Reduced Duration Stanford V Chemotherapy With or Without Low-Dose Tailored-Field Radiation Therapy For Favorable Risk Pediatric Hodgkin Lymphoma
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Sponsor: St. Jude Children's Research Hospital

HOD08
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023
St. Jude
HOD08 - NCT00846742
Initial version, 12-24-2008, submitted to CPSRMC 1-5-2009.  Resubmitted 1-27-2009.  Resubmitted to IRB 2-12-
2009 (IRB approved: 2-10-2009)
Activation date: 2-17-2009
Amendment 1.0: October 13, 2009 (IRB approved: December 10, 2009)
Activation date: December 17, 2009
Amendment 2.0: April 8, 2010 (IRB approved: June 11, 2010)
Letter of Amendment (LOA) #1, June 15, 2010 (IRB approved: June 28, 2010)
Activation date: July 12, 2010
Revision 2.1 November 12, 2010 (IRB approved: November 18, 2010) 
Activation date: November 30, 2010
Amendment 3.0: March 14, 2013 (IRB approved: June 4, 2013) Resubmitted to IRB April 22, 2013 and May 31, 
2013 Activation Date: June 6, 2013
Revision 3.1: July 23, 2014 (IRB approved: August 4, 2014) Activation Date: August 13, 2014
Un-numbered revision dated: October 11, 2017 (IRB approved: October 13, 2017)
Revision 3.2, February 1, 2018 (IRB approved: February 19, 2018) Superseded
Revision 3.3, October 22, 2018 (IRB approved:  October 13, 2018) Activated: November 1, 2018 )
UNR (PI Change) dated: May10, 2022 (IRB approved: May 25, 2022)
UNR (PI Change) dated: September 15, 2023 (IRB approved:  )
REDUCED DURATION STANFORD V CHEMOTHERAPY WITH OR WITHOUT 
LOW-DOSE TAILORED-FIELD RADIATION THERAPY FOR FAVORABLE RISK 
PEDIATRIC HODGKIN LYMPHOMA
PRINCIPAL INVESTIGATOR
Matt Ehrhardt MD., M.S.
Department of Oncology
St. Jude Children's Research Hospital
SUB-INVESTIGATORS
Jeffrey Rubnitz, M.D., PhD.
Melissa M. Hudson, M.D.
Department of Oncology 
Matthew Krasin, M.D.
Department of Radiation Oncology
Sue Kaste, D.O.
Barry Shulkin, M.D., M.B.A.
Department of Diagnostic Imaging
Hui Zhang, PhD.
Zhaohau Lu, PhD.
Chen Li
Jiahui Xu
Department of Biostatistics
Principal site:
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN  38105-3678
Telephone (901) 595-3300
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD08
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
Additional contact information for St. Jude Principal Investigator:
 
In collaboration with Co-Investigators from:
Amy Billett, MD
Amy Geddis, MD
Dana-Farber Cancer Institute
Rady Children’s Hospital San Diego
44 Binney St. SW360C
3020 Children’s Way, MC 5035
Boston, MA 02115
San Diego, CA 92123 
Eric Larsen, MD
Angela Punnett, MD
Maine Children's Cancer Program
The Hospital for Sick Children
100 Campus Drive – Unit 107
Division of Haematology/Oncology
Scarborough, ME 04074
555 University Avenue
Toronto, Ontario, M5G 1X8
 
Alison M. Friedmann, MD
Karen Fernandez, MD
Massachusetts General Hospital
Children’s Hospital of Illinois @ OSF Saint 
Pediatric Hematology/Oncology
Francis Medical Center
Yawkey 8; 55 Fruit Street
530 N.E. Glen Oak Avenue
Boston, MA 02114
Peoria, IL 61637 
 
                              
Michael Link, MD
Stanford University Medical Center
1000 Welch Road, Suite 300
Palo Alto, CA 94304
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD08
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
MEMORANDUM
Department of Oncology
Leukemia/Lymphoma Division
TO: 
CPSRMC/IRB
FROM:
Monika Metzger, MD, M.Sc.
DATE:
June 15, 2010
 
RE:
HOD08: REDUCED DURATION STANFORD V CHEMOTHERAPY 
WITH OR WITHOUT LOW-DOSE TAILORED-FIELD RADIATION 
THERAPY FOR FAVORABLE RISK PEDIATRIC HODGKIN 
LYMPHOMA
Addition of Rady Children’s Hospital and the University of California at San 
Diego (UCSD) as an alliance
Amendment 2 LOA #1
 
We would like to add Rady Children’s Hospital and UCSD as an alliance on the HOD08 study.
St. Jude Children’s Research Hospital and Rady Children’s Hospital have entered into a research 
alliance agreement which allows Rady to collaborate on St. Jude clinical research protocols.  
Rady has been tasked with enrolling 25 research participants in the next year, and opening as 
many protocols as possible.  Dr. Raul Ribeiro is the St. Jude liaison for Rady.
Rady has expressed an interest in participating in the HOD08 study. Catherine Madigan, MD 
will be the PI; however the radiation therapy will be done at UCSD. Rady plans to enroll 1-2 
participants per year.
Thank you for your consideration.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD08
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
Table of Contents
1.0
OBJECTIVES............................................................................................................................1
1.1
Primary objective.............................................................................................................1
1.2
Secondary objectives .......................................................................................................1
2.0
BACKGROUND AND RATIONALE......................................................................................2
2.1
Introduction......................................................................................................................2
2.2
Evolution of Pediatric Hodgkin Lymphoma Therapy .....................................................2
2.3
Summary of Combined Modality Therapy Results.........................................................3
2.4
Rationale for Risk-Adapted Therapy...............................................................................4
2.5
Proposed Study and Definition of Prognostic Groups.....................................................7
3.0
RESEARCH PARTICIPANT ELIGIBILITY CRITERIA......................................................12
3.1
Inclusion Criteria ...........................................................................................................12
3.2
Exclusion Criteria ..........................................................................................................12
3.3
Research Participant Recruitment and Screening..........................................................12
3.4
Enrollment on Study at St. Jude ....................................................................................12
3.5
Enrollment Instructions for Collaborating Sites............................................................13
4.0
TREATMENT PLAN..............................................................................................................13
4.1
Chemotherapy Doses and Schedule...............................................................................13
4.2
Therapy Sequence..........................................................................................................14
4.3
Chemotherapy Administration Guidelines and Supportive Medical Care ....................14
4.4
Radiotherapy..................................................................................................................15
5.0
DRUG INFORMATION .........................................................................................................18
5.1
Bleomycin (Blenoxane)...............................................................................................18
5.2
Doxorubicin (Adriamycin) .........................................................................................20
5.3
Etoposide (VP-16) (Vepesid) .....................................................................................21
5.4
Mechlorethamine Hydrochloride (Nitrogen Mustard, Mustargen) .............................21
5.5
Prednisone......................................................................................................................23
5.6
Vinblastine (Velban)....................................................................................................23
5.7
Vincristine (Oncovin)..................................................................................................24
5.8
Filgrastim (G-CSF, Neupogen) ...................................................................................25
6.0
EVALUATIONS, TESTS, AND OBSERVATIONS .............................................................25
6.1
Required Clinical Staging Evaluation ...........................................................................25
6.2
Other Pre-therapy Evaluations.......................................................................................26
6.3
Recommended and Required Schedule of On-Therapy Evaluations ............................26
6.4
Off Therapy Evaluations................................................................................................26
7.0
EVALUATION CRITERIA....................................................................................................28
7.1
Response Criteria...........................................................................................................28
7.2
Toxicity Evaluation Criteria ..........................................................................................30
8.0
CRITERIA FOR off THERAPY AND OFF-STUDY ............................................................30
8.1
Off-Therapy Criteria:.....................................................................................................30
8.2
Off-Study Criteria:.........................................................................................................30
9.0
ADVERSE EVENT REPORTING AND Grading..................................................................31
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD08
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
9.1
Recording and Reporting Adverse Events.....................................................................31
9.2
Reporting Unanticipated Problems to the St. Jude IRB ................................................31
10.0
DATA COLLECTION, MONITORING AND CONFIDENTIALITY..................................33
10.1
On-Study Forms.............................................................................................................34
10.2
During Treatment...........................................................................................................34
10.3
After Treatment .............................................................................................................34
10.4
Study Monitoring...........................................................................................................35
10.5
Confidentiality ...............................................................................................................36
11.0
STATISTICAL CONSIDERATIONS.....................................................................................36
11.1
Sample Size ...................................................................................................................36
11.2
Accrual...........................................................................................................................37
11.3
Statistical Methods & Analysis .....................................................................................37
11.4
Data Safety Monitoring Board.......................................................................................40
12.0
Obtaining Informed Consent....................................................................................................40
12.1
Consent at the Age of Majority .....................................................................................40
12.2
Consent When English is Not the Primary Language ...................................................40
13.0
REFERENCES ........................................................................................................................41
APPENDICES
APPENDIX I:  ANN ARBOR STAGING CLASSIFICATION FOR HODGKIN'S DISEASE
APPENDIX II:  HOD08 FAVORABLE RISK TREATMENT SCHEMA WITH NITROGEN 
MUSTARD
APPENDIX III:  SCHEDULE OF ON- AND OFF-THERAPY EVALUATION
APPENDIX IV:  RECOMMENDED SCHEDULE OF OFF THERAPY FOLLOW-UP FOR 
DISEASE STATUS
APPENDIX V:  REQUIRED OFF THERAPY FOLLOW-UP FOR LATE ORGAN TOXICITY 
APPENDIX VI:  EXAMPLES OF TAILORED RADIATION THERAPY TREATMENT FIELDS
APPENDIX VII:  TESTS PERFORMED AS PART OF STANDARD CLINICAL CARE
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD08
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
Protocol Summary
HOD08, REDUCED DURATION STANFORD V CHEMOTHERAPY WITH LOW-DOSE 
TAILORED-FIELD RADIATION THERAPY FOR FAVORABLE RISK PEDIATRIC HODGKIN 
LYMPHOMA
Principal Investigator: Matt Ehrhardt, MD
IND holder: This is a non-IND study. 
Brief overview:  This is a phase II clinical trial using risk-adapted, multi-modality therapy. The goals of 
this study are to 1) Increase the proportion of patients that will be in complete remission at the end of 8 
weeks of chemotherapy and therefore will not require radiation therapy; 2) maintain treatment outcomes by 
using a combined-modality approach with an abbreviated dose-intensive chemotherapy regimen with 
limited-volume, conformal radiotherapy for patients that are not in CR at the end of chemotherapy; and 3) 
reduce acute and long-term treatment sequelae by a) minimizing the cumulative doses of anthracyclines, 
bleomycin, and alkylating agents, b) increasing the number of complete responders, thus decreasing the 
number of patients requiring radiation, and c) tailoring the volume of radiation to initially involved nodal 
sites.
Intervention: Combined-modality therapy with abbreviated dose-intensive chemotherapy regimen 
(STANFORD V) with limited-volume, conformal radiotherapy for participants who are not in complete 
remission at the end of chemotherapy.
Brief outline of treatment plan: Patients will be treated with 8 weeks of Stanford V chemotherapy.  
Radiation therapy will be omitted for patients achieving a complete response after 8 weeks of 
chemotherapy. Patients who achieve less than a complete response after 8 weeks of chemotherapy will 
receive 25.5 Gy to individual nodal sites (tailored fields) starting 2-3 weeks following completion of all 
chemotherapy and recovery of ANC to at least 1000.
Objectives:
Primary objectives

To increase the complete response rate after 8 weeks Stanford V by at least 20% compared to 
patients on HOD 99 after 8 weeks VAMP.
Secondary objectives: 

To estimate the disease failure rate within the radiation fields.

To examine patterns of treatment failure for children treated with low dose tailored field radiation 
therapy.

To describe acute hematologic and infectious toxicities as they relate to transfusion requirements, 
growth factor support, episodes of febrile neutropenia and hospitalizations, according to the NCI 
Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.

To compare the survival distributions (event free, overall and local failure) and toxicities of 
favorable risk patients treated with 8 weeks of Stanford V chemotherapy and low-dose tailored-field 
radiation to those on the favorable risk group of the HOD99.

To compare the survival distributions between patients that will not be prescribed radiotherapy after 
8 weeks Stanford V and those patients on HOD99 that did not receive radiotherapy after VAMP.

To estimate the event-free survival distributions of favorable risk patients treated with                    
Stanford V chemotherapy alone and patients treated with Stanford V chemotherapy                        
plus low dose tailored field radiation.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD08
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
HOD08, REDUCED DURATION STANFORD V CHEMOTHERAPY WITH LOW-DOSE 
TAILORED-FIELD RADIATION THERAPY FOR FAVORABLE RISK PEDIATRIC HODGKIN 
LYMPHOMA
Hypotheses/estimates:  With the success of current chemotherapy for Hodgkin lymphoma, the primary 
goal of this protocol is to increase the proportion of favorable risk Hodgkin lymphoma patients treated 
with 8 weeks Stanford V chemotherapy alone that will not require any radiotherapy by at least 20% 
compared to favorable risk patients treated with VAMP on HOD99.  In HOD99 44% (27/62) of favorable 
risk patients (excluding stage I nodular lymphocyte predominant histology) achieved a complete response 
(CR) at 8 weeks after two cycles of VAMP chemotherapy, and thus required no radiotherapy. A historical 
control design is used to test the hypothesis of a 20% increase (from 44% to 64%) in the proportion of 
patients not requiring radiotherapy.
Criteria for evaluation: At the end of all prescribed chemotherapy, response will be determined for each 
individual nodal group.  The response evaluation will be based on the multidisciplinary (oncologist, 
radiotherapist, and radiologist) interpretation of physical examination, laboratory and diagnostic imaging 
and response criteria listed in Section 7.1 of the protocol.  Toxicity and performance reporting will be 
according to CTCAE Version 3.0.
Study design: Multicenter, phase II study utilizing risk adapted multi-modality therapy.
Study population:  Participants with previously untreated Hodgkin lymphoma with localized disease 
designated as “favorable” comprise those with asymptomatic non-bulky stage I/II disease involving less 
than 3 nodal regions.  
Sample size: 80 evaluable participants (stage IA nodular lymphocyte predominant histology patients are 
excluded from the primary objective. 
Randomization: N/A
Data analyses: 
Primary aims

To increase the proportion of patients that will not require any radiotherapy by at least 20% 
compared to the favorable risk arm in HOD99.  The hypothesis test will be performed for the 
proportion of patients not requiring any radiotherapy (which is equivalent to the complete response 
(CR) rate) compared with the historical control for HOD99 which was 27/62 (44%) by using an 
exact binominal test. A 95% confidence interval of the complete response (CR) rate will be 
provided.
Secondary aims

To estimate the disease failure rate within the radiation fields.  Disease failure within the radiation 
field is defined as disease that recurs in the initially involved nodal region within the field of 
irradiation. The disease failure rate within the radiation field will be estimated with a 95% 
confidence interval using appropriate methods (e.g., estimate cumulative incidence in the presence 
of competing risks).

To examine patterns of treatment failure for children treated with tailored field radiation therapy.  In 
relapsed patients, nodal sites of disease, as well as extra-nodal sites of disease, will be evaluated for 
treatment failure. A local failure is classified as disease that recurs in the initially involved nodal 
region within the field of irradiation; otherwise it will be classified as a distant failure. If both 
failures (local and distant) are observed, it will be treated as a local failure. Bone marrow failure 
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD08
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
HOD08, REDUCED DURATION STANFORD V CHEMOTHERAPY WITH LOW-DOSE 
TAILORED-FIELD RADIATION THERAPY FOR FAVORABLE RISK PEDIATRIC HODGKIN 
LYMPHOMA
will always be classified as a distant site of failure.  Descriptive statistics related to local/distant 
failure will be produced. The cumulative incidence of local failure will be estimated and effects of 
prognostic factors will be examined. Effect of competing risks (distant failure, second malignancy 
and death) will be taken into account. Relapse rate within the radiation fields will be estimated and 
confidence interval will also be calculated.

