 7 YEARS AFTER REGISTRATION: 
 
Submit the Follow-Up Form (Form #64587). 
 


 
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Page 42 
 
 
 
 
14.16 
WITHIN FOUR WEEKS OF KNOWLEDGE OF SUBSEQUENT MALIGNANCY: 
 
Submit the Notice of Second Malignancy (Form #27456) documenting date, site, and 
method for determining malignancy. 
 
14.17 
WITHIN FOUR WEEKS OF KNOWLEDGE OF DEATH: 
 
Submit a copy of the Notice of Death (Form #49467) documenting death information. 
 
 
15.0 
SPECIAL INSTRUCTIONS 
 
15.1 
Instructions for obtaining institutional approval and training prior to registration and I-131 
treatment of patients: 
 
Prior to registration of any patient the registering institution must be approved by 
GlaxoSmithKline for the delivery of iodine-131 tositumomab antibody therapy.  The Site 
Contact Information Form (Appendix 19.4) and radioactive materials license must be 
faxed to GlaxoSmithKline at the number listed on the bottom of the form.  If approved, 
GlaxoSmithKline will send the institution an approval notice. 
 
GlaxoSmithKline will contact the institution to provide assistance and to arrange for an 
on-site training session for iodine-131 tositumomab antibody therapy (if required or 
requested).  Training may occur at any time after initial patient registration, but it must be 
completed before the patient can receive the iodine-131 tositumomab antibody therapy.    
 
NOTE:  GlaxoSmithKline approval and training must be performed prior to I-131 
treatment only for the first patient registered to and treated on this study at any 
one institution.  Institutions that have previously completed on-site training for the 
Southwest Oncology Group studies, S0016 or S0433, or as Expanded Access 
Program sites (EAP) need not repeat the training.  However, retraining is available 
upon institutional request. 
 
15.2 
Institutions are encouraged to submit serum and tissue for banking for future correlative 
studies (see Section 5.4) by registering to SWOG-8819 and SWOG-8947. 
 
15.3 
General Specimen Submission Instructions 
 
a. 
All submitted specimens must be labeled with the protocol number (S0801), 
SWOG patient number, patient's initials, and date of specimen collection. 
 
b. 
The Federal Guidelines for Shipment are as follows: 
 
1. 
The specimen must be wrapped in an absorbable material; 
 
2. 
The specimen must then be placed in an AIRTIGHT container (like a 
resealable bag); 
 
3. 
Pack the resealable bag and specimen in a styrofoam shipping 
container; 
 
4. 
Pack the styrofoam shipping container in a cardboard box. 
 
5. 
The cardboard box must be marked as "BIOHAZARD". 
 


 
S0801 
 
Page 43 
 
 
 
 
15.4 
Specimen Tracking System   
 
All specimen submissions for this study must be entered and tracked using the SWOG 
online Specimen Tracking system.  SWOG members may log on to the Specimen 
Tracking system via the CRA Workbench (https://gill.crab.org/txwb/logon.aspx) using 
their SWOG roster ID numbers and passwords.  First-time non-SWOG users must refer 
to start-up instructions located at https://gill.crab.org/SpecTrack/.  
 
In the online Specimen Tracking system laboratory ID numbers are used to identify the 
laboratories to which specimens are shipped.  The laboratory number for specimen 
submission is outlined in Section 15.5c.   
 
ALL SPECIMENS MUST BE LOGGED VIA THIS SYSTEM; THERE ARE NO 
EXCEPTIONS.  
 
To report technical problems with Specimen Tracking, such as database errors or 
connectivity issues, please send an email to technicalquestion@crab.org.  For procedural 
help with logging and shipping specimens, there is an introduction to the system on the 
Specimen 
Tracking 
main 
page 
(https://gill.crab.org/SpecTrack/Documents/Instructions.pdf); 
or 
contact 
the 
Data 
Operations Center at 206/652-2267 to be routed to the Data Coordinator for further 
assistance. 
 
A copy of the Shipment Packing List produced by the Specimen Tracking system should 
be printed and placed in the pocket of the specimen bag if it has one, or in a separate 
resealable bag. 
 
15.5 
Directions for collecting and shipping serum and tissue samples for banking 
 
 
a. 
Serum collection 
 
1. 
For serum sample collections, institutions should register patients to 
SWOG-8947 (Central Lymphoma Serum Repository Protocol).   
 
2. 
Timing of collection:  Serum for S0801 should be obtained prior to 
treatment on Day 1 of Cycle 1.   
 
3.   
Refer to SWOG-8947 for specimen processing and shipping instructions.  
SWOG-8947 provides guidelines on whether to spin/separate sample 
and when to use cool packs or dry ice depending on the day of the week 
the specimen is shipped. 
 
b. 
Tissue collection 
 
1. 
For tissue sample collection, institutions should register patients to 
SWOG-8819 (Central Lymphoma Repository Tissue Procurement 
Protocol).   
 
2. 
Timing of collection:  Snap-frozen tissue (> 5 mm3, "pea size" to "almond 
size") from the pre-treatment diagnostic biopsy should be obtained.   
 
3. 
Refer to SWOG-8819 for specimen processing and shipping instructions 
regarding regulations for packaging and use of dry ice. 
 


 
S0801 
 
Page 44 
 
 
 
 
c. 
All specimens above should be shipped to the following address: 
 
Lab #2:   
SWOG Lymphoma Repository – University of Arizona 
 
Arizona Health Science Center 
 
Department of Pathology, Room 5211, Box 245043 
 
1501 North Campbell Avenue 
 
Tucson, AZ 85724-5043 
 
Contact: 
Yvette Frutiger/Lisa M. Rimsza, M.D. 
Phone:  
520/626-7477 
FAX: 
 
520/626-6081 
Email:  
frutiger@email.arizona.edu 
 
NOTE:  DO NOT SEND SPECIMENS ON FRIDAY.  SEND MONDAY – 
THURSDAY ONLY! 
 
15.5 
Serum and tissue specimens will be collected and stored at the SWOG Lymphoma 
Repository until funding is obtained to perform future correlative studies. 
 
 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS 
 
The following must be observed to comply with Food and Drug Administration regulations for the 
conduct and monitoring of clinical investigations; they also represent sound research practice: 
 
Informed Consent 
 
The principles of informed consent are described by Federal Regulatory Guidelines (Federal 
Register Vol. 46, No. 17, January 27, 1981, part 50) and the Office for Protection from Research 
Risks Reports:  Protection of Human Subjects (Code of Federal Regulations 45 CFR 46).  They 
must be followed to comply with FDA regulations for the conduct and monitoring of clinical 
investigations. 
 
Institutional Review 
 
This study must be approved by an appropriate institutional review committee as defined by 
Federal Regulatory Guidelines (Ref. Federal Register Vol. 46, No. 17, January 27, 1981, part 56) 
and the Office for Protection from Research Risks Reports:  Protection of Human Subjects (Code 
of Federal Regulations 45 CFR 46). 
 
Monitoring 
 
This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0.  
Cumulative CDUS data will be submitted quarterly to CTEP by electronic means.  Reports are 
due January 31, April 30, July 31 and October 31. 
 
16.1 
Adverse Event Reporting Requirements  
 
a. 
Purpose 
 
Adverse event data collection and reporting, which are required as part of every 
clinical trial, are done to ensure the safety of patients enrolled in the studies as 
well as those who will enroll in future studies using similar agents.  Adverse 
events are reported in a routine manner at scheduled times during a trial. 
(Directions for routine reporting are provided in Section 14.0.)  Additionally, 
certain adverse events must be reported in an expedited manner to allow for 
more timely monitoring of patient safety and care.  The following guidelines  
 


 
S0801 
 
Page 45 
 
Revised 1/12/10 
 
Revised 3/28/14 
 
 
 
 
prescribe expedited adverse event reporting for this protocol.  See also Appendix 
19.5 for general and background information about expedited reporting. 
 
b. 
Reporting methods 
 
 
This study requires that expedited adverse event reporting use the 
Cancer Therapy Evaluation Program Adverse Event Reporting System 
(CTEP-AERS). CTEP’s guidelines for CTEP-AERS can be found at 
http://ctep.cancer.gov. A CTEP-AERS report must be submitted to the 
Southwest Oncology Group Operations Office electronically via the 
CTEP-AERS Web-based application located at 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adve
rse_events.htm.  
 
c. 
When to report an event in an expedited manner 
 
Some adverse events require 24-hour notification (refer to Table 16.1) via CTEP-
AERS.  When Internet connectivity is disrupted, a 24-hour notification is to be 
made to CTEP by telephone at 301/897-7497.  Once Internet connectivity is 
restored, a 24-hour notification phoned in, must be entered electronically into 
CTEP-AERS by the original submitter at the site. 
 
When the adverse event requires expedited reporting, submit the report within 
the number of calendar days of learning of the event specified in Table 16.1, as 
applicable.  
 
 
d. 
Other recipients of adverse event reports 
 
The Operations Office will forward reports and documentation to the appropriate 
regulatory agencies and drug companies as required. 
 
Adverse events determined to be reportable must also be reported according to 
local policy and procedures to the Institutional Review Board responsible for 
oversight of the patient. 
 
e. 
Expedited reporting for commercial agents 
 
Commercial reporting requirements are provided in Table 16.1.  If there is any 
question about the reportability of an adverse event, please telephone or email 
the SAE Program at the Operations Office, 210/614-8808 or adr@swog.org, 
before preparing the report. 
 


Revised 1/12/10 
S0801 
Revised 11/5/10 
Page 46 
 
Revised 3/28/14 
 
 
 
 
Table 16.1. Expedited reporting requirements for adverse events 
experienced by patients who have received the commercial drug(s).  
 
 
Attribution 
 
Grade 4 
 
Grade 5a 
Unexpected 
Expected 
Unexpected 
Expected 
Unrelated or Unlikely 
 
 
CTEP-
AERS 
CTEP-AERS 
Possible, Probable, Definite 
CTEP-AERS 
 
CTEP-
AERS 
CTEP-AERS 
CTEP-AERS:  Indicates an expedited report is to be submitted via CTEP-AERS within 10 
calendar days of learning of the event.b 
 
a This includes all deaths within 30 days of the last dose of treatment with a commercial 
agent(s), regardless of attribution. Any death that occurs more than 30 days after the last 
dose of treatment with a commercial agent(s) and is attributed (possibly, probably, or 
definitely) to the agent(s) and is not due to cancer recurrence must be reported according to 
the instructions above. 
 
b Submission of the on-line CTEP-AERS report plus any necessary amendments generally 
completes the reporting requirements. You may, however, be asked to submit supporting 
clinical data to the Operations Office in order to complete the evaluation of the event. If 
requested, the specified data should be sent by fax to 210-614-0006. 
 
 
f.  
Reporting secondary AML/MDS/ALL 
 
1. 
All cases of acute myeloid leukemia (AML), acute lymphocytic leukemia 
(ALL), and myelodysplastic syndrome (MDS) that occur in patients on 
NCI-sponsored trials following chemotherapy for cancer must be 
reported in CTEP-AERS.  
 
i. 
In protocols using CTCAE Version 4.0 for SAE reporting, three 
options are available to describe treatment-related events: 
 
 
Leukemia secondary to oncology chemotherapy 
 
Myelodysplastic syndrome.  NOTE:  The only grading option 
for "Myelodysplastic syndrome" is Grade 4, life-threatening. 
If reporting MDS that is other than Grade 4, use “Neoplasms 
benign, malignant and unspecified (incl cysts and polyps) - 
Other, (specify,__)” and insert MDS as the specify term. 
 
Treatment related secondary malignancy 
 
ii. 
In protocols using CTCAE Version 3.0 for SAE reporting, the 
event(s) can be reported as “Secondary malignancy-Other 
(specify, ___)”.    Report MDS as “Myelodysplasia,” in the 
BLOOD/BONE MARROW category. 
 
iii. 
Secondary malignancies other than AML/ALL/MDS that are 
related to protocol treatment must also be reported in CTEP-
AERS. 
 
iv. 
Non-treatment related cases of AML/ALL/MDS must be reported 
as follows: 


 
S0801 
 
Page 46a 
 
Revised 11/5/10 
 
Revised 3/28/14 
 
 
 
 
 
In protocols using CTCAE Version 4.0 for SAE reporting, report 
as “Neoplasms benign, malignant and unspecified (incl cysts 
and polyps) - Other, specify” 
 
In protocols using CTCAE Version 3.0 for SAE reporting, report 
MDS as “Myelodysplasia” and Leukemias as “Blood/Bone 
Marrow - Other (Specify, __)” 
 
For more information see: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adve
rse_events.htm.  
 
2. 
The following supporting documentation must also be submitted within 
30 days: 
 
 
a copy of the pathology report confirming the AML/ALL /MDS 
diagnosis 
 
(if available) a copy of the cytogenetics report   
 
Submit the Report and documentation to: 
 
Investigational Drug Branch    and 
Southwest Oncology Group 
by fax at 301-230-0159  
 
ATTN: SAE Program 
 
 
4201 Medical Drive, Suite 250 
 
 
San Antonio, Texas 78229 
 
NOTE: If a patient has been enrolled in more than one NCI-sponsored 
study, the report must be submitted for the most recent trial. 
 


 
S0801 
 
Page 47 
 
 
 
 
17.0 
BIBLIOGRAPHY 
 
1.   
Jemal A, Siegel R, Ward E, et al.  Cancer statistics, 2007. CA Cancer J Clin 57:43-66, 2007. 
 
2.   
Fisher R, LeBlanc M, Press O, et al.  New treatment options have changed the survival of 
patients with follicular lymphoma. J Clin Oncol 23:8447-52, 2005. 
 
3.   
McLaughlin P, Grillo-Lopez A, Link B, et al.  Rituximab chimeric anti-CD20 monoclonal antibody 
therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment 
program.  J Clin Oncol 16:2825-2833, 1998. 
 
4. 
Hiddemann W, Kneba M, Dreyling M, et al.  Frontline therapy with rituximab added to the 
combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly 
improves the outcome for patients with advanced-stage follicular lymphoma compared with 
therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade 
Lymphoma Study Group. Blood 106:3725-32, 2005. 
 
5. 
Kaminski M, Estes J, Zasadny K, et al.  Radioimmunotherapy with iodine (131)I tositumomab for 
relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of 
the University of Michigan experience. Blood 96:1259-1266, 2000. 
 
6. 
Vose J, Wahl R, Saleh M, et al.  Multicenter phase II study of iodine-131 tositumomab for 
chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's 
lymphomas. J Clin Oncol 18:1316-1323, 2000. 
 
7. 
Witzig T, Gordon L, Cabanillas F, et al.  Randomized controlled trial of yttrium-90-labeled 
ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with 
relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.  J 
Clin Oncol 20:2453-2463, 2002. 
 
8. 
Press O, Unger J, Braziel R, et al.  A phase 2 trial of CHOP chemotherapy followed by 
tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: 
Southwest Oncology Group Protocol S9911.  Blood 102:1606-1612, 2003. 
 
9. 
Morschhauser F, Illidge T, Huglo D, et al. Efficacy and safety of yttrium-90 ibritumomab tiuxetan 
in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for 
autologous stem-cell transplantation.  Blood 110:54-8, 2007. 
 
10. 
Hagenbeek A, Bischof-Delaloye A, Radford J, et al.  Y-ibrotumomab tiuxetan consolidation of first 
remission in advanced stage follicular non-Hodgkin’s lymphoma: first results of the international 
randomized phase 3 first-line indolent trial in 414 patients.  ASH abstract, 2007. 
 
11. 
Forstpointner R, Unterhalt M, Dreyling M, et al.  Maintenance therapy with rituximab leads to a 
significant prolongation of response duration after salvage therapy with a combination of 
rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring 
and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of 
the German Low Grade Lymphoma Study Group (GLSG). Blood 108:4003-8, 2006.   
 
12. 
van Oers M, Klasa R, Marcus RE, et al.  Rituximab maintenance improves clinical outcome of 
relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab 
during induction: results of a prospective randomized phase 3 intergroup trial.  Blood 108:3295-
301, 2006. 
 
13. 
Cheson B, Pfister B, Suweid M, et al.  Revised response criteria for malignant lymphoma.  J Clin 
Oncol 25:579-586, 2007. 
 
 


 
S0801 
 
 Page 48 
 
Revised 1/12/10 
 
Revised 2/8/10 
 
 
 
 
18.0 
MASTER FORMS SET 
 
18.1 
The Model Informed Consent Form is included in this section, preceded by "Notes for 
Local Institution Consent Form Authors" and "Notes for Local Investigators."  The study - 
as well as the local consent form meeting the guidelines noted in these documents - must 
be reviewed and approved by the Institutional Review Board prior to registration and 
treatment of patients on this study. 
 
