A Safety and Efficacy Trial of Vaccine Boosting With Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected With the GM-CSF Gene for the Treatment of Pancreatic Adenocarcinoma
Phase: PHASE2
Conditions: Pancreatic Cancer
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Cover Page for Protocol – J0619 
NCT Number: 
NCT00389610 
Official title of study 
A Safety and Efficacy Trial of Vaccine Boosting 
with Lethally Irradiated Allogeneic Pancreatic 
Tumor Cells Transfected with the GM-CSF Gene 
for the Treatment of Pancreatic Adenocarcinoma 
Document Date: 
October 7, 2019 

 
1
A Safety and Efficacy Trial of Vaccine Boosting with Lethally Irradiated Allogeneic Pancreatic Tumor Cells 
Transfected with the GM-CSF Gene for the Treatment of Pancreatic Adenocarcinoma 
 
 
Johns Hopkins Protocol #: 
J0619, NA_00002731 
 
IND: 
 
 
 
BB IND 7136 
 
Principal Investigator:  
Daniel Laheru, MD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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-
-
 
 
IND Sponsor:  
 
Elizabeth Jaffee, MD 
 
 
 
Research Nurse: 
 
Beth Onners, RN 
 
 
 
Data Management: 
 
Xiaowei (Nancy) Sun   
   
 
 
Internal Regulatory Affairs:    Xiaowei (Nancy) Sun   
    
 
Jennifer Durham, PhD  
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-
 
 
 
IRB: 
Johns Hopkins Medicine- Institutional Review Board 
         
1620 McElderry St, Reed Hall, Suite B-130, Baltimore, MD 21205-1911 
 
Submitted: February 20, 2006, revised April 12, 2006, revised June 29, 2006 
Amendment #1, Submitted April 21, 2007 
Amendment #2, Submitted October 24, 2007, Revised December 17, 2007 
Amendment #3, Submitted August 5, 2008 
Amendment #4, Submitted May 19, 2009 
Amendment #5, Submitted July 25, 2011 
Amendment #6, Submitted December 3, 2012,  
Amendment #7, October 9, 2018 
Amendment #8, December 13, 2018 
Amendment #9, April 5, 2019 
Amendment #10, October 7, 2019 
 

 
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Table of Contents 
 
Table of Contents .............................................................................................................................. 2 
1.0  
Study Synopsis ....................................................................................................................... 4 
2.0  
Background and Rationale .................................................................................................. 6 
2.1 Introduction ............................................................................................................................. 6 
2.2 Rationale for Cell-Based Immunotherapy of Pancreatic Adenocarcinoma ............................ 6 
2.3 Vaccine-Based Strategies Currently Undergoing Testing in Subjects with Pancreatic 
Adenocarcinoma ..................................................................................................................... 7 
2.4 Rationale for the use of a GM-CSF secreting whole cell vaccine approach .......................... 7 
2.5  Biologic endpoints including pancreas tumor antigens such as mesothelin may serve as in 
vitro predictors of clinical response ........................................................................................ 8 
2.6  Rationale for Including Quality of Life Measurements .......................................................... 9 
2.7  Phase I Study of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected                       
with the GM-CSF Gene. Phase I Study at Johns Hopkins ...................................................... 9 
2.7.1   Summary of Results ....................................................................................................... 10 
2.7.2 
Serum GM-CSF Levels............................................................................................... 10 
2.7.3  
Disease Free Survival ................................................................................................. 11 
2.7.4  
Toxicity Events ........................................................................................................... 11 
2.8 Phase II Study of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected with 
the GM-CSF Gene. ............................................................................................................... 13 
2.8.1  
Preliminary Data ......................................................................................................... 13 
2.8.2  
Early Safety Data ........................................................................................................ 14 
3.0 
Study Design and Treatment Plan..................................................................................... 14 
3.1 Trial Overview ...................................................................................................................... 14 
3.2 Study Population ................................................................................................................... 15 
3.2.1  
Eligibility Criteria ....................................................................................................... 16 
3.2.2 
Inclusion Criteria for the First Vaccination: ............................................................... 16 
3.2.3 
Exclusion Criteria for First Vaccination: .................................................................... 17 
3.2.4 
Inclusion Criteria for Boost Vaccination: ................................................................... 17 
3.2.5 
Exclusion Criteria for Boost Vaccination: .................................................................. 18 
3.3 Vaccine Production ............................................................................................................... 18 
3.4  Study Plan ............................................................................................................................. 21 
3.4.1  
Schedule ...................................................................................................................... 21 
3.4.2  
Leukapheresis ............................................................................................................. 28 
3.4.3  
Evaluation for Safety and Anticipated Toxicities ....................................................... 28 
3.4.4  
Interval Health Care .................................................................................................... 29 
3.4.5  
Continuation of Therapy ............................................................................................. 29 
3.4.6  
Off-study ..................................................................................................................... 30 
3.5  Management of Toxicities .................................................................................................... 30 
4.0  
Statistical Considerations ................................................................................................... 31 
4.1 Sample Size ........................................................................................................................... 31 
4.2 Analysis of Primary Endpoint: Safety and toxicity measurements ...................................... 31 
4.3  Analysis of Secondary Endpoints ......................................................................................... 32 
4.3.1  
Efficacy endpoints ...................................................................................................... 32 
4.3.2  
Relating immune response to clinical response .......................................................... 33 

 
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4.3.3  
Longevity of an allogeneic vaccine ............................................................................ 33 
4.3.4  
Psychosocial and symptom profiles ............................................................................ 33 
5.0  
Response Criteria ................................................................................................................ 34 
5.1 Evaluation of Clinical Activity ............................................................................................. 34 
5.2 Evaluation of Immune Responses ......................................................................................... 34 
5.2.1 
In vitro analysis of induction of antitumor immunity ................................................. 35 
5.2.2 
Biopsy of Vaccine Site................................................................................................ 35 
5.3  Evaluation of psychosocial and symptom responses ............................................................ 35 
6.0 
Adverse and Problem Event Reporting ............................................................................ 37 
6.1. Responsibilities ..................................................................................................................... 37 
6.2. Recording of an Adverse Event ............................................................................................ 38 
6.3.  Reporting Guidelines ............................................................................................................ 39 
7.0 
Clinical Trial Monitoring ................................................................................................... 39 
8.0 
References ............................................................................................................................ 40 
Appendices ....................................................................................................................................... 43 
 

 
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1.0  
Study Synopsis 
 
Objectives: 
 
Primary:  
 
1.  To evaluate the safety of primary and boost vaccinations with lethally irradiated allogeneic 
pancreatic tumor cells transfected with the GM-CSF gene vaccine in the treatment of patients with 
surgically resected adenocarcinoma of the head, neck, or uncinate of the pancreas  
 
Secondary: 
 
1.  To estimate the association of specific in vivo parameters of immune response including, but not 
limited to mesothelin, prostate stem cell antigen (PSCA), and mutated k-ras-specific T cell 
responses, with clinical responses in patients who are receiving semi-annual vaccine boosting with 
lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF gene. 
 
2.  To estimate the efficacy of vaccine boosts in the treatment of patients with adenocarcinoma of 
the pancreas in terms of overall and recurrence free survival. 
 
3.  To use the serum GM-CSF levels as a measure of longevity of an allogeneic vaccine following a 
semi-annual boosting with lethally irradiated allogeneic pancreatic tumor cells transfected with the 
GM-CSF gene. 
 