To describe acute hematologic and infectious toxicities as they relate to transfusion requirements, 
growth factor support, episodes of febrile neutropenia and hospitalizations, according to the NCI 
Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.  The acute hematologic 
and infectious toxicities will be summarized by descriptive statistics.

To compare the survival distributions (event-free, overall and local failure) and toxicities of 
favorable risk patients treated with this reduced Stanford V chemotherapy and low-dose tailored-
field radiation to those on the favorable risk group of the HOD99 that received VAMP and low-
dose involved-field radiation.  Log-rank and Gray’s tests will be used to compare outcome (event-
free survival and overall survival distributions and cumulative incidence of local failure) of 
favorable risk patients treated on this protocol vs. patients treated on HOD99 and distributions 
between patients that will not be prescribed radiotherapy after 8 weeks Stanford V and those 
patients on HOD99 treated with VAMP and did not receive radiotherapy. In the presence of 
competing risks, Gray’s test will be used to compare outcome distributions (e.g., cumulative 
incidence of local failure).
Anticipated primary completion date:    July 2017
Anticipated study completion date:  Anticipated July 2017
Timeframe for primary outcome measure:  8.5 years
Data management: Provided by St. Jude Children’s Research Hospital, Comprehensive Cancer Center 
research personnel, Leukemia/Lymphoma Division.  
Human subjects: The risks to participants will be related to the toxicity of multi-modality chemotherapy 
and radiation.  There is also the risk that reducing therapy will increase the risk of relapse.  Participants 
will be informed of this and other potential side effects during informed consent.  Adverse events will be 
monitored and reported and treated appropriately.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD 08
Page 1 of 46
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
1.0
OBJECTIVES
1.1
Primary objective
(Applied to non-stage IA non-LP favorable risk patients only)
1.1.1
To increase the complete response rate of favorable risk patients 
(excluding all patients with stage IA nodular lymphocyte predominant 
Hodgkin lymphoma) after 8 weeks Stanford V by at least 20% compared 
to favorable risk patients on HOD 99 after 8 weeks VAMP.
1.2
Secondary objectives
(Applied to all favorable risk patients)
1.2.1
To estimate the disease failure rate within the radiation fields.
1.2.2
To examine patterns of treatment failure for children treated with low dose 
tailored field radiation therapy.
1.2.3
To describe acute hematologic and infectious toxicities as they relate to 
transfusion requirements, growth factor support, episodes of febrile 
neutropenia and hospitalizations, according to the NCI Common 
Terminology Criteria for Adverse Events (CTCAE), version 3.0.
1.2.4
To compare the survival distributions (event-free and overall) and 
cumulative incidence of local failure and toxicities of favorable risk 
patients treated with 8 weeks of Stanford V chemotherapy and low-dose 
tailored-field radiation to those on the favorable risk group of the HOD99 
study that received VAMP and low-dose involved-field radiation.
1.2.5
To compare the survival distributions between patients that will not be 
prescribed radiotherapy after 8 weeks Stanford V and those patients on 
HOD99 that did not receive radiotherapy after VAMP.
 1.2.6 To estimate the event-free survival distributions of favorable risk patients 
treated with Stanford V chemotherapy alone and patients treated with 
Stanford V chemotherapy plus low dose tailored field radiation.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD 08
Page 2 of 46
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
2.0
BACKGROUND AND RATIONALE
2.1
Introduction
Cure rates for pediatric Hodgkin lymphoma have improved dramatically over the past 30 
years.  Currently 90% - 100% of patients with localized disease and 70% - 90% of 
patients with advanced stage disease achieve long-term disease-free survival. 1-3,3-17 With 
improved survival in pediatric Hodgkin lymphoma, treatment and management decisions 
have become more complex because of considerations regarding acute and late effects of 
therapy, as well as quality of life. 
2.2
Evolution of Pediatric Hodgkin Lymphoma Therapy
In early stage Hodgkin lymphoma standard-dose (35-44 Gy) extended-volume 
radiotherapy (RT) alone achieves excellent long-term disease-free survival, but results in 
growth abnormalities such as intraclavicular narrowing, shortened sitting height, 
decreased mandibular growth and neck size, and atrophy of soft tissues and muscle 
development that can severely affect quality of life.18-20 Concern for these effects led to 
pediatric trials implemented in the 1970s which modified treatment strategies to address 
the specific needs of children.6,21-26 These studies determined that multi-agent 
chemotherapy could be used to treat subclinical disease and reduce the required dose of 
radiation at involved sites.    
In the 1980s, with long-term follow-up demonstrating feasibility and efficacy of 
combination chemotherapy in pediatric Hodgkin lymphoma, study objectives were 
modified to improve cure rates for advanced stage patients and reduce the MOPP 
(mechlorethamine, vincristine, procarbazine, prednisone)-related sequelae of infertility 
and secondary leukemia.  During this era, treatment with standard-dose radiation therapy 
alone was restricted to adolescents with localized disease who had achieved skeletal 
maturity. In combined modality regimens, radiation was reduced in dose (15-25.5 Gy) 
and volume (involved fields rather than extended fields).  By the end of the era, six 
treatment cycles of non-cross-resistant combination chemotherapy plus low-dose, 
involved field RT evolved as the standard.  As a result of these changes, follow-up of 
patients treated in the 1980s had indicated improvement in disease-free survival with a 
reduced incidence of cardiopulmonary, gonadal, and neoplastic complications.2,3,7-10 
The goal of therapy in the 1990s focused on further reducing therapy among patients with 
favorable disease presentations to minimize acute and late complications, without 
compromising disease control. These objectives resulted from long-term follow-up 
studies of Hodgkin lymphoma survivors that showed that the decline in event-free 
survival for patients followed more than 10 years from diagnosis resulted from late 
toxicity of therapy rather than from Hodgkin lymphoma itself.27-30  These late events 
resulted in early mortality, most commonly from the development of second malignant 
neoplasms (SMN) or non-neoplastic treatment complications and could be attributed to 
specific treatment modalities (e.g., anthracycline chemotherapy, radiation therapy).  
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD 08
Page 3 of 46
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
Treatment programs throughout the 1990s have attempted to reduce or eliminate agents 
or modalities associated with unacceptable cancer-related morbidity and mortality. 
However, reductions in therapy intensity must be made cautiously, since they may 
compromise disease-control.
The desire to avoid radiation-related SMN in long-term Hodgkin survivors has been a 
major objective of pediatric investigations evaluating regimens prescribing chemotherapy 
alone.  Results from the Late Effects Study Group indicate a standardized incidence ratio 
(SIR) of 11.8 (95% CI, 8.7-15.4) for developing a SMN following treatment for 
Hodgkin's disease.31 The most common solid tumors observed in the cohort were breast 
(SIR 75.3, CI 44.9-118.4), thyroid (SIR 32.7, CI 15.3-55.3), bone (SIR 24.6, CI 6.4-54.5), 
brain (SIR 10.5, CI 2.7-23.4), colorectal (SIR 38.9, CI 7.3-95.3), and gastric cancer (SIR 
12.3, CI 11.4-145.2).  Other pediatric investigators have similarly reported excess risks of 
second solid tumors in survivors of pediatric Hodgkin lymphoma.32-36 SMN were the 
second most frequent cause of death (after Hodgkin lymphoma) in patients treated on St. 
Jude Hodgkin lymphoma trials from 1962 to 1990 28  a fact that emphasizes the need for 
further refinements in pediatric Hodgkin lymphoma therapy.
Several investigators have demonstrated disease-free survival rates in children treated with 
chemotherapy alone which are comparable to those observed after combined modality 
therapy.37-45  However, these studies have predominantly been reported with brief follow-
up, from non-industrialized countries, or have used supplemental radiation therapy in select 
patients.  Chemotherapy-alone protocols offer advantages for children treated at centers in 
developing countries where radiation facilities and trained personnel may be lacking and 
precise clinical staging difficult to perform. The use of chemotherapy-alone regimens also 
avoids the long-term growth and neoplastic complications associated with higher doses of 
radiation therapy. The potential disadvantages of chemotherapy alone regimens include 1) 
a higher cumulative alkylating drug exposure (compared to those prescribed in combined 
modality therapy regimens) and 2) increased morbidity from myelosuppression, gonadal 
toxicity, and secondary leukemia.   
2.3
Summary of Combined Modality Therapy Results
The development of the four drug combination of MOPP 46 in the 1960s, and the 
appreciation of the adverse effects of high-dose radiation therapy on musculoskeletal 
development in growing children provided the background for the first  combined 
modality therapy investigations in pediatric patients with Hodgkin lymphoma.11 The 
major toxicity of MOPP, given for 6 cycles, has been an associated risk of acute 
leukemia,46-49 sterility in males and a risk of sterility in females that increases with 
advancing age.50 ABVD (doxorubicine, bleomycin, vinblastine and dacarbazine)51 has 
also been used as first line therapy with results similar to MOPP,52 but without the same 
risk of second malignancy and sterility.53 The primary adverse side effects of ABVD are 
pulmonary toxicity related to bleomycin and cardiovascular side effects secondary to 
doxorubicin.  These effects are even more evident when mediastinal or mantle irradiation 
is used in conjunction with ABVD, and are dose-related.54,55
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023