18.2 
This section includes copies of all data forms which must be completed for this study. 
 
a. 
S0801 Registration Worksheet, Registration Step 1 (Form #45592) (12/15/08) 
 
b. 
S0801 Registration Worksheet, Registration Step 2 (Form #14379) (12/15/08) 
 
c. 
S0801 Prestudy Form (Form # 62797) (12/1/08)  
 
d. 
S0801 Induction R-CHOP Treatment Form (Form #23097) (12/1/08)  
 
e. 
S0801 Tositumomab Treatment Form (Form #57447)   
  
f. 
S0801 Maintenance Therapy Treatment Form (Form #14046) (12/1/08)  
 
g. 
S0801 Induction Therapy Adverse Event Form (Form #33275) (12/1/08)  
 
h. 
S0801 Maintenance Therapy Adverse Event Form (Form # 57656) (12/1/08) 
 
i. 
S0801 Patient Re-Evaluation Form (Form #19777) (12/1/08) 
 
j. 
Lymphoma Baseline Tumor Assessment Form (Form #39601) (12/15/08) 
 
k. 
Lymphoma Follow-Up Tumor Assessment Form (Form #27780) (12/15/08) 
 
l. 
Off Treatment Notice (Form #28829) (6/15/06) 
 
m. 
Notice of Death (Form #49467) (9/1/03) 
 
n. 
Follow-up Form (Form #64587) (9/15/03) 
 
o. 
Notice of Second Malignancy (Form #27456) (10/15/00) 
 


 
S0801 
 
Page 49 
 
 
 
 
Informed Consent Model for S0801 
 
*NOTES FOR LOCAL INSTITUTION INFORMED CONSENT AUTHORS:  
 
• This model informed consent form has been reviewed by the DCT/NCI and is the official 
consent document for this study. Local IRB changes to this document are allowed.  
(Institutions should attempt to use sections of this document that are in bold type in their 
entirety.)  Editorial changes to these sections may be made as long as they do not change 
information or intent.  If the institutional IRB insists on making deletions or more 
substantive modifications to the risks or alternatives sections, they may be justified in 
writing by the investigator and approved by the IRB.  Under these circumstances, the 
revised language, justification and a copy of the IRB minutes must be forwarded to the 
Southwest Oncology Group Operations Office for approval before a patient may be 
registered to this study.   
 
Please particularly note that the questions related to banking of specimens for future 
study are in bolded type and may not be changed in any way without prior approval from 
the Southwest Oncology Group Operations Office. 
 
Readability Statistics:   
 
Flesch Reading Ease  
52.4 (targeted above 55) 
Flesch-Kincaid Grade Level 10.2 (targeted below 8.5) 
 
• Instructions and examples for informed consent authors are in [italics].  
• A blank line,  __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective research 
participant.  
• The term "study doctor" has been used throughout the model because the Principal 
Investigator of a cancer treatment trial is a physician.   If this model is used for a trial in 
which the Principal Investigator is not a physician, another appropriate term should be 
used instead of "study doctor".  
• The dates of protocol updates in the header and in the text of the consent is for reference 
to this model only and should not be included in the informed consent form given to the 
prospective research participant.  
• Suggestion for Local Investigators:  An NCI pamphlet explaining clinical trials is 
available for your patients.  The pamphlet is entitled: "If You Have Cancer…What You 
Should Know about Clinical Trials".  This pamphlet may be ordered on the NCI Web site 
at http://cissecure.nci.nih.gov/ncipubs/details.asp?pid=1035 or call 1-800-4- CANCER 
(1-800-422-6237) to request a free copy.  
• Optional feature for Local Investigators: Reference and attach drug sheets, 
pharmaceutical information for the public, or other material on risks.  Check with your 
local IRB regarding review of additional materials. 
 


 
S0801 
 
Page 50 
 
 
 
 
*NOTES FOR LOCAL INVESTIGATORS:  
• The goal of the informed consent process is to provide people with sufficient information 
for making informed choices.   The informed consent form provides a summary of the 
clinical study and the individual's rights as a research participant.  It serves as a starting 
point for the necessary exchange of information between the investigator and potential 
research participant.  This model for the informed consent form is only one part of the 
larger process of informed consent. For more information about informed consent, 
review the "Recommendations for the Development of Informed Consent Documents for 
Cancer Clinical Trials" prepared by the Comprehensive Working Group on Informed 
Consent in Cancer Clinical Trials for the National Cancer Institute.  The Web site 
address for this document is http://cancer.gov/clinicaltrials/understanding/simplification-
of-informed-consent-docs/ 
• A blank line,  __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective research 
participant.  
• Suggestion for Local Investigators:  An NCI pamphlet explaining clinical trials is 
available for your patients.  The pamphlet is entitled: "If You Have Cancer…What You 
Should Know about Clinical Trials".  This pamphlet may be ordered on the NCI Web site 
at http://cissecure.nci.nih.gov/ncipubs/details.asp?pid=1035 or call 1-800-4- CANCER 
(1-800-422-6237) to request a free copy.  
• Optional feature for Local Investigators: Reference and attach drug sheets, 
pharmaceutical information for the public, or other material on risks.  Check with your 
local IRB regarding review of additional materials. 
 
*These notes for authors and investigators are instructional and should not be included in the 
informed consent form given to the prospective research participant.  


 
S0801 
 
Page 51 
 
 
 
 
S0801, "A Phase II Study of Iodine-131-Labeled Tositumomab in 
Combination With Cyclophosphamide, Doxorubicin, Vincristine, 
Prednisone and Rituximab Therapy for Patients With Advanced 
Stage Follicular Non-Hodgkin’s Lymphoma" 
 
This is a clinical trial, a type of research study.  Your study doctor will explain the clinical trial 
to you.   Clinical trials include only people who choose to take part. Please take your time to 
make your decision about taking part.  You may discuss your decision with your friends and 
family.  You can also discuss it with your health care team.  If you have any questions, you can 
ask your study doctor for more explanation.  
 
You are being asked to take part in this study because you have a kind of cancer called follicular 
B-cell lymphoma.  This is a cancer of the lymph nodes, which is rarely cured with current 
treatments. 
 
Why is this study being done? 
 
Treatment of follicular lymphoma uses a combination of drugs (called CHOP) with 
an antibody (rituximab).  The rituximab antibody is a protein that is partly of 
mouse origin and partly of human origin. Rituximab attaches to white blood cells (B 
cells) in your blood and tumor.  This leads to death of lymphoma cells using your 
immune system.  These treatments are usually given once every 3 weeks for 6 times.  
 
The Iodine-131 tositumomab antibody is a mouse antibody attached to radioactive 
Iodine (radiolabeled).  These antibodies also attach to white blood cells (B cells) in 
your blood and tumor.  The combination of CHOP chemotherapy and this antibody 
have been used to treat patients with lymphoma and have been shown to be active 
against lymphoma.  We are doing this experimental study to see if patients treated 
with CHOP chemotherapy and rituximab followed by I-131 tositumomab followed 
by long-term rituximab therapy alone may have longer lasting tumor shrinkage, 
than patients treated with CHOP chemotherapy and rituximab alone. 
 
There are numerous therapeutic options currently utilized for patients with 
follicular lymphoma.  The best responses have been observed when monoclonal 
antibodies like rituximab and iodine-131 tositumomab are combined with 
chemotherapy.  With these combinations, the length of response may exceed 5 years.  
The current research study hopes to further improve on these response durations by 
adding rituximab maintenance therapy to a standard approach, which in other 
trials has been shown to be safe and well-tolerated. 
 
Researchers would also like to do laboratory testing on tissue samples in order to 
find out as much as possible about non-Hodgkin's lymphoma and how this 
treatment might affect the disease.  Some of your tissue must be submitted for this  
 


 
S0801 
 
Page 52 
 
Revised 1/12/10 
 
 
 
 
study for testing in order to confirm your type of non-Hodgkin's lymphoma, and 
evaluate for proteins on the surface of the lymphoma cells.  In addition, your bone 
marrow will be evaluated to determine if the treatment affects normal blood cells 
over time.  If any tissue is left over, you may choose to allow this tissue to be kept 
for research purposes.  Also, you may choose to allow additional tissue and serum to 
be sent to a lab and used for research purposes. 
 
How many people will take part in the study? 
About 80 people will take part in this study. 
 
What will happen if I take part in this research study?   
 
Before you begin the study …  
 
You will need to have the following exams, tests or procedures to find out if you can be in the 
study.  These exams, tests or procedures are part of regular cancer care and may be done even if 
you do not join the study.  If you have had some of them recently, they may not need to be 
repeated.  This will be up to your study doctor. 
• Medical History and Physical Exam 
• Weight and Performance Status 
• Disease Assessment including a CT scan or PET/CT scan. 
• Routine blood and urine tests (to measure your kidney, liver, and thyroid function). 
• Hepatitis B virus (HBV) screening (recommended for patients at high risk of infection) 
• A MUGA scan or echocardiogram to monitor your heart function. 
• You will also have your bone marrow examined (called "bone marrow aspiration and 
biopsy") at the start of this study.  (1/11/10)  A bone marrow biopsy will also be taken at 
the end of treatment with chemotherapy, and at one year after completion of treatment if 
the first bone marrow biopsy is abnormal.  (1/11/10)  Your skin over your hipbone will 
be numbed by a shot of local anesthetic (lidocaine) given just under your skin.  A needle 
will be inserted through the numbed skin and into the hipbone.  The bone marrow will be 
removed by using suction and a twisting motion of the needle.  You may have minor 
discomfort, and minor infection is also possible.  Sometimes allergic reactions to the 
anesthetic may occur.  These are regular tests for many patients with lymphoma.  The 
bone marrow will be looked at to find out if any lymphoma cells are present, and to 
determine the status of normal blood cells.  With your consent, bone marrow samples 
will be sent to a lab and stored for future laboratory studies. 
• Your initial biopsy sample will be sent to our pathology laboratory to confirm your 
diagnosis.  Extra tests may be done on your tissue sample to classify your tumor type and 
to see if a certain protein (CD20) that is targeted with this therapy is present on your 
tumor cells. 
 


 
S0801 
 
Page 53 
 
 
 
 
During the study …  
If the exams, tests and procedures show that you can be in the study, and you choose to take part, 
then you will need the following tests and procedures.  They are part of regular cancer care.  
• Routine laboratory blood tests (to measure your kidney, liver, and thyroid function):  
Tests will be done on Day of each treatment cycle (every 21 days), 12 weeks after 
tositumomab treatment is completed, one year after starting treatment, and at follow-up. 
• You will receive the drugs cyclophosphamide, doxorubicin, and vincristine and rituximab 
through a needle in your vein on the first day of each treatment "cycle".  Each "cycle" 
lasts 21 days.  You will also receive the drugs acetaminophen and diphenhydramine by 
mouth before the rituximab to help control pain and prevent possible allergic reaction.  
You will also take the drug prednisone by mouth (pills) for the first five days of the 
cycle.  This combination of drugs is known as CHOP and rituximab.  It will take about 
15 - 45 minutes to receive the cyclophosphamide, 5 - 20 minutes for the doxorubicin, and 
5 - 15 minutes for the vincristine, and up to 6 hours to receive the rituximab.  This 
treatment will be repeated every 21 days for 6 cycles as long as your disease is getting 
better.  The rituximab will not be given during the last two cycles.  If your disease or 
symptoms get worse, you will stop treatment on this study and be offered other options 
by your doctor.   
 
• Standard medications will be used to help prevent side effects, such as nausea, fevers, 
and allergic reactions. Stool softeners will be given to prevent constipation.  These 
medications do not require a prescription, and are commonly used during CHOP and 
rituximab therapy. In certain cases, your physician may recommend a medication to help 
prevent kidney problems from death of lymphoma cells (“tumor lysis”).  Finally, in 
certain cases, your physician may suggest a medication to help your body produce red 
blood cells or white blood cells.  In all cases, your physician will provide detailed 
instructions and information regarding these treatments. 
 
• In addition, about four weeks after you finish the sixth cycle of the rituximab-CHOP 
chemotherapy, you will receive a test dose of iodine-131 tositumomab (called the 
"dosimetric" dose).  It will take about 1 1/2 hours to receive your test dose.  You will first 
receive the "cold" non-radioactive antibody through your vein over 60 minutes, followed 
by the "hot" radioactive antibody through your vein over 20 - 30 minutes.  Following this 
test dose, your whole body will be scanned three times with a special machine (called 
gamma scans) over the period of a week as an outpatient to determine the correct 
treatment dose of the antibody.  One to two weeks after the test dose, you will receive a 
treatment dose (called the "therapeutic" dose) of the Iodine-131 tositumomab antibody 
over about 1/2 to 1 hour.  You will again receive the "cold" and then the "hot" antibody 
through your vein as described above.  Each time you receive the antibody you will 
receive the drugs acetaminophen and diphenhydramine before your antibody dose to help 
control pain and prevent allergic reaction.  You will also be given either a potassium 
iodide solution or potassium iodide tablets to protect your thyroid gland from damage at 
least 24 hours before you receive the first dose of the iodine -131 tositumomab antibody 
(dosimetric dose).  You will continue to receive the potassium iodide for at least 14 days 
after you receive the second dose of the antibody (therapeutic dose). You may also 
receive the drug meperidine if you have trouble with muscle stiffening (rigors) during or  


 
S0801 
 
Page 54 
 
 
 
 
after your infusions.  Patients who have bad side effects with the test dose will not 
receive the treatment dose of the antibody.   
 
• Four or five visits to a nuclear medicine physician will be required during this period of 
time in order to receive the test dose of I-131-tositumomab, have three gamma scans 
performed and then receive the treatment dose of I-131 tositumomab.  As mentioned 
above, you will need to take potassium iodide beginning the day before and continuing 
for several weeks after I-131-tositumomab to prevent damage to your thyroid gland from 
the radioactive iodine.  Depending on the regulations in your state, you may have to stay 
in "radiation isolation" in the hospital for two to four days following the radiolabeled 
antibody treatment.  If your state permits outpatient therapy with I-131 tositumomab, you 
will be given special instructions by the nuclear medicine physician on how to limit 
exposure of other family members to the radioactivity which has been given to you.  If 
your disease or symptoms get worse, you will stop treatment on this study and be offered 
other treatment by your doctor. 
 
• Beginning approximately 1 year after entering the study, you will receive a single dose of 
rituximab through a needle in your vein once every 3 months for 4 years.  Each single 
dose will take about 3-4 hours to complete. 
 
How long will I be in the study? 
We think it will take you about 5 months to finish the initial CHOP-rituximab + 1-131 
tositumomab treatments.  You will return to your doctor about 3 months after you complete your 
initial treatment for tests and scans.  You will then return for a follow-up visit to your doctor 
every 3 months for 4 years for rituximab maintenance treatment.  During the rituximab 
maintenance phase of protocol treatment, follow-up visits to your doctor will occur every 6 
months.   
 
After completion of rituximab maintenance treatment, you will return to your doctor once a year 
for a maximum of 7 years (from the time you first entered the study).   Your doctor may wish to 
see you more often.   
 
If you do not complete the rituximab maintenance treatment, you will return to your doctor every 
6 months for 2 years, and then once a year for maximum of 7 years (from the time you first 
entered the study).   
 
Your doctor may decide to take you off this study if your disease gets worse despite the 
treatment; the side effects of the treatment are too dangerous for you; new information about the 
treatment becomes available and this information suggests the treatment will be ineffective or 
unsafe for you.  It is unlikely, but the study may be stopped early due to lack of funding.. 
 
Can I stop being in the study? 
 
Yes.  You can decide to stop at any time.  Tell the study doctor if you are thinking about 
stopping or decide to stop.  He or she will tell you how to stop safely.  


 
S0801 
 
Page 55 
 
Revised 1/12/10 
 
 
 
 
It is important to tell the study doctor if you are thinking about stopping so any risks from the 
experimental drug combination can be evaluated by your doctor.  (12/15/08) (1/11/10) Another 
reason to tell your doctor that you are thinking about stopping is to discuss what follow-up care 
and testing could be most helpful for you. 
 
The study doctor may stop you from taking part in this study at any time if he/she believes it is 
in your best interest; if you do not follow the study rules; or if the study is stopped. 
What side effects or risks can I expect from being in the study?  
 
You may have side effects while on the study.  Everyone taking part in the study will be 
watched carefully for any side effects.  However, doctors don’t know all the side effects that 
may happen.  Side effects may be mild or very serious.  Your health care team may give 
you medicines to help lessen side effects.  Many side effects go away soon after the 
completion of this experimental drug combination.  (1/11/10)  In some cases, side effects 
can be serious, long lasting, or may never go away.  
 
You should talk to your study doctor about any side effects that you have while taking part in 
the study.    
 
Risks and side effects related to the CHOP chemotherapy treatment (cyclophosphamide, 
doxorubicin, vincristine, prednisone) include the following: 
 
Likely 
 
• 
Nausea/vomiting 
• 
Hair loss 
• 
Less appetite 
• 
Blood cell counts go down 
• 
Swelling/puffy appearance (face/stomach area) 
 
Less Likely 
 
• 
Allergic reaction (like rash, itching, swelling, cough, lowered blood pressure) 
• 
Inflammation of the blood vessels in the skin where the drugs are given 
• 
Sores in the mouth 
• 
Skin and nails change color 
• 
Fingernails and toenails become loose 
• 
Flushing 
• 
Itching of skin 
• 
Headache 
• 
Stomach pain 
• 
Jaw pain 
• 
Weak bones 


Revised 6/3/10 
S0801 
 
Page 56 
 
 
 
 
• 
Diarrhea/constipation 
• 
Fever 
• 
Infection 
• 
Chills 
• 
Tiredness 
• 
Lower or higher blood pressure 
• 
Muscle weakness 
• 
Tingling in the arms and legs 
• 
Itchy, swollen eyes 
• 
Watery eyes 
• 
Changes in eyesight 
• 
Changes in the test to measure heart functions 
• 
Bladder irritation (avoided by drinking 8-10 glasses of water a day) 
• 
Change in color of urine 
• 
Dizziness 
• 
Mood swings/depression 
• 
Changes in personality 
• 
Menstrual changes 
 
Rare, but Serious 
 
• 
Scarring of lungs/shortness of breath 
• 
Shaking 
• 
Heart failure 
• 
Chance of blood cancer 
• 
Dehydration requiring intravenous fluids 
• 
Pneumonia which may require antibiotics 
• 
Your blood counts may become very low from drug.  You may be given GCSF 
to help prevent this risk.  If you get fever during the time your blood counts are 
low, you may require antibiotic therapy, or admission to the hospital.  Severe, 
life-threatening infections may occur under these circumstances.  Your 
physician will provide detailed instructions on what to do if you get fever. 
 