4.  To determine the psychosocial and symptom profiles of patients with pancreatic cancer treated 
with an irradiated allogeneic GM-CSF secreting vaccine, and to explore changes over time. The 
psychosocial profile will include information about, but is not limited to demographics, quality of 
life, hope, trust, social support, decision control and advanced directives. The symptom profile will 
include but is not limited to pain, anorexia, fatigue, and mood state.  
 
Study population: 
 
In order to be considered for this study, patients need to meet following major criteria for inclusion: 
History of surgically resected pathologic stage 1 (no direct tumor extension beyond pancreas and 
no regional lymph node metastases), 2 (direct extension of tumor beyond pancreas), and/or 3 
(regional lymph node metastases) adenocarcinoma of the head, neck, tail, or uncinate of the 
pancreas.  
Have no radiographic evidence of pancreatic cancer disease recurrence. 
Have not received any anti-cancer therapy in the past 28 days. 
 
Study Design: 
 
Eligible subjects will receive by intradermal administration the pancreatic tumor vaccine consisting 
of two irradiated, allogeneic pancreatic tumor cell lines transfected with the granulocyte 
macrophage-colony stimulating factor (GM-CSF) gene. There will be two cohorts of research 
participants: those who have previously received the pancreatic cancer vaccine (up to 17) and those 

 
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who are vaccine naïve (30-45).   For those patients who have received the vaccine, the boosts will 
be offered as a continuation of care.  For those patients who are vaccine naïve, the feasibility of 
investigating the use of vaccine priming and boosting to prolong disease free status will be tested. 
Up to 100 patients may be consented to obtain the targeted accrual goal. 
 
For research participants who have previously received the pancreatic cancer vaccine, the first 
vaccine boost will be given at least six months after the anniversary date of their last vaccination 
(+/- 30 days). Since the last vaccination date from the parent vaccine study for some subjects has 
occurred more than one year ago, they may establish a new semi-annual dates for vaccine boosting. 
As of Amendment #9, participants will be switched to annual vaccinations. One of the semi-annual 
or annual vaccine boost dates will be the same as their annual long term-follow-up visit date. 
 
For research participants who are vaccine naïve, their first vaccine will be given at least 28 days 
after their last anti-cancer therapy. The vaccine naïve research participant will receive priming 
vaccinations once every month for a total of three vaccines, and then will receive the vaccine 
boosting on a semi-annual basis. As of Amendment #9, participants will be switched to annual 
vaccinations. 
 
The vaccine will be administered once every six months (+/- 30 days) after the previous vaccine 
until the subject no longer meets the eligibility criteria, no longer wishes to participate in the study, 
or the vaccine supply is exhausted. In the event that the eligibility criteria are not met, the subject 
may be re-evaluated if the Principal Investigator anticipates that the research participant may meet 
the eligibility criteria later. As of Amendment #9, participants will be switched to annual 
vaccinations (+/- 30 days). If eligibility is later established, a new anniversary date for vaccine 
boosting and long-term follow-up will also be set as the date of the most recent vaccination.  
 
In the event that a research participant has evidence of persistent vaccine-related responses 
(including, but not limited to: vaccine site flares such as recurrent erythema, induration, and 
pruritus at previous vaccine administration sites; urticaria) occurring at the frequency of more than 
once in the previous three months, the research participant may choose to delay the semi-annual or 
annual boost vaccination for up to one year after the last vaccine-related response. The research 
participant may also choose to continue to receive the semi-annual or annual boost vaccinations per 
protocol with evidence of persistent vaccine-related responses. Research participants experiencing 
urticaria must wait at least one month since the last hive before receiving another vaccine.  
 
Study Drug: 
 
 
 
 
-
 
 
 
 
 
 
 Each vaccination will consist of six total 
intradermal injections, two each in the right and left thighs, and two in the non-dominant arm. In 
the event that the specified limb is contraindicated, the dominant arm may be used.  The vaccine 
consists of equal numbers (2.5 x 108 each) of Panc 6.03 and Panc 10.05 cells.  The combined 5 x 

 
6
108 cells of Panc 6.03 and Panc 10.05 cells will be divided evenly amongst 6 syringes for 
intradermal injection. 
 
2.0  
Background and Rationale 
 
2.1 
Introduction 
 
Pancreatic cancer is the fourth leading cause of all cancer deaths. Although only 33,730 Americans 
are expected be diagnosed with pancreatic cancer, 32,300 will die from pancreatic cancer in 2006 
(American Cancer Society, 2006). Only about 20% of patients diagnosed with pancreatic cancer 
will be eligible for surgical resection with a pancreaticodudectomy, the only potentially curative 
treatment. However, even among those patients who undergo surgery and adjuvant therapy 79% 
will eventually die of recurrent disease (Ahlgren, 1996).  Pancreatic cancer has the most dismal 
prognosis among 18 cancer diagnoses. The statistics for 1995-2000 for the five- year relative 
survival rates for pancreatic cancer by stage are: 4.4% for all stages, 15.2% for localized, 6.8% for 
regional, and 1.8% for distant (American Cancer Society, 2006). Despite significant efforts to 
develop new therapies, locally advanced unresectable disease has a median survival of 10-12 
months and subjects with metastatic pancreatic adenocarcinoma have a median survival of 3-6 
months. While surgical resection is the only curative option, the majority of subjects (80-85%) 
unfortunately present with advanced unresectable disease. These dismal survival rates support the 
development of novel approaches for the treatment of pancreatic cancer.  
 
2.2 
Rationale for Cell-Based Immunotherapy of Pancreatic Adenocarcinoma 
 
Adjuvant chemoradiation with a 5-Fluorouracil (5-FU) containing chemotherapy regime has been 
the gold standard for patients undergoing complete pancreatic cancer resection. However, even the 
most recent studies have demonstrated only modest improvements in disease-free survival 
(Smeenk, Tran, Erdmann, van Eijck, & Jeekel, 2005). Immunotherapy is a potentially therapeutic 
approach to the treatment of pancreatic adenocarcinoma for several reasons. First, immunologic 
killing of tumor cells acts by a mechanism that is distinct from standard chemotherapy and 
radiation therapy, and thus may represent a non-cross resistant treatment modality. Second, the 
immune system is capable of recognizing a broad diversity of potential antigens while orchestrating 
selective and specific cytotoxic responses, two features that may be particularly important in killing 
a heterogeneous tumor population while avoiding normal tissue toxicity.  Third, preclinical animal 
models using a vaccine approach for immunotherapy have been able to eliminate small burdens of 
established tumors, a situation that corresponds to the state of minimal residual disease commonly 
found after resection of human tumors (Burris, Moore, Cripps et al., 1997; Heineman, Quietzsch, 
Giesler et al., 2003). Fourth, a completed Phase I trial evaluating an allogeneic, irradiated, 
granulocyte-macrophage colony stimulating factor (GM-CSF) secreting tumor vaccine in patients 
with adenocarcinoma of the pancreas demonstrated both clinical and immunologic responses 
(Jaffee et al., 2001).  This study, together with the increasing evidence that human tumor-specific 
antigens can be recognized by the immune system, strongly suggests that specific immune 
responses can be generated against pancreatic adenocarcinoma if the immune system is sufficiently 
primed. 
 