HOD 08
Page 4 of 46
Revision 3.3, dated:  10-22-2018
IRB approval date: 
Protocol document date:09-15-2023                                                
The development of ABVD and the desire to avoid MOPP sequelae of infertility and 
secondary leukemia resulted in the use of alternating multiagent chemotherapy 
regimens.52,56 The prototype MOPP/ABVD regimen has the theoretical advantage of 
enhanced antineoplastic activity, reduced MOPP-related sequelae because of the lower 
cumulative exposure to alkylating agent chemotherapy, and reduced ABVD-related 
sequelae because of the limited doses of doxorubicin and bleomycin.3,22,24,52 Pediatric 
trials of alternating multiagent drug combinations with MOPP/ABVD or similar hybrid 
therapies have been uniformly efficacious and have led to subsequent pediatric studies in 
which radiation doses and volumes have been further reduced.2,3,7-10,25 
2.4
Rationale for Risk-Adapted Therapy
Pediatric trials in the early 1990s established that excellent outcomes could be achieved 
in early-stage patients with “favorable” presentations with fewer cycles of multi-agent 
chemotherapy and lower radiation doses and volumes in clinically staged patients. 
“Favorable” localized disease was characterized by the absence of bulk of mediastinal 
and peripheral lymphadenopathy.  The designation of bulky mediastinal 
lymphadenopathy was assigned if the ratio of mediastinal lymphadenopathy to the 
maximal trans-thoracic dimension was 33% or more, a clinical presentation previously 
reported to have an improved outcome with combined modality therapy.25 The prognostic 
implications of peripheral nodal bulk have not been consistently considered in earlier 
pediatric Hodgkin trials.  The definition of “bulky” has varied in recent clinical trials 
from 4 to 6 and even 10 cm, and its prognostic implication is felt to be analogous to 
bulky mediastinal lymphadenopathy, although this has not been prospectively evaluated. 
Combined modality programs currently under study emphasize chemotherapy regimens 
that limit the cumulative doses of alkylating agents, anthracyclines, and bleomycin and 
use low-dose, involved-field radiation therapy to reduce the frequency and severity of 
treatment sequelae.57  Some modifications of therapy, particularly those attempting to 
limit alkylating agent chemotherapy,25,58,59 have been associated with inferior disease 
control and emphasize the need for investigators to proceed with caution in their attempts 
to reduce late treatment effects.
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2.4.1
Summary of risk-adapted therapy trials
Many multi-institutional trials have shown that children with favorable stage (IA and IIA, 
non-bulky) Hodgkin lymphoma can be cured with abbreviated chemotherapy followed by 
15 to 25 Gy involved field radiotherapy (Table 1):60
Table 1: Selected Trials of Combined Modality Therapy in Favorable-Risk Pediatric 
Hodgkin Lymphoma
Table cited from Hodgson, et al60. References for the individual trials: 2,3,7,12-16,61
The major focus of these trials is to reduce treatment-related toxicity while maintaining 
high rates of cure.
2.4.2
Results of Pediatric Hodgkin's Group Collaborative Trials
Study design for favorable risk patients
In 1990, investigators from Stanford, Dana Farber, and St. Jude initiated studies with 
objectives of reducing cardiopulmonary, gonadal, and neoplastic treatment sequelae with 
the use of combination chemotherapy regimens that eliminated or reduced exposure to 
alkylating agents, anthracyclines and bleomycin.  Patients with favorable (peripheral 
nodal disease < 6 cm or mediastinal mass to thoracic cavity ratio < 33% by chest 
radiograph) localized disease received 4 cycles of vinblastine, Adriamycin, methotrexate, 
and prednisone (VAMP) chemotherapy. Patients with localized, unfavorable bulky 
presentations and advanced disease received 6 cycles of vinblastine, etoposide, 
prednisone, and adriamycin (VEPA) chemotherapy.  All patients received involved-field 
radiation with the prescribed dose based on disease response after 2 cycles of 
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chemotherapy.  Patients with a complete response received 15 Gy; those with a partial 
response or bulky disease at presentation received 25.5 Gy. 
Outcome and toxicity of VAMP plus RT
Mature results of the VAMP plus radiotherapy regimen among 110 patients show a 5- 
and 10-year overall survival of 99% (SE,1.0%) and 96%, (SE, 2.6%)  respectively, and 5-
and 10-year event-free survival (EFS) were 93% (SE, 2.5%) and 89% (SE, 4.2%) with a 
median follow up of 9.6 years (range, 1.7 to 15 years).11,61 The regimen is very well 
tolerated and acute toxicity is easily managed in the outpatient setting. Blood product 
transfusions and admissions for neutropenic fever are rare. In regard to long term 
toxicity, the most frequently observed endocrine abnormality was subclinical 
hypothyroidism (42%) after neck radiation. Thyroid nodules were detected in three 
children, 8 years after diagnosis. Soft tissue hypoplasia was recorded in three children. 
Osteopenia and/or osteoporosis occurred in 13 children, which may represent an 
underestimate since bone density studies were not routinely preformed. Weight gain 
and/or obesity were noted in 16 children, with body mass index values of 26.4 to 41.2. 
Mild asymptomatic changes in pulmonary volumes, diffusion, or both were recorded in 
34% of tested patients. One girl had a decline in left ventricular fractional shortening, 
which dropped to less than 25% 3 years after diagnosis with symptomatic cardiac failure 
during pregnancy. Fertility is believed to have been maintained in all girls, since all girls 
of pubertal age had normal menses. One boy was found to be azoospermic after receiving 
25 Gy pelvic/15 Gy para-aortic/splenic RT. Two patients developed a second malignancy. 
One patient was diagnosed with follicular thyroid cancer, 8 years after 25.5 Gy to a field 
that included the thyroid gland, presumably radiation induced. This patient is disease free 
and believed cured after subtotal thyroidectomy and [I131] thyroid ablation. The second 
patient developed Ewing sarcoma 4 years after treatment for his Hodgkin lymphoma, 
outside his prior radiation field of 25.5 Gy to the high cervical nodal chain. He died of 
refractory metastatic sarcoma. Four girls, routinely screened for breast disease, have 
undergone breast biopsies; all revealed a benign tumor.
Outcome of VEPA plus RT
Accrual to the VEPA plus radiotherapy regimen was closed in 1993 because of the 
inferior event-free survival experienced by advanced and unfavorable patients.58   Mature 
results of this trial suggest that disease control in patients with advanced stage Hodgkin 
lymphoma is compromised when patients are treated with regimens that do not contain 
alkylating agent chemotherapy.  The 5-year event-free survival for this cohort was 
68%±6% and overall survival was 81%±5%, survival rates below the range typically 
observed for pediatric patients with advanced stage disease treated with combined 
modality therapy. 
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Outcome of VAMP/COP plus RT
The subsequent study for unfavorable and advanced disease prescribed alternating cycles 
of VAMP and COP chemotherapy with low-dose involved-field radiation therapy and 
started in 1993.62  The dose of radiation was the same as that given on the earlier study: 
15 Gy for patients achieving a complete response after the first 2 cycles, and 25.5 Gy for 
patients with a partial response and to all sites of bulky lymphadenopathy.  Between 1993 
and 2000, 159 children were enrolled on the VAMP/COP + RT arm. The 5-year event-
free survival for the entire VAMP/COP + RT cohort was 76%  4% and 5-year overall 
survival was 93%+2.5%.  Event-free survival was somewhat higher for the 77 patients 
with localized unfavorable stage I/II disease than  for the 88 patients with advanced stage 
III/IV disease though the difference was not statistically significant (5-year estimates: 
82%  5% versus 68%  6.5%, p=0.09).
Overall, treatment outcomes following the VAMP/COP + RT regimen are no better than 
other regimens used for unfavorable and advanced stage pediatric Hodgkin lymphoma.  
Follow-up is ongoing to determine whether regimen-related long-term toxicity will be 
significantly less than that observed after combined modality treatment protocols including 
higher doses of alkylating agents, higher radiation doses, and larger RT volumes.  
2.5
Proposed Study and Definition of Prognostic Groups
The HOD 2008 study for low risk pediatric Hodgkin lymphoma patients aims to: 1) 
increase the proportion of patients that will be in complete remission at the end of 8 
weeks of chemotherapy and therefore will not require radiation therapy, 2) maintain 
excellent treatment outcomes by using a combination of an abbreviated dose-intensive 
chemotherapy regimen plus limited-volume, conformal radiotherapy for patients that are 
not in CR at the end of chemotherapy; and 3) reduce acute and long-term treatment 
sequelae by a) minimizing cumulative exposure to anthracyclines, bleomycin, and 
alkylating agents, b) increasing the number of complete responders thus decreasing the 
number of patients requiring radiation and c) tailoring the volume of radiation to initially 
involved nodal sites.
Patients with localized disease designated as “favorable” comprise those with 
asymptomatic non-bulky stage I/II disease involving less than 3 nodal regions.  The 
treatment will comprise 8 weeks of Stanford V chemotherapy. Patients with less than a 
complete response at the end of chemotherapy will proceed to receive low-dose, 25.5 Gy 
tailored-field radiation therapy. 
2.5.1
Rationale for testing 8 weeks of Stanford V chemotherapy with or without low-
dose tailored-field radiation therapy in favorable-risk pediatric Hodgkin lymphoma
Stanford V experience
The Stanford V regimen is an abbreviated, multi-agent, dose-intensive regimen that 
utilizes many of the most active chemotherapy agents for Hodgkin lymphoma: 
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vinblastine, doxorubicin, vincristine, bleomycin, mechlorethamine, etoposide, and 
prednisone.  The regimen features increased dose-intensity of individual drugs, reduction 
in the cumulative doses of bleomycin and doxorubicin compared with ABVD or hybrid 
regimens, and substantial reduction of mechlorethamine with omission of procarbazine 
(see Tables 1, 2).  It has been used in the adult Hodgkin lymphoma population with 
promising results.  In a series of 142 patients, 12 weeks of Stanford V and 36 Gy of 
radiation therapy to all initially bulky sites and macroscopic splenic disease were given to 
all stage III/IV patients and stage I/II patients with bulky mediastinal adenopathy.63 The 
5-year freedom from progression rate was 89% (95% CI, 83% to 94%) with 97% 
freedom from progression in the 32% of patients with unfavorable stage I/II disease and 
85% in the stage III/IV patients.  A reduced Stanford V version (8 weeks) for favorable 
risk stage I/II patients in adults is underway at Stanford. Although results of the entire 
study have not yet been published, patients who had a negative PET scan at the end of 
chemotherapy had superior EFS.64
HOD99 and HOD05 experience with Stanford V
There is accumulating data and experience with other dose-intensive chemotherapy 
regimens in pediatrics that suggest such an approach is safe and effective.  The Children 
Oncology Group has been studying a relatively dose-intensive regimen, DBVE-PC 
(doxorubicin, bleomycin, vincristine, etoposide – prednisone and cyclophosphamide) for 
intermediate risk patients and AV-PC (doxorubicin, vincristine, prednisone, 
cyclophosphamide) for favorable risk patients.  Our own group has been using Stanford 
V chemotherapy with response-based, low dose, involved-field radiotherapy in the 
unfavorable-risk patients since 2002 (HOD 99) and the same regimen with tailored field 
radiation in intermediate risk patients (HOD 05) since 2006.  To date, we have enrolled 
125 patients with stage IB, II (bulky mediastinum, “E” lesion, or > 2 nodal sites), III, and 
IV disease to treatment with 12 weeks of Stanford V chemotherapy and 15 to 25.5 Gy 
involved-field (tailored-field in the intermediate risk protocol) radiation.  Early response 
is assessed at week 8 and the radiation dose determined on the basis of this response.  
There has been no treatment-related mortality, the regimen has been easy to administer 
and well tolerated.  Grade III/IV neutropenia has been the most commonly observed 
toxicity, but the rate of hospitalizations for febrile neutropenia has been extremely low.
Historical control for HOD08
Our current trial treats favorable risk patients with four cycles of the efficacious and well-
tolerated VAMP regimen.  Based on the promising experience of other groups in omitting 
radiation therapy in favorable risk patients, we have been prospectively evaluating this 
approach since 1999 (in the HOD 99 study).  Patients who have a rapid early response  to 
the first two cycles of VAMP, defined as at least 75% reduction in the product of all 
lesions in conjunction with a negative positive emission tomography (PET) scan are not 
receiving radiation therapy, whereas patients with a partial early response receive low-
dose (25.5 Gy) involved-field radiotherapy.  On this arm there have been 5 events, and to 
date, the 2-year EFS (SE) is 95.0% (3.0%) and 3-year EFS rate is 90.8% (4.4%) (April, 
2008 DSMB report) with so far a 100% overall-survival. Of these patients 58% did not 
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receive radiation therapy. However if we discount all stage IA nLP HL 27 of 62 patients 
(44%) achieved a complete response (CR) at 8 weeks and did not require radiation. When 
looking at intermediate risk patients treated on HOD 05 with Stanford V, the early 
response evaluation data at 8 weeks suggests that it is reasonable to assume that at least 
20% more favorable risk patients will achieve a CR after 8 weeks of Stanford V and 
therefore avoid radiotherapy.
Our interest in further testing the Stanford V regimen in pediatric favorable risk patients 
is generated by its tolerability, its relatively low cumulative doses of agents with 
potentially significant acute and long-term sequelae compared to other standard regimens 
for favorable-risk disease, and the desire to further increase the proportion of patients that 
will not require radiation therapy.  Table 2 shows the dose-intensity of Stanford V and 
other pediatric regimens.  Table 3 shows the cumulative doses of the important agents 
that are associated with adverse acute and long-term sequelae, where 8 weeks of Stanford 
V compares favorably in all respects.  While some of the other pediatric regimens have 
shown excellent efficacy in controlling disease, there are still significant acute and late 
effects associated with their use.  Many of the currently open national and international 
trials also require hospitalization for the administration of the chemotherapy. Further, the 
German pediatric regimens have utilized higher doses of radiation with its attendant risks 
of growth abnormalities and second malignancies, and have documented gonadal toxicity 
in both males and females.16  Our own previous VAMP experience has been excellent 
with a 5- and 10-year overall survival of 99% (SE,1.0%) and 96% (SE,2.6%), 
respectively, and a 5-and 10-year event-free survival (EFS) of 93% (SE,2.5%) and 89% 
(SE,4.2%) at a median follow-up of 9.6 years (range, 1.7 to 15).11 These patients also 
were cured without an alkylating agent, bleomycin, etoposide, or high-dose, extended-
field radiotherapy, however they all received involved field radiation (15 Gy if they had a 
CR at early response evaluation or 25.5 Gy for less than a CR). Treating our favorable 
risk patients with 8 weeks of Stanford V and limiting the radiation to those patients that 
exhibit less than a complete response at the end of therapy will make the therapy easier to 
administer, even more tolerable, and will allow us to learn more about the efficacy of this 
regimen in pediatric patients.
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Table 2: Dose Intensities of Pediatric Hodgkin lymphoma Regimens (mg/m2/week)
Stanford V
4 
VAMP
2 
OPPA
2 
OEPA
4 
ABVD
3 
AV-PC
4 
COPP/ABV 
(CCG5942)
2 (4) 
DBVE
4 
VBVP
Anthracyclines
Doxorubicin
12.5
12.5
20
20
12.5
16.7
8.75
12.5
Alkylators
Cyclophosphamide
400
150
Procarbazine
375
175
Dacarbazine
187.5
Mustargen
1.5
Vinca alkaloids
Vincristine
0.7
1.125
1.125
0.93
0.35
0.75
Vinblastine
3
3
3
1.5
4
Epipodophyllotoxins
Etoposide
30
125
125
167
Other
Prednisone
140
140
210
210
93
140
107
Methotrexate
10
Bleomycin
2.5
5
2.5
5
3.3
Table 3: Cumulative Doses of Agents Associated with Long-Term Sequelae in Pediatric 
Hodgkin Lymphoma Regimens (mg/m2)
8 week
Stanford V
4
VAMP
2
OPPA
2
OEPA
4
ABVD
3
AV-PC
4 
COPP/ABV 
(CCG 5942)
2 (4) 
DBVE
4
VBVP
Radiation [IFRT] (Gy)
+/- 25 
+/- 25 
+ 20-35 
+ 20-35 
+ 20–40 
+ 21 
+ 21 
+ 25.5 
+ 20 
Anthracyclines
Doxorubicine
100
200
160
160
200
150
140
100 (200)
Alkylators
Cyclophosphamide
3600
2400
Procarbazine
3000
2800
    Dacarbazine
3000
Mustargen
12
Vinca alkaloids
Vincristine
5.6
9
9
8.4
5.6
6 (12)
Vinblastine
24
48
48
24
48
Epipodophyllotoxins
Etoposide
240
1000
1000 
(2000)
2000
Other
Prednisone
1120
2240
1680
1680
840
2240
1280
Methotrexate
160
Bleomycin
20
80
40
40 (80)
40
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Limited volume conformal radiation therapy will be utilized in this study to treat patients 
with less than a CR following Stanford V.8 systemic therapy.  This limited volume approach 
is based on the findings that infield recurrences in our previous collaborative studies 
(HOD90, HOD94 and HOD99) occurred primarily at sites of initial nodal involvement.65  
Involved field irradiation delivered in these clinical trials included entire nodal region even 
when only a limited number of lymph nodes within the region were involved.  Resulting 
lymphatic regions were treated with anterior and posterior oriented portals that would 
encompass the lymphatics at risk and adjacent normal tissue (thyroid, lung, heart, breast, 
kidney and bowel).  Though doses to the normal structures were low this exposure still 
carries a long term risk that is well documented in studies of long term survivors of pediatric 
HL31,54,66,67.  The dose of radiation and subsequent risk to normal tissue is most simply 
reduced by avoidance during planning, an approach more easily accomplished with 
techniques such as conformal or intensity modulated radiation therapy.  This has been carried 
out uniformly in several large pediatric studies in children with brain tumors and sarcomas. 
68,69   The evolution towards this approach in pediatric HL was initiated in several German 
pediatric Hodgkin lymphoma studies utilizing a more conformed radiation therapy approach 
delivering limited volume treatment to involved lymphatics rather than traditional nodal 
regions.15,70  In patients that received no radiation therapy all failures were in initially 
involved lymphatics; patients that did receive radiation experienced only a 7% risk of 
recurrence of which 65% had a component of failure in an initially involved lymph node.  
The ongoing HOD05 trial builds on this experience delivering tailored field radiation to the 
initially involved lymph nodes with a 2 cm treatment margin.  In this trial the entire 
lymphatic region is not necessarily targeted and the dose of radiation is prescribed based on 
each lymph node’s individual response at 8 weeks of therapy (CR – 15 Gy, PR – 25.5 Gy).  
This study’s primary objective is to reduce the exposure of children with early stage HL to 
significant radiation by inducing early complete remission.  As a corollary to this objective 
we will also limit the exposure of normal tissue to radiation in the cohort that achieves a less 
than complete response by delivering RT to tailored fields with less volume than involved 
fields treated on prior protocols. Limited volume conformal radiation therapy will be used in 
this trial treating at risk lymphatics with a small margin.  It is hoped that further reductions in 
treatment volume, even if minor, may result in reductions in long term musculoskeletal, 
pulmonary, cardiac, endocrine and genitourinary toxicity and a lower risk of second cancer. 
3.0
RESEARCH PARTICIPANT ELIGIBILITY CRITERIA
3.1
Inclusion Criteria
3.1.1
Histologically confirmed, previously untreated Hodgkin lymphoma.
3.1.2
Age: Participants must be 21 years of age or younger
3.1.3
Stage must be classified as one of the following:
Ann Arbor stage IA or IIA with:
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a.
Non-bulky mediastinal disease (< 33% mediastinal to thoracic 
ratio on CXR)
b. < 3 nodal regions involved on the same side of the diaphragm
c.
No “E” lesion
3.1.4
Female patients who are post-menarchal must have a negative pregnancy 
test. Patients of reproductive potential must agree to use an effective 
contraceptive method.
3.1.5
Signed informed consent.
3.1.6
If re-evaluation of a patient’s disease shows unfavorable risk features or 
intermediate risk features, the patient will be removed from the HOD08 
study and consented to the HOD99 or the HOD05 study. 
3.2
Exclusion Criteria
3.2.1
Intermediate or High risk disease, defined as Stage IB, IIIA, any IV or 
IA/IIA with “E” lesion(s), 3 or more nodal sites involved, or bulky 
mediastinal adenopathy
3.3
Research Participant Recruitment and Screening
Research participants will be recruited by study investigators at St. Jude and 
collaborating sites through regular clinical practice.
3.4
Enrollment on Study at St. Jude
Register all research participants with the Protocol office and notify the 
Leukemia/Lymphoma Clinical Research Office.  A member of the study team will 
confirm potential participant eligibility as defined in Section 3.1-3.2, complete 
and sign the ‘Participant Eligibility Checklist’.  The study team will enter the 
eligibility checklist information into the St. Jude Clinical Trials Management 
System (CTMS). Eligibility will be reviewed, and a research participant-specific 
consent form and assent document (where applicable) will be generated. The 
complete signed consent/assent form(s) must be faxed or emailed to the CPDMO 
at 
to complete the enrollment process.
The CPDMO is staffed 7:30 am-5:00 pm CST, Monday through Friday.  A staff 
member from the Milli helpline is on call Saturday, Sunday, and holidays from 
8:00 am to 6:00 pm.  If you have a therapeutic research enrollment and need 
assistance releasing your consent, please call the Milli helpline 
 on 
call number.
3.5
Enrollment Instructions for Collaborating Sites
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Collaborating Sites must register a potential research participant to receive a 
“Research Identification Number” (RIN), this is an eight digit automated number 
beginning with an “R”, before screening and/or enrolling the participant. The RIN 
request form will be sent to St. Jude.  Once form received, St. Jude will register 
the research participant and then email the RIN to email address provided on the 
registration form.  This will register the participant only, it will not enroll the 
participant on the study.
 St Jude should be notified within 24 hours of enrollment and confirmation of 
eligibility at the site.  The completed Eligibility Checklist should be faxed to 
.  Call 
 if confirmation of the enrollment information is 
needed. The Protocol Eligibility Coordinator will then record the screening and/or 
enrollment into St. Jude’s centralized enrollment system. 
4.0
TREATMENT PLAN
4.1
Chemotherapy Doses and Schedule
(See also appendix 1I):
Drug/Agent
Dose
Route
Schedule (days)
Max Dose
Adriamycin
 25 mg/m2
IV
Day 1 of weeks 1, 3, 5, 7
Vinblastine
  6 mg/m2
IV
Day 1 of weeks 1, 3, 5, 7
*Mechlorethamine
  6 mg/m2
IV
Day 1 of weeks 1, 5
Vincristine
1.4 mg/m2
IV
Day 1 of weeks 2, 4, 6, 8
2 mg
Bleomycin
  5 units/m2
IV
Day 1 of weeks 2, 4, 6, 8
Etoposide
120 mg/m2
IV
Day 1 of weeks 3, 7
Prednisone
40 mg/m2/day
divided in 3 
doses
PO
Every other day of weeks 1-8
20 mg 
three times 
daily given 
every other 
day
4.2
Therapy Sequence
Patients will be treated with 8 weeks of Stanford V chemotherapy in the schedule 
outlined above.  Radiation therapy will be omitted for patients achieving a 
complete response after 8 weeks of chemotherapy. Patients who achieve less than 
a complete response after 8 weeks of chemotherapy will receive 25.5 Gy to 
individual nodal sites (tailored fields) starting 2-3 weeks following completion of 
all chemotherapy and recovery of ANC to at least 1000.
4.3
Chemotherapy Administration Guidelines and Supportive Medical Care
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These guidelines are provided to help physicians caring for patients treated on this 
protocol.  They are guidelines not protocol requirements.  Nothing in these 
guidelines is intended to supplant the judgment of the treating physician regarding 
patient management.  Institutional policy and custom may dictate other 
approaches to the management of the areas discussed in this section.
4.3.1
Deliver full dose (100%).  Delay drug at weeks 3, 5, and 7 if necessary, to 
give full dose.
4.3.2
Administer chemotherapy at weeks 3, 5, and 7 when ANC > 500/mm3, 
and platelets > 100,000/mm3.
4.3.3
Chemotherapy will not be delayed at weeks 2, 4, or 6 due to low counts.
4.3.4
No dose modifications will be made in obese patients with the exception 
of prednisone that will be capped at a total dose of 60 mg per day and 
vincristine at 2 mg.
4.3.5
Administer Pneumocystis carinii prophylaxis as follows or as 
recommended by institutional guidelines: Trimethoprim-sulfamethoxazole 
150 mg TMP/m2:750 mg SMX/m2 for 3 consecutive days per week at the 
onset of therapy and continue for 6 weeks after chemotherapy or 
radiotherapy is completed.
4.3.6
G-CSF (5 mcg/kg) should only be used if needed for severe infection 
during a period of neutropenia or to shorten treatment delays due to 
myelosuppression at weeks 3, 5, and 7.  It should be discontinued if the 
ANC is > 2,000/mm3 on any one measurement or > 1000/mm3 two days in 
a row.
4.3.7
It is recommended that Bleomycin be withheld if the DLCO drops below 
70% at the discretion of the treating physician.
4.4
Radiotherapy
4.4.1
Timing of initiation of tailored-field radiation therapy
Radiation therapy will be initiated approximately 2-3 weeks after 
completion of the last chemotherapy week or as soon as counts have 
recovered to ANC > 1000/mm3, and platelets > 100,000/mm3 and 
radiation treatment planning is complete.
4.4.2
Dose:
4.4.2.1 In patients who experience a mixed response, defined as a CR at 
one Ann Arbor nodal site (e.g. neck) and a PR at another (e.g. 
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mediastinum), no radiation will be given to the site with complete 
response and 25.5 Gy will be given to the site with partial 
response..
4.4.2.2 The dose will be 25.5 Gy in 150 cGy fractions administered five 
times per week for 17 days to nodal volumes that do not achieve a 
CR after 8 weeks of Stanford V chemotherapy.
4.4.3
Volume of treatment for limited volume conformal radiation therapy
General:  Patients will receive radiation therapy to the sites of initial nodal 
involvement.  The classic entire nodal regions do not need to be treated when only 
a portion of the nodal region is involved (e.g. for low cervical nodal involvement 
the high cervical lymph nodes will not be treated).  Contoured target volumes are 
required for treatment on this study.
ICRU 50 and ICRU 62 volume guidelines are used in defining volumes for this 
study. The gross tumor volume (GTV), clinical target volume (CTV), and 
planning target volume (PTV) as well as adjacent normal tissue structures 
including thyroid, heart, lungs, kidneys, liver, bladder and other adjacent normal 
tissues as appropriate will be delineated for each tumor site on the treatment 
planning CT prior to undergoing treatment.  
Volume definitions: 
GTV – Sites of initial lymphatic involvement that do not achieve a CR after 8 
weeks of systemic therapy will be contoured as the GTV.  The volume of the 
GTV will be drawn on the post-systemic therapy simulation CT study.  
Administration of intravenous contrast is encouraged to differentiate lymphatics 
from adjacent normal tissues.  Adjustments to the GTV should be made to 
account for reductions in the size of the involved node following systemic 
therapy.  Multiple GTVs may be necessary as a larger conglomerate of lymphatics 
resolves into distinct lymph nodes following systemic therapy.
CTV – A 1 cm anatomically constrained margin incorporating the adjacent 
lymphatic region will be added to the GTV(s).  These volumes do not have to be 
contiguous (e.g. neck and mediastinal volumes may not necessarily touch).  
PTV – a planning target volume will be added to account for set-up uncertainty 
and target motion. This will be determined by the treating radiation therapist, who 
will account for local institutional practices and adequacy of patient 
immobilization.  
Normal tissue volumes
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The following normal tissues should be delineated based on the location of the 
lymphatics requiring radiation.  Delineation of other normal tissues is at the 
discretion of the radiation oncologist:
Neck
Thyroid
Chest 
Heart 
Lungs
Abdomen 
Liver
Kidneys
Pelvis 
Bladder
4.4.4
Target dose
Prescription point – The prescription point is to a point within the PTV with the 
goal of coverage of the PTV with the 95% isodose volume
Prescribed total dose
PTV-1 – A total dose of 25.5 Gy delivered at 1.5 Gy per fraction.  Lymphatic 
tumors that achieve a CR following chemotherapy will not be targeted or radiated 
Treatment fraction size and fractionation - The daily radiation fraction size will be 
150 cGy prescribed once daily.  
Tissue heterogeneity - Dose corrections are encouraged for tissue heterogeneity 
but are not required.
Dose heterogeneity - Treatment plans must have no more than 10% of the 
combined GTV, CTV and PTV volume exceed 110% of the prescribed dose.
Dose limitations – Normal tissues should be maximally shielded as allowed by the 
target volume.  Portions of the target volume may be partially shielded if 
necessitated by normal tissue tolerance.  The following are recommended 
guidelines for normal tissue tolerances but individual patient and tumor 
circumstances may require deviation from these normal tissue limits.
Heart:  The whole heart may not receive more that 20 Gy and 50% of the heart 
may not receive more than 25 Gy.
Lung: The volume of the total lung receiving more than 20 Gy should be limited to 
less than 40% (V20Gy<40%)
Liver: The entire liver should not receive more than 15 Gy 
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Kidney: Maximum of 15 Gy to the entire kidney volume bilaterally.
Treatment interruptions – Treatment interruptions should be kept to a minimum, but 
may be necessary for significant events such as infection, neutropenia or 
thrombocytopenia.
4.4.5
Equipment
Energy:  Megavoltage linear accelerators utilizing 6MV - 18MV photons or 6 MeV 
through 18 MeV electrons
Field Shaping:  Multileaf collimator or cerrobend block shaped fields.
Immobilization:  Immobilization devices are encouraged for daily positioning for 
treatment.
4.4.6
Techniques
Only external beam radiotherapy techniques are allowed on this study.  Techniques 
may range from en face and parallel-opposed treatment techniques to multiple static 
non-coplanar beam arrangements using conformal techniques with single (3-D 
conformal) or multiple (intensity modulated) field segments. Intensity-modulated 
radiation therapy using dynamic multileaf collimation will be allowed. Regardless 
of the chosen technique, 3-dimensional imaging will be required for treatment 
planning and target and normal tissue definitions.  All treatment fields will be 
irradiated daily and weekly portal imaging is required. The treating radiation 
oncologist may choose to perform portal imaging more frequently depending on the 
requirements of treatment for a specific case.
4.4.7
Urgent radiotherapy
Urgent radiotherapy at the time of presentation and prior to chemotherapy will be 
given for those presenting with life threatening conditions such as airway 
compromise, spinal cord compression, or disease interfering with optimal and 
timely work-up of the patient.
4.4.8
Oophoropexy
Oophoropexy should be offered prior to pelvic radiotherapy in all females who 
require pelvic radiotherapy.  A testicular shield should be used for male patients 
requiring radiation therapy to the pelvic region during that course of therapy when 
feasible.
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4.4
Participation of St. Jude Affiliates in the Treatment Plan (St. Jude 
participants only)
Participants may receive standard chemotherapy, as well as laboratory/tests to 
monitor for toxicity at St. Jude affiliates and local physicians’ offices, as 
recommended by treating investigator.  Radiotherapy and all protocol required 
response assessments will be done at St. Jude.
5.0
DRUG INFORMATION
5.1
Bleomycin (Blenoxane)
Source and pharmacology:  Bleomycin is an antitumor antibiotic produced by the 
fermentation of Streptomyces verticillus.  It is thought to act by inhibiting the 
incorporation of thymidine into DNA, thus inhibiting DNA synthesis.  Bleomycin 
also appears to labilize the DNA structures causing both double and single strand 
DNA breaks.  It exerts its major effects in the G2 and M1 phases of the cell cycle.  
It is poorly absorbed via the GI tract and must be given via the parenteral route.  
Approximately 50-70% of a dose is excreted as unchanged drug by the kidneys, 
with the remainder being hydrolyzed by intracellular aminopeptidase, found in 
most tissues.  Bleomycin has an elimination half-life of 3-5 hours for patients with 
“normal” kidney function.  The dosage of bleomycin should be reduced for 
patients with renal dysfunction.   
Formulation and stability: Bleomycin is available in vials containing 15 units and 
30 units of bleomycin sulfate as a white or yellowish lyophilized powder. Intact 
vials should be stored under refrigeration. The contents of each vial should be 
diluted with 1 to 5 ml or 2-10 ml of 0.9% NaCl respectively, resulting in final 
concentrations of 15 to 3 units/ml.  It may be further diluted in 0.9% NaCl but 
should not be diluted in D5W due to a loss in potency.  Diluted solutions (in 
sodium chloride) are stable for 24 hours at room temperature     
Supplier:  Commercially available from Mead Johnson.
Toxicity:   Toxicities include mild nausea and vomiting, anorexia, alopecia and 
skin rash, hyperpigmentation and tenderness.  Less common reactions include 
renal toxicity, hepatotoxicity, MI, and myelosuppression.   Anaphylactic reactions 
are rare but potentially life threatening and can be characterized by severe fever, 
chills, hypotension and wheezing.  Pneumonitis can occur and may progress to 
pulmonary fibrosis.  This occurs most commonly with cumulative dosages of > 
400 units (200 units/m2) in adults.  Oxygen inhalation therapy accentuates 
pulmonary toxicity and should be used with caution.  It is recommended that 
follow-up pulmonary function tests be done during the course of therapy and for 1 
year following completion of therapy.
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5.2
Doxorubicin (Adriamycin)
Source and pharmacology:  Doxorubicin is an anthracycline antibiotic produced 
by Streptomyces peucetius.  Doxorubicin exerts its anti-tumor effects in several 
different ways. Doxorubicin intercalates between base pairs of DNA causing 
steric obstruction, disruption of DNA function and inhibition of RNA synthesis.  
In addition, doxorubicin inhibits topoisomerase II, an enzyme responsible for 
allowing strands of DNA to pass through one another as they unwind.  Lastly, 
doxorubicin undergoes enzymatic electron reduction to generate highly reactive 
species, including the hydroxyl free radical, which is thought to be responsible for 
the drug’s cardiac toxicity, but may play a role in its anti-tumor activity as well.   
Doxorubicin is cell-cycle, phase non-specific.  Doxorubicin is widely distributed 
in the tissues and plasma, but does not cross the blood brain barrier to an 
appreciable extent. It is metabolized to doxorubicinol, which is thought to be the 
major active metabolite, and aglycones. Doxorubicin and its metabolites are 
excreted mainly in the bile and feces (80%).  The remainder is excreted in the 
urine.  Dosage should be reduced in patients with liver dysfunction (bilirubin > 
1.2 mg/dl) or renal dysfunction (creatinine > 3 mg/dl).
Formulation and stability:  Doxorubicin is available in vials containing 10 mg, 20 
mg, 50 mg and 200 mg as a 2mg/ml red-orange solution.  It is also available in 
vials containing 10 mg, 20 mg, 50 mg, 100 mg and 150 mg of doxorubicin as a 
red-orange lyophilized powder.  Intact vials of doxorubicin solution should be 
stored under refrigeration while the lyophilized product should be stored at room 
temperature.  Both products should be protected from light. Lyophilized 
doxorubicin can be reconstituted by adding 5, 10, 25, 50 or 75 ml of 0.9% NaCl 
respectively to the 10, 20, 50, 100 and 150 mg vials to produce a final 
concentration of 2 mg/ml.  Bacteriostatic diluents are not recommended.  After 
reconstitution, the resultant solution should be protected from light and is stable 
for 7 days at room temperature and 15 days if refrigerated.
Supplier:  Commercially available
Toxicity: Dose-limiting toxicities include myelosuppression and cardiotoxicity. 
Two forms of cardiac toxicity can occur.  Acute toxicity may take the form of 
arrhythmias, heart block or pericarditis and may be fatal.  The chronic form of   
cardiotoxicity is related to total cumulative dose and is characterized by heart 
failure. Mediastinal radiotherapy and/or other cardiotoxic drugs may increase the 
risk of cardiotoxicity.  In general, total lifetime dosages of 450-550mg/m2 should 
not be exceeded.  Other toxicities include nausea and vomiting, mucositis, 
alopecia, diarrhea and red discoloration of the urine and other body fluids. Severe 
tissue damage and necrosis can occur upon extravasation.  Radiation recall 
reactions can occur and can be severe.  Rarely, allergic reactions have occurred.  
Typhilitis can occur when combined with cytarabine.
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5.3
Etoposide (VP-16) (Vepesid)
Source and pharmacology:  Etoposide is an epipodophyllotoxin derived from 
Podophyllum pelatatum. It is thought to act mainly by inhibiting topoisomerase II, 
causing double and single strand DNA breaks.  Etoposide is cell cycle, phase-
specific, with activity in the G2 and S phases.  Absorption of etoposide is 
approximately 30-40% and is highly variable and somewhat dose-dependent.  It is 
extensively bound to serum proteins and is metabolized in the liver, including 
cytochrome P450 3A metabolism to several moieties that include a reactive 
oxidized species.  Etoposide and its metabolites are excreted mainly in the urine 
with a smaller amount excreted in the feces.  Dosage adjustments should be 
considered in patients with liver dysfunction, kidney dysfunction or 
hypoalbuminemia.
    