Risks and side effects related to the antibody rituximab include the following: 
 
Likely  
• Fever 
• Chills 
• (deleted 6/3/10) 
• (updated and moved to Less Likely 6/3/10) 
• (updated and moved to Less Likely 6/3/10) 
• Decreased number of a type of white blood cell (lymphocyte) (updated 6/3/10) 
• Reaction that can occur during or following the infusion of the drug.  The reaction 
may include fever, chills, rash, low blood pressure, and difficulty breathing. 
(updated and added from Rare but Serious 6/3/10) 
 


Revised 6/3/10 
S0801 
 
Page 57 
 
 
 
 
Less Likely  
• Vomiting 
• Diarrhea 
• Headache or head pain (updated 6/3/10) 
• Skin rash with the presence of macules (flat discolored area) and papules (raised 
bump) (updated 6/3/10) 
• Hives (updated 6/3/10) 
• Swelling of body tissue underneath the skin (updated 6/3/10) 
• Sudden reddening of the face and/or neck (updated 6/3/10) 
• Cough (updated 6/3/10) 
• Sore throat (updated 6/3/10) 
• (deleted 6/3/10) 
• Joint pain (updated 6/3/10) 
• Back pain (updated 6/3/10) 
• Muscle pain (updated 6/3/10) 
• Belly pain (updated 6/3/10) 
• Pain in the area of the tumor (updated 6/3/10) 
• Dizziness (or sensation of lightheadedness, unsteadiness, or giddiness) (updated 
6/3/10) 
• (deleted 6/3/10) 
• (deleted 6/3/10) 
• (deleted 6/3/10) 
• (deleted 6/3/10) 
• Excess sweating (updated 6/3/10) 
• Lack of enough red blood cells (anemia) (updated 6/3/10) 
• Decreased number of a type of red blood cell that help to clot blood (platelet) 
(updated 6/3/10) 
• (deleted 6/3/10) 
• High blood pressure (updated 6/3/10) 
• Low blood pressure (updated 6/3/10) 
• (deleted 6/3/10) 
• Swelling of the arms and/or legs (updated 6/3/10) 
• Stuffy or runny nose, sneezing (updated 6/3/10) 
• Sudden constriction of the small airways of the lung that can cause wheezing and 
shortness of breath (updated 6/3/10) 
• (deleted 6/3/10) 
• Allergic reaction by your body to the drug product that can occur immediately or 
may be delayed.  The reaction may include hives, low blood pressure, wheezing, 
swelling of the throat, and difficulty breathing. (updated 6/3/10) 
• Thickening of blood/serum as found in Waldenstrom’s macroglobulinemia (a 
cancer of certain blood cells) (added 6/3/10) 
• Fever associated with dangerously low levels of a type of white blood cell 
(neutrophils) (added 6/3/10) 


Revised 6/3/10 
S0801 
 
Page 58 
 
 
 
 
• Heart attack caused by a blockage of a blood vessel supplying part of the heart 
(added 6/3/10) 
• Fast heartbeat; regular rhythm (added 6/3/10) 
• Fast heartbeat usually originating in an area located above the ventricles (added 
6/3/10) 
• Nausea or the urge to vomit (updated and moved from Likely) 
• Fatigue or tiredness (updated and moved from Likely) 
• Pain (added 6/3/10) 
• Allergic reaction to certain medications, injected proteins, or antisera (blood 
product) used to treat certain medical conditions (such as an infectious or poisonous 
substance) (added 6/3/10) 
• Infection (added 6/3/10) 
• Awakening of viruses which have been latent/dormant (added 6/3/10) 
• Infection in HIV positive patients (added 6/3/10) 
• Decreased number of a type of white blood cell (neutrophil/granulocyte) (added 
6/3/10) 
• Decrease in the total number of white blood cells (leukocytes) (added 6/3/10) 
• Increased blood sugar level (added 6/3/10) 
• Decreased blood level of calcium (added 6/3/10) 
• Decreased blood level of potassium (added 6/3/10) 
• Abnormal drowsiness or sluggishness, an unusual lack of energy (added 6/3/10) 
• Convulsion or seizures (updated and added from Rare but Serious 6/3/10) 
• Sudden or traumatic injury to the kidney (updated and added from Rare but Serious 
6/3/10) 
• Shortness of breath (added 6/3/10) 
• Decrease in the oxygen supply to a tissue (added 6/3/10) 
• Inflammation of the lungs that may cause difficulty breathing and can be life-
threatening (added 6/3/10) 
• Itching (added 6/3/10) 
 
Rare, but serious  
• (deleted 6/3/10) 
• (updated and moved to Less Likely 6/3/10) 
• (updated and moved to Less Likely 6/3/10) 
• (deleted 6/3/10) 
• Group of signs and symptoms due to rapid breakdown of tumor that can occur after 
treatment of cancer has started that causes increased levels of blood potassium, uric 
acid, and phosphate, decreased levels of blood calcium, and kidney failure. (updated 
6/3/10) 
• (updated and moved to Likely 6/3/10)   
• (deleted 6/3/10) 


Revised 6/3/10 
S0801 
Revised 9/24/10 
Page 58a  
 
 
 
 
• (deleted 6/3/10) 
• (deleted 6/3/10) 
• Serious, life-threatening allergic reaction requiring immediate medical treatment by 
your doctor.  The reaction may include extremely low blood pressure, swelling of 
the throat, difficulty breathing, and loss of consciousness. (added 6/3/10) 
• Disease affecting brain tissue, caused by the JC virus. (added 6/3/10) (9/24/10) 
• Severe potentially life-threatening damage to the lungs which can lead to fluid in the 
lungs (added 6/3/10) 
• Severe reaction of the skin and gut lining that may include rash and shedding or 
death of tissue (added 6/3/10) 
• Potentially life-threatening condition affecting less than 10% of the skin in which 
cell death causes the epidermis (outer layer) to separate from the dermis (middle 
layer) (added 6/3/10) 
• Life-threatening condition affecting greater than 30% of the skin in which cell death 
causes the epidermis (outer layer) to separate from the dermis (middle layer) (added 
6/3/10) 
 


 
S0801 
 
Page 59 
 
 
 
 
Immunizations:  The safety of immunization with any vaccine, particularly live viral 
vaccines, following rituximab therapy has not been studied.  It is recommended that 
you consult with your doctor before receiving immunizations following rituximab 
therapy.   
 
Risks and side effects related to the antibody tositumomab include the following: 
 
Likely 
 
• 
Fever 
• 
Weakness 
• 
Chills 
• 
Loss of appetite 
• 
Nausea/vomiting 
• 
Diarrhea 
• 
Rash 
• 
Tumor site pain 
• 
Decrease in blood counts 
 
Less Likely 
 
• 
Lowered blood pressure causing lightheadedness/dizziness 
• 
Allergic reaction including rash, hives, itching, shortness of breath 
• 
Development of "human anti-mouse antibodies" (limiting ability for further 
treatment with antibodies) 
• 
Infection 
• 
Joint pain 
• 
Muscle pain 
• 
Abdominal pain 
• 
Headache 
• 
Nose inflammation 
• 
Throat inflammation 
• 
Cough 
• 
Diarrhea 
• 
Reduced thyroid gland activity (fatigue, feeling cold, dry skin, constipation)   
• 
Rapid heartbeat at time of injection 
• 
Flushing 
• 
Numbness 
• 
Infrequent urination  
• 
Bronchitis 
 
Rare, but Serious 
 
• 
Severe allergic reaction 
• 
Bone marrow damage 


 
S0801 
 
Page 60 
 
 
 
 
• 
Chance of developing acute leukemia or other cancers 
• 
Increased calcium and/or potassium  
• 
Increased uric acid 
• 
Kidney failure 
• 
Blood clot in the lung 
 
Reproductive risks:  You should not become pregnant or father a baby while on this study 
because the drugs in this study can affect an unborn baby.  It is important you understand 
that you need to use birth control while on this study.  Check with your study doctor about 
what kind of birth control methods to use and how long to use them.   
 
For more information about risks and side effects, ask your study doctor. 
 
 
Are there benefits to taking part in the study? 
 
Taking part in this study may or may not make your health better.  While doctors hope 
this experimental technique will be more useful against cancer compared to the usual 
treatment, there is no proof of this yet.  We hope the information learned from this study 
will benefit other patients with non-Hodgkin's lymphoma in the future.  This information 
could help future cancer patients. 
 
 
What other choices do I have if I do not take part in this study? 
 
Your other choices may include: 
• Getting treatment or care for your cancer without being in a study 
• Taking part in another study 
• Getting no treatment 
 
Talk to your doctor about your choices before you decide if you will take part in this study. 
 
Will my medical information be kept private?  
 
We will do our best to make sure that the personal information in your medical record will be 
kept private.  However, we cannot guarantee total privacy.  Your personal information may be 
given out if required by law.  If information from this study is published or presented at 
scientific meetings, your name and other personal information will not be used.  
 
Organizations that may look at and/or copy your medical records for research, quality assurance, 
and data analysis include: 
• Your local Institutional Review Board (IRB) 
• The National Cancer Institute (NCI); 
• The Food and Drug Administration (FDA), involved in keeping research safe for people; 
• The Southwest Oncology Group 
• GlaxoSmithKline (the manufacturer of tositumomab) 


 
S0801 
 
Page 61 
 
 
 
 
What are the costs of taking part in this study? 
 
You and/or your health plan/ insurance company will need to pay for some or all of the costs of 
treating your cancer in this study.  Some health plans will not pay these costs for people taking 
part in studies.  Check with your health plan or insurance company to find out what they will pay 
for.  Taking part in this study may or may not cost your insurance company more than the cost of 
getting regular cancer treatment.  
 
Administration of the drug will be (provided free of charge/charged in the usual way).  The parts 
of the research consisting of keeping research records will be paid by those organizing and 
conducting the research.  The research requires that you receive certain standard medical tests 
and examinations.  These standard tests and examinations will be (charged in the usual 
way/provided at a reduced rate).  (local institutions must choose the option that best fits the 
hospital's situation) 
 
The cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab are commercially 
available.  Iodine-131 tositumomab is also commercially available, but will be supplied for this 
study by GlaxoSmithKline at no cost to you.   
 
You will not be paid for taking part in this study. 
 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage .    You 
can print a copy of the “Clinical Trials and Insurance Coverage” information from this Web site. 
 
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask them 
to send you a free copy. 
 
 
What happens if I am injured because I took part in this study? 
 
It is important that you tell your study doctor, __________________ [investigator’s name(s)], if 
you feel that you have been injured because of taking part in this study.  You can tell the doctor 
in person or call him/her at __________________ [telephone number]. 
 
You will get medical treatment if you are injured as a result of taking part in this study.  You 
and/or your health plan will be charged for this treatment.   The study will not pay for medical 
treatment.   
 
 
What are my rights if I take part in this study? 
 
Taking part in this study is your choice.  You may choose either to take part or not to take part in 
the study.  If you decide to take part in this study, you may leave the study at any time.  No 
matter what decision you make, there will be no penalty to you and you will not lose any of your 
regular benefits.  Leaving the study will not affect your medical care.  You can still get your 
medical care from our institution.    


 
S0801 
 
Page 62 
 
 
 
 
We will tell you about new information or changes in the study that may affect your health or 
your willingness to continue in the study. 
 
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form.   
 
 
Who can answer my questions about the study? 
 
You can talk to your study doctor about any questions or concerns you have about this study.  
Contact your study doctor __________________ [name(s)] at __________________ [telephone 
number]. 
 
For questions about your rights while taking part in this study, call the 
________________________ [name of center] Institutional Review Board (a group of people 
who review the research to protect your rights) at __________________ (telephone number).  
[Note to Local Investigator: Contact information for patient representatives or other individuals 
in a local institution who are not on the IRB or research team but take calls regarding clinical 
trial questions can be listed here.]    
 
 
Please note:  This following section of the informed consent form is about 
additional research studies that are being done with people who are taking part in 
the main study.   You may take part in these additional studies if you want to.  You 
can still be a part of the main study even if you say ‘no’ to taking part in any of 
these additional studies. 
 
You can say "yes" or "no" to each of the following studies.  Please mark your 
choice for each study.   
 
Occasionally, researchers working with the Southwest Oncology Group (SWOG) may have 
another research idea that relates to people who were on a SWOG study. In some cases, to carry 
out the new research, we would need to contact participants in a particular study.  You can agree 
or not agree to future contact. 
 
Future Contact 
I agree to allow my study doctor, or someone approved by my study doctor, to contact me 
regarding future research involving my participation in this study.  
Yes 
No 
 


 
S0801 
 
Page 63 
 
 
 
 
Consent for use of excess diagnostic tissue for research purposes. 
 
Preserved tissue from your tumor must be submitted for this study in order to confirm your type 
of non-Hodgkin's lymphoma.  There may be some tissue remaining once your diagnosis has been 
confirmed.  If you are willing to allow this excess tissue to be used for research purposes, please 
specify your consent below. 
 
Also, if you are willing to submit additional frozen and preserved tissue and blood for research 
purposes, you will be registered to the Central Lymphoma Repository Tissue Procurement 
Protocol, SWOG-8819 and/or the Central Lymphoma Serum Repository Protocol, SWOG-
8947.  Your responses will also apply to any specimens sent for these studies.   


 
S0801 
 
Page 64 
 
 
 
 
 
SWOG Lymphoma Repository 
 
c/o Lisa M. Rimsza, M.D. 
 
Arizona Health Science Center 
 
Department of Pathology, Room 5211, Box 245043 
 
1501 North Campbell Avenue 
 
Tucson, AZ  85724-5043 
 
Phone:  520/626-7477 
 
Consent Form for Use of Specimens for Research 
About Using Specimens for Research  
You are going to have a biopsy (or surgery) to see if you have cancer. Your doctor will remove 
some tissue and blood to do some tests. The results of these tests will be given to you by your 
doctor and will be used to plan your care.  
We would like to keep some of the specimens that are left over for future research.  If you agree, 
these specimens will be kept and may be used in research to learn more about cancer and other 
diseases.  Please read the information sheet called "How are Specimens Used for Research" to 
learn more about specimen research.  
Your specimens may be helpful for research whether you do or do not have cancer. The research 
that may be done with your specimens is not designed specifically to help you. It might help 
people who have cancer and other diseases in the future.  
Reports about research done with your specimens and will not be given to you or your doctor. 
These reports will not be put in your health record. The research will not have an effect on your 
care.  
Things to Think About  
The choice to let us keep the left over specimens for future research is up to you. No matter what 
you decide to do, it will not affect your care.  
If you decide now that your specimens can be kept for research, you can change your mind at 
any time. Just contact us and let us know that you do not want us to use your tissue. Then any 
specimens that remain will no longer be used for research.  
In the future, people who do research may need to know more about your health. While the 
Southwest Oncology Group may give them reports about your health, it will not give them your 
name, address, phone number, or any other information that will let the researchers know who 
you are.  
Sometimes specimens are used for genetic research (about diseases that are passed on in 
families). Even if your specimens are used for this kind of research, the results will not be put in 
your health records.  
Your specimens will be used only for research and will not be sold. The research done with your 
specimens may help to develop new products in the future.  


 
S0801 
 
Page 65 
 
Revised 1/12/10 
 
 
 
 
Benefits 
The benefits of research using specimens include learning more about what causes cancer and 
other diseases, how to prevent them, and how to treat them.  
Risks  
The greatest risk to you is the release of information from your health records. We will do our 
best to make sure that your personal information will be kept private.  The chance that this 
information will be given to someone else is very small.  
Making Your Choice  
Please read each sentence below and think about your choice. After reading each sentence, circle 
"Yes" or "No". If you have any questions, please talk to your doctor or nurse, or call our research 
review board at IRB's phone number.  
No matter what you decide to do, it will not affect your care. 
1.  
My specimens may be kept for use in research to learn about, prevent, treat, or cure 
cancer. (1/11/10) 
Yes 
No 
2.  
My specimens may be kept for use in research about other health problems (for 
example: diabetes, Alzheimer's disease, or heart disease). (1/11/10) 
Yes 
No 
3.  
Someone may contact me in the future to ask me to allow other uses of my 
specimen. (1/11/10) 
Yes 
No 
If you decide to withdraw your specimens from a Southwest Oncology Group Specimen 
Repository in the future, a written withdrawal of consent should be submitted through 
your treating physician to the Southwest Oncology Group Operations Office.  Please 
designate in the written withdrawal whether you would prefer to have the specimens 
destroyed or returned to the treating physician. 
Where can I get more information? 
 