 
7
An early analysis of a follow-up 60 patient study testing the safety and efficacy of the highest dose 
of vaccine tested in the above-mentioned phase I study, has shown an 88% one-year survival and a 
78% two-year survival. A proportion of patients from both the phase I and the phase II studies 
remain disease-free. This current trial is designed to test the hypothesis that boosting with an 
allogeneic paracrine cytokine tumor vaccine induces immune responses that are associated with a 
continuous pancreatic cancer free survival.  
 
2.3 
Vaccine-Based Strategies Currently Undergoing Testing in Subjects with Pancreatic 
Adenocarcinoma 
 
There are a number of vaccine approaches that have been tested or are undergoing testing in 
pancreatic cancer subjects. Most of these approaches target one candidate tumor antigen. Such 
targets include: MUC-1, CEA, and mutated k-ras. The approaches used have included 
immunization with HLA class I and class II peptides, immunization with the whole protein, or 
delivery by antibody, heat shock protein or dendritic cells (Apostolopos & McKenzie, 1994; 
Kabayashi, Terao, & Kawashima, 1992; Brossart, Heinrich, & Stuhler, 1999; Apostolopous, 
Karanikas, Haurum et al., 1997; Abrams, Hand, Tsang et al., 1996). To date, these studies have 
demonstrated the induction of T cell responses. Significant clinical responses have not yet been 
observed. This may be due to the lack of potency of these approaches, to the existence of host 
mechanisms of immune tolerance, or both. More recent pre-clinical studies suggest that combined 
vaccine approaches integrating vaccine with immunomodulatory agents are significantly more 
effective than vaccines alone in models of tumor tolerance.  
2.4 
Rationale for the use of a GM-CSF secreting whole cell vaccine approach 
 
We have developed a cytokine secreting tumor vaccine approach that can cure mice of pre-existing 
tumors. This approach is based on the concept that certain cytokines are required at the site of the 
tumor to effectively prime cancer-specific immunity. In the only study to directly compare a large 
number of immune stimulating cytokines, GM-CSF stood out as the most potent cytokine capable 
of inducing systemic anti-tumor immunity when expressed by the tumor cells for the initial 24-72 
hours of immune priming. GM-CSF is now recognized to be the critical growth and differentiation 
factor for dendritic cells, the most potent professional antigen presenting cell responsible for 
priming immune responses against infectious agents and tumor antigens. Both autologous and 
allogeneic GM-CSF secreting vaccines have been tested in phase I and II trials in subjects with 
melanoma, renal cell, prostate, lung, breast and pancreatic cancers. Most of these studies 
demonstrated evidence of immune activation associated with clinical responses in 10-40% of 
treated subjects.  
 
While the use of autologous tumor cells may preserve unique antigens expressed by each subject’s 
cancer, the development of an autologous vaccine requires that extensive processing, in vitro 
expansion, and regulatory testing be performed for each individual subject vaccine. These 
limitations preclude the use of autologous cellular vaccine for most cancers including pancreatic 
adenocarcinoma. A growing body of evidence supports the immunologic rationale for using 
allogeneic tumor cells rather than autologous cells as the source of antigen used for the vaccination. 
First, studies evaluating human melanoma antigens have demonstrated that most of the human 
tumor antigens identified are shared among at least 50% of known human melanoma tumor cell 
lines, regardless of whether or not they share the same human leukocyte antigen (HLA) type (Cox, 

 
8
Skipper, Chen et al., 1994; Kawakami, Eliyahu, & Delago, 1994).  In addition, there is now both 
pre-clinical and human data in pancreatic cancer subjects treated with a GM-CSF vaccine to 
support host derived professional antigen presenting cells (APCs) as the critical cells required to 
present immunogen to T cells in the context of MHC (Dranoff, Jaffee, Golumbek et al., 1993; 
Jaffee, Hruban, Biedrzycki et al, 2001; Thomas, Santarsiero, Lutz et al., 2004).  Therefore, the 
vaccine cells do not need to be HLA compatible with the host’s immune system as long as they can 
release cellular proteins (the tumor antigens) for uptake by professional APCs (macrophages and 
dendritic cells) that are attracted to the vaccine site by GM-CSF.  Taken together, the data suggest 
that relevant tumor antigens can be delivered by an allogeneic tumor and still sufficiently mount an 
effective immune response.  
 
Two allogeneic cell lines have been developed from neoplastic tissue harvested from the surgical 
specimens of subjects undergoing pancreaticoduodenectomy at The Johns Hopkins Hospital. These 
cell lines have been characterized as 100% epithelial by cytokeratin staining (Jaffee, Abrams, 
Cameron et al., 1998). In addition, these cell lines carry the same k-ras mutation as the original 
tumor specimen that supports the conclusion that these lines are derived from malignant pancreatic 
tumor cells. The cell lines Panc 10.05 and Panc 6.03 both contain the most common k-ras mutation 
at codon 12 found in greater than 90% of pancreatic cancer. These lines secrete GM-CSF at 80-90 
ng/ 106 cells/ 24 hrs for up to 5 days in culture (Jaffee, Abrams, Cameron et al., 1998; Jaffee, 
Drandoff, Cohen et al., 1993). These lines have undergone extensive regulatory testing and have 
been shown to maintain GM-CSF secretion, MHC class I levels, cytokeratin positive staining and 
the original K-ras mutation (Jaffee, Abrams, Cameron et al., 1998). These lines also express 2 new 
immunogenic pancreatic tumor antigens, mesothelin and PSCA. These lines have already been 
demonstrated to be safe and feasible to produce and administer in a phase I and two phase II studies 
in both the adjuvant and metastatic setting. The clinical lots for this study will be produced in the 
Johns Hopkins GMP Cell and Gene Therapy facility. 
 
2.5  
Biologic endpoints including pancreas tumor antigens such as mesothelin may serve as 
in vitro predictors of clinical response 
 
The major limitation to developing cancer vaccines has been the lack of identified pancreatic tumor 
antigens that are the known targets of the immune response.  As such, current immune based 
approaches either target a small group of candidate antigens expressed by the tumor or rely on 
whole tumor cells as the immunogen.  However, with the recent sequencing of the human genome 
and the development of rapid methods for identifying genes that are differentially expressed by 
tumor cells (Iacobuzio-Donahue, Maitra, Shen-Ong et al., 2002), potential candidate immune 
targets are being discovered that may serve as immunogens for treatment as well as prevention.  
Recently, mesothelin, a transmembrane glycoprotein member of the mesothelin/megakaryocyte 
potentiating factor (MPF) family was identified by differential gene expression to be over-
expressed by most pancreatic adenocarcinomas (Argani, Iacobuzio-Donahue, Ryu et al., 2001). 
More recently, mesothelin has been shown to be recognized by vaccinated uncultured CD8+ T cells 
isolated from the three subjects who are long-term survivors from the previously described phase I 
GM-CSF pancreatic cancer vaccine study but not in the other subjects who received the vaccine but 
subsequently relapsed (Thomas, Santarsiero, Lutz et al., 2004). These data suggest that mesothelin 
may serve as an in vitro marker of vaccine induced T cell responses.  
 