Formulation and stability:  Etoposide is available in multi-dose vials containing 
100mg, 150mg, 500mg and 1000mg of etoposide as a 20mg/ml solution and 30% 
alcohol.   Etoposide is also available as a 50 mg capsule.  The intact vials of 
etoposide solution should be stored at room temperature. The capsules should be 
stored under refrigeration.  Etoposide solution should be diluted in D5W or 0.9% 
NaCl prior to administration.  Solutions with a final concentration of 0.2 and 0.4 
mg/ml are stable at room temperature for 96 hours and 24 hours respectively.
Supplier:  Commercially available
Toxicity:  Dose limiting toxicity is myelosuppression.  Nausea and vomiting 
(usually of low to moderate severity), diarrhea, mucositis (particularly with high 
doses), alopecia and anorexia are fairly common.  Hypotension can occur with 
rapid infusions.  Other side effects reported less commonly include hepatitis, 
fever and chills, anaphylaxis and peripheral neuropathy. Secondary leukemia has 
been reported.
5.4
Mechlorethamine Hydrochloride (Nitrogen Mustard, Mustargen)
Source and pharmacology: Mechlorethamine hydrochloride is a nitrogen analog 
of sulfur mustard. It is a bifunctional alkylating agent that interferes with DNA 
replication and transcription of RNA, resulting in disruption of nucleic acid 
function. Mechlorethamine possesses weak immunosuppressive activity. 
Mechlorethamine by intracavity administration results in sclerosing caused by an 
inflammatory reaction on serous membranes adherence of serosal surfaces. 
Mechlorethamine is absorbed orally, but should not be given by this route as it is 
extremely irritating to tissues. When administered by the intravenous route, 
mechlorethamine is rapidly transformed, with less than 0.01% being excreted 
unchanged in the urine. Within minutes of an IV dose, unchanged 
mechlorethamine is undetectable in the blood. 
Formulation and stability: Mechlorethamine hydrochloride is supplied in vials 
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containing 10 mg of light yellow brown crystalline powder that is very soluble in 
water. The vials of powder should be stored at room temperature protected from 
light. Each vial should be reconstituted with sterile water for injection or normal 
saline to a concentration of 1 mg/ml immediately prior to administration. The 
colorless mechlorethamine solution is highly unstable and undergoes rapid 
chemical transformation.  Mechlorethamine is a highly toxic drug and caution 
should be used in admixture and administration of this agent. 
Toxicity:  Major and dose limiting toxicities of mechlorethamine include 
hematologic toxicities, nausea and vomiting. Anorexia, diarrhea, severe 
hematemesis, and peptic ulcers have been reported after intravenous 
administration. Immediate and delayed neurotoxicity (sometimes severe) have 
been reported in patients receiving high doses or intra-arterial and regional 
perfusion administration. CNS adverse effects reported following IV 
administration include weakness, headache, drowsiness, vertigo, light-
headedness, convulsions, progressive muscle paralysis, paresthesia, cerebral 
degeneration, coma, and death. Neurotoxicity appears to increase with age and 
dose administered. It also occurs more frequently in patients who receive 
procarbazine or cyclophosphamide. Hyperuricemia has been reported following 
administration of mechlorethamine, especially in lymphoma patients. Rare 
adverse effects reported include alopecia, jaundice, tinnitus, diminished hearing, 
fever, and metallic taste. Mechlorethamine is a powerful vesicant, and great care 
should be taken to avoid contact with skin or mucous membranes. If eye contact 
occurs, the eye(s) should immediately be irrigated with copious amounts of 
normal saline or ophthalmic irrigation solution followed by an ophthalmologic 
examination. If skin contact occurs, the affected area should be irrigated with 
copious amounts of water for at least 15 minutes, followed by 2% sodium 
thiosulfate solution. Extravasation of even small amounts of mechlorethamine 
will result in painful inflammation and induration. In severe reactions, sloughing 
may occur. If extravasation occurs, as much infiltrated drug as possible should be 
removed by aspiration. The local reaction may be minimized by promptly 
infiltrating the area with isotonic sodium thiosulfate injection and applying cold 
compresses for 6 – 12 hours. Thrombosis and thrombophlebitis may result from 
direct vein contact or as a result of insufficient dilution.
Supplier: Commercially available.
5.5
Prednisone
Source and pharmacology: Prednisone is a synthetic congener of hydrocortisone, 
the natural adrenal hormone.  Prednisone is a white or yellowish crystalline 
powder.  It binds with steroid receptors on nuclear membranes, impairs cellular 
mitosis and inhibits protein synthesis.  Prednisone also has potent anti-
inflammatory effects and suppresses the immune system. Prednisone is well 
absorbed orally.  It is converted to prednisolone, the pharmacologically active 
metabolite, in the liver.  Prednisolone is further metabolized to inactive 
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compounds in the liver.  The metabolites are excreted mainly in the urine.  
Formulation and stability: Prednisone is available as various strength tablets and 
oral solution from multiple manufacturers.   All dosage forms can be stored at 
room temperature.  At St. Jude Children’s Research Hospital, prednisolone oral 
solution may be substituted for prednisone liquid at equal doses due to its superior 
palatability.
Supplier: commercially available
Toxicity: Side effects of prednisone vary depending on the duration of its use.  
Side effects that can occur with short term use include sodium and water retention 
with associated hypertension, peptic ulcer with possible perforation and 
hemorrhage, increased susceptibility to infections, emotional instability, 
insomnia, increased appetite, weight gain, acne and hyperglycemia. Side effects 
more commonly associated with prolonged use include cataracts, increased 
intraocular pressure and associated glaucoma, development of a “cushingoid” 
state, compression fractures, menstrual irregularities, suppression of growth in 
children, secondary adrenocortical and pituitary unresponsiveness particularly in 
times of stress as in trauma, surgery or illness, osteoporosis and muscle wasting.
5.6
Vinblastine (Velban)
Source and pharmacology:  Vinblastine is an alkaloid extracted from the 
periwinkle plant (Vinca Rosea).  It reversibly binds to microtubule and spindle 
proteins causing metaphase arrest.  It may also block cellular utilization of 
glutamic acid, thereby inhibiting purine synthesis and urea formation via the citric 
acid cycle.  Vinblastine is highly protein bound and poorly penetrates the CSF.  
Metabolism in the liver is extensive with one metabolite, deacetyl vinblastine, 
being more active than the parent drug.  The major route of elimination is via the 
bile. Dosages should be adjusted for patients with impaired liver function 
(bilirubin > 3 mg/dl).    
Formulation and stability:  Vinblastine is available in 10 ml vials containing 
1mg/ml of vinblastine in solution. Intact vials of vinblastine solution and 
lyophilized vinblastine should be stored under refrigeration. 
Supplier:  Commercially available
Toxicity:  The dose limiting toxicity is myelosuppression.  Other toxicities 
reported commonly include alopecia, mild nausea and vomiting and constipation.  
Vinblastine is a vesicant and may cause severe tissue damage if extravasation 
occurs.  Vinblastine rarely produces neurotoxicity characterized by peripheral 
neuropathy, loss of deep tendon reflexes, weakness, jaw pain and “foot drop”.  
This toxicity is much less common than with vincristine.  Acute shortness of 
breath and severe bronchospasm have been reported following the administration 
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of vinca alkaloids.
5.7
Vincristine (Oncovin)
Source and pharmacology:  Vincristine is an alkaloid obtained from the periwinkle 
(Vinca rosea) plant.  It reversibly binds to microtubule and spindle proteins 
causing metaphase arrest.  Vincristine has poor penetration into the CSF.  It is 
approximately 75% protein bound.  Extensive metabolism occurs in the liver.  
Excretion is primarily in the bile.  A dosage decrease is recommended in patients 
with a bilirubin > 3 mg/dl.      
Formulation and stability:  Vincristine is supplied in multiple-dose 1 mg/ml vials 
containing 1 ml, 2 ml and 5 ml. The intact vials should be stored under 
refrigeration and protected from light.  
Supplier:  Commercially available
Toxicity:  Dose limiting toxicity is neurotoxicity.  This can be characterized by 
constipation and/or paralytic ileus, ptosis, vocal chord paralysis, weakness, jaw 
pain, abdominal pain, peripheral neuropathies, loss of deep tendon reflexes and 
“foot drop”.  Peripheral neuropathy is often the first sign of neurotoxicity and is 
initially reversible.  Other toxicities reported include alopecia, mild nausea and 
vomiting, SIADH, myelosuppression, orthostatic hypotension, optic atrophy, 
transient cortical blindness, and auditory damage.  Acute shortness of breath and 
severe bronchospasm have been reported following the administration of vinca 
alkaloids.  Myelosuppression is rare at usual doses.  Vincristine is a vesicant and 
may cause severe tissue damage if extravasation occurs. NOTE:  dose reduction 
may be necessary in patients < 1 year of age. Dosing on a per kg (rather than per 
m2) basis has been advocated for infants in order to decrease toxicity.
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5.8
Filgrastim (G-CSF, Neupogen)
Source and pharmacology:  G-CSF (granulocytic colony stimulating factor), is a 
biosynthetic hematopoietic agent that is made using recombinant DNA 
technology in cultures of Escherichia coli.  G-CSF stimulates production, 
maturation and activation of neutrophils.  In addition, endogenous G-CSF 
enhances certain functions of mature neutrophils, including phagocytosis, 
chemotaxis and antibody--dependent cellular cytotoxicity.
Formulation and stability:  G-CSF is supplied in vials containing 300 mcg and 
480 mcg of G-CSF at a concentration of 300 mcg/ml.  The intact vials should be 
stored under refrigeration.   The vials can be left out of refrigeration for 24 hours, 
but should be discarded if left at room temperature for longer periods of time.  G-
CSF can be drawn up into tuberculin syringes for administration and stored under 
refrigeration for up to 7 days prior to usage.  G-CSF can be further diluted for IV 
infusion in 5% dextrose.  Do not dilute in saline---precipitate may form.  If the 
final concentration of this product is < 15 mcg/ml, it is recommended that 
albumin be added to a final concentration of 2mg/ml (0.2%) to minimize 
adsorption of the drug to infusion containers and equipment.  
Supplier:  Commercially available
Toxicity:  G-CSF causes marked leukocytosis.  Adverse reactions reported 
commonly include bone pain, thrombocytopenia, diarrhea, nausea, rash, alopecia, 
fever, anorexia and pain or bruising at the injection site.  Allergic reactions, MI, 
atrial fibrillation, and splenomegaly have been reported rarely.  G-CSF is 
contraindicated in patients with allergy to E. coli derived products.
6.0
EVALUATIONS, TESTS, AND OBSERVATIONS
6.1
Required Clinical Staging Evaluation
(See also Appendix III):