You may call the National Cancer Institute's Cancer Information Service at:  
 
1-800-4-CANCER (1-800-422-6237) or TTY: 1-800-332-8615 
 
You may also visit the NCI Web site at http://cancer.gov/ 
 
• For NCI’s clinical trials information, go to: http://cancer.gov/clinicaltrials/ 
 
• For NCI’s general information about cancer, go to http://cancer.gov/cancerinfo/ 


 
S0801 
 
Page 66 
 
 
 
 
You will get a copy of this form.    If you want more information about this study, ask your study 
doctor. 
 
Signature 
 
I have been given a copy of all _____ [insert total of number of pages] pages of this form.  I 
have read it or it has been read to me.  I understand the information and have had my questions 
answered.  I agree to take part in this study. 
 
 
Participant ________________________________ 
 
Date _____________________________________ 
 


 
S0801 
 
Page 67 
 
 
 
 
Specimen Consent Supplemental Sheets 
 
How are Specimens Used for Research? 
 
Where do specimens come from? 
 
A specimen may be from a blood sample or from bone marrow, skin, toenails or other body materials.  
People who are trained to handle specimens and protect donors' rights make sure that the highest 
standards of quality control are followed by the Southwest Oncology Group.  Your doctor does not work 
for the Southwest Oncology Group, but has agreed to help collect specimens from many patients.  Many 
doctors across the country are helping in the same way.   
 
Why do people do research with specimens? 
 
Research with specimens can help to find out more about what causes cancer, how to prevent it, how to 
treat it, and how to cure it.  Research using specimens can also answer other health questions.  Some of 
these include finding the causes of diabetes and heart disease, or finding genetic links to Alzheimer's. 
 
What type of research will be done with my specimen? 
 
Many different kinds of studies use specimens.  Some researchers may develop new tests to find 
diseases.  Others may develop new ways to treat or even cure diseases.  In the future, some of the 
research may help to develop new products, such as tests and drugs.  Some research looks at diseases 
that are passed on in families (called genetic research).  Research done with your specimen may look for 
genetic causes and signs of disease. 
 
How do researchers get the specimen? 
 
Researchers from universities, hospitals, and other health organizations conduct research using 
specimens.  They contact the Southwest Oncology Group and request samples for their studies.  The 
Southwest Oncology Group reviews the way that these studies will be done, and decides if any of the 
samples can be used. The Southwest Oncology Group gets the specimen and information about you 
from your hospital, and sends the specimen samples and some information about you to the researcher.  
The Southwest Oncology Group will not send your name, address, phone number, social security number 
or any other identifying information to the researcher. 
 
Will I find out the results of the research using my specimen? 
 
You will not receive the results of research done with your specimen.  This is because research can take 
a long time and must use specimen samples from many people before results are known.  Results from 
research using your specimen may not be ready for many years and will not affect your care right now, 
but they may be helpful to people like you in the future. 
 
Why do you need information from my health records? 
 
In order to do research with your specimen, researchers may need to know some things about you.  (For 
example:  Are you male or female?  What is your race or ethnic group? How old are you?  Have you ever 
smoked?)  This helps researchers answer questions about diseases.  The information that will be given 
to the researcher may include your age, sex, race, diagnosis, treatments and family history.  This 
information is collected by your hospital from your health record and sent to the Southwest Oncology 
Group.  If more information is needed, the Southwest Oncology Group will send it to the researcher. 
 
Will my name be attached to the records that are given to the researcher? 
 
No.  Your name, address, phone number and anything else that could identify you will be removed before 
they go the researcher.  The researcher will not know who you are. 
 


 
S0801 
 
Page 68 
 
 
 
 
How could the records be used in ways that might be harmful to me? 
 
Sometimes, health records have been used against patients and their families.  For example, insurance 
companies may deny a patient insurance or employers may not hire someone with a certain illness (such 
as AIDS or cancer).  The results of genetic research may not apply only to you, but to your family 
members too.  For disease caused by gene changes, the information in one person's health record could 
be used against family members. 
 
How am I protected? 
 
The Southwest Oncology Group is in charge of making sure that information about you is kept private.  
The Southwest Oncology Group will take careful steps to prevent misuse of records.  Your name, 
address, phone number and any other identifying information will be taken off anything associated with 
your specimen before it is given to the researcher.  This would make it very difficult for any research 
results to be linked to you or your family.  Also, people outside the research process will not have access 
to results about any one person which will help to protect your privacy. 
 
What if I have more questions? 
 
If you have any questions, please talk to your doctor or nurse, or call our research review board at (Insert 
IRB's Phone Number). 
 
 
 


12/1/2008
Page 1 of 2
SOUTHWEST ONCOLOGY GROUP
S0801 REGISTRATION WORKSHEET
12/1/2008
Registrar's SWOG Roster ID Number:
SWOG Investigator Number:
continued on next page
Page 1 of 2
SWOG Treating Institution Number:
Check that IRB approval is current for this institution prior to registering.  Registrations are not allowed if the IRB approval is expired.
SOUTHWEST ONCOLOGY GROUP
S0801 REGISTRATION WORKSHEET
SWOG Patient ID:
SWOG Patient ID Status:
New Patient
Previous Patient:
If the patient has a SWOG Patient ID assigned by a prior registration or Specimen Tracking, choose "Previous Patient" and use that number.
Projected Start Date of Treatment:
/
/
Date Informed Consent Signed:
/
/
Date HIPAA Authorization signed:
/
/
(Not required if Country of Residence is not USA)
Patient's Date of Birth:
/
/
If Canada, Social Insurance Number:
-
-
Postal Code:
-
If USA, Patient Social Security Number:
-
-
ZIP Code:
Country of Residence:
US (USA)
CA (Canada)
Other:
Both Social Security Number and Social Insurance Number are desired, but optional.  Do not enter invalid numbers in either field.
(Full names preferred, initials OK)
Patient's Name:
INSTRUCTIONS: All of the information on this Registration Worksheet and the Protocol Eligibility Section must be answered appropriately for a
patient to be considered eligible for registration.  This Registration Worksheet must be entirely filled out and referred to during the registration.  Do
NOT submit this worksheet as part of the patient data.
Patient Gender:
Female
Male
No (not Spanish)
Yes, Mexican
Yes, Puerto Rican
Yes, Cuban
Yes, Central American
Yes, South American
Yes, NOS
Yes, Other:
Unknown
Patient's Ethnicity:
Method of Payment:
Black or African American
Native Hawaiian or Other Pacific Islander
Asian
Unknown
Patient's Race (select all that apply):
American Indian or Alaska Native
White
Private insurance
Veterans-sponsored
Military or Veterans-sponsored, NOS
Medicare
Medicare and Private insurance
Medicaid
Medicaid and Medicare
Self Pay (no insurance)
No means of payment (no insurance)
Unknown
Other:
A Phase II Study of Iodine-131-Labeled Tositumomab in Combination
with Cyclophosphamide, Doxorubicin, Vincristine, Prednisone and
Rituximab Therapy for Patients with Advanced Stage Follicular
Non-Hodgkin's Lymphoma
Activation Date: December 1, 2008
Registration Step: 1
Last Amended Date:
45592


12/1/2008
Page 2 of 2
SOUTHWEST ONCOLOGY GROUP
S0801 REGISTRATION WORKSHEET
Indicate how the patient answered the following questions on the consent form
If this is not the EXACT WORDING on the consent form, phone in the registration and tell the registrar how the wording was changed.
My specimens may be kept for use in research to learn about, prevent, treat, or cure cancer.
My specimens may be kept for use in research about other health problems (for example:
diabetes, Alzheimer's disease, or heart disease).
Someone may contact me in the future to ask me to allow other uses of my specimens.
I agree to allow my study doctor, or someone approved by my study doctor, to contact me
regarding future research involving my participation in this study.
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Has the Southwest Oncology Group Registration Worksheet been completed entirely and is the
patient eligible according to the current version of protocol section 5.0?
Comments (notes from Confirmation of Registration):
SWOG Patient ID:
Assigned Treatment Arm:
Other Notes:
Expectations Notes:
Treatment Name:
45592


12/1/2008
Registrar's SWOG Roster ID Number:
SWOG Investigator Number:
Page 1 of 1
SWOG Treating Institution Number:
SOUTHWEST ONCOLOGY GROUP
S0801 REGISTRATION WORKSHEET
SWOG Patient ID:
SWOG Patient ID Status:
New Patient
Previous Patient:
INSTRUCTIONS: All of the information on this Registration Worksheet and the Protocol Eligibility Section must be answered appropriately for a
patient to be considered eligible for registration.  This Registration Worksheet must be entirely filled out and referred to during the registration.  Do
NOT submit this worksheet as part of the patient data.
Activation Date: December 1, 2008
Registration Step: 2
Last Amended Date:
Projected Start Date of Treatment:
/
/
Method of Payment:
Private insurance
Veterans-sponsored
Military or Veterans-sponsored, NOS
Medicare
Medicare and Private insurance
Medicaid
Medicaid and Medicare
Self Pay (no insurance)
No means of payment (no insurance)
Unknown
Other:
A Phase II Study of Iodine-131-Labeled Tositumomab in Combination
with Cyclophosphamide, Doxorubicin, Vincristine, Prednisone and
Rituximab Therapy for Patients with Advanced Stage Follicular
Non-Hodgkin's Lymphoma
continued on next page
Comments (notes from Confirmation of Registration):
Yes
No
Has the Southwest Oncology Group Registration Worksheet been completed entirely and is the
patient eligible according to the current version of protocol section 5.0?
Assigned Treatment Arm:
Treatment Name:
Other Notes:
14379


SOUTHWEST ONCOLOGY GROUP
S0801 PRESTUDY FORM
Page 1 of 3
Patient Initials
(L, F M)
12/1/2008
SOUTHWEST ONCOLOGY GROUP
S0801 PRESTUDY FORM
Page 1 of 3
Physician
Institution / Affiliate
Patient Initials
(L, F M)
SWOG Patient ID
Instructions:  Submit this form within 14 days of registration.  All dates are MONTH, DAY, YEAR.  Explain any blank fields or blank
dates in the Comments section.  Place an    X    in appropriate boxes.  Circle AMENDED items in red and write AMENDED across top
of form.
12/1/2008
(PS0801)
SWOG Study No. S 0 8 0 1
Registration Step 1
continued on next page
ELIGIBILITY VERIFICATION:
Each of the fields below corresponds to a criterion in Section 5 and must be completed for patient to be eligible.
PATIENT AND DISEASE DESCRIPTION
Performance status:
Symptoms:
A (No Symptoms)
B (Fever, Weight Loss, and/or Night Sweats)
Stage of disease at diagnosis:
I
II
III
IV
Has the patient received any prior chemotherapy, radiation, or antibody treatment for lymphoma?
No
Yes
Date of unilateral or bilateral bone marrow biopsy and aspirate:
/
/
No
Yes
Result:
Positive
Negative
(Note: CT scans may have been performed at the same time or separately)
Date of chest CT scan:
/
/
Date of abdomen/pelvis CT scan:
/
/
Hematologic:
ANC
Platelets
WBC
Lymphocytopenia (% of total WBC)
Hemoglobin
Serum Beta2 Microglobulin
Collection date:
LABORATORY VALUES
Document values in units listed
.
/
/
µg/mL
Date of first pathologic diagnosis:
/
/
/
/
≥
Does the patient have bulky disease (any mass    10 cm in diameter or a mediastinal mass > 1/3 chest 
diameter)?
Were any laboratory or radiographic tests performed to assess CNS involvement?
No
Yes
Result:
Positive
Negative
Date of tests to assess CNS involvement:
/
/
/ mcL
,
/ mcL
,
x 10   / mcL
.
³
/
/
/
/
/
/
g/dL
.
/
/
SWOG Patient ID
62797


SOUTHWEST ONCOLOGY GROUP
S0801 PRESTUDY FORM
Page 2 of 3
Patient Initials
(L, F M)
12/1/2008
Hepatic:
Total bilirubin
Please record the appropriate transaminase lab value:
SGOT
  OR
SGPT
Renal:
Serum creatinine
LDH:
Cardiac:
Ejection fraction (select one)
LABORATORY VALUES, continued
ADDITIONAL PRESTUDY DATA:
CURRENT LYMPHATIC TISSUE INVOLVEMENT
Is there current nodal involvement above the diaphragm?
No
Yes
Is there current nodal involvement below the diaphragm?
No
Yes
Is there current splenic involvement?
No
Yes
* Instructions for counting the number of involved nodal sites are on page 3 of this form.
If Yes, number of sites involved above the diaphragm*:
If Yes, number of sites involved below the diaphragm*:
If Yes, select all that apply:
Is there current extranodal involvement?
No
Yes
CURRENT EXTRANODAL INVOLVEMENT
Bone Marrow
GI Tract
Lung
Other:
Liver
CNS/Brain
continued on next page
mg/dL
.
 ULN
mg/dL
.
/
/
/
/
U/L
ULN
U/L
mg/dL
.
 ULN
mg/dL
.
/
/
U/L
 ULN
U/L
/
/
Collection date:
Collection date:
U/L
 ULN
U/L
/
/
MUGA
ECHO
%
/
/
Collection date:
SWOG Study No. S 0 8 0 1
Registration Step 1
SWOG Patient ID
62797


SOUTHWEST ONCOLOGY GROUP
S0801 PRESTUDY FORM
Page 3 of 3
Patient Initials
(L, F M)
12/1/2008
Instructions: The figure below indicates how to count the number of involved nodal sites according to Solal-Celigny et al., Blood,
2004. Each box represents a nodal area. Multiple involved nodes within a single nodal area (or box) are counted as 1 nodal site.
Bilateral disease is counted as 2 nodal sites. Bilateral nodal areas include axillary, cervical, inguinal, epitrochlear, and popliteal.
The mediastinal, mesenteric, and para aortic nodal areas are not considered to be bilateral; in these cases multiple involved nodes
from each are counted as at most only 1 nodal site. Iliac nodes are a component of the para aortic nodal area and are also NOT
considered to be bilateral. (Note: Other non-bilateral sites include preaortic and subcarinal; these are counted as 1 nodal site.)
Comments:
SWOG Study No. S 0 8 0 1
Registration Step 1
SWOG Patient ID
62797


 SOUTHWEST ONCOLOGY GROUP
S0801 INDUCTION R-CHOP TREATMENT FORM
SWOG Patient ID
12/1/2008
SWOG Study No. S 0 8 0 1
Registration Step 1
(L, F M)
Patient Initials
Comments:
Page 1 of 1
TREATMENT FOR THIS CYCLE
STATUS
Date of Last Contact or Death:
/
/
Has the patient progressed per the definition in Section 10.0 of the protocol?
No
Yes
(submit Follow-up Form)
Current Cycle Number
(see instructions)
Institution/Affiliate
Physician
Vital Status:
Alive
Dead
(submit Notice of Death)
Date of last treatment for this cycle:
/
/
Cycle start date:
/
/
Report total dose/number of days for reporting period
Agent
Total Dose
Number of Days
Cyclophosphamide
Doxorubicin
Vincristine
Prednisone
Rituximab
mg
mg
mg
.
mg
mg
kg
Weight (first day this cycle):
.
m2
BSA (first day this cycle):
.
No
Yes, planned (per protocol guidelines), specify in comments
Yes, unplanned (not per protocol guidelines), specify in comments
Were there any dose modifications or additions/omissions to protocol treatment?
(TX0801I)
Instructions:  Please complete this form after each cycle (1 cycle = 21 days) of induction R-CHOP therapy.  All dates are MONTH,
DAY, YEAR.  Explain any blank dates or fields in a Comments section.  Place an   X   in appropriate boxes.  Circle AMENDED items in
red and write AMENDED across the top of the form.
23097


 SOUTHWEST ONCOLOGY GROUP
S0801 TOSITUMOMAB TREATMENT FORM
SWOG Patient ID
3/1/2010
SWOG Study No. S 0 8 0 1
Registration Step 1
(L, F M)
Patient Initials
Comments:
Page 1 of 1
STATUS
Date of Last Contact or Death:
/
/
Has the patient progressed per the definition in Section 10.0 of the protocol?
No
Yes
(submit Follow-up Form)
Institution/Affiliate
Physician
Vital Status:
Alive
Dead
(submit Notice of Death)
Date of last treatment:
/
/
Start date:
/
/
Report total dose for reporting period
Agent
Dose
Dosimetric: Unlabeled Tositumomab
Dosimetric: I-131 labeled Tositumomab
Dosimetric: Iodine-131 dose
Therapeutic: Unlabeled Tositumomab
Therapeutic: I-131 labeled Tositumomab
Therapeutic: Iodine-131 dose
kg
Weight (first day this cycle):
.
m2
BSA (first day this cycle):
.
No
Yes, planned (per protocol guidelines), specify in comments
Yes, unplanned (not per protocol guidelines), specify in comments
Were there any dose modifications or additions/omissions to protocol treatment?
TOSITUMOMAB TREATMENT
(TX0801T)
Instructions:  Please complete this form at the end of I-131 treatment.  All dates are MONTH, DAY, YEAR.  Explain any blank dates or
fields in a Comments section.  Place an   X   in appropriate boxes.  Circle AMENDED items in red and write AMENDED across the top
of the form.
mg
mg
mg
mg
mCi
mCi
57447