 
9
 
 
2.6  
Rationale for Including Quality of Life Measurements 
 
The significance of cancer survivorship and quality of life (QoL) has recently come to the forefront 
with the Institute of Medicine’s (IOM) report (2005a). The IOM indicates “Survival rates are 
increasing, but no one knows at what cost to the health and well-being of cancer survivors.” (IOM, 
page 1, 2005b). 
 
Of the 33,730 Americans who are diagnosed each year with pancreatic cancer (American Cancer 
Society, 2006), those who are eligible for surgery are the most fortunate. While surgical resection is 
the only curative option, the majority (80-85%) have advanced unresectable disease at the time of 
diagnosis. Those patients who are eligible for surgical resection have a median survival of 18 
months for pancreatic adenocarcinoma (Yeo et al., 1997) to 24 months for all malignant pancreas 
tumors (Billings et al., 2005).  The threat of recurrence is real with many people having disease 
recurrence one year after surgery. The American Cancer Society’s surveillance research indicates 
that the five-year survival for local pancreatic cancer is only 16%, and for all stages combined 5% 
(ACS, 2006). Overall, pancreatic cancer is one of, if not the most, feared cancers due to its dismal 
prognosis.  
 
The impact of this ever-present threat of recurrence and uncertainty on health and QoL is under-
researched. Recent studies have explored the long-term health consequences of some cancers, 
including head and neck (Mehanna & Morton, 2006), cervical (Wenzel et al., 2005), and breast 
cancer (Schou, Ekeberg, Sandvik, Hjermstad, & Ruland, 2005).  However, the QoL and the health 
consequences of living with a cancer that is usually rapidly fatal are relatively unknown. 
 
While cancer is the most ominous threat, other chronic conditions, such as diabetes that is 
surgically induced with a total pancreatectomy, may also impact the patient with pancreatic cancer. 
Billings (2005) surveyed a sample of 27 patients who had undergone a total pancreatectomy for 
either a benign and malignant pathology, and reported that their QoL was decreased compared to 
age and gender specific samples, but was similar to other people with diabetes.    
 
This study will include past participants of the phase I and II pancreatic cancer vaccine research 
studies, as well as pancreatic cancer survivors who are pancreatic cancer vaccine naïve. There are 
three participants from the phase I study who remain pancreatic cancer free for more than eight 
years after diagnosis, including a working senior 72 years of age. While we believe that the 
pancreatic cancer survivors have good QoL we have yet to evaluate this with scientific rigor. 
Through qualitative research, Dr. D. Fitzsimmons found general consistencies between the 
perceptions of health care professionals and patients on QoL, but also noted differences (1999). 
Health care professionals think about QoL from a mechanistic view, focusing on the symptom 
impact, while patients incorporate coping as an essential component of their QoL (Fitzsimmons, 
George, Payne, & Johnson, 1999). 
 
2.7  
Phase I Study of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected                       
with the GM-CSF Gene. Phase I Study at Johns Hopkins 
 

 
10
 
2.7.1   Summary of Results 
 
This study was the first clinical trial to test the hypothesis that allogeneic GM-CSF secreting 
pancreatic tumor cell lines can prime a systemic immune response in subjects with resected 
pancreatic adenocarcinoma. Fourteen subjects with stage 2 or 3 disease received an initial 
vaccination 8 weeks following resection. This was a dose escalation study in which 3 subjects each 
received 1 X 107, 5 X 107, and 1 X 108 vaccine cells.  An additional 5 subjects received 5 X 108 
vaccine cells.  Study subjects were jointly enrolled in an adjuvant chemoradiation protocol for 6 
months. Following the completion of adjuvant chemoradiation, subjects were re-assessed and those 
who were still in remission were treated with 3 additional vaccinations given one month apart at the 
same original dose that they received for the first vaccination. Toxicities were limited to grade I/II 
local reactions at the vaccine site, and self-limited systemic rashes, including one documented case 
of Grover's syndrome (Davis, Dineen, Landa et al., 1999).  Systemic GM-CSF levels were 
evaluated as an indirect measure of the longevity of vaccine cells at the immunizing site. As was 
observed in pre-clinical studies, GM-CSF levels peaked at 48 hours following vaccination.  In 
addition, serum GM- CSF levels could be detected for up to 96 hours following vaccination. These 
data, together with data from pre-clinical models, would suggest that detectable serum GM-CSF 
levels may serve as a bio-marker of immune response.  The vaccine sites were also evaluated as a 
measure of the local immune reaction to the vaccine. Eleven of 14 subjects demonstrated a similar 
local inflammatory response to what has been observed in pre-clinical models and autologous GM-
CSF vaccine clinical trials. Post-vaccination DTH responses to autologous tumor cells have been 
used in previously reported vaccine studies as a surrogate to identify and characterize specific 
immune responses that are associated with vaccination. In the pancreatic cancer vaccine trial, post-
vaccination DTH responses to autologous tumor cells were observed in 1 of 3 subjects receiving 1 
X 108 and in 2 of 5 subjects receiving 5 X 108 vaccine cells. Three long-term survivors of the initial 
phase I study are currently participants in the long-term follow-up study (IRB application number 
NA_00036444, J0248), remain disease-free and have expressed an interest in receiving additional 
vaccinations. No additional long-term toxicities have been uncovered in this cohort. 
 
An ongoing Phase II clinical trial of the pancreatic cancer vaccine in subjects with operable 
pancreatic cancer who receive the vaccine after surgical resection of tumor and adjuvant radiation 
chemotherapy is currently being conducted at Johns Hopkins. The study recently completed 
enrollment of the 60 planned subjects. The toxicities associated with the vaccine in this study 
include: local vaccine site skin reactions and systemic rashes similar in severity (grade 1-2) to what 
was observed in the phase I trial.  
 
2.7.2 Serum GM-CSF Levels 
 
Serum GM-CSF levels were measured in the patients participating in the first pancreatic tumor 
vaccine study at time 0, 24, 48, 72, 96 and 120 hours following the first vaccine. The peak 
concentration of serum GM-CSF levels was seen at 48 hours in 83% (5/6) of the patients who 
achieved a measurable serum GM-CSF level.  Only one patient who received dose level one had a 
measurable serum GM-CSF level at a minimum level of 1.0 pg/ml at 48 hours. There was no 
measurable serum GM-CSF level in any of the six patients who received dose levels two and three 
at any time point. All five patients who received dose level four had measurable serum GM-CSF 

 
11
levels with the range of 1.2 to 14.0 pg/ml. GM-CSF levels became undetectable by 120 hours in all 
patients on study. No side effects other than asymptomatic eosinophilia were associated with these 
low but detectable serum GM-CSF levels. 
 
2.7.3  Disease Free Survival 
 
There are three patients who participated in the original study who remain pancreatic cancer disease 
free. The pancreatic cancer disease free survival of patients is defined as the time interval from date 
of diagnosis with adenocarcinoma of the pancreas to the date of radiographic evidence of disease 
recurrence. Only 14 of the 15 patients who participated in this trial were considered for the disease-
free analysis, as one patient had stage 4 disease with liver metastasis prior to entering the study.  An 
increase in the disease-free survival was associated with increasing total vaccine dose, which is 
equal to the dose level of cells multiplied by the number of doses, received. Using the 
nonparametric correlation of Spearman’s rho the association of total pancreatic tumor vaccine dose 
and disease free survival is statistically significant (p=0.028).  
 
Study participants had a 43% (6/14) one year disease free survival and 86% (12/14) one year 
overall survival. 
 