History and physical exam

Complete blood count with differential

C-Reactive Protein (CRP) or  erythrocyte sedimentation rate (ESR)

LDH, alkaline phosphatase and albumin

Urine pregnancy test for female patients after menarche.

Chest x-ray (mediastinal adenopathy must be expressed as 33% or greater 
of the maximum intrathoracic diameter, less than 33%  of the maximum 
intrathoracic diameter, or no mediastinal involvement)

CT scan of the neck and chest with contrast

CT scan or MRI of the abdomen and pelvis with contrast

PET scan
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Surgical staging 
Staging laparotomy with splenectomy is not required; however, untreated patients 
who have been surgically staged when referred are eligible.
Initial staging
Initial staging will be based on the primary physician’s interpretation of physical 
examination, laboratory and diagnostic imaging evaluations.
6.2
Other Pre-therapy Evaluations 
These studies are recommended for good clinical care or as clinically indicated:

Blood chemistry profile including electrolytes, BUN, creatinine, bilirubin, 
SGOT, and SGPT.

Urinalysis

Echocardiogram and EKG

Pulmonary function studies

Panorex and dental evaluation
6.3
Recommended and Required Schedule of On-Therapy Evaluations
The recommended and required schedule of evaluations during chemotherapy is 
outlined in Appendix III. 
All patients will be evaluated for chemotherapy response after finishing all 8 
weeks of chemotherapy. Required response evaluation will comprise a history and 
physical exam, CT scan or MRI of areas of nodal involvement and PET scan (if 
previously positive). For patients not requiring radiotherapy (because they are in 
CR) this will be considered their end of therapy evaluation. 
6.4
Off Therapy Evaluations
6.4.1
Required Off Therapy (Post-RT) Evaluation
Required end of therapy evaluation for patients receiving radiotherapy should be 
performed approximately 4-8 weeks after completion of all radiation, and will 
comprise of a CT scan or MRI of areas of initial nodal involvement and PET 
(only if previously positive), as well as physical examination, CBC with 
differential, and ESR/CRP.
Pulmonary function studies should be obtained at response evaluation or off therapy.
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Note that patients with residual imaging abnormalities may be designated to be in 
complete remission unconfirmed based on the definition outlined in section 7.1.5.1.  
Required 1-year and 2-year off-therapy evaluations should include a physical 
examination, ESR or CRP and diagnostic imaging studies and CT scan. PET is 
optional. See section 6.4.3 and appendix V for specific late effects testing 
required at the 1-, 2-, 5- and 10-year off-therapy anniversary evaluations.
A schedule of off-therapy studies to be obtained is listed in tabular form in 
Appendix IV. If there is a suspicion of recurrent disease by signs or symptoms, 
specific exams should be performed as indicated.  All patients with suspected 
relapse or progressive disease should undergo biopsy of the most accessible site 
of recurrence or progression whenever possible.
6.4.2
Recommended schedule of off-therapy evaluations
After confirmation of disease status at the first off-therapy evaluation, study 
patients should have regular follow-up with a recommended schedule of every 3 
months for 1 year, every 4 months for the next 2 years, every 6 months for the 4th 
year, and annually thereafter. Follow-up studies are recommended as clinically 
indicated for patients with abnormal baseline and to monitor organ dysfunction 
related to the toxic effects of chemotherapy and include a physical examination, 
CBC with differential and ESR or CRP. Chest radiograph is recommended as 
clinically indicated during follow-up for patients with mediastinal disease (see 
appendix IV and V for specific guidelines). 
6.4.3
Recommended late effects evaluations
Specific late effects testing should follow the Children’s Oncology Group Long-
Term Follow-up Guidelines for Survivors of Childhood, Adolescent, and Young 
Adult Cancers http://www.survivorshipguidelines.org.
Recommended late effects testing should include evaluation of the following 
organ systems as outlined in Appendix V:

Heart:  echocardiogram, electrocardiogram at 1, 2, 5 and 10 years.

Lung: pulmonary function studies at 1, 2, 5 and 10 years 

Growth:  physical examination with attention to growth abnormalities of 
soft tissues and bones with every physical exam.

Dental: panorex and dental evaluation at 5 years.

Thyroid:  Free T4 and TSH yearly if patient received radiation possibly 
encompassing the thyroid, but need to be captured only at 1, 2, 5, and 10 
years.

Document initiation date for thyroid hormone replacement therapy, if 
applicable.
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
Fertility:  Record menstrual cycle and pregnancy information.  Referral of 
men for semen analysis or measurement of testosterone levels is optional 
and should be performed when appropriate.