 SOUTHWEST ONCOLOGY GROUP
S0801 MAINTENANCE THERAPY TREATMENT FORM
SWOG Patient ID
12/1/2008
SWOG Study No. S 0 8 0 1
Registration Step 2
(L, F M)
Patient Initials
Comments:
Page 1 of 1
TREATMENT FOR THIS CYCLE
STATUS
Date of Last Contact or Death:
/
/
Has the patient progressed per the definition in Section 10.0 of the protocol?
No
Yes
(submit Follow-up Form)
Current Cycle Number
Institution/Affiliate
Physician
Vital Status:
Alive
Dead
(submit Notice of Death)
Date of last treatment for this cycle:
/
/
Cycle start date:
/
/
Total dose of Rituximab for this reporting period:
mg
kg
Weight (first day this cycle):
.
m2
BSA (first day this cycle):
.
No
Yes, planned (per protocol guidelines), specify in comments
Yes, unplanned (not per protocol guidelines), specify in comments
Were there any dose modifications or additions/omissions to protocol treatment?
(TX0801M)
Instructions:  Please complete this form after each cycle (1 cycle = 3 months) of rituximab maintenance therapy.  All dates are
MONTH, DAY, YEAR.  Explain any blank dates or fields in a Comments section.  Place an   X   in appropriate boxes.  Circle AMENDED
items in red and write AMENDED across the top of the form.
14046


 SOUTHWEST ONCOLOGY GROUP
S0801 INDUCTION THERAPY ADVERSE EVENT FORM
Page 1 of 2
(L, F M)
12/1/2008
Cycle submission:
 SOUTHWEST ONCOLOGY GROUP
S0801 INDUCTION THERAPY ADVERSE EVENT FORM
SWOG Patient ID
* Attribution codes:    1-unrelated           2-unlikely           3-possible           4-probable         5-definite
Page 1 of 2
Patient Initials
(L, F M)
continued on next page
12/1/2008
SWOG Study No. S 0 8 0 1
Registration Step 1
No
Yes, but no reportable adverse events occurred
Yes, and reportable adverse events occurred (report below)
Were adverse events assessed during this time period?
Reporting period end date:
/
/
Reporting period start date:
/
/
ADVERSE EVENTS
(Day 1 of this Cycle)
(Day one of next cycle.  If final cycle, date
of first visit or contact after resolution of
acute adverse events.)
CTCAE (3.0)
Grade
(1 - 5)
CTC Adverse Event Term
CTC Adverse
Event
Attribution
Code*
CTC Adverse Event Term
CTCAE (3.0)
Grade
(1 - 5)
CTC Adverse
Event
Attribution
Code*
IM00
Allergic reaction
HE20
Hemoglobin
HE00
Leukocytes
HE40
Lymphopenia
HE30
Neutrophils
HE10
Platelets
CA50
Hypertension
CA51
Hypotension
CA06
Left ventricular diastolic
dysfunction
CA07
Left ventricular systolic
dysfunction
CL20
PTT
FL40
Fatigue
FL01
Fever
FL20
Insomnia
FL10
Rigors/chills
FL30
Sweating
SK90
Alopecia
SK11
Rash
GI01
Anorexia
GI23
Dehydration
GI20
Diarrhea
GI00
Nausea
GI10
Vomiting
IN30
Febrile neutropenia
Infection with Grade 0-2 ANC
INL05
Lung
Infection with Grade 3-4 ANC
ICL05
Lung
Infection with unknown ANC
IUL05
Lung
LY01
Edema: head and neck
LY02
Edema: limb
LY03
Edema: trunk/genital
LY04
Edema: visceral
Physician
Institution/Affiliate
Cycle submission:
R-CHOP cycle 1
R-CHOP  cycle 2
R-CHOP  cycle 3
R-CHOP  cycle 4
R-CHOP  cycle 5
R-CHOP  cycle 6
Post I-131 tx
Instructions:  Please complete this form at the end of every cycle of R-CHOP (cycles 1-6) and 2 weeks after completion of I-131
therapy.  Report adverse events occurring up until the next cycle of treatment begins.   Document the worst Grade seen during the
reporting period.  Do not code a condition existing prior to registration as an adverse event unless it worsens.  All dates are MONTH,
DAY, YEAR.  Explain any blank dates or fields in the Comments section.  Place an   X   in appropriate boxes.  Circle AMENDED items in
red and write AMENDED across the top of the form.
SWOG Patient ID
Patient Initials
R-CHOP cycle 1
R-CHOP  cycle 2
R-CHOP  cycle 3
R-CHOP  cycle 4
R-CHOP  cycle 5
R-CHOP  cycle 6
Post I-131 tx
33275


 SOUTHWEST ONCOLOGY GROUP
S0801 INDUCTION THERAPY ADVERSE EVENT FORM
Page 2 of 2
(L, F M)
12/1/2008
Cycle submission:
Comments: (Please explain any "other" adverse events reported above)
SWOG Study No. S 0 8 0 1
Registration Step 1
ADVERSE EVENTS, continued
CTC Adverse Event Term
CTCAE (3.0)
Grade
(1 - 5)
CTC Adverse
Event
Attribution
Code*
CTC Adverse Event Term
CTCAE (3.0)
Grade
(1 - 5)
CTC Adverse
Event
Attribution
Code*
* Attribution codes:    1-unrelated           2-unlikely           3-possible           4-probable         5-definite
PAM14
Muscle
LU00
Dyspnea
LU10
Hypoxia
GU53
Renal failure
GU03
Urinary frequency
SY10
Tumor lysis syndrome
LY05
Lymphedema - related
fibrosis
ME04
AST
ME05
Bilirubin
ME06
Creatinine
ME31
Hyperglycemia
ME30
Hypoglycemia
ME90
Hypophosphatemia
NR50
Neuropathy-motor
NR60
Neuropathy-sensory
Pain
PAM02
Bone
PAN37
Headache
PAM11
Joint
CTC Adverse Event Term, Other
(specify using CTCAE 3.0 terminology)
SWOG Patient ID
Patient Initials
R-CHOP cycle 1
R-CHOP  cycle 2
R-CHOP  cycle 3
R-CHOP  cycle 4
R-CHOP  cycle 5
R-CHOP  cycle 6
Post I-131 tx
33275


 SOUTHWEST ONCOLOGY GROUP
S0801 MAINTENANCE THERAPY ADVERSE EVENT FORM
Page 1 of 2
(L, F M)
12/1/2008
 SOUTHWEST ONCOLOGY GROUP
S0801 MAINTENANCE THERAPY ADVERSE EVENT FORM
SWOG Patient ID
Page 1 of 2
(L, F M)
continued on next page
12/1/2008
SWOG Study No. S 0 8 0 1
Registration Step 2
Current Cycle Number:
Patient Initials
Physician
Institution/Affiliate
* Attribution codes:    1-unrelated           2-unlikely           3-possible           4-probable         5-definite
No
Yes, but no reportable adverse events occurred
Yes, and reportable adverse events occurred (report below)
Were adverse events assessed during this time period?
Reporting period end date:
/
/
Reporting period start date:
/
/
ADVERSE EVENTS
(Day 1 of this Cycle)
(Day one of next cycle.  If final cycle, date
of first visit or contact after resolution of
acute adverse events.)
CTCAE (3.0)
Grade
(1 - 5)
CTC Adverse Event Term
CTC Adverse
Event
Attribution
Code*
CTC Adverse Event Term
CTCAE (3.0)
Grade
(1 - 5)
CTC Adverse
Event
Attribution
Code*
IM00
Allergic reaction
HE20
Hemoglobin
HE00
Leukocytes
HE40
Lymphopenia
HE30
Neutrophils
HE10
Platelets
CA50
Hypertension
CA51
Hypotension
CA06
Left ventricular diastolic
dysfunction
CA07
Left ventricular systolic
dysfunction
CL20
PTT
FL40
Fatigue
FL01
Fever
FL20
Insomnia
FL10
Rigors/chills
FL30
Sweating
SK90
Alopecia
SK11
Rash
GI01
Anorexia
GI23
Dehydration
GI20
Diarrhea
GI00
Nausea
GI10
Vomiting
IN30
Febrile neutropenia
Infection with Grade 0-2 ANC
INL05
Lung
Infection with Grade 3-4 ANC
ICL05
Lung
Infection with unknown ANC
IUL05
Lung
LY01
Edema: head and neck
LY02
Edema: limb
LY03
Edema: trunk/genital
LY04
Edema: visceral
Instructions:  Please complete this form at the end of every cycle (1 cycle = 3 months) of rituximab maintenance therapy.  Report
adverse events occurring up until the next cycle of treatment begins.   Document the worst Grade seen during the reporting period.  Do
not code a condition existing prior to registration as an adverse event unless it worsens.  All dates are MONTH, DAY, YEAR.  Explain any
blank dates or fields in the Comments section.  Place an   X   in appropriate boxes.  Circle AMENDED items in red and write
AMENDED across the top of the form.
SWOG Patient ID
Current Cycle Number:
Patient Initials
57656


 SOUTHWEST ONCOLOGY GROUP
S0801 MAINTENANCE THERAPY ADVERSE EVENT FORM
Page 2 of 2
(L, F M)
12/1/2008
Comments: (Please explain any "other" adverse events reported above)
SWOG Study No. S 0 8 0 1
Registration Step 2
ADVERSE EVENTS, continued
CTC Adverse Event Term
CTCAE (3.0)
Grade
(1 - 5)
CTC Adverse
Event
Attribution
Code*
CTC Adverse Event Term
CTCAE (3.0)
Grade
(1 - 5)
CTC Adverse
Event
Attribution
Code*
* Attribution codes:    1-unrelated           2-unlikely           3-possible           4-probable         5-definite
PAM14
Muscle
LU00
Dyspnea
LU10
Hypoxia
GU53
Renal failure
GU03
Urinary frequency
SY10
Tumor lysis syndrome
LY05
Lymphedema - related
fibrosis
ME04
AST
ME05
Bilirubin
ME06
Creatinine
ME31
Hyperglycemia
ME30
Hypoglycemia
ME90
Hypophosphatemia
NR50
Neuropathy-motor
NR60
Neuropathy-sensory
Pain
PAM02
Bone
PAN37
Headache
PAM11
Joint
CTC Adverse Event Term, Other
(specify using CTCAE 3.0 terminology)
SWOG Patient ID
Current Cycle Number:
Patient Initials
57656


SWOG Patient ID
SWOG Study No. S 0 8 0 1
Registration Step 1
Patient Initials
(L, F M)
Institution / Affiliate
Physician
SOUTHWEST ONCOLOGY GROUP
S0801 PATIENT RE-EVALUATION FORM
Page 1 of 1
Instructions:  Please complete this form after patient re-evaluation 4-8 weeks after the completion of R-CHOP chemotherapy.  All
dates are MONTH, DAY, YEAR.  Explain any blank fields or blank dates in the Comments section.  Place an    X    in appropriate
boxes.  Circle AMENDED items in red and write AMENDED across top of form.
(S0801EVAL)
12/1/2008
BONE MARROW INVOLVEMENT
Date of bone marrow biopsies to assess lymphoma involvement after 6 cycles of R-CHOP:
/
/
Mean intrabecular marrow space involvement after 6 cycles of R-CHOP:
%
Hematologic:
AGC
Peripheral
platelet count
Collection date:
/
/
/ mcL
,
/ mcL
,
/
/
TOSITUMOMAB TREATMENT SCHEDULE
Will patient receive Tositumomab therapy?
Yes
No
If Yes, planned date of dosimetric infusion:
/
/
Comments:
LABORATORY VALUES
Note: Lab values must be collected within 14 days of the planned dosimetric infusion.
19777


SOUTHWEST ONCOLOGY GROUP
LYMPHOMA BASELINE TUMOR ASSESSMENT FORM
12/15/2008
Page 1 of 2
Patient Initials
(L, F M)
Instructions:  Record the requested information for all measurable lesions and all sites of non-measurable disease, including sites
visualized only by PET scan.  Please refer to Section 10.1 of the protocol for definitions.  If an organ or site has too many
measurable lesions to measure at each evaluation, choose three to follow as measurable disease and record the rest as
evaluable disease.  Circle AMENDED items in red and write AMENDED across the top of the form.
The same test procedures used for baseline disease assessment must be used for all required subsequent disease assessments.
SOUTHWEST ONCOLOGY GROUP
LYMPHOMA BASELINE TUMOR ASSESSMENT FORM
12/15/2008
Page 1 of 2
Sites
L1
L2
L3
L4
L5
L6
SITES OF MEASURABLE LESIONS
SITES OF NON-MEASURABLE DISEASE
Extent
Sites Visualized Only by PET Scan
Date of Assessment
/
/
/
/
/
/
/
/
/
/
P1
P2
P3
P4
P5
continued on next page
Participating Group:  Group Name/Study No./Patient ID
/
/
Physician
Institution / Affiliate
Patient Initials
(L, F M)
SWOG Patient ID
SWOG Study No. S
Registration Step
(CORETB_BTA)
Other Sites of Disease
Assessment
Code*
Date of Assessment
/
/
/
/
/
/
/
/
/
/
05-Endoscopy
10-Plain film/X-ray without contrast
11-Plain film/X-ray with contrast
12-CT scan
13-MRI scan
14-Radioisotope scan
15-Ultrasound
17-Spiral CT scan
20-Histologic confirmation
21-Cytologic confirmation
01-Palpation
02-Visualization
03-Colposcopy
04-CA-125 assay
* Assessment Codes:
99-Other (specify below and indicate
     lesion number)
** PET Status:
0-Negative
1-Positive
8-Not applicable
9-Not imaged by PET
PET
Status **
PET
Status **
S1
S2
S3
S4
S5
Tumor Measurement (cm)
Assessment
Code*
Date of Assessment
x
x
x
x
x
x
/
/
/
/
/
/
/
/
/
/
/
/
.
.
.
.
.
.
.
.
.
.
.
.
SWOG Patient ID
SWOG Study No. S
Registration Step
39601


SOUTHWEST ONCOLOGY GROUP
LYMPHOMA BASELINE TUMOR ASSESSMENT FORM
12/15/2008
Page 2 of 2
Patient Initials
(L, F M)
Comments:
List all negative diagnostic tests/studies used to evaluate patient for malignancy.
Tests/studies
Date
/
/
/
/
Tests/studies
Date
/
/
/
/
SWOG Patient ID
SWOG Study No. S
Registration Step
39601


SOUTHWEST ONCOLOGY GROUP
LYMPHOMA FOLLOW-UP TUMOR ASSESSMENT FORM
12/15/2008
Page 1 of 2
Patient Initials
(L, F M)
SOUTHWEST ONCOLOGY GROUP
LYMPHOMA FOLLOW-UP TUMOR ASSESSMENT FORM
12/15/2008
(CORETB_FUTA)
Page 1 of 2
Instructions:  Record the requested information for all measurable lesions and all sites of non-measurable disease, including sites
visualized only by PET scan.  Please refer to Section 10.1 of the protocol for definitions.  If an organ or site has too many
measurable lesions to measure at each evaluation, choose three to follow as measurable disease and record the rest as
evaluable disease.  Circle AMENDED items in red and write AMENDED across the top of the form.
The same test procedures used for baseline disease assessment must be used for all required subsequent disease assessments.
Sites
L1
L2
L3
L4
L5
L6
SITES OF MEASURABLE LESIONS
SITES OF NON-MEASURABLE DISEASE
Extent
Sites Visualized Only by PET Scan
Date of Assessment
/
/
/
/
/
/
/
/
/
/
P1
P2
P3
P4
P5
05-Endoscopy
10-Plain film/X-ray without contrast
11-Plain film/X-ray with contrast
12-CT scan
13-MRI scan
14-Radioisotope scan
15-Ultrasound
17-Spiral CT scan
20-Histologic confirmation
21-Cytologic confirmation
01-Palpation
02-Visualization
03-Colposcopy
04-CA-125 assay
* Assessment Codes:
99-Other (specify below and indicate
     lesion number)
** PET Status:
0-Negative
1-Positive
8-Not applicable
9-Not imaged by PET
Participating Group:  Group Name/Study No./Patient ID
/
/
Physician
Institution / Affiliate
Patient Initials
(L, F M)
SWOG Patient ID
SWOG Study No. S
Registration Step
Reporting Period Start Date:
/
/
Tumor Measurement (cm)
Assessment
Code*
Date of Assessment
x
x
x
x
x
x
/
/
/
/
/
/
/
/
/
/
/
/
.
.
.
.
.
.
.
.
.
.
.
.
Other Sites of Disease
S1
S2
S3
S4
S5
Assessment
Code*
Date of Assessment
/
/
/
/
/
/
/
/
/
/
PET
Status **
PET
Status **
SWOG Patient ID
SWOG Study No. S
Registration Step
Reporting Period Start Date:
/
/
27780