 
  
 
2.7.4  Toxicity Events 
 
The most frequently occurring toxicities of the vaccine were injection site reactions. See Table 1 
for a summary of the toxicities. All were grade 1 or 2 by the National Cancer Institute (NCI) 
Common Toxicity Criteria. The total number of injection site reactions in the phase I allogeneic 
pancreatic tumor vaccine study was 28 out of 30 (93%) vaccine treatments. Patients who received 
the second, third, and fourth dose levels of the allogeneic pancreatic tumor vaccine all had grade 2 
injection site reactions. Of these grade 2 injection site reactions all had erythema and induration, 
with 69% (18/26) of the injection site reactions also having local pruritus at the vaccine sites. One 
patient experienced tenderness at the vaccine sites lasting up to three days after the first and third 
vaccine at dose level four. The patient required no analgesics. All injection site reactions were self-
limiting and no one had any limitations on their activities of daily living related to these local signs 
and symptoms. Sixty-four percent (18/28) of the injection site reactions completely resolved within 
a week. Sixty-nine percent (9/13) of the patients who experienced injection site reactions were free 
of all local toxicities within a week. Thirty-one percent (4/13) of the patients experienced injection 
site reactions lasting more than a week with pruritus at the injection sites being the symptom of 
longest duration, lasting up to 41 days. Two of the four patients with the lengthy local toxicities 
also experienced systemic pruritus and rash. One of which was confirmed by biopsy to be Grover’s 
Syndrome. The other person with the systemic rash and pruritus did not have a skin biopsy at that 
time. The same patient who experienced the Grover’s Syndrome also developed recurrent swelling 
at the vaccine sites at that time which was seven to ten days after the second vaccine at level 4. 
After the third vaccine, this patient also had grade 1 lymphedema with erythema and swelling in the 
lymph drainage areas, particularly in the upper right extremity where two or the six vaccines were 
administered. 
 

 
12
 
Systemic toxicities included: Grade 1 musculoskeletal stiffness and generalized pruritus lasting two 
hours. One patient on dose level 3 experienced acute anemia (hemoglobin dropped to 6.3 gm/dl), 
thrombocytopenia (platelets dropped to 5,800/mm3), asymptomatic jaundice (total bilirubin 
increased to 9.8 mg/dl, direct bilirubin to 7.8 gm/dl). This occurred approximately six weeks after 
completing Mitomycin-C containing chemotherapy.  There was also asymptomatic anemia with 
hematocrit nadir of 19.8 %, hemoglobin nadir 6.6 g/dl and asymptomatic thrombocytopenia with 
platelet nadir of 77,000 / mm3 during the chemotherapy course which included Fluorouracil (5-FU), 
Leucovorin, Mitomycin-C, and Dipyridamole (Persantine) prior to this event. Therefore, these 
adverse events were consistent with Mitomycin-C associated thrombocytopenic purpura (TTP). 
Twenty-four days after second vaccine at dose level three, and seven days after the blood 
transfusions, the same person experienced a grand mal seizure. It is unlikely that this adverse event 
is related to the vaccine. After receiving the vaccine this patient developed symptoms that have 
since been attributed to thrombotic thrombocytopenic purpura (TTP). Although we believe this 
condition was due to the Mitomycin-C treatment completed one month previously, this was 
reported to the IRB as a possible adverse event due to the temporal proximity to immunization with 
the vaccine. The patient was taken off study. The patient’s condition improved, the symptoms of 
TTP resolved, and the patient remains in complete remission at this time. This adverse event has 
not recurred on the 60 patient follow-up vaccine study. 
 
With dose level four, 50% (3/6) patients experienced a systemic reaction. One patient experienced 
grade 1 constitutional symptom of fatigue and grade 1 musculoskeletal, and achy joints.  
Another patient on vaccine dose level 4 experienced multiple vaccine related symptomatic 
toxicities, including: a grade 2 rash, systemic pruritus, and Grover’s Syndrome, a grade 1 urticaria, 
and a grade 1 recall induration at the vaccine sites.  
 
Table 1.   Toxicity Events Associated with Phase I Allogeneic Pancreatic Tumor Vaccine 
 
Total of thirty evaluated vaccine treatments.   (Number of patients experiencing the toxicity) 
Local Toxicities 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Erythema at vaccine sites 
     1a  (1)  
  26a,b,c,d (12) 
 
 
Induration at vaccine site 
 
  26a,b,c,d (12) 
 
 
Pruritus at vaccine sites 
     1b  (1) 
  18a,b,c,d (11) 
 
 
Tenderness at vaccine sites 
       
    2d (1) 
 
 
Recall induration at vaccine 
sites 
     1d  (1) 
       
 
 
Lymphedema 
of 
one 
extremity 
     1d  (1) 
 
 
 
 
Systemic Toxicities 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Pruritus (not vaccine sites) 
 
     3b,d (3) 
 
 
Urticaria 
 
     1d  (1) 
 
 
Skin rash  
 
     2d,e (2) 
 
 
Joint stiffness/achy 
     2b,d  (2) 
 
 
 
Fatigue 
     1d  (1) 
 
 
 
Otherf 
 
 
    1c,f (1) 
    1c,f (1) 

 
13
 
N=15 patients 
 
a   Occurred after dose level one of  1 x 107 cells. 
b  Occurred after dose level two of 5.10 x 107 cells.  
c   Occurred after dose level three of 1.08 x 108  cells. 
d  Occurred after dose level four of 5.04 x 108 cells. 
e   One rash was biopsied to reveal Grover’s syndrome.  
f   After receiving dose level three of 1.08 x 108  cells, one patient experienced Grade 2 
thrombocytopenia, Grade 2 elevated SGOT (AST), Grade 3 seizure, Grade 3 anemia, Grade 3 
elevated SGPT (ALT), Grade 3 elevated bilirubin. The symptoms have been attributed to 
thrombotic thrombocytopenia purpura (TTP). Although we believe this condition was due to the 
Mitomycin treatment that was completed one month earlier, this was reported to the IRB as a 
possible adverse event unlikely to be related to the vaccine. The patient was taken off study. The 
patient’s condition improved, symptoms of TTP have resolved, and the patient remains in complete 
remission. 
 
2.8 
Phase II Study of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected 
with the GM-CSF Gene.  
 
2.8.1  Preliminary Data 
 
Sixty research participants received at least one and a maximum of five vaccinations of two 
pancreatic cancer cell lines each delivering 2.5 x 108 cells intradermally distributed among three 
lymph node regions in the Johns Hopkins study, IRB # 00-01-13-02 (SKCCC J9988) entitled, A 
safety and efficacy trial of lethally irradiated allogeneic pancreatic tumor cells transfected with the 
GM-CSF gene in combination with adjuvant chemoradiotherapy for the treatment of 
adenocarcinoma of the pancreas. See Table 2 for the demographic details. Vaccine one was 
administered 8-10 weeks following surgical resection. Patients were subsequently treated with 5-
fluoruracil (5-FU) continuous infusion based chemotherapy integrated with radiotherapy. Research 
participants who remained disease-free one month after completing the chemoradiotherapy 
received the vaccines two through four one month apart. A fifth and final vaccine was administered 
six months after the fourth vaccine. 
 