Obtain pathology of second tumors for histological review.
Patients in first CR will be followed for at least 10 years after completion of 
therapy.  A HOD08 Follow-Up Form for Patients in First Remission should be 
submitted every year. 
A Late Effects Follow-Up Form for Patients in First Remission should be 
submitted at years 1, 2, 5 and 10.
Evaluations at 1, 2, 5, and 10 years should be performed within 6 months of the 
Off-Therapy anniversary date. We recognize, however, that patients may be 
monitored more frequently and that off therapy evaluations and diagnosis of 
treatment-related toxicity may not adhere exactly to 1, 2, 5, or 10 years after 
completion of therapy. For patients in first remission, whose off therapy 
evaluations are performed beyond the 6 month anniversary date, a HOD08 Late 
Organ Function Screening Form For Patients in First Remission and a HOD08 
Late Effects Follow-Up Form can be submitted as part of good clinical practice.
A HOD08 Follow-Up After Relapse Form should be submitted on an annual basis 
on patients with a history of progressive disease or relapse for as long as the study 
is open for follow-up.
7.0
EVALUATION CRITERIA
7.1
Response Criteria
At the end of all prescribed chemotherapy, response will be determined for each 
individual nodal group.  The response evaluation will be based on the 
multidisciplinary (oncologist, radiotherapist, and radiologist) interpretation of 
physical examination, laboratory and diagnostic imaging and the following criteria:
7.1.1
Complete response (CR):
Disappearance of all measurable or evaluable disease, signs, symptoms and 
biochemical changes related to the tumor.  Biopsy confirmation is not mandatory.  
Residual PET-negative CT scan abnormalities representing > 75% reduction (as 
measured by the product of 2 perpendicular diameters of lesions by CT or MR 
imaging) in the original tumor volume will be considered scar tissue without 
active tumor.
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7.1.1.1 Complete response unconfirmed (CRu):
Persistent radiographic abnormalities (PET negative) at a site of previous disease 
not thought to represent active disease as long as residual abnormalities are stable 
or improved when compared to previous evaluations.  Biopsy is not required to 
confirm a complete remission status.
7.1.2
Partial response (PR):
Reduction of 50% to 75% in the original tumor volume of any measurable lesion 
by CT scan regardless of PET avidity. Persistence of PET avidity in residual 
nodal masses that shrunk ≥ 75% (as measured by the product of 2 perpendicular 
diameters of lesions by CT or MR imaging) from original tumor volume.
7.1.3
Stable disease (SD):
Neither sufficient shrinkage (<50%) to qualify for partial response, nor sufficient 
increase (<25%) or appearance of new lesions to qualify for progressive disease. 
7.1.4
Progressive disease (PD):
An increase in the product of two perpendicular diameters of any measured lesion 
by >25% over the size present at entry on study or the appearance of new areas of 
biopsy proven disease.
7.1.5
Remission evaluation after completion of therapy
Patients that did not achieve a complete response after 8 weeks of chemotherapy 
and went on to receive radiation therapy will undergo a complete disease 
evaluation 4 to 6 weeks after completing all prescribed radiotherapy. Patients will 
be designated to be in complete remission after the completion of all of the 
protocol-prescribed chemotherapy and radiotherapy as long as off therapy 
evaluations do not reveal new abnormalities suggestive of disease progression. 
7.1.5.1
Complete response unconfirmed (CRu):
Persistent radiographic abnormalities (PET negative) at a site of previous disease 
not thought to represent active disease as long as residual abnormalities are stable 
or improved when compared to previous evaluations.  Biopsy is not required to 
confirm a complete remission status.
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7.1.6
Evaluation of progressive disease or relapse
Biopsy is required (whenever possible) for confirmation of progression during 
planned therapy, or for relapse following completion of therapy.
Patients with progressive disease on therapy will be taken off treatment.  All patients 
will be followed for survival and remain on study.  Patients will receive salvage 
therapy according to investigator preference.  When progression or relapse occurs, a 
protocol outcomes event form and off-treatment form should be submitted. 
7.2
Toxicity Evaluation Criteria
This study will utilize the CTCAE Version 3.0 for toxicity and performance 
reporting. A copy of the CTCAE version 3.0 can be downloaded from the CTEP 
home page (http://ctep.info.nih.gov). The toxicities are to be reported on the 
appropriate data collection forms.
8.0
CRITERIA FOR OFF THERAPY AND OFF-STUDY
8.1
Off-Therapy Criteria:

Therapy completed

Progressive disease

Development of unacceptable toxicities or if protocol therapy or testing 
become detrimental to the patient’s health (with the concurrence of the 
principal investigator).

Participant/family decision to withdraw consent for protocol treatment at 
any time for any reason. Patients who withdraw consent for therapy 
remain on study unless they also withdraw consent for study participation.
8.2
Off-Study Criteria:

Death

Ineligible for study

Loss to follow-up (with the concurrence of the principal investigator)

Participant/family decision to withdraw consent from protocol and follow 
up at any time for any reason.

Noncompliance (with the concurrence of the principal investigator)

Completion of 10 year follow-up
If re-evaluation of a patient’s disease shows unfavorable risk features or 
intermediate risk features, the patient will be removed from the HOD08 study and 
consented to the HOD99 study or the HOD05 study. The HOD99 study is for the 
treatment of patients with unfavorable risk features and the HOD05 study is for 
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the treatment of patients with intermediate risk features. Chemotherapy treatment 
for the HOD99 unfavorable risk group, HOD08 favorable risk group and HOD05 
intermediate risk group is the same. Radiation therapy will be given based on the 
patient’s response to treatment and according to protocol.
9.0
ADVERSE EVENT REPORTING AND GRADING
9.1
Recording and Reporting Adverse Events
This study will utilize the CTCAE Version 3.0 for toxicity and performance 
reporting.  A copy of the CTCAE version 3.0 can be downloaded from the CTEP 
home page (http://ctep.info.nih.gov).  Additionally, the toxicities are to be 
reported on the appropriate data collection forms.  The following procedures will 
be followed:
1. Identify the event using the protocol-defined criteria ((as delineated in 
CTCAE v3);
2. Determine if the AE is unexpected or expected (refer to protocol, consent, 
investigator’s brochures, package insert and/or product labeling);
3. Assign grade of the event using the CTCAE criteria;
4. Determine attribution (i.e., if the AE is related to the medical 
intervention).
5. Identify whether the AE requires expedited reporting 
Adverse events will be collected and recorded in the protocol-specific research 
database for the study, and reviewed by treating investigators and study PI. 
9.2
Reporting Unanticipated Problems to the St. Jude IRB
Adverse events that are considered “unanticipated problems” will be reported in 
an expedited manner according to the guidelines outlined below.  Unanticipated 
problems include those events which (1) are not expected given the nature of the 
research procedures and the subject population being studied; and (2) suggest that 
the research places subjects or others at a greater risk of harm or discomfort 
related to the research than was previously known or recognized.  Specifically, 
adverse events that fall into the following categories will be reported under the 
HHS regulations at 45 CFR 46.103(a) and 46.103(b)(5):
1. Adverse events determined to be serious, unexpected, and related or 
possibly related to participation in research.
2. Serious adverse events that are expected in some subjects, but are 
determined to be occurring at a significantly higher frequency or 
severity than expected.
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3. Other unexpected adverse events, regardless of severity, that may alter 
the IRBs analysis of the risk versus potential benefit of the research, 
and, as a result, warrant consideration of substantive changes in the 
research protocol or informed consent process/document.
Adverse events meeting any of the above categories for participants enrolled on 
St. Jude trials (both at St. Jude and at collaborating sites) will be reported to the 
St. Jude IRB, and to all collaborating sites’ IRBs (if applicable) using expedited 
procedures.
FURTHER GUIDELINES FOR REPORTING ADVERSE EVENTS AND 
UNANTICIPATED PROBLEMS
To determine whether an adverse event is an unanticipated problem, and therefore 
requires expedited reporting under 45 CFR part 46, the PI will take into account 
the following:
1. The description of known or foreseeable adverse events and risks in the 
IRB-approved research protocol, any applicable investigator brochure, the 
current IRB-approved informed consent document, and other relevant 
sources of information, such as scientific literature, product labeling, and 
package inserts.
2. Any underlying diseases or conditions of the subject experiencing the 
adverse event.
3. A careful assessment of whether the adverse event is related or possibly 
related to the subject’s participation in the research study.
Particular AEs and SAEs require more prompt reporting to the various governing 
regulatory authorities.  The key to whether a SAE should be reported 
expeditiously or not to the St. Jude IRB is based on its expectedness of the event.  
Is this SAE an expected or unexpected event?  Expeditious reporting to the 
various Federal governing regulatory authorities is based on the relationship of 
the unexpected event to the protocol treatment and the seriousness of the event.  
Serious adverse events that are identified by the PI or designated sub-investigator 
as expected, regardless of causality are not subject to expedited reporting.  All 
expected SAEs will be reported to the St. Jude IRB and St. Jude Office of 
Regulatory Affairs in a summary type format on an annual or semi-annual basis 
or more frequently if requested by the IRB, FDA, or PI.
All unexpected SAEs that are at least possibly related to the protocol 
treatment need to be reported to the IRB’s at all participating sites (and FDA for 
IND studies) expeditiously.  The nature and severity of the event will dictate the 
exact time frame for expeditious reporting (24 – 48 hours vs. 10 days).  
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Expeditious Adverse Event Reporting Requirements to the St. Jude IRB

All deaths that occur while participants are on active therapy or 
within 30 days of protocol therapy OR deaths that are deemed 
unexpected and at least possibly related to study treatment will be 
reported to the St. Jude IRB immediately (within 24-48 hours of 
notification) using the electronic TRACKS system.  Immediate reporting 
is required even if few event specific facts are available at the time of the 
initial report.  In this case, a complete follow-up report detailing the event 
should be submitted to the IRB within 10 days of the event.

All life threatening SAEs that are deemed unexpected and at least 
possibly related to study treatment will be reported to the St. Jude IRB as 
soon as possible using the electronic TRACKS system but no later then 24 
- 48 hours and followed up in with a complete report within 10 working 
days of the occurrence of the event. 

All other unexpected SAEs (not fatal or life threatening) determined to be 
at least possibly related to study treatment will need to be reported to the 
St. Jude IRB within 10 working days of the occurrence.
Follow-up reports
Follow-up reports for the expedited adverse event reports submitted to the St. Jude 
IRB are required for those that are checked as “unresolved” at the time of the 
report.  Typically, follow-up reports should be submitted when the investigator 
becomes aware of significant new information regarding the initial event or 
subsequent patient status, or when the event has completely resolved and any 
sequelae have been identified and/or resolved.
10.0
DATA COLLECTION, MONITORING AND CONFIDENTIALITY
Data Management will be supervised by the Director of Clinical Trials Management, and 
Manager of Clinical Research Operations for the Leukemia/Lymphoma Division, 
working with Dr. Ehrhardt or his designee. All protocol-specific data and all grade 3-5 
adverse events will be recorded by the clinical research associates into the CRIS 
database, ideally within 1-2 weeks of completion of study phase (chemotherapy or 
radiation therapy). All questions will be directed to the attending physician and/or PI and 
reviewed at regularly-scheduled working meetings. The attending physicians (or their 
designees) are responsible for keeping up-to-date roadmaps in the patient’s primary 
medical chart.
Regular (at least monthly) summaries of toxicity and protocol events will be generated 
for the PI and study team to review.  
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For collaborating sites, data collection forms will be sent to Matt Ehrhardt, M.D., St. Jude 
Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105-3678; 
 (see Appendix II). Data will be entered into 
the HOD08 database, by a Clinical Research Associate (CRA), within 1-2 weeks of 
receiving the information. For participants seen at St. Jude, data will be entered within 7 
days of the clinical encounter, laboratory test and/or radiological exam.
10.1
On-Study Forms
At the time of patient entry, a HOD08 Registration Form and HOD08 
Registration Sites of Involvement Form.
10.2
During Treatment
After 8 weeks of chemotherapy, a HOD08 Response Assessment Form will be 
completed; after completion of all chemotherapy and radiation therapy, a HOD08 
Off-Therapy Response Assessment Form will be completed.  For patients in CR 
after 8 weeks of chemotherapy the Response Evaluation form will serve as the 
Off-Therapy Response form.
10.3
After Treatment

After completion of all chemotherapy, a HOD08 Treatment Schema, 
HOD08 Toxicity Screening Form and HOD08 Grade III/IV Adverse 
Event/Toxicity/Blood Product Administration Form, if applicable.

After completion of radiation therapy, a HOD08 Radiation Therapy Form 
and Radiation Dose to Site of Involvement Form.

At years 1-10 after completion of therapy, a HOD08 Follow-Up Form for 
Patients in First Remission or Follow-Up after Relapse Form. 

At the time of relapse, death or second tumor, a HOD08 Protocol 
Outcomes Event Form.

At the time a patient is taken off treatment or off study, a HOD08 Off-
Treatment/Off-Study Form.

At year 1, year 2, year 5 and year 10 after completion of therapy, a 
HOD08 Late Organ Function Screening Form For Patients In First 
Remission and a HOD08 Late Effects Follow-Up Form for Patients in 
First Remission.  These evaluations should be performed within 6 months 
of the 1-, 2-, 5- and 10-year Off-Therapy (Post-RT) anniversary date if the 
patient remains on study.  The forms can also be used to provide 
information for patients in first remission, whose off therapy evaluations 
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are performed beyond the 6 month anniversary date as part of good 
clinical care.
10.4
Study Monitoring
This study is considered moderate risk for monitoring purposes. Protocol and 
regulatory compliance, including essential regulatory documentation, will be 
assessed as well as the accuracy and completeness of data points related to the 
primary study objective semi- annually. If the study design has strata, accrual 
will be tracked continuously. The first two enrollees and then 10% of 
participants will be monitored semi-annually.  
The PI and study team are responsible for protocol and regulatory compliance, and 
for data accuracy and completeness.  The study team will meet at appropriate 
intervals to review case histories or quality summaries on participants and retain 
copies of the minutes which are signed by the PI.
The Eligibility Coordinators in the Central Protocol and Data Monitoring Office 
(CPDMO) will verify informed consent documentation of and eligibility status for 
50% of the St. Jude participants within 5 working days of enrollment completion. 
During semi-annual routine monitoring events, the Monitor will verify 
informed consent documentation and eligibility status for 50% of non-St. Jude 
participants as well as perform consent and eligibility verification on 
selected St. Jude enrollments.  Overall study conduct, compliance with 
primary objectives, age of majority consenting, safety assessments and 
reporting, and the timeliness and accuracy of database entries are monitored 
routinely.  
Study documents routinely monitored on selected participants include medical 
records, database entries, study worksheets, and case report forms.  Study 
documents are monitored for participant status, demographics, staging, 
subgroup assignment, treatments, investigational drug accountability, 
evaluations, responses, participant protocol status, off-study and off-therapy 
criteria, and for all other specifics as detailed in a separate study-specific 
monitoring plan. The study-specific monitoring plan may be revised over time, 
to adapt monitoring frequency and/ or intensity to a changing environment 
when appropriate (for example:  new safety signals; positive history of 
compliance; all participants are in long term follow-up; or the enrollment period 
has ended).
The recording and reporting of Adverse Events, Serious Adverse Events (SAEs), 
and Unanticipated Problems (UPs) to include type, grade, attribution, duration, 
timeliness and appropriateness will be reviewed by the Monitor/ CRM. The CRM 
will generate a formal report which is shared with the Principal Investigator (PI), 
study team and the Internal Monitoring Committee (IMC).
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Continuing reviews by the Internal Review Board (IRB) and Scientific Review 
Committee (CT-SRC) will occur at least annually.  In addition, unanticipated 
problems are reviewed in a timely manner by the IRB.
St. Jude affiliates and domestic collaborating study sites will be monitored on-site 
by a representative of St. Jude as needed.  International collaborators will be 
monitored by a Contract Research Organization (CRO), or other mechanism 
according to the study specific monitoring plan.
10.5
Confidentiality
All data will be maintained in a secure, password-protected database accessible 
only by study personnel.
11.0
STATISTICAL CONSIDERATIONS 
 