SOUTHWEST ONCOLOGY GROUP
LYMPHOMA FOLLOW-UP TUMOR ASSESSMENT FORM
12/15/2008
Page 2 of 2
Patient Initials
(L, F M)
List all negative diagnostic tests/studies used to evaluate patient for malignancy.
Tests/studies
Date
/
/
/
/
Tests/studies
Date
/
/
/
/
Comments:
SWOG Patient ID
SWOG Study No. S
Registration Step
Reporting Period Start Date:
/
/
27780


6/15/2006
Comments:
SOUTHWEST ONCOLOGY GROUP
OFF TREATMENT NOTICE
SWOG Patient ID
SWOG Study No. S
Registration Step
Physician
Institution / Affiliate
(If more room is needed, please continue on a separate page)
(L, F M)
Patient Initials
Page 1 of 1
Participating Group:  Group Name/Study No./Patient ID
Off Treatment Date
Date of completion, progression, death or decision to discontinue therapy:
/
/
Will patient receive further treatment?
No
Yes, specify:
Unknown
Date of Last Contact or Death:
/
/
Vital Status:
Alive
Dead (submit Notice of Death form)
/
/
Systemic Therapy:
List regimens, start and end dates.  For multidrug regimens, do not list individual drugs separately;
end date would be the date all drugs in the regimen were discontinued.
Surgery:
List type of surgery, and in the "end date" column, the date of surgery.
Radiation:
List sites, start and end dates (inclusive of boosts and implants).
Instructions:
For each registration step, submit this form within 2 weeks after completion (or discontinuation) of treatment.
List protocol-directed treatments that the patient received.
All dates are MONTH, DAY, YEAR.  Explain any blank fields or blank dates in the Comments section.
Place an   X   in appropriate boxes.  Circle AMENDED items in red and write AMENDED at the top of the form.
Treatment Start Date
Treatment End Date
Regimen or Procedure or Site(s)
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
For any patient refusal, was reason due to adverse event/side effects/complications?
Yes, specify:
No, specify other reason for refusal:
Off Treatment Reason
Treatment completed per protocol criteria
Adverse event/side effects/complications, specify:
Patient withdrawal/refusal after beginning protocol therapy, specify:
Patient withdrawal/refusal prior to beginning protocol therapy, specify:
Disease progression, relapse during active treatment; Sites:
Death on study (submit Notice of Death form)
Other, specify:
(select one):
For any adverse event, was treatment termination medically required?
No
Yes, specify:
28829


9/1/2003
Comments:
SOUTHWEST ONCOLOGY GROUP
NOTICE OF DEATH
Autopsy?
No
Yes
Unknown
If cancer was the primary cause or if cancer possibly or definitely contributed to death, and the patient
had had multiple tumor types, specify those which were causes of death:
No
Primary Cause
Contributory
Possible
Unknown
Any cancer (select one):
CAUSES OF DEATH
(month / day / year)
Date of Death:
/
/
SWOG Patient ID
Most Recent SWOG Study No. S
Physician
Institution / Affiliate
(L, F M)
Patient Initials
Cancer of most recent SWOG study, specify cancer:
Cancer of other SWOG study, specify cancer:
Other cancer, specify:
If Primary Cause, Contributory or Possible, specify treatment and toxicity:
No
Primary Cause
Contributory
Possible
Unknown
Toxicity from disease related treatment (select one):
If Primary Cause, Contributory or Possible, specify:
No
Primary Cause
Contributory
Possible
Unknown
Non-cancer and non-treatment related causes (select one):
Source(s) of death information:
Autopsy report
Medical record / Death certificate
Physician
Relative or friend
Other, specify:
Instructions:  Answer all questions and explain any blank fields or blank dates in the Comments section.
Place an   X   in appropriate boxes.  Circle AMENDED items in red.
Participating Group:  Group Name/Study No./Patient ID
/
/
Page 1 of 1
49467


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Instructions:  Report any malignancy of a new histologic type or any malignancy of a previous type which is judged to be a
new primary.  Do not report recurrences on this form.  Note: If available, submit pathology report documenting the second
malignancy along with this form.  Refer to the protocol regarding sample submission instructions for second malignancies.
All dates are MONTH, DAY, YEAR.  Circle AMENDED items in red.
SOUTHWEST ONCOLOGY GROUP
NOTICE OF SECOND MALIGNANCY
10/15/2000
Notes:
Page 1 of 1
(PRIM2)
Protocol Step 1
SWOG Study No. S
SWOG Patient No.
Date of First Pathologic Diagnosis:
/
/
Type (site, histology) of second malignancy:
Patient Initials
(L, F, M)
Groups Other than SWOG:  Group Name/Study No./Pt. No.
Physician
Institution/Member
/
/
27456


 
S0801 
 
Page 89 
 
Revised 1/12/10 
 
 
 
 
19.0 
APPENDIX 
 
19.1 
Dosimetry Instructions and Worksheets 
 
a. 
Dosimetry Instructions 
 
b. 
Worksheet #1 - Gamma Camera Daily Quality Control 
 
c. 
Worksheet #2 - Gamma Camera Whole Body Dosimetry  
 
d. 
Table 1 - Maximum Effective Mass 
 
e. 
Table 2 - Activity Hours 
 
f. 
Graph 1 - Total Body Residence Time Estimation 
 
19.2 
Assessment of Bone Marrow Involvement  
 
19.3 
Drug Ordering Instructions for Tositumomab and Iodine I-131 Tositumomab 
 
19.4 
SWOG S0801 Site Contact Information Form  
 
19.5 
Determination of Expedited Adverse Event Reporting Requirements 
 


 
S0801 
 
Page 90 
 
 
 
 
19.1a 
Dosimetry Instructions 
 
Dosimetry Instructions for Iodine I-131 Tositumomab Therapeutic Regimen 
Anterior and Posterior Counts 
 
a. 
INTRODUCTION:  Dosimetry is required to determine the necessary 
administered therapeutic activity (mCi dose of Iodine I-131) for each 
subject to receive a specified total body absorbed radiation dose.  The 
administered activity of Iodine I-131 is subject specific and affected by 
body mass and how rapidly the  body 
eliminates 
the 
Iodine 
I-131 
(clearance).  On average, clearance is more rapid for subjects with 
enlarged spleen, high tumor burden or bone marrow involvement. The 
intersubject variability can be accounted for by adjusting the 
administered activity based on the subject measured total body 
clearance.   
 
A pre-therapy dosimetric dose is administered to determine the subject’s 
total body clearance, or residence time. Whole body gamma camera 
counts are done at three time points after the dosimetric infusion.  These 
counts are then used to calculate the total body residence time for each 
subject.  Subject weight is used to determine the activity hours.  The 
Iodine I-131 therapeutic activity needed to deliver a fixed total body 
radiation dose can then be calculated using the residence time and 
activity hours. The following sections describe the techniques, schedules 
and procedures for quality control, whole body gamma camera scans, 
background determination, gamma camera sensitivity measurement, and 
the calculation of the Iodine-131 therapeutic dose.  Worksheets are 
provided to capture the data and calculations.  These worksheets will be 
monitored to ensure compliance and accurate calculations. 
 
b. 
SCANNING SCHEDULE:  Following administration of the dosimetric 
dose, three anterior and posterior whole body scans are performed.  The 
first scan is on Day 0 (within 1 hour of the dosimetric infusion prior to 
voiding); the second is on Day 2, 3 or 4; and the third is on Day 6 or 7.  
The second and third scans occur after voiding. The dosing and 
administration schedule is diagrammed below.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time Points 
Procedure 
Day 0 – within 1 
hour after the 
dosimetric 
infusion 
Gamma camera quality control, I-131 source scan, 
background scan  
Whole body anterior and posterior camera scan 
(before voiding) 
Day 2, 3, or 4 
Gamma camera quality control, I-131 source scan, 
background scan  
Whole body anterior and posterior camera scan 
after voiding  
Day 6 or 7 
Gamma camera quality control, I-131 source scan, 
background scan  
Whole body anterior and posterior camera scan 
after voiding  
Complete Iodine 131 activity calculation 


 
S0801 
 
Page 91 
 
 
 
 
c. 
GAMMA CAMERA:  Manufacturer-specific quality control procedures 
should be followed for the gamma camera/computer system, the 
collimator, and the dose calibrator.  Less than 20% variance between 
maximum and minimum pixel count values in the useful field of view is 
acceptable on Iodine-131 intrinsic flood fields and variability < 10% is 
preferable.  Iodine-131-specific camera uniformity corrections are 
strongly recommended, rather than applying lower energy correction to 
the Iodine-131 window.  Camera extrinsic uniformity should be assessed 
at least monthly using 99mTc or 57 Co as a source with imaging at the 
appropriate window. 
 
Additional (non-routine) quality control procedures are required.  To 
assure the accuracy and precision of the subject total body counts, the 
gamma camera must undergo validation and daily quality control on 
each day it is used to collect subject images.   
 
Use the same setup and region of interest (ROI) for calibration, 
determination of background, and whole body subject studies.  
 
The gamma camera must have a large or extra large field of view with a 
digital interface.  It must be equipped with a parallel-hole medium or high 
energy collimator.   
 
Set up computer and camera as follows: 
 
• 
Parallel hole medium or high energy collimator  
• 
Symmetric window (20-25%) centered on the 364 keV photo peak of  
 
Iodine-131 (314 - 414 keV)   
• 
Matrix Size:  appropriate whole body matrix  
• 
Scanning speed:  10-30 cm/minute  
 
All whole body scans must be stored electronically and made available 
to GSK, its designee, and/or the FDA, if requested. 
 
The same equipment and parameters (computer and camera setup, 
collimator, and scanning speed) must be used for the source, 
background and subject scans at each of the three time points.   
 
d. 
QUALITY CONTROL:  Prior to scanning the subject, a quality control 
check must be done on the equipment to be used.  Institution- and/or 
manufacturer-specific quality control procedures for the gamma camera, 
computer, collimator(s), and dose calibrator should be followed each day 
the camera is used.  The performance of the dose calibrator and the 
gamma camera must be within performance guidelines.  Steps must be 
taken to ascertain reasons for variation and corrective measures must be 
taken before infusing or scanning the subject. 
 
1. 
Iodine I-131 Calibration Source:  Camera sensitivity for Iodine-
131 must be determined each day. Determination of the gamma 
camera’s sensitivity is obtained by scanning a calibrated activity 
of Iodine-131 (e.g., 200–250 μCi in at least 20 mL of saline 
within a sealed pharmaceutical vial).  The radioactivity of the 
Iodine-131 source is first determined using a NIST-traceable-
calibrated clinical dose calibrator at the Iodine-131 setting. 
 
 


 
S0801 
 
Page 92 
 
 
 
 
Record the activity (μCiI-131). 
 
Using the computer and camera setup described above, obtain 
an anterior and posterior whole body scan with the Iodine-131 
source positioned on the center of the imaging table near where 
the subject’s navel would be located.  The camera should be at 
distance of 30cm above the table to simulate subject imaging 
parameters and should be of the same length as the subject 
scans. 
 
Draw regions of interest (ROIs) around the entire fields of view of 
the anterior image and posterior image to obtain the anterior 
source counts and posterior source counts (ROI is not 
necessary if the camera displays the total counts after each 
acquisition).  Record the source anterior counts (CSA) and source 
posterior counts (CSP).  The same ROIs should be used for 
source, background, and whole body subject counts for each 
scan. 
 
2. 
Background Count:  The background in the imaging room must 
be determined within one hour of each subject scan. 
 
Maintain the same camera and computer setup, collimator, and 
scanning speed used for scanning the Iodine-131 source.  Scan 
the table with the camera at a distance of 30cm above the table 
to simulate subject imaging parameters and should be of the 
same length as the subject scans. 
 
Draw ROIs around the entire fields of view to obtain the anterior 
background counts and posterior background counts (ROI is not 
necessary if the camera displays the total counts after each 
acquisition).  These ROIs should be the same as the ones used 
for the Iodine-131 source.  Record the anterior background 
counts (CBA) and posterior background counts (CBP).   
 
3. 
Gamma Camera Sensitivity Measurement:  For each time point, 
calculate the background-corrected source count (defined as the 
geometric mean).  The following equation is used:   
 
Background-corrected source  
 
Count = CBCS = 
)
C
C
)(
C
C
(
BP
SP
BA
SA
−
−
   
 
Next, divide the background-corrected source count (CBCS) by 
the calibrated Iodine-131 source activity (μCiI-131) measured that 
day near the time of the scanning of the source, to obtain the 
calibration factor in counts per μCi, 
 
Counts per μCi = CBCS / μCiI-131. 
 
The calibration factor is a measure of camera sensitivity and 
should be relatively constant.  When values vary by more than 
10%, the reason for the discrepancy should be determined. For 
example, this may be due to abnormally high or low background 
counts or inaccurate dose calibrator measurement. In this case, 
verify that the same camera, acquisition parameters, and ROIs 
have been used and also that there is no contamination present; 
if appropriate, the subject should be rescanned or the calibrated 
source activity should be measured again. 


 
S0801 
 
Page 93 
 
 
 
 
e. 
WHOLE BODY SUBJECT SCANS:  Once the proper quality control 
steps have been taken and confirmed, the whole body subject scans can 
then be performed.   
 
Maintain the camera and computer setup from the source and 
background scans.  For any particular subject, the same gamma 
camera, collimator(s), scan speed and field of view or length must be 
used for all scans.  The camera head(s) should be as close as possible 
to the subject, and the scans should be centered on the midline of the 
subject.  Extremities should be included in the field of view of the scans, 
and the arms should not cross over the body.  Record the start time (t).  
Scan the whole length of the subject.  Acquire the anterior and posterior 
whole body images for gamma camera counts. 
 
Draw ROIs around the entire fields of view to obtain the anterior subject 
counts and posterior subject counts (ROI is not necessary if the camera 
displays the total counts after each acquisition).  The same ROIs should 
be used as the ones used for the Iodine-131 source and background.  
Record the subject anterior counts (CA) and subject posterior counts 
(CP).   
 
1. 
Subject Whole Body Counts 
 
The same background counts (CBA and CBP) obtained for the 
quality control step can be used to determine the background-
corrected subject count.  For each time point, calculate the 
background corrected total body count (defined as the geometric 
mean).  The following equation is used: 
 
Background-corrected subject  
 
count = C = 
)
C
C
)(
C
C
(
BP
P
BA
A
−
−
  
 
The background corrected subject counts at each of the three 
timepoints  
are referred to as C1, C2, and C3. 
 
f. 
CALCULATION OF IODINE-131 ACTIVITY (THERAPEUTIC DOSE):  
The data obtained from the three whole body scans will be used to 
calculate the subject specific Iodine-131 activity needed to administer the 
fixed total body dose of radiation. 
 
For a physician that has not completed the Bexxar certification process, 
that individual must send the dosimetry calculations for the first 3 
subjects for review to Bexxar Service Center prior to the administration of 
the Iodine I-131 Tositumomab. 
 
To calculate the subject specific Iodine-131 activity, the activity hours 
(mCi h) and residence time (h) need to be determined. 
 
1. 
Activity Hours (mCi h) 
 
Gender, height, and weight determine the activity hours (mCi h).  
For  obese subjects (subjects weighing more than 137% of their 
lean body mass), the maximum effective mass will be used to 
determine the activity hours rather than their actual body weight.  
Table 1, Maximum Effective Mass, will confirm which mass to 
use.   
 


 
S0801 
 
Page 94 
 
 
 
 
Table 1 is separated by gender.  Look up the subject’s height 
under the appropriate gender column.  Record the maximum 
effective mass (kg) given for that particular height.  For heights 
not included in the table, convert the height into centimeters 
(inches x 2.54) and use the following formula: 
 
Males:  Maximum Effective Mass (kg) = 65.76 + (1.452) (Ht. in 
cm – 152) 
Females:  Maximum Effective Mass (kg) = 62.34 + (1.247) (Ht. in 
cm – 152) 
 
Compare the subject’s actual weight in kilograms (pounds x 
0.454) to the maximum effective mass (kg), whichever value is 
less will be the mass (kg) used to determine the activity hours 
(mCi h) in Table 2.   
 
Look up the appropriate mass in Table 2, Activity Hours.  Record 
the activity hours (mCi h) given for that particular mass.  If 
necessary, round the mass (eg, 59.2 kg should be rounded to 59 
kg).  For mass between 140kg and 160kg, use the following 
formula: 
 
Activity hours (mCi hr) = 14287 + (88.74) (Wt. in kg – 140) 
 
2. 
Residence Time (h) 
 
Residence time (h) is determined by using the Graphical 
Estimate of The Total Body Residence Time graph, labeled 
Graph 1.  By plotting percent-injected activity (%IA) versus the 
time from dosimetric dose (hours) for all three scans, the 
residence time can be estimated.   
 
To calculate the percent-injected activity (%IA), use the 
background-corrected subject counts (C1, C2, and C3) for each 
scan.  Since the first scan is done the day of the infusion, the 
percent-injected activity for scan 1 (%IA1) will always be 100%.  
For scans 2 and 3, the percent-injected activity remaining is 
calculated by dividing C(2 or 3) by C1 multiplied by 100: 
 
%IA1 = 100% 
%IA2 = 
%
100
1
2
C
C ×
  
%IA3 = 
%
100
1
3
C
C ×
  
 
Next, determine the amount of time (T in hours) elapsed since 
the start of the Iodine .131 Tositumomab dosimetric dose 
infusion to the start of each subject count. 
 