Table 2. Research Participants’ Demographic Data 
 
Characteristic 
N=60 
Male 
37 
Female 
23 
Median age 
56.7 
Age range 
41-83 
Node + 
52 
Margin + 
18 
Node + and Margin + 
18 
 
 

 
14
 
Enrollment was completed in January of 2005. At an early analysis, 56 patients were evaluable at 
one year and 36 patients were evaluable at two years. The one and two year survival rates are 88% 
and 76%, respectively. This data compares very favorably with the available published data. 
 
2.8.2  Early Safety Data 
 
Based on an early analysis if the data we conclude that the administration of the GM-CSF 
allogeneic cancer vaccine is safe and well tolerated. Treatment related side effects were similar to 
those side effects seen in the phase I study. The most common side effects were local responses of 
transient vaccine injection site reactions of induration and erythema in all research participants 
while some people had also transient vaccine injection site reactions of tenderness and pruritus. The 
systemic reactions included transient elevation in eosinophil counts, rashes and flu-like symptoms 
that have included low grade fever, chills, malaise, arthralgias, myalgias, and fatigue. Most patients 
have a transient elevation in their eosinophil count. All vaccine related toxicities have been on the 
same intensity and duration as those seen in the phase I study. 
 
3.0 
Study Design and Treatment Plan 
 
3.1 
Trial Overview 
 
This vaccine boost trial will evaluate an equal mixture of two allogeneic GM-CSF secreting 
pancreatic vaccine cell lines Panc 10.05 and Panc 6.03 for:  (1) safety of administration, (2) 
induction of antitumor immune responses, and (3) disease-free and overall survival in patients with 
resected adenocarcinoma of the head, neck, tail, or uncinate of the pancreas. Candidates for this 
study have either: 1) previously been treated at Johns Hopkins with the allogeneic GM-CSF 
secreting pancreatic cell lines Panc 10.05 and Panc 6.03 per protocol application number 96-01-25-
01 entitled “A Phase I Clinical Trial of Lethally Irradiated Allogeneic Pancreatic Tumor Cells 
Transfected with the GM-CSF Gene for the Treatment of Adenocarcinoma of the Pancreas”, 
SKCCC J9617, or protocol application number 00-01-13-02, entitled “A Safety and Efficacy Trial 
of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected with the GM-CSF Gene in 
Combination with Adjuvant Chemoradiotherapy for the Treatment of Adenocarcinoma of the 
Pancreas”, SKCCC J9988; or, 2) received other adjuvant chemoradiation and are now interested in 
participating in a vaccine study. All patients must meet the eligibility criteria including having no 
radiographic evidence of disease recurrence at the first vaccination and every semi-annual 
vaccination. As of Amendment #9, participants will be switched to annual vaccinations. 
 
In this study research participants will receive 5 x 108 cells of a equal mixture of two allogeneic 
GM-CSF secreting pancreatic vaccine cell lines Panc 10.05 and Panc 6.03 divided into six 
intradermal injections every year until there is radiographic evidence of disease recurrence, 
toxicities occur, or the vaccine supply is exhausted. This is the same dose found to be safe and to 
induce immune responses in the phase I study, and has been shown to be safe in the follow-up of 60 
patients in the phase II study. For research participants who had previously received the pancreatic 
cancer vaccine, one of the semi- annual vaccination boost dates will be the same as the annual 
follow-up date per protocol application number NA_00036444 (SKCCC J0248), entitled “Long 
term follow-up of patients who received lethally irradiated pancreatic tumor cells transfected with 

 
15
the GM-CSF gene.” Assessments and tests included in the long term follow-up will not be 
duplicated if included in this protocol.  
 
3.2 
Study Population 
 
Patients with surgically resected pathologic stage 1 (no direct tumor extension beyond pancreas and 
no regional lymph node metastases), 2 (direct extension of tumor beyond pancreas), and/or 3 
(regional lymph node metastases) adenocarcinoma of the head, neck, tail, or uncinate of the 
pancreas and who have no radiographic evidence of pancreatic cancer disease recurrence may be 
eligible to participate in this study.  
 
There will be two cohorts of research participants: those who have previously received the 
pancreatic cancer vaccine (no more than 17) and those who are vaccine naïve (30-45). At the time 
of the initial application of this study there appeared to be 18 research participants of previous 
pancreatic cancer vaccine studies who may have been eligible for this study. This includes three 
research participants from the Phase I study and 1 research participants who have completed the 
protocol-specified vaccines in the Phase II study. Also in this study we estimate enrolling between 
30 and 45 research participants who are pancreatic cancer vaccine naïve. Both cohorts of research 
participants will need to be off all anti-cancer therapy for at least 28 days. It is estimated that we 
may need to consent up to 100 patients to obtain the targeted accrual goal. 
 
For research participants who have previously received the pancreatic cancer vaccine, the first 
vaccine boost will be given at least six months after the anniversary date of the off-study visit (+/- 
30 days). Since the off-study date from the parent vaccine study may have occurred more than one 
year ago, new semi-annual dates for vaccine boosting may be established. For research participants 
who are vaccine naïve, their first vaccine will be given at least 28 days after their last adjuvant anti-
cancer therapy.  
 
One of the semi-annual vaccine boost dates will be the same as their annual long term-follow-up 
visit date. Subsequent vaccine boosts will be administered every six months (+/- 30 days) after the 
previous vaccine until the subject no longer meets the eligibility criteria, no longer wishes to 
participate in the study, or the vaccine supply is exhausted. As of Amendment #9, participants will 
be switched to annual vaccinations (+/- 30 days). In the event that the eligibility criteria are not 
met, the subject may be re-evaluated if the Principal Investigator anticipates that the research 
participant may later meet the eligibility criteria. There is no time limit. If eligibility is later 
established, semi-annual or annual dates for vaccine boosting and long term follow-up will be re-
set as the date of the most recent vaccination. 
 
In the event that a research participant has evidence of persistent vaccine-related responses 
(including, but not limited to: vaccine site flares such as recurrent erythema, induration, and 
pruritus at previous vaccine administration sites; urticaria) occurring at the frequency of more than 
once in the previous three months, the research participant may choose to delay the semi-annual or 
annual boost vaccination for up to one year after the last vaccine-related response. The research 
participant may also choose to continue to receive the semi-annual or annual boost vaccinations per 
protocol with evidence of persistent vaccine-related responses. Research participants experiencing 
urticaria must wait at least one month since the last hive before receiving another vaccine.  

 
16
 
3.2.1  Eligibility Criteria 
 
Eligibility to receive a vaccination must be determined with the first vaccination (section 3.2.2. and 
3.2.3) and then again with each semi-annual or annual boost vaccination (section 3.2.4 and 3.2.5.) 
by the Principal Investigator or his designee prior to the administration of the research product. 
There will be no re-evaluation of eligibility for the second and third priming vaccines for the 
vaccine naïve cohort. 
 
If the patient does not initially meet the eligibility requirements, the criterion that is not met may be 
re-evaluated within four weeks of the planned vaccination date without repeating all other 
screening criteria. In the event that eligibility is not met within four weeks of the planned 
vaccination date, all screening criteria must be re-evaluated. 
 
If the eligibility criteria for vaccination are not met the research participant may be re-evaluated if 
the Principal Investigator anticipates that the research participant may later meet the eligibility 
criteria. There is no time limit. If vaccination eligibility is later established, new semi-annual or 
annual dates for vaccine boosting and long term follow-up will be re-set as the date of the most 
recent vaccination. 
 