11.1
Sample Size
With the success of current chemotherapy for Hodgkin lymphoma, one of the 
goals of this protocol is to increase the proportion of favorable risk Hodgkin 
lymphoma patients treated with Stanford V alone that will not require any 
radiotherapy by at least 20% compared to favorable risk patients treated with 
VAMP on HOD99. In HOD 99, 44% (27/62) of favorable risk patients achieved a 
complete response (CR) at 8 weeks after two cycles of VAMP chemotherapy, and 
thus required no radiotherapy. A patient is considered to have achieved complete 
response if all nodal regions of this patient achieve complete responses. A 
historical control design is used to test the hypothesis of a 20% increase (from 
44% to 64%) in the proportion of patients not requiring radiotherapy. The sample 
size was calculated based on a two-sample binomial test with historical control 
group (Makuch and Simon, 1980, implemented in DSTPlan; one-sided test). A 
total of 64 evaluable patients (stage IA nodular lymphocyte predominant 
histology subjects are excluded from the analysis) will be needed for the trial to 
have 80% power with a 5% type I error to detect a 20% increase compared with 
data from the historical HOD99 trial. 
Update 3/14/2013:  Given the recently published data on the impact of 
mechlorethamine drug shortage on children with Hodgkin lymphoma (Metzger et 
al. NEJM 2012), as evaluated on patients treated with a modified Stanford V 
regimen with cyclophosphamide on HOD99 and HOD05, we will substitute all 
participants on HOD08 treated with cyclophosphamide. 
In order to be able to properly prove the primary objective on HOD08 (to increase 
the number of patients in CR after 8 weeks of Stanford V and therefore reducing 
the number of patients requiring radiotherapy,  as well as to have an accurate EFS 
estimate), participants treated with cyclophosphamide will need to be excluded 
from the analysis.
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11.2
Accrual
As of October 2008 (the most recent DSMB report) 72 eligible favorable risk 
patients (excluding stage IA nLP patients) were enrolled on HOD99 over an 
eight-year period (see Table S1) with an average of 8 patients per year.  Based on 
this data, we estimate that the annual accrual rate will be 8 favorable risk patients 
per year and the study will need approximately 8 years to finish accrual. The 
study PI anticipates a yearly accrual of 10 favorable risk patients (see statement 
below) and with such an accrual rate, the duration of the study would be 
approximately 6.5 years.
Update 5/31/13:  By adding the additional 16 participants for the primary 
objective to replace participants treated with cyclophosphamide, the duration of 
the study will be approximately 8.5 years.
Statement regarding accrual from Dr. Matt Ehrhardt: Given the short therapy and 
anticipated low toxicity, we believe that we can attract at least 2 patients per year 
specifically for this protocol. 
Table S1:  Annual accrual rate for favorable risk patients after excluding stage IA 
nLP patients enrolled on HOD99
2000
2001
2002
2003
2004
2005
2006
2007
2008
5
6
7
11
11
6
7
12
7
11.3
Statistical Methods & Analysis
Primary Objective
Objective 1.1.1: To increase the proportion of patients that will not require any 
radiotherapy by at least 20% compared to the favorable risk arm in HOD99
The hypothesis test will be performed for the proportion of patients not requiring 
any radiotherapy (which is equivalent to the complete response (CR) rate) 
compared with the historical control for HOD99 which was 27/62 (44%) by using 
an exact two-sample binominal test. A 95% confidence interval of the complete 
response (CR) rate also will be provided.
Note: patients with stage IA nodular lymphocyte predominant Hodgkin disease do 
not contribute to the primary objective.
Interim analysis for response rate: 
The CR rate will be monitored by a two-stage historical control design71. It gives 
early evidence of the efficacy of the treatment plan.
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This design provides a 5% significance level for testing that the 8-week Stanford 
V chemotherapy regimen achieves at most a 44% CR rate, and 80% power against 
the alternative that Stanford V achieves at least a 64% CR rate. The sample size 
for this study is 64 patients. The study is to be monitored by a group sequential 
approach (Xiong et al.73) with one interim analysis following evaluation of the 
first group of 32 patients (Table S2). If 13 or fewer of these patients have CR after 
8 weeks of chemotherapy, then consideration will be given to closing the study to 
accrual. If 14 or more of the first group of patients have CR after 8 weeks, patient 
accrual will continue until 64 patients have been evaluated for response unless the 
stopping rule of 37 patients not achieving CR is met.     
To make the interim analysis sufficiently flexible to facilitate reporting at DSMB 
meetings, the time frame for interim analysis may be adjusted to the date of the 
DSMB meeting. 
The interim analyses results will be masked to the PI and reported only to the 
DSMB to facilitate their decision making for continuation of patient accrual.
Table S2: Eight-week Stanford V chemotherapy feasibility: two-stage monitoring 
rule based on Xiong’s SCPRT.
Group number 
Group size
Total size
Lower bound (# of patients 
who do not achieve CR)
1
32
32
13
2
32
64
37
Secondary objectives
Note: patients with stage IA nodular lymphocyte predominant Hodgkin disease 
will contribute to all secondary objectives. 
Objective 1.2.1: To estimate the disease failure rate within the radiation fields.
Disease failure within the radiation fields is defined as disease that recurs in the 
initially involved nodal region within the field of irradiation. The disease failure 
rate within the radiation fields will be estimated with a 95% confidence interval 
using appropriate methods (e.g., estimate cumulative incidence in the presence of 
competing risks)
Objective 1.2.2: To examine patterns of treatment failure for children treated with 
tailored field radiation therapy.
In relapsed patients, nodal sites of disease, as well as extra-nodal sites of disease, 
will be evaluated for treatment failure. A local failure is classified as disease that 
recurs in the initially involved nodal region within the field of irradiation; 
otherwise it will be classified as a distant failure. If both failures (local and 
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distant) are observed, it will be treated as a local failure. Bone marrow failure will 
always be classified as a distant site of failure.  Descriptive statistics related to 
local/distant failure will be produced. The cumulative incidence of local failure 
will be estimated and effects of prognostic factors will be examined. Effect of 
competing risks (distant failure, second malignancy and death) will be taken into 
account. Relapse rate within the radiation fields will be estimated and confidence 
interval will also be calculated.
Objective 1.2.3: To describe acute hematologic and infectious toxicities as they 
relate to transfusion requirements, growth factor support, episodes of febrile 
neutropenia and hospitalizations, according to the NCI Common Terminology 
Criteria for Adverse Events (CTCAE), version 3.0. 
The acute hematologic and infectious toxicities will be summarized descriptively.
Objectives 1.2.4 and 1.2.5: To compare the outcome (event-free and overall 
survival distributions and cumulative incidence of local failure) and toxicities of 
favorable risk patients treated with this reduced Stanford V chemotherapy and 
low-dose tailored-field radiation to outcome and toxicities in the favorable risk 
group of HOD99. To compare the event-free survival distributions between 
patients that will not be prescribed radiotherapy after 8 weeks Stanford V and 
those patients on HOD99 that received VAMP without radiotherapy.  
Log-rank tests will be used to compare event-free survival and overall survival. 
Event-free survival will be defined as the time interval from the date of study 
enrollment to the date of first event (relapsed or progressive disease, second 
malignancy, or death from any cause) or to the date of last follow-up for patients 
without events. Survival will be defined as the time interval from study 
enrollment to date of death from any cause or to date of last follow-up. Gray’s test 
will be used to compare the cumulative incidence of local failure between 
favorable risk patients treated on this protocol vs. patients treated on HOD99 and 
other regimens.
Update 3/14/2013: A stratified log-rank test will be used to compare the event-
free survival and overall survival distribution by stratifying patients who received 
cyclophosphamide versus mechlorethamine.
Objective 1.2.6-1.2.7: To estimate the event-free survival distributions of 
favorable risk patients treated with Stanford V chemotherapy alone and patients 
treated with Stanford V chemotherapy plus low dose tailored field radiation.
Event-free survival distributions of favorable risk patients treated with Stanford V 
chemotherapy alone and patients treated with Stanford V chemotherapy plus low 
dose tailored field radiation will be estimated by the Kaplan-Meier method.
  
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11.4
Data Safety Monitoring Board
This study has been referred to the St. Jude Data and Safety Monitoring Board 
(DSMB) for regular monitoring, and will be sent to the DSMB upon approval by 
the St. Jude CPSRMC and IRB.  The DSMB is charged with advising the Director 
and other senior leaders of St. Jude Children’s Research Hospital (SJCRH) on the 
safety of clinical protocols being conducted by SJCRH investigators and on their 
continuing scientific validity.  Refer to the DSMB Charge and Criteria for 
Protocol Referral for more information regarding DSMB review.
12.0
OBTAINING INFORMED CONSENT
The process of obtaining informed consent will follow the institutional guidelines.  
Informed consent will be obtained by the attending physician or his/her designee in the 
presence of at least one witness.  At the time of initial examination, consent will be 
sought for banking of tissue specimens (currently TBANK at St Jude).  After the 
diagnosis is confirmed and the research participant is deemed eligible, we will seek 
consent from the parents or guardians to enroll the research participant on HOD08 
protocol.  
Verbal assent will be obtained from research participants 7 to 14 years old and written 
assent from research participants 14 to 18 years old. Patients 18 years old and older will 
sign for themselves.
12.1
Consent at the Age of Majority
Research participants must be consented at the next clinic visit after reaching age 
of majority.  In the state of TN, this is 18 years old.  At affiliate and collaborating 
sites, research participants must be consented at the age of majority according to 
local laws.
12.2
Consent When English is Not the Primary Language
When English is not the participant, parent, or legally authorized representative’s 
primary language, the Social Work department will determine the need for an 
interpreter. This information will be documented in the participant’s medical 
record. Either a certified interpreter or the telephone interpreter’s service will be 
used to translate the consent information.
 