Plot each point (%IA, T) on the graph; there will be three points 
representing each scan.  Draw a best-fit line from 100% (the pre-
plotted Day 0 value) through the 2 plotted points (if the line does 
not intersect the two plotted points, one point must lie above the 
best-fit line and one point must lie below the best-fit line).  
Determine the x-axis value of the graph at the point where the 
best-fit line intersects the horizontal 37% injected activity line; 
this is the total body residence time (h).  
 


 
S0801 
 
Page 95 
 
 
 
 
3. 
Iodine I-131 Activity 
 
Using the activity hours, residence time, and the prescribed total 
body dose, the  Iodine I-131 activity can now be calculated: 
 
I-131 Activity (mCi) = Activity Hours (mCi h) x Prescribed Total Body Dose (cGy) 
 
Residence Time (h) 
75 (cGy) 
 
4. 
Sample Calculation 
 
R-H is a 63-year-old, 5’6” male who weighs 90 kg.  His baseline 
platelet count is 121,000 cells/mm3 and his percent injected 
activities at 1 h, 72 h, and 168 h were 100%, 50%, and 20%, 
respectively.  From Table 1, his maximum effective mass is 
determined to be 88.5 kg.  Because his maximum effective mass 
is less than his actual weight, the maximum effective mass is 
used to look up the value for activity hours in Table 2; the activity 
hours are 9490 mCi h. By plotting the time and percent injected 
activity values for the last 2 time points on Graph 1, the 
residence time is determined to be 103 hours.  The equation for 
the Iodine-131 therapeutic activity required is then solved as 
follows: 
 
Iodine-131 Activity (mCi) =  9490 mCi h X 65 cGy = 80 mCi 
     
             103 h         75 cGy  
 
 


19.1b 
S0801 
 
Page 96 
 
 
Site Number (GSK will complete):   
              
    Patient Identification Number:  
              
                 Patient Initials (LFM):  
              
 
 
 
 
DOSIMETRY CALCULATION WORKSHEETS FOR SWOG S0801 PROTOCOL 
 
Instructions for completing worksheets: 
 
• 
Enter all dates as MM/DD/YYYY and times as HH:MM based on a 24-hour clock (i.e. 13:30) 
• 
Gamma Camera and settings should be consistent for all scans done (i.e. I-131 source, background, and patient 
counts) 
• 
A preliminary dose estimate must be done after the second scan.  The estimated dose must be communicated to the 
Bexxar Service Center to determine if an additional vial may be required for the therapeutic dose. 
• 
When patient dose calculation is complete, fax all Worksheets to GSK at (877) 279-1512 or via email to 
BEXXARServiceCenter@GSK.com for confirmation of calculations (for the first 3 patients enrolled at the study site or 
until GSK determines it is no longer necessary). 
• 
If using a commercial radiopharmacy, fax Worksheet #2 to radiopharmacy, after receiving confirmation of 
calculations. 
 
Worksheet #1 — Equipment and Settings Evaluation 
STUDY DAY 
Day 0 
 
 
Day 2, 3, or 4 
 
 
Day 6 or 7 
 
DATE 
 
 
 
 
 
 
 
 
DOSE CALIBRATOR ACTIVITY 
 
 
 
 
 
 
 
 
Time Measured 
 
 
 
 
 
 
 
 
I-131 source activity (As) in µCi 
 
 
 
 
 
 
 
 
GAMMA CAMERA SETTINGS 
 
 
 
 
 
 
 
 
Camera Name 
 
 
 
 
 
 
 
 
Energy Window Setting (20%-25%) 
      % 
 
 
      % 
 
 
      % 
 
Collimator:  
 Medium Energy 
 
 High Energy 
 
 
 
 
 
 
 
 
Total Body Scan Speed (10 – 30 cm/min) 
 
 
 
 
 
 
 
 
Scan Length (cm)  
 
 
 
 
 
 
 
 
Camera anterior height above table (cm) 
 
 
 
 
 
 
 
 
IODINE-131 SOURCE COUNTS (Anterior and 
Posterior 
 
 
 
 
 
 
 
 
Time started (t) 
 
 
 
 
 
 
 
 
 
 
 
Total Anterior Count (CSA) 
Total Posterior Count (CSP) 
 
 
 
 
 
 
 
 
BACKGROUND COUNTS (Anterior and Posterior) 
 
 
 
 
 
 
 
 
Time started 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total Anterior Count (CBA) 
Total Posterior Count (CBP) 
 
 
 
 
 
 
 
 
CALCULATIONS 
 
 
 
 
 
 
 
 
Background Corrected Source Count 
CS = 
)
C
C
)(
C
C
(
BP
SP
BA
SA
−
−
 
 
 
 
 
 
 
 
 
Calibration Factor (counts per µCi) 
CF = CS /AS (µCi) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date Recorded/Initials 
 
 
 
 
 
 
 
 
 
Reference:  1. Wahl RL, Kroll S, Zasadny KR, Patient specific whole-body dosimetry:  principles and a simplified method for clinical 
implementation.  J Nucl Med.  1998;39(suppl): 145-205. 
 
For more information, visit our Web site at www.BEXXAR.com or call the Bexxar Service Center at 1-877-4-BEXXAR (877-423-9927)


19.1c 
S0801 
 
Page 97 
 
 
Site Number (GSK will complete):   
              
    Patient Identification Number:  
              
                 Patient Initials (LFM):  
              
 
 
 
 
 
Worksheet #2a — Determination of Iodine-131 Activity for the Therapeutic Dose of BEXXAR 
(Continued) 
A. Dosimetric Dose Infusion 
Date of Infusion:  
 
Start Time (tINF):  
  
End Time:  
(not including flush) 
B.  Determination of Activity Hours 
Patient gender:       
 Male       
 Female 
Patient height:  
 cm    Patient weight:  
kg 
 
Residual after infusion:                 mCi                      time 
 
Net activity to patient:                         mCi 
Patient maximum effective mass (Table 1)  
kg  
Is patient weight above maximum effective mass?   
 Yes  - Use maximum effective mass (from 
Table 1) 
to determine Activity Hours 
 
 
 No   - Use patient’s actual weight to determine 
Activity Hours 
 
Activity Hours (Table 2):   
 mCi-hour 
C. Determination of Total Body Dose (cGy) 
Baseline platelet count:  
 cells/ mm3 
Date:  
 
Prescribed Total Body Dose:  
  65 cGy   (for PLT count of 100,000 to <150,000 
cells/mm3)  
 
  75 cGy   (for PLT count of >150,000 cells/mm3) 
 
D.  Calculation of Actual Administered Activity for Dosimetric Dose 
 
Measured Activity (ActD) of Dose Prior to 
Administration 
 
 
 
 
 
 
 
 
 
Activity (mCi) 
 
Initials 
 
Date 
 
Time 
 
Measured Residual Activity (ActDR) After 
Administration 
 
 
 
 
 
 
 
 
 
Activity (mCi) 
 
Initials 
 
Date 
 
Time 
 
Actual Administered Activity (ActDA) 
 
 
 
 
 
 
 
 
 
ActD 
-
ActDR 
=
ActDA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Worksheet #2a continued on next page) 
 


19.1c 
S0801 
 
Page 98 
 
 
Site Number (GSK will complete):   
              
    Patient Identification Number:  
              
                 Patient Initials (LFM):  
              
 
 
 
 
Worksheet #2a — Determination of Iodine-131 Activity for the Therapeutic Dose of BEXXAR 
(Continued) 
 
E. Determination of Residence Time (h) Using Whole Body Gamma Camera Counts 
STUDY DAY 
 
 
Day 0 
 
Day 2, 3, or 4 
 
Day 6 or 7 
 
DATE 
 
 
 
 
 
 
 
 
 
SAME CAMERA AND ACQUISITION 
PARAMETERS AS WORKSHEET #1 
 
 
 
 
 
 
 
 
 
GAMMA CAMERA COUNTS 
PATIENT TOTAL BODY COUNTS 
(Anterior AND Posterior) 
 
 Yes 
 
 
 Yes 
 
 
 Yes 
 
Time Started (ts)  
 
 
 
 
 
 
 
 
 
Total Anterior Count (CA) 
Total Posterior Count (CP) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BACKGROUND COUNTS (Anterior and 
Posterior) 
 
 
 
 
 
 
 
 
 
Time 
 
 
 
 
 
 
 
 
 
Total Anterior Count (CBA) 
Total Posterior Count (CBP) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Calculations 
 
 
 
 
 
 
 
 
 
Background Corrected Patient Counts  
C=
)
C
C
)(
C
C
(
BP
P
BA
A
−
−
 
 
 
 
C1= 
 
 
 
 
 
 
C2= 
 
 
 
 
C3= 
 
 
 
 
 
 
 
 
 
 
 
Time from start of 131I Tositumomab 
Infusion to start of Patient Counts (t) = tS – 
tINF 
 
 
t1= 
 
 
 
T2= 
 
 
 
T3= 
 
 
 
 
 
 
 
 
 
 
 
Percent Injected Activity  
%IA = C2 or C 3) / C1 X 100 
 
 
%IA1 = 100% 
 
 
 
%IA2 =          
 
 
 
%IA3 =   
 
Date Recorded/Initials
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F. Determination of Residence Time 
From Graph 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TOTAL BODY RESIDENCE TIME (TBRT est) 
=  
hours* 
 
 
 
TOTAL BODY RESIDENCE TIME (TBRT) 
=  
   
 
hours^ 
 
 
 
 
*After Day 2, 3, or 4, complete section G (Worksheet 2B) 
^After Day 6 or 7, complete section H (Worksheet 2B) 
 
 
 
 
 
 
Reference:  1. Wahl RL, Kroll S, Zasadny KR, Patient specific whole-body dosimetry:  principles and a 
simplified method for clinical implementation.  J Nucl Med.  1998;39(suppl): 145-205. 
 
For more information, visit our Web site at www.BEXXAR.com or call the Bexxar Service Center at 1-
877-4-BEXXAR (877-423-9927) 


19.1c 
S0801 
 
Page 99 
 
Site Number (GSK will complete):   
              
    Patient Identification Number:  
              
                 Patient Initials (LFM):  
              
 
 
 
 
 
Worksheet #2b — Determination of Iodine-131 Activity for the therapeutic dose of BEXXAR 
G. Estimated Iodine-131 Activity From Day 0 and Day 2, 3, or 4       Date Calculated/Initials:  
 
 
Estimated 131Iodine Activity (mCi)  =   
cGy
 
75
(cGy)
 
Dose
Body 
 
Total
 
Desired
(est)
 
TBRT
h)
 
(mCi
 
Hours
Activity 
×
 
Estimated 131Iodine Activity (mCi)  =   
cGy
 
75
    
          
          
          
          
 
          
          
          
×
= 
 
                  
 
mCi 
 
DATE AND TIME OF PLANNED ADMINISTRATION:  
 
                                                                                             Date                    Time                    
 
Physician’s Signature                                                                                             
 
 
 
H. Prescribed Iodine-131 Activity From Day 0 and Day 2, 3, or 4      Date Calculated/Initials:  
 
                        131Iodine Activity (mCi)  =   
cGy
 
75
(cGy)
 
Dose
Body 
 
Total
 
Desired
(h)
 
TBRT
h)
 
(mCi
 
Hours
Activity 
×
 
 
                131Iodine Activity (mCi)  =   
cGy
 
75
    
          
          
          
          
 
          
          
          
×
= 
 
                    mCi 
 
DATE AND TIME OF PLANNED ADMINISTRATION: 
                                                                                             Date                    Time                    
 
Physician’s Signature                                                                                             
 
After completing this section, fax worksheets 1, 2A, and 2B to the BEXXAR Service Center
at (877) 279-1512 
 
I.  Calculation of Actual Administered Activity for Therapeutic Dose 
 
Measured Activity (ActT) of Dose Prior to 
Administration 
 
 
 
 
 
 
 
 
Activity (mCi)
Initials
 
Date 
 
Time
 
Measured Residual Activity (ActTR) After 
Administration 
 
 
 
 
 
 
 
 
Activity (mCi)
Initials
 
Date 
 
Time
 
Actual Administered Activity (ActTA) 
 
 
 
 
 
 
 
 
ActT 
ActTR 
=
ActTA 
 
 
 
 
Reference:  1. Wahl RL, Kroll S, Zasadny KR, Patient specific whole-body dosimetry:  principles and a 
simplified method for clinical implementation.  J Nucl Med.  1998;39(suppl): 145-205. 
 
For more information, visit our Web site at www.BEXXAR.com or call the Bexxar Service Center at 1-877-4-
BEXXAR (877-423-9927) 


19.1d 
S0801 
 
Page 100 
 
 
Site Number (GSK will complete):   
              
    Patient Identification Number:  
              
                 Patient Initials (LFM):  
              
 
 
 
 
 
Table 1 
Maximum Effective Mass  
 
MEN 
 
 
WOMEN 
Height 
(ft—inches) 
Height 
(cm) 
Maximum 
Effective 
Mass 
(kg) 
 
Height 
(ft—inches
Height 
(cm) 
Maximum 
Effective 
Mass 
(kg) 
4'-5" 
134.5 
40.5 
 
4'-5" 
134.5 
40.7 
4'-6" 
137.0 
44.2 
 
4'-6" 
137.0 
43.8 
4'-7" 
140.0 
47.9 
 
4'-7" 
140.0 
47.0 
4'-8" 
142.0 
51.6 
 
4'-8" 
142.0 
50.2 
4'-9" 
145.0 
55.3 
 
4'-9" 
145.0 
53.3 
4'-10" 
147.5 
59.0 
 
4'-10" 
147.5 
56.5 
4'-11" 
150.0 
62.7 
 
4'-11" 
150.0 
59.7 
5'-0" 
152.5 
66.3 
 
5’-0" 
152.5 
62.8 
5'-1" 
155.0 
70.0 
 
5’-1" 
155.0 
66.0 
5'-2" 
157.5 
73.7 
 
5’-2" 
157.5 
69.2 
5'-3" 
160.0 
77.4 
 
5’-3" 
160.0 
72.3 
5’-4" 
162.5 
81.1 
 
5’-4" 
162.5 
75.5 
5'-5" 
165.0 
84.8 
 
5’-5" 
165.0 
78.7 
5'-6" 
167.5 
88.5 
 
5’-6" 
167.5 
81.8 
5’-7" 
170.0 
92.2 
 
5’-7" 
170.0 
85.0 
5’-8" 
172.5 
95.8 
 
5’-8" 
172.5 
88.2 
5'-9" 
175.5 
99.5 
 
5’-9" 
175.5 
91.3 
5'-10" 
178.0 
103.2 
 
5’-10" 
178.0 
94.5 
5'-11" 
180.5 
106.9 
 
5’-11" 
180.5 
97.7 
6'-0" 
183.0 
110.6 
 
6’-0" 
183.0 
100.8 
6'-1" 
185.5 
114.3 
 
6'-1" 
185.5 
104.0 
6'-2" 
188.0 
118.0 
 
6'-2" 
188.0 
107.2 
6'-3" 
190.5 
121.7 
 
6'-3" 
190.5 
110.3 
6'-4" 
193.0 
125.4 
 
6'-4" 
193.0 
113.5 
6'-5" 
195.5 
129.0 
 
6'-5" 
195.5 
116.7 
6'-6" 
198.0 
132.7 
 
6'-6" 
198.0 
119.8 
6'-7" 
200.5 
136.4 
 
6'-7" 
200.5 
123.0 
6'-8" 
203.0 
140.0 
 
6'-8" 
203.0 
126.2 
6'-9" 
205.5 
143.8 
 
6'-9" 
205.5 
129.3 
6'-10" 
208.5 
147.5 
 
6'-10" 
208.5 
132.5 
6'-11" 
211.0 
151.2 
 
6'-11" 
211.0 
135.7 
7'-0" 
213.5 
154.9 
 
7'-0" 
213.5 
138.8 
Multiply pounds by 0.454 to obtain kilograms.  Multiply inches by 2.54 to 
obtain centimeters.  To calculate the maximum effective mass for patient 
heights not included in above table, use the following formulas: 
 
Males: 
Maximum Effective Mass (kg) =  65.76 + 1.452 (Ht. in cm - 152) 
Females: Maximum Effective Mass (kg) =  62.34 + 1.247 (Ht. in cm - 152) 
 


19.1e 
S0801 
 
Page 101 
 
 
Site Number (GSK will complete):   
              
    Patient Identification Number:  
              
                 Patient Initials (LFM):  
              
 
 
 
 
Adapted from (K. Zasadny, R. Wahl, et al., J Nuc Med 1995; 36(5):214. “Total Body Mass 
Lean”). 
Table 2 
Activity Hours 
 
 
Activity  
 
Activity 
 
Activity 
 
Activity 
 
 
Activity 
Mass1 
Hours 
 Mass1 
Hours 
Mass1
Hours 
Mass1
Hours 
 Mass1 
Hours 
(kg) 
(mCi h) 
 
(kg) 
(mCi h) 
(kg) 
(mCi h) 
(kg) 
(mCi h) 
 