In the event that a priming or boost vaccination is not given as scheduled due to health issues 
(examples include but are not limited to infection or inflammatory process) or other reasons beyond 
the control of the research participant (examples include but are not limited to inclement weather 
and serious illness or death within the family) the vaccination may be delayed for up to three 
weeks. If an extension longer than three weeks is needed, the IRB will be consulted for a protocol 
exemption.  
 
3.2.2 Inclusion Criteria for the First Vaccination: 
 
Research participants must meet the following criteria. 
 
1. Have a history of surgically resected pathologic stage 1 (no direct tumor extension beyond 
pancreas and no regional lymph node metastases), 2 (direct extension of tumor beyond 
pancreas), and/or 3 (regional lymph node metastases) adenocarcinoma of the head, neck, 
tail, or uncinate of the pancreas.  
 
2.  Received the last lethally irradiated GM-CSF transfected allogeneic pancreatic cell lines 
Panc 10.05 and Panc 6.03 as a participant in either one of the Hopkins IRB protocols: 
application number 96-01-25-01 entitled “A Phase I Clinical Trial of Lethally Irradiated 
Allogeneic Pancreatic Tumor Cells Transfected with the GM-CSF Gene for the Treatment 
of Adenocarcinoma of the Pancreas”, SKCCC J9617, or application number 00-01-13-02, 
entitled “A Safety and Efficacy Trial of Lethally Irradiated Allogeneic Pancreatic Tumor 
Cells 
Transfected 
with 
the 
GM-CSF 
Gene 
in 
Combination 
with 
Adjuvant 
Chemoradiotherapy for the Treatment of Adenocarcinoma of the Pancreas”, SKCCC J9988, 
at least 6 months ago; 
 
OR 

 
17
Completed surgery and any adjuvant therapy at least 28 days prior. Treatment administered 
in conjunction with surgery is at the discretion of the local oncologists. Options may 
include: neo-adjuvant chemotherapy, neo-adjuvant radiation, post-surgical adjuvant 
chemotherapy, post-surgical adjuvant radiation. 
  
3.   Received the last anti-cancer therapy at least 28 days ago. 
 
4.   Provide informed consent. 
 
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 
 
6. Have adequate hematologic function (Hemoglobin ≥ 9 gm/dl, ANC ≥ 1500 #/cu mm,  
platelets ≥100,000 K/cu mm) 
 
7.   Have adequate renal function (Serum creatinine ≤ 2 mg/dL). 
 
8.   Have adequate hepatic function  (Bilirubin ≤ 2.0 mg/dL, unless known Gilbert's Syndrome;  
AST, ALT and amylase ≤ 2x upper limit of normal:  Alk Phos ≤ 5x upper limit of normal.) 
  
9. Agree to use adequate birth control, if of childbearing potential. 
 
3.2.3 Exclusion Criteria for First Vaccination: 
 
Research participants with any of the following will be excluded from study entry: 
 
1. Radiographical evidence of pancreatic cancer disease recurrence. 
 
2. Documented history of autoimmune diseases including systemic lupus erythematosus, 
sarcoidosis, rheumatoid arthritis, glomerulonephritis, or vasculitis. 
 
3.    Uncontrolled medical problems. 
 
4.    Systemic steroid therapy within 28 days before vaccine administration. 
 
5.    Anticipated need for systemic steroid therapy within 28 days after vaccine administration. 
 
6.    Evidence of active infections. 
 
7.    Pregnant. 
 
8.  History of another cancer (other than pancreatic cancer) in the past five years except for 
treated non-melanoma skin cancer, superficial bladder cancer, or carcinoma-in-situ of the 
cervix.   
 
3.2.4 Inclusion Criteria for Boost Vaccination: 
 

 
18
Research participants must meet the following criteria. 
 
1.  Received the last lethally irradiated GM-CSF transfected allogeneic pancreatic cell lines 
Panc 10.05 and Panc 6.03 at least 12 months prior (+/- 30 days). 
 
2. 
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 
 
3. 
Have adequate hematologic function (Hemoglobin ≥ 9 gm/dl, ANC ≥ 1500,/cu mm,      
platelets ≥100,000/cu mm) 
 
4.   Have adequate renal function (Serum creatinine ≤ 2 mg/dl). 
 
5.    Have adequate hepatic function (Bilirubin ≤ 2.0 mg/dl, unless known Gilbert's Syndrome;     
       AST, ALT and amylase ≤ 2x upper limit of normal:  Alk Phos ≤ 5x upper limit of normal.) 
  
6. 
Agree to use adequate birth control, if of childbearing potential. 
 
3.2.5 Exclusion Criteria for Boost Vaccination: 
 
Patients with any of the following will be excluded from study entry or will not be able to continue: 
 
1. Radiographical evidence of pancreatic cancer disease recurrence. 
 
2. Documented history of autoimmune diseases including systemic lupus erythematosus, 
sarcoidosis, rheumatoid arthritis, glomerulonephritis, or vasculitis. 
 
3.    Uncontrolled medical problems. 
 
4.   Systemic steroid therapy within 28 days before vaccine administration (except for short-
term steroid therapy ending at least two days prior to vaccine administration). 
 
5.    Anticipated need for systemic steroid therapy within 28 days after vaccine administration. 
 
6.    Evidence of active infections. 
 
7.    Pregnant. 
 
3.3 
Vaccine Production 
 
 
 
 
 
 
 
 
-
 
 

 
19
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
-
  
 
-
  
  
 
  
 
  
  
  
 
  
 
  

 
20
- -
- -
-
  
  
 
-
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
  
 
   
 
 
 
  
 
 
   
 
Vaccine Administration 
 
 
 
 
 
-
 
 
 

 
21
 
 
 
 
 
 
 
 
3.4  
Study Plan 
 
3.4.1  Schedule 
 
The previously vaccinated cohort receives the vaccine boost once every six months (+/- 30 days). 
As of Amendment #9, participants will be switched to annual vaccinations (+/- 30 days). 
 
The vaccine naïve cohort receives the priming vaccine once every month (+/- 3 days) for three 
months, then a vaccine boost every six months (+/-30 days) beginning six months after prime 
vaccine #3. As of Amendment #9, participants will be switched to annual vaccinations (+/- 30 
days). 
 
At any time during the study additional leukapheresis or approximately 200 cc of blood may be 
obtained, and skin biopsies and photos may be taken of the vaccine sites and rashes, as clinical 
indicated, as long as the research participant is in agreement. 
 
All research participants will be seen in the oncology outpatient center for vaccine administration 
and monitoring. Research participants will be monitored for at least 30 minutes following 
vaccination for evidence of acute reaction to the injected vaccine cells.  
 
Research participants and the study team may request additional optional study visits for 
discussions and evaluations. During these patient-requested or clinically-indicated visits, additional 
assessments may be obtained, including, but not limited to a history and physical examination, 
toxicity assessment, vital signs, skin biopsy, photos, imaging tests, and clinical laboratory testing.   
 
3.4.1.1.Both Cohorts- Vaccination #1:  
 
This is the Prime Vaccination #1 for Vaccine Naïve Cohort and the Boost Vaccination #1 for 
Previously Vaccinated Cohort. 
 