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 13.0
REFERENCES
(1) Bramswig J, Hornig-Franz I, Riepenhausen M. The challenge of pediatric Hodgkin's 
disease - where is the balance between cure and long-term toxicity?  A report of the 
West German Multicenter Studies DAL-HD-78, DAL-HD-82, DAL-HD-85. Leuk and 
Lymph. 1990;2:183.
(2) Hudson M, Greenwald C, Thompson E et al. Efficacy and toxicity of multiagent 
(COP/ABVD) chemotherapy and low-dose involved-field radiotherapy in children and 
adolescents with Hodgkin's disease. J Clin Oncol. 1993;11:100-108.
(3) Hunger SP, Link MP, Donaldson SS. ABVD/MOPP and low-dose involved-field 
radiotherapy in pediatric Hodgkin's disease: the Stanford experience. J Clin Oncol. 
1994;12:2160-2166.
(4) Hutchinson RJ, Fryer CJ, Davis PC et al. MOPP or radiation in addition to ABVD in 
the treatment of pathologically staged advanced Hodgkin's disease in children: results 
of the Children's Cancer Group Phase III Trial. J Clin Oncol. 1998;16:897-906.
(5) Jenkin D, Chan H, Freedman M et al. Hodgkin's disease in children: treatment results 
with MOPP and low- dose, extended-field irradiation. Cancer Treat Rep. 1982;66:949-
959.
(6) Maity A, Goldwein JW, Lange B, D'Angio GJ. Comparison of high-dose and low-dose 
radiation with and without chemotherapy for children with Hodgkin's disease: an 
analysis of the experience at the Children's Hospital of Philadelphia and the Hospital of 
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chemotherapy in childhood Hodgkin's disease: the experience of the French Society of 
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disease. J Clin Oncol. 2007;25:332-337.
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Disease Who Achieve a Complete Response to Chemotherapy. J Clin Oncol. 
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(15) Ruhl U, Albrecht M, Dieckmann K et al. Response-adapted radiotherapy in the 
treatment of pediatric Hodgkin's disease: an interim report at 5 years of the German 
GPOH-HD 95 trial. Int J Radiat Oncol Biol Phys. 2001;51:1209-1218.
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in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The 
German-Austrian Pediatric Hodgkin's Disease Study Group. J Clin Oncol. 
1999;17:3736-44.
(17) Tebbi CK, Mendenhall N, London WB, Williams JL, de Alarcon PA, Chauvenet AR. 
Treatment of stage I, IIA, IIIA(1) pediatric Hodgkin disease with doxorubicin, 
bleomycin, vincristine and etoposide (DBVE) and radiation: A Pediatric Oncology 
Group (POG) study. Pediatr Blood Cancer. 2005.
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(24) Lange B, Littman P. Management of Hodgkin's disease in children and adolescents. 
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for Hodgkin's disease. J Clin Oncol. 1998;16:3592-600.
(29) Mauch PM, Kalish LA, Marcus KC et al. Long-Term Survival in Hodgkin's Disease. 
Cancer J Sci Am. 1995;1:33.
(30) Wolden SL, Lamborn KR, Cleary SF, Tate DJ, Donaldson SS. Second cancers 
following pediatric Hodgkin's disease. J Clin Oncol. 1998;16:536-44.
(31) Bhatia S, Robison LL, Oberlin O et al. Breast cancer and other second neoplasms after 
childhood Hodgkin's disease. N Engl J Med. 1996;334:745-751.
(32) Beaty O, Hudson M, Greenwald C et al. Subsequent malignancies in children and 
adolescents after treatment for Hodgkin disease. J Clin Oncol. 1995;13:609.
(33) Donaldson SS, Hancock SL. Second cancers after Hodgkin's disease in childhood. N 
Engl J Med. 1996;334:792-794.
(34) Meadows AT, Obringer AC, Marrero O et al. Second malignant neoplasms following 
childhood Hodgkin's disease: treatment and splenectomy as risk factors. Med Pediatr 
Oncol. 1989;17:477-484.
(35) Sankila R, Garwicz S, Olsen JH et al. Risk of subsequent malignant neoplasms among 
1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a 
population-based cohort study in the five Nordic countries. Association of the Nordic 
Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology. J 
Clin Oncol. 1996;14:1442-1446.
(36) Tarbell NJ, Gelber RD, Weinstein HJ, Mauch P. Sex differences in risk of second 
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malignant tumours after Hodgkin's disease in childhood. Lancet. 1993;341:1428-1432.
(37) Baez F, Ocampo E, Conter V et al. Treatment of childhood Hodgkin's disease with 
COPP or COPP-ABV (hybrid) without radiotherapy in Nicaragua. Ann Oncol. 
1997;8:247-50.
(38) Behrendt H, Van Bunningen BN, Van Leeuwen EF. Treatment of Hodgkin's disease in 
children with or without radiotherapy. Cancer. 1987;59:1870-1873.
(39) Ekert H, Fok T, Dalla-Pozza L, Waters K, Smith P, White L. A pilot study of 
EVAP/ABV chemotherapy in 25 newly diagnosed children with Hodgkin's disease. Br 
J Cancer. 1993;67:159-162.
(40) Jacobs P, King HS, Karabus C, Hartley P, Werner D. Hodgkin's disease in children. A 
ten-year experience in South Africa. Cancer. 1984;53:210-213.
(41) Lobo-Sanahuja F, Garcia I, Barrantes JC, Barrantes M, Gonzalez M, Jimenez R. 
Pediatric Hodgkin's disease in Costa Rica: twelve years' experience of primary 
treatment by chemotherapy alone, without staging laparotomy. Med Pediatr Oncol. 
1994;22:398-403.
(42) Olweny CL, Katongole-Mbidde E, Kiire C, Lwanga SK, Magrath I, Ziegler JL. 
Childhood Hodgkin's disease in Uganda: a ten year experience. Cancer. 1978;42:787-
792.
(43) Sackmann-Muriel F, Zubizarreta P, Gallo G et al. Hodgkin disease in children: results 
of a prospective randomized trial in a single institution in Argentina. Med Pediatr 
Oncol. 1997;29:544-552.
(44) Sripada PV, Tenali SG, Vasudevan M, Viswanadhan S, Sriraman D, Kandasamy R. 
Hybrid (COPP/ABV) therapy in childhood Hodgkin's disease: a study of 53 cases 
during 1989-1993 at the Cancer Institute, Madras. Pediatr Hematol Oncol. 
1995;12:333-41.
(45) Van Den BH, Zsiros J, Behrendt H. Treatment of childhood Hodgkin's disease without 
radiotherapy. Ann Oncol. 1997;8 Suppl 1:15-17.
(46) DeVita VT, Jr., Canellos GP, Moxley JH, III. A decade of combination chemotherapy 
of advanced Hodgkin's disease. Cancer. 1972;30:1495-1504.
(47) Coleman CN, Williams CJ, Flint A, Glatstein EJ, Rosenberg SA, Kaplan HS. 
Hematologic neoplasia in patients treated for Hodgkin's disease. N Engl J Med. 
1977;297:1249-1252.
(48) Tucker MA, Meadows AT, Boice JD, Jr. et al. Leukemia after therapy with alkylating 
agents for childhood cancer. J Natl Cancer Inst. 1987;78:459-64.
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(49) Tucker MA, Coleman CN, Cox RS, Varghese A, Rosenberg SA. Risk of second 
cancers after treatment for Hodgkin's disease. N Engl J Med. 1988;318:76-81.
(50) Ortin TT, Shostak CA, Donaldson SS. Gonadal status and reproductive function 
following treatment for Hodgkin's disease in childhood: the Stanford experience. Int J 
Radiat Oncol Biol Phys. 1990;19:873-80.
(51) Bonadonna G. Chemotherapy strategies to improve the control of Hodgkin's disease: 
the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 
1982;42:4309-4320.
(52) Santoro A, Bonadonna G, Valagussa P et al. Long-term results of combined 
chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus 
radiotherapy versus MOPP plus radiotherapy. J Clin Oncol. 1987;5:27-37.
(53) Valagussa P, Santoro A, Fossati BF, Franchi F, Banfi A, Bonadonna G. Absence of 
treatment-induced second neoplasms after ABVD in Hodgkin's disease. Blood. 
1982;59:488-494.
(54) Green DM, Gingell RL, Pearce J, Panahon AM, Ghoorah J. The effect of mediastinal 
irradiation on cardiac function of patients treated during childhood and adolescence for 
Hodgkin's disease. J Clin Oncol. 1987;5:239-45.
(55) Mefferd JM, Donaldson SS, Link MP. Pediatric Hodgkin's disease: pulmonary, cardiac, 
and thyroid function following combined modality therapy. Int J Radiat Oncol Biol 
Phys. 1989;16:679-685.
(56) Klimo P, Connors JM. MOPP/ABV hybrid program: combination chemotherapy based 
on early introduction of seven effective drugs for advanced Hodgkin's disease. J Clin 
Oncol. 1985;3:1174-1182.
(57) Longo DL, Glatstein E, Duffey PL et al. Radiation therapy versus combination 
chemotherapy in the treatment of early-stage Hodgkin's disease: seven-year results of a 
prospective randomized trial. J Clin Oncol. 1991;9:906-917.
(58) Friedmann AM, Hudson MM, Weinstein HJ et al. Treatment of unfavorable childhood 
Hodgkin's disease with VEPA and low-dose, involved-field radiation. J Clin Oncol. 
2002;20:3088-3094.
(59) Schellong G, Bramswig JH, Hornig-Franz I. Treatment of children with Hodgkin's 
disease--results of the German Pediatric Oncology Group. Ann Oncol. 1992;3 Suppl 
4:73-76.
(60) Hodgson DC, Hudson MM, Constine LS. Pediatric hodgkin lymphoma: maximizing 
efficacy and minimizing toxicity. Semin Radiat Oncol. 2007;17:230-242.
(61) Donaldson SS, Hudson MM, Lamborn KR et al. VAMP and low-dose, involved-field 
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radiation for children and adolescents with favorable, early-stage Hodgkin's disease: 
results of a prospective clinical trial. J Clin Oncol. 2002;20:3081-3087.
(62) Hudson MM, Krasin M, Link MP et al. Risk-adapted, combined-modality therapy with 
VAMP/COP and response-based, involved-field radiation for unfavorable pediatric 
Hodgkin's disease. J Clin Oncol. 2004;22:4541-4550.
(63) Horning SJ, Hoppe RT, Breslin S, Bartlett NL, Brown BW, Rosenberg SA. Stanford V 
and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results 
of a prospective clinical trial. J Clin Oncol. 2002;20:630-637.
(64) Advani R, Maeda L, Lavori P et al. Impact of positive positron emission tomography 
on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin's 
disease. J Clin Oncol. 2007;25:3902-3907.
(65) Krasin M, Merchant T, Peterson M, Kun L, Hudson M. Patterns of treatment failure in 
pediatric Hodgkin's disease treated with combined modality therapy. Int J Radiat Oncol 
Biol Phys. 2002;Suppl.
(66) Metzger ML, Howard SC, Hudson MM et al. Natural history of thyroid nodules in 
survivors of pediatric Hodgkin lymphoma. Pediatr Blood Cancer. 2005.
(67) Metzger ML, Hudson MM, Somes GW et al. White race as a risk factor for 
hypothyroidism after treatment for pediatric Hodgkin's lymphoma. J Clin Oncol. 
2006;24:1516-1521.
(68) Merchant TE, Mulhern RK, Krasin MJ et al. Preliminary results from a phase II trial of 
conformal radiation therapy and evaluation of radiation-related CNS effects for 
pediatric patients with localized ependymoma. J Clin Oncol. 2004;22:3156-3162.
(69) Hua C, Gray JM, Merchant TE, Kun LE, Krasin MJ. Treatment planning and delivery 
of external beam radiotherapy for pediatric sarcoma: the St. Jude Children's Research 
Hospital experience. Int J Radiat Oncol Biol Phys. 2008;70:1598-1606.
(70) Dieckmann K, Potter R, Hofmann J, Heinzl H, Wagner W, Schellong G. Does bulky 
disease at diagnosis influence outcome in childhood Hodgkin's disease and require 
higher radiation doses? Results from the German-Austrian Pediatric Multicenter Trial 
DAL-HD-90. Int J Radiat Oncol Biol Phys. 2003;56:644-52.
(71) Xiong X, Tan M, Boyett J. Sequential conditional probability ratio tests for normalized 
test statistic on information time. Biometrics. 2003;59:624-631.
(72) Montoto S, Camos M, Lopez-Guillermo, A, Bosch F, Cervantes F, Blade J, Esteve J, 
Cobo F, Nomdedeu B, Campo E, Montserrat E.  Hybrid chemotherapy consisting of 
Cyclophosphamide, Vincristine, Procarbazine, Prednisone, Doxorubicin, Bleomycin, 
and Vinblastine (C-MOPP/ABV) as first-line treatment for patients with advanced 
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Hodgkin disease. Cancer 2000;88:2142-2148.
(73) Hamilton V, Norris C, Bunin N, Goldwein JW, Bunin GR, Lange B, Meadows AT. 
Cyclophosphamide-based, seven-drug hybrid and low-dose involved field radiation 
for the treatment of childhood and adolescent Hodgkin disease. J Pediatr Hematol 
Oncol 2001;23:84-88.
(74) Sieber M, Tesch H, Pfistner B, Rueffer U, Paulus U, Munker R, Hermann R, 
Doelken G, Koch P, Oertel J, Roller S, Worst P, Bischof H, Glunz A, Greil R, von 
Kalle K, Schalk KP, Hasenclever D, Brosteanu O, Duehmke E, Georgii A, Engert A, 
Loeffler M, Diehl V. On behalf of the German Hodgkin’s Lymphoma Study Group. 
Treatment of advanced Hodgkin’s disease with COPP/ABV/IMEP versus 
COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin’s 
Lymphoma Study Group HD6 trial. Ann Oncol 2004;15:276-282
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APPENDIX I:
ANN ARBOR STAGING CLASSIFICATION FOR HODGKIN'S 
DISEASE
Definition
Stage I
Involvement of a single lymph node region (I) or of a single extralymphatic organ 
or site (IE).
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 one 
or more lymph node regions on the same side of the diaphragm (IIE).
Stage III
Involvement of lymph node regions on both sides on the diaphragm (III) which 
may also be accompanied by involvement of the spleen (IIIS) or by localized 
involvement of an extralymphatic organ or site (IIIE) or both (IIISE).
Stage IV
Diffuse or disseminated involvement of one or more extralymphatic organs or 
tissues, with or without associated lymph node involvement.
The absence or presence of fever >38°C (100.4°F) for three consecutive days, night sweats, 
and/or unexplained loss of 10% of more of body weight in the six months preceding admission 
are to be denoted in all cases by the suffix letters A or B, respectively.
E = extranodal extension
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Appendix II:
HOD 08 FAVORABLE RISK TREATMENT with Nitrogen mustard
SCHEMA    HT _________cm  WT __________kg  BSA _________
Week
Date 
given
Agent
Dose
Agent
Dose
Agent
Dose
Agent
Dose
 1 
_______
_________
Mustard 
(6mg/m2)
________
Adriamycin 
(25mg/m2)
________  
Velban 
(6mg/m2)
________
 2 
_______
_________
*Vincristine 
(1.4mg/m2)
________
Bleomycin 
(5u/m2)
________
 3 
_______
_________
VP-16 
(120 mg/m2)
________
Adriamycin (25 
mg/m2)
________
Velban 
(6mg/m2)
________
 4 
_______
_________
*Vincristine 
(1.4mg/m2)
________
Bleomycin 
(5u/m2)
________
 5 
_______
_________
Mustard 
(6mg/m2)
________
Adriamycin 
(25mg/m2)
________  
Velban 
(6mg/m2)
__________
 6 
_______
_________
*Vincristine 
(1.4mg/m2)
________
Bleomycin 
(5u/m2)
________
 7 
_______
_________
VP-16 
(120 mg/m2)
________
Adriamycin (25 
mg/m2)
________
Velban 
(6mg/m2)
__________
 8 
_______
Prednisone* 
____________  
(40 mg/m2/day divided in 
3 doses,  60 mg max dose 
[20 mg three times daily 
given every other day] x 
8 weeks)       
**Indicate yes/no if 
prednisone received.
_________
*Vincristine 
(1.4mg/m2)
________
Bleomycin 
(5u/m2)
________
*Prednisone 60 mg/day max dose
 *Vincristine 2 mg max dose
**Explain reasons Prednisone not given during each cycle, if applicable. Include dates.
Signature of Primary Attending:____________________________
Date: ____________________________  
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Appendix III: SCHEDULE OF ON AND OFF THERAPY EVALUATION
X = Required study evaluations
O = Evaluations suggested for good patient care.
1CBC obtained pre-therapy during staging does not need to be repeated prior to week 1 of chemotherapy and is else only required prior to weeks 3, 5, 7, and 
response evaluations
2Repeat imaging studies of involved areas.
3LDH, alkaline phosphatase and albumin are required as part of the clinical staging evaluation.
4PET only needs to be repeated if previously positive.
5Post-RT restaging will include diagnostic imaging studies previously positive. 
6For patients achieving a CR at the end 8 weeks of chemotherapy this evaluation will be considered their off therapy evaluation.                                                     
7Obtain PFTs at response evaluation or off therapy.
8 Echocardiogram and EKG as clinically indicated
9Chest radiograph as clinically indicated during therapy and Post-RT for patients with mediastinal disease.
H&P
CBC1
ESR
or
CRP
Chest 
XR
Urine
Pregnancy
UA
Chemistry 
Profile
PFT
ECHO/
EKG
CT
neck & 
chest
CT or MRI 
abdomen & 
pelvis
PET
Panorex and 
dental 
assessment
Pre-therapy
X
X
X
X
X
O
X3
O
O
X
X
X
O
Week 1
X
X
Week 2
O
O
Week 3
X
X
Week 4
O
O
Week 5
X
X
Week 6
O
O
Week 7
X
X
Week 8
Evaluate 
Response6
X
X
X
O
X
X7
X2
X2
X4
Post-
RT/Off 
Therapy
X
X
X
X9
O
O
X7
X8
X5
X5
X5
1 and 2 year 
evaluation
X
X
X
X
X5
X5
O
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Appendix IV:RECOMMENDED SCHEDULE OF OFF THERAPY FOLLOW-UP FOR DISEASE STATUS
      
1 Chest radiograph is recommended as clinically indicated during follow-up for patients with mediastinal disease
         2 Optional
         3 1 and 2 year off therapy CT or MRI, only re-image sites that are positive at diagnosis
Time since End of 
Therapy
H&P
CBC
ESR
or
CRP
CXR1
CT3 
neck/ 
chest
CT or MRI3
abdomen/pelvis
PET2
Scan
3 months
X
X
6 months
X
X
9 months
X
X
1-year-off therapy 
evaluation
X
X
X
X
X
X
O
16 months
X
X
20 months
X
X
2-year off therapy 
evaluation
X
X
X
X
X
X
O
28 months
X
X
32 months
X
X
3 years 
X
X
3 ½ years
X
X
4 years
X
X
4 ½ years
X
X
5 years and yearly   
thereafter
X
X
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Appendix V: RECOMMENDED OFF THERAPY FOLLOW-UP FOR LATE ORGAN TOXICITY
Off Therapy Follow-Up 
for Late Organ Toxicity
Physical Exam1
(includes growth and 
fertility information)
Dental2
ECHO/
EKG
T4/TSH
3
PF
T
Annually
X
X
1-year evaluation
X
X
X
2-year evaluation
X
X
X
5-year evaluation
X
X
X
X
10 -year evaluation
X
X
X
Specific late effects testing should include evaluation of the following organ systems:
1Growth:  physical examination with attention to growth abnormalities of soft tissues and bones.
1Fertility:  Record menstrual cycle and pregnancy information.  Refer men for semen analysis when appropriate.
2Dental: A panorex and dental evaluation at 5 years off therapy is recommended for good clinical practice.
3Thyroid:  Free T4 and TSH annually for patients treated with cervical and upper mediastinal irradiation should be followed 
annually for good clinical practice, but are required only at 1, 2, 5, and 10 years.
Document initiation date for Thyroid hormone replacement therapy, if applicable.
Obtain pathology of second tumors for histological review
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Appendix VI: 
EXAMPLE TAILORED RADIATION THERAPY TREATMENT FIELDS
(case 1)  - Patient with clinical stage IA Hodgkin lymphoma with a PR following 8 weeks of chemotherapy.  Contoured target volumes are shown 
based on the post-chemotherapy residual in the left axilla.  Treatment fields are shaped in 3-dimensions
Dose: 25.5Gy / 1.5Gy fxn
Volume: Initial nodal sites with a 1 cm margin
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APPENDIX VII:
TESTS PERFORMED FOR GOOD CLINICAL CARE

History & Physical Exams

Complete Blood Counts

Chest X-ray

Urine pregnancy test

Blood chemistry profile including electrolytes, BUN, creatinine, bilirubin, alkaline 
phosphatase, SGOT, and SGPT

C-Reactive Protein (CRP) or  erythrocyte sedimentation rate (ESR)

Urinalysis

Thyroid Function Tests

Pulmonary Function Tests

Echocardiogram

EKG
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CT neck and chest with contrast
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CT or MRI abdomen & pelvis with contrast

PET scan
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Referral for sperm cryopreservation for male patients.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00000864
IRB APPROVAL DATE: 10/12/2023