(kg) 
(mCi h) 
40.0 
4638 
 
60.0 
6686 
80.0 
8670 
100.0 
10595 
 120.0 
12463 
40.5 
4690 
 
60.5 
6737 
80.5 
8718 
100.5 
10643 
 120.5 
12509 
41.0 
4743 
 
61.0 
6787 
81.0 
8767 
101.0 
10690 
 121.0 
12556 
41.5 
4796 
 
61.5 
6838 
81.5 
8816 
101.5 
10738 
 121.5 
12602 
42.0 
4848 
 
62.0 
6888 
82.0 
8864 
102.0 
10785 
 122.0 
12648 
42.5 
4901 
 
62.5 
6938 
82.5 
8913 
102.5 
10833 
 122.5 
12694 
43.0 
4953 
 
63.0 
6989 
83.0 
8961 
103.0 
10880 
 123.0 
12741 
43.5 
5005 
 
63.5 
7039 
83.5 
9010 
103.5 
10927 
 123.5 
12787 
44.0 
5057 
 
64.0 
7089 
84.0 
9058 
104.0 
10975 
 124.0 
12833 
44.5 
5109 
 
64.5 
7139 
84.5 
9106 
104.5 
11022 
 124.5 
12879 
45.0 
5160 
 
65.0 
7189 
85.0 
9154 
105.0 
11069 
 125.0 
12925 
45.5 
5212 
 
65.5 
7238 
85.5 
9202 
105.5 
11116 
 125.5 
12971 
46.0 
5264 
 
66.0 
7288 
86.0 
9251 
106.0 
11163 
 126.0 
13017 
46.5 
5315 
 
66.5 
7338 
86.5 
9299 
106.5 
11210 
 126.5 
13063 
47.0 
5366 
 
67.0 
7387 
87.0 
9347 
107.0 
11257 
 127.0 
13109 
47.5 
5418 
 
67.5 
7437 
87.5 
9394 
107.5 
11304 
 127.5 
13155 
48.0 
5469 
 
68.0 
7486 
88.0 
9442 
108.0 
11351 
 128.0 
13200 
48.5 
5520 
 
68.5 
7536 
88.5 
9490 
108.5 
11398 
 128.5 
13246 
49.0 
5571 
 
69.0 
7585 
89.0 
9538 
109.0 
11445 
 129.0 
13292 
49.5 
5621 
 
69.5 
7634 
89.5 
9585 
109.5 
11492 
 129.5 
13337 
50.0 
5672 
 
70.0 
7683 
90.0 
9633 
110.0 
11538 
 130.0 
13383 
50.5 
5724 
 
70.5 
7733 
90.5 
9682 
110.5 
11585 
 130.5 
13429 
51.0 
5775 
 
71.0 
7783 
91.0 
9730 
111.0 
11632 
 131.0 
13474 
51.5 
5826 
 
71.5 
7833 
91.5 
9779 
111.5 
11678 
 131.5 
13520 
52.0 
5878 
 
72.0 
7883 
92.0 
9827 
112.0 
11725 
 132.0 
13565 
52.5 
5929 
 
72.5 
7932 
92.5 
9875 
112.5 
11771 
 132.5 
13611 
53.0 
5980 
 
73.0 
7982 
93.0 
9924 
113.0 
11818 
 133.0 
13656 
53.5 
6031 
 
73.5 
8031 
93.5 
9972 
113.5 
11864 
 133.5 
13701 
54.0 
6082 
 
74.0 
8081 
94.0 
10020 
114.0 
11910 
 134.0 
13747 
54.5 
6133 
 
74.5 
8130 
94.5 
10068 
114.5 
11957 
 134.5 
13792 
55.0 
6184 
 
75.0 
8180 
95.0 
10117 
115.0 
12003 
 135.0 
13837 
55.5 
6234 
 
75.5 
8229 
95.5 
10165 
115.5 
12049 
 135.5 
13882 
56.0 
6285 
 
76.0 
8278 
96.0 
10213 
116.0 
12095 
 136.0 
13928 
56.5 
6335 
 
76.5 
8327 
96.5 
10261 
116.5 
12141 
 136.5 
13973 
57.0 
6386 
 
77.0 
8376 
97.0 
10309 
117.0 
12187 
 137.0 
14018 
57.5 
6436 
 
77.5 
8425 
97.5 
10357 
117.5 
12233 
 137.5 
14063 
58.0 
6486 
 
78.0 
8474 
98.0 
10404 
118.0 
12279 
 138.0 
14108 
58.5 
6536 
 
78.5 
8523 
98.5 
10452 
118.5 
12325 
 138.5 
14153 
59.0 
6586 
 
79.0 
8572 
99.0 
10500 
119.0 
12371 
 139.0 
14198 
59.5 
6636 
 
79.5 
8621 
99.5 
10548 
119.5 
12417 
 139.5 
14242 
1 The minimum of the patient’s actual weight (kg) or maximum effective mass (kg) from Table 1.  For 
values between 140 kg and 160 kg, use the following formula: 
Activity Hours (mCi h) = 14287 + (88.74) (Wt in kg - 140) 
 


19.1f 
S0801 
 
Page 102 
 
Site Number (GSK will complete):   
              
    Patient Identification Number:  
              
                 Patient Initials (LFM):  
              
 
 
 
 
 
Graph 1 
Total Body Residence Time Estimation 
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
5
10
20
30
40
50
60
70
80
90
100
  
Percent Injected Activity (%IA)
Time from Dosimetric Dose (hours)
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
5
10
20
30
40
50
60
70
80
90
100
37% - - -
- - -  37%
o
RT (37% Line) =  ______ hours
 
 


 
S0801 
 
Page 103 
 
 
 
 
19.2 
ASSESSMENT OF BONE MARROW INVOLVEMENT 
 
Pathology procedure for determining percentage of bone marrow involvement with 
lymphoma by bilateral biopsy. 
 
1.  
Bone marrow core biopsies are collected bilaterally.  Results of a unilateral 
biopsy are acceptable if that result indicates that less than 10% of the 
intratrabecular space is lymphoma.  The results of reading the two biopsies are 
averaged and extrapolated to the entire bone marrow.  The core biopsy 
specimens are sectioned longitudinally if they are longer than 0.5 cm in length.  
Three or 4 of these sections for each biopsy specimen can be positioned on a 
slide, stained, and read.  One slide is prepared per biopsy sample.  If a biopsy 
specimen is 0.5 cm or less in length, then it is sectioned sagittally and about 10 
to 12 sections of each biopsy are positioned on a slide, stained, and read. Again 
one slide is prepared from each specimen.  
   
2. 
The sections for each patient are generally fixed, embedded, and stained using 
hematoxylin and eosin.  Where the histopathology of the specimen is not clear 
with H & E, sections of the specimen will be analyzed for cell surface markers by 
immunohistopathology using antibodies, such as L26, which binds to the CD20 
antigen.  The monoclonal nature of lymphoma cells cannot be established on 
fixed specimens, as the kappa and lambda antigens are denatured by fixation.   
 
3.  
The lymphoma disease of almost all patients occurs as foci of disease cells 
within the bone marrow.  The percentage of the total field areas that are 
composed of these foci are estimated visually over each section.  A few patients 
have diffuse disease which is more difficult to quantitate, but again the 
percentage of bone marrow area on sections which is involved with lymphoma is 
visually estimated.  The mean percentage of the total fields consisting of 
lymphoma cells is calculated for the two biopsy specimens.  It is assumed that all 
bone marrow has a similar level of infiltration with disease as the core biopsies. 
 
 


19.3a 
S0801 
 
Page 104 
 
 
 
DRUG ORDERING INSTRUCTIONS FOR TOSITUMOMAB AND IODINE  
I-131 TOSITUMOMAB 
 
 
 
Step 1:  Determining scheduling dates for treatment 
 
 
¾ Availability of study drug varies according to the manufacturing schedule.  Please contact 
the Service Center at 1/877-423-9927 as far in advance as possible to confirm drug 
availability on the potential treatment dates.  
 
⎯ The Dosimetric and Therapeutic doses are administered 7 to 14 days apart. 
 
⎯ Alternate dates for the Dosimetric and Therapeutic doses should also be considered. 
 
 
 
 
Step 2:  Ordering Product 
 
 
After the treatment dates have been scheduled, the Study/Site Coordinator completes the first 
section of the Study Drug Order Form and faxes it to GlaxoSmithKline (Fax #:  877/279-
1512) no later than Wednesday 4pm EST the week prior to scheduled Dosimetric dose. 
 
¾ GlaxoSmithKline will fax the Study Drug order form back to the Study/Site Coordinator to 
confirm initiation of the order. 
 
¾ The Study/Site Coordinator then faxes the returned Study Drug order form, along with the 
written physician order, to the radiopharmacy. 
 
¾ GlaxoSmithKline will forward radiopharmacy contact information to the Service Center.  
The Service Center will contact the radiopharmacy to complete the order.  
¾  
⎯ When completing an order, a Service Center Consultant will ask the radiopharmacy for 
the information provided on the Study Drug Order Form. 
⎯ The order must be completed by Thursday 4pm the week prior to the Dosimetric dose. 
⎯ The Service Center is open 5 days per week (Monday-Friday) from 8am and 6pm 
(EST).  A recording will provide you with alternatives if you contact the Service Center 
outside of these hours. 
 
Radiopharmacy is the department that will be preparing the radioactive doses for 
administration.  This may be an in-house radiopharmacy, commercial radiopharmacy or 
someone in the nuclear medicine department. 


 
S0801 
 
Page 105 
 
 
 
 
Step 3:  Shipment of Prepared Doses 
 
 
The nonradiolabeled and radiolabeled components of Study Drug are supplied from 2 
distinct locations. 
 
¾ All study drug (both nonradiolabeled and radiolabeled) is shipped to the radiopharmacy. 
¾  
The radiopharmacy prepares the Dosimetric and Therapeutic doses and delivers the doses 
to the nuclear medicine facility within the treatment center. 
 
¾ The radiopharmacy also delivers the nonradiolabeled components of the study drug to the 
pharmacy at the treatment center.  
 
 
 
Step 4 ⎯ Treating the Patient  
 
 
The patient should be treated with the Dosimetric and Therapeutic doses of Study Drug  
according to the scheduled treatment dates. 
 
¾ The estimated mCi requirements for the Therapeutic dose should be calculated based on 
results of the first and second gamma-camera whole-body counts. 
 
 
The radiopharmacy or Study/Site Coordinator must contact Service Center with the 
estimated mCi requirements to determine if a second vial of Study Drug may be 
necessary. 
 
¾ The actual mCi requirements for the Therapeutic dose should be calculated based on 
results of all three gamma-camera whole-body counts and forwarded to the 
radiopharmacy, along with the written physician order, so that the dose may be prepared. 
 
¾ Check Pharmacy Insert, provided with the drug shipment, for expiration date. DO NOT USE 
STUDY DRUG AFTER EXPIRATION DATE. 
 
 
 
For answers to any questions, please contact the 
Service Center at 1-877-423-9927. 
 
 


 
S0801 
 
Page 106 
 
Revised 1/12/10 
 
 
 
 
19.3b   
 
 
 
This page left intentionally blank to prevent extensive repagination. 
 
 
 


19.4 
 
S0801 
 
Page 107 
 
 
 
SWOG S0801 SITE CONTACT INFORMATION FORM 
 
Medical Oncology Investigator Information 
Name: 
 
Degree: 
 
Institution: 
 
 
 
CCOP affiliate 
if applicable: 
 
 
 
Address: 
 
 
 
Address: 
 
 
 
City: 
 
State: 
Zip: 
Telephone: 
 
Fax: 
 
Email: 
 
 
 
 
Research Nurse/Study Coordinator (for this study): _______________________________________ 
Tel:  _______________________  Fax:  _____________________________  E-mail:  _____________________ 
Nuclear Medicine/Radiation Oncology/Radiopharmacy Information 
1)  Which department will administer the radiolabeled component of BexxarTM? 
 
 
  Nuclear Medicine  
  Radiation Oncology 
 
(Provide name of appropriate contact person in Nuclear Medicine or Radiation Oncology) 
 
Contact Name:  
____________________________ 
Phone:  
____________________________   Fax:  
_ 
E-mail:  
 
 
 
2) 
Does your current radioactive materials license allow you to have up to 300mCi of Liquid Iodine131 (not capsules)?
 
  Yes  
 
  No 
 
If no, please explain_________________________________________________________ 
 
3) 
Who will prepare the BexxarTM  dose? 
 
 
  Commercial Radiopharmacy   
 
 
    Onsite Radiopharmacy  
 
                                                                      Name of Radiopharmacy 
 
         (Provide name of appropriate contact person in Commercial or Onsite Radiopharmacy) 
 
 
 
 
 
      Contact Name:  
____________________________ 
      Phone:  
______________________________  Fax:  
 
      E-mail:  
____________________________ 
 
 
 
4)    Does the Gamma Camera(s) have whole body scanning capability? 
 
  Yes  
 
  No 
 
 
Collimator:  
 
  High Energy  
  Medium Energy 
 
5) 
Has your institution implemented the new Nuclear Regulatory Commission (NRC) guidelines  
          release of patients administered radioactive materials? 
 
    
  Yes  
 
  No  
 
  Would like to implement, need assistance 
 
 
PLEASE FAX THIS FORM, THE RADIOACTIVE MATERIALS LICENSE FOR YOUR INSTITUTION, AND FOR THE COMMERCIAL 
RADIOPHARMACY (IF APPLICABLE) TO GLAXOSMITHKLINE AT (610/917-6119). 


 
S0801 
 
Page 108 
 
 
 
 
19.5 
Determination of Expedited Adverse Event Reporting Requirements 
 
Adverse event data collection and reporting, which are required as part of every clinical 
trial, are done to ensure the safety of patients enrolled in the studies as well as those 
who will enroll in future studies using similar agents. Adverse events are reported in a 
routine manner at scheduled times during a trial. (Directions for routine reporting are 
provided in Section 14.0.) Additionally, certain adverse events must be reported in an 
expedited manner to allow for more timely monitoring of patient safety and care. 
Expedited adverse event reporting principles and general guidelines follow; specific 
guidelines for expedited adverse event reporting on this protocol are found in Section 
16.0. 
 
Reporting requirements may include the following considerations: 1) whether the patient 
has received an investigational or commercial agent; 2) the characteristics of the adverse 
event including the grade (severity), the relationship to the study therapy (attribution), and 
the prior experience (expectedness) of the adverse event; 3) the Phase (1, 2, or 3) of the 
trial; and 4) whether or not hospitalization or prolongation of hospitalization was 
associated with the event.  
 
An investigational agent is a protocol drug administered under an Investigational New 
Drug Submission (IND). In some instances, the investigational agent may be available 
commercially, but is actually being tested for indications not included in the approved 
package label.  
 
Commercial agents are those agents not provided under an IND but obtained instead 
from a commercial source. The NCI, rather than a commercial distributor, may on some 
occasions distribute commercial agents for a trial. 
 
When a study includes both investigational and commercial agents, the following rules 
apply. 
 
• 
Concurrent administration: When an investigational agent(s) is used in 
combination with a commercial agent(s), the combination is considered to be 
investigational and expedited reporting of adverse events would follow the 
guidelines for investigational agents. 
• 
Sequential administration: When a study includes an investigational agent(s) and 
a commercial agent(s) on the same study arm, but the commercial agent(s) is 
given for a period of time prior to starting the investigational agent(s), expedited 
reporting of adverse events that occur prior to starting the investigational 
agent(s) would follow the guidelines for commercial agents. Once therapy with 
the investigational agent(s) is initiated, all expedited reporting of adverse events 
should follow the investigational guidelines. 
 
Steps to determine if an adverse event is to be reported in an expedited manner 
 
Step 1: Identify the type of event using the NCI Common Terminology Criteria for 
Adverse Events (CTCAE). The CTCAE provides descriptive terminology and a 
grading scale for each adverse event listed. A copy of the CTCAE can be 
downloaded from the CTEP home page (http://ctep.cancer.gov). Additionally, if 
assistance is needed, the NCI has an Index to the CTCAE that provides help for 
classifying and locating terms. All appropriate treatment locations should have 
access to a copy of the CTCAE. 
 
Step 2: Grade the event using the NCI CTCAE version specified. 
 
Step 3: Determine whether the adverse event is related to the protocol therapy 
(investigational or commercial). Attribution categories are as follows: Unrelated, 
Unlikely, Possible, Probable, and Definite. 
 


 
S0801 
 
Page 109 
 
 
 
 
Step 4:  Determine the prior experience of the adverse event. Expected events are those 
that have been previously identified as resulting from administration of the agent. 
An adverse event is considered unexpected, for expedited reporting purposes 
only, when either the type of event or the severity of the event is not listed in  
 
• 
the current NCI Agent-Specific Adverse Event List (for treatments using agents 
provided under an NCI-held IND); 
• 
the drug package insert (for treatments with commercial agents only); 
• 
Section 3.0 of this protocol. 
 
Step 5: Review Table 16.1 in the protocol to determine if there are any protocol-specific 
requirements for expedited reporting of specific adverse events that require 
special monitoring.  
 
Step 6: Determine if the protocol treatment given prior to the adverse event included an 
investigational agent(s), a commercial agent(s), or a combination of 
investigational and commercial agents. 
 
NOTE: This includes all events that occur within 30 days of the last dose of protocol 
treatment.  Any event that occurs more than 30 days after the last dose of treatment and 
is attributed possibly, probably, or definitely to the agent(s) must be reported according to 
the instructions above.