Baseline data and samples (May be obtained from Day-28 to Day 0) 
 
1. A clinical evaluation to include vital signs, ECOG status, weight, review of systems, 
physical examination, and toxicity evaluation. 
2. CT scans of the abdomen, pelvis, and chest. If the CT scan is not done at Hopkins, the 
research participant must provide the report and a copy of the scans. If the research 
participant is allergic to the CT scan contrast or the contrast is contraindicated (as in the 
case for renal insufficiency), a non-contrast CT of the chest and a MRI of the abdomen and 
pelvis will be obtained. 

 
22
3. A leukapheresis for in vitro studies will be encouraged. If the research participant refuses a 
leukapheresis, approximately 200 cc of blood will be drawn. 
4. Blood testing to include CBC/diff, absolute eosinophils, absolute neutrophils, absolute 
lymphocytes, comprehensive chemistry panel including electrolytes, albumin, BUN, 
creatinine, AST, ALT, total bilirubin, alkaline phosphatase, amylase, and CA 19-9.  
5. Research blood: 20 cc for serum banking. 
6. 10 cc for HLA typing and 10 cc for EBV testing for vaccine naïve research participants 
only.  
7. Skin biopsy for vaccine naïve research participants only. 
8. Pregnancy test for women of childbearing potential. Urine pregnancy test preferred. 
9. Several psychosocial and symptom instruments, including: quality of life, hope, trust and 
pancreatic cancer survivor surveys. (See appendices for copies of the instruments).  
10. If not previously enrolled on IRB # NA_00036444 (SKCCC J0248) entitled, Long term        
follow-up of patients who received lethally irradiated allogeneic pancreatic tumor cells 
transfected with the GM-CSF gene, the research participant will be encouraged to join the 
long-term follow-up study.  
 
Day 0    
1. Administration of vaccine (Topical lidocaine-based anesthetic may be placed 1-2 hours prior to 
planned vaccine administration time to the intended vaccine sites.) 
2. Day 0 serum GM-CSF level 
3. Vital signs before and after vaccine administration 
4. Photograph of vaccine sites (if clinically indicated) 
5. Assessment for toxicities 
6. Monitor for 30 minutes after vaccine administration  
7. Tetanus toxoid boost if last tetanus vaccination > 10 years. Tetanus/diphtheria (Td) may be 
substituted if tetanus alone is not available. If both are not available, no tetanus vaccine will be 
administered. 
8. Provide diary to record vaccine reactions, health/medical complaints and medication changes. 
 
Day 1 
1. Vital signs 
2. Assessment of vaccine sites. This will include: number of sites that have erythema, induration, 
pruritus, and tenderness; and measurement of induration and erythema of largest vaccine site. 
3. Assessment for toxicities 
4. Day 1 serum GM-CSF level 
5.   Photograph of vaccine sites (if clinically indicated) 
 
Day 2 
1.    Day 2 serum GM-CSF level 
 
Day 3 
1.   Vital signs 
2.    Assessment of vaccine sites. This will include: number of sites that have erythema, induration,  
       pruritus, and tenderness; and measurement of induration and erythema of largest vaccine site. 
3.    Assessment of toxicities 

 
23
4.    Day 3 serum GM-CSF level 
5.  Heme-8 with differential, including absolute eosinophil count. absolute neutrophils, absolute   
lymphocytes  
6.    Photograph of vaccine sites (if clinically indicated) 
7.    3 mm punch skin biopsy of representative vaccine site (if clinically indicated) 
 
Day 4   
1.  Day 4 serum GM-CSF level 
 
3.4.1.2. Vaccine Naive Cohort Only: 
 
Prime Vaccination #2 Day 0 is the same as Day 28 (+/- 3 days) after Prime Vaccination #1 
 
Day 0 
1. A leukapheresis for in vitro studies will be encouraged. If the research participant refuses a 
leukapheresis, approximately 200 cc of blood will be drawn. 
2. Vital signs before and after vaccine administration 
3. Assessment for toxicities and vaccine site reactions from previous vaccinations, and 
medications. 
4. Administration of vaccine (Topical lidocaine-based anesthetic may be placed about 1-2 
hours prior to planned vaccine administration time to the intended vaccine sites.) 
5. Photograph of vaccine sites (if clinically indicated) 
6. Assessment for toxicities. 
7. Monitor for 30 minutes after vaccine administration. 
     8.   Several psychosocial and symptom instruments, including: quality of life, hope, and trust        
surveys. (See appendices for copies of the instruments).  
     9.  If not previously enrolled on IRB # NA_00036444 (SKCCC J0248) entitled, Long term        
follow-up of patients who received lethally irradiated allogeneic pancreatic tumor cells 
transfected with the GM-CSF gene, the research participant will be encouraged to join the 
long-term follow-up study.  
   10.    Collect and review the diary of prime vaccine #1. Provide new diary. 
 
3.4.1.3. Vaccine Naive Cohort Only: 
 
Prime Vaccination #3 Day 0 is the same as Day 28 (+/- 3 days) after Prime Vaccination #2 
 
Day 0 
 
1. A leukapheresis for in vitro studies will be encouraged. If the research participant refuses a 
leukapheresis, approximately 200 cc of blood will be drawn. 
2. Vital signs before and after vaccine administration 
3. Assessment for toxicities and vaccine site reactions from previous vaccinations, and       
medications. 
4.  Administration of vaccine (Topical lidocaine-based anesthetic may be placed about 1-2 hours       
prior to planned vaccine administration time to the intended vaccine sites.) 
     5.   Photograph of vaccine sites (if clinically indicated) 
6.   Assessment for toxicities 

 
24
7.   Monitor for 30 minutes after vaccine administration 
     8.   Several psychosocial and symptom instruments, including: quality of life, hope, and trust      
surveys. (See appendices for copies of the instruments).  
     9.   If not previously enrolled on IRB # NA_00036444 (SKCCC J0248) entitled, Long term 
follow-up of patients who received lethally irradiated allogeneic pancreatic tumor cells            
transfected with the GM-CSF gene, the research participant will be encouraged to join the 
long-term follow-up study.  
    10.  Collect and review the diary of prime vaccine #2. Provide new diary. 
 
Day 28 after Prime Vaccine #3 (-3 /+ 14 days) 
1. A leukapheresis for in vitro studies will be encouraged. If the research participant refuses a 
leukapheresis, approximately 200 cc of blood will be drawn. 
2. Vital signs. 
3. Assessment for toxicities and vaccine site reactions from previous vaccinations, and 
medications. 
     4.   Photograph of vaccine sites or reactions (if clinically indicated) 
5.  Several psychosocial and symptom instruments, including: quality of life, hope, and trust 
surveys. (See appendices for copies of the instruments).  
     6.  If not previously enrolled on IRB # NA_00036444 (SKCCC J0248) entitled, Long term 
follow-up of patients who received lethally irradiated allogeneic pancreatic tumor cells 
transfected with the GM-CSF gene, the research participant will be encouraged to join the 
long-term follow-up study.  
      7.  Collect and review the diary. 
 
3.4.1.4. Both Cohorts- Semi-annual or Annual Boost Vaccinations after the previous 
vaccination:  
 
In the event that a research participant has evidence of persistent vaccine-related responses 
(including, but not limited to: vaccine site flares such as recurrent erythema, induration, and 
pruritus at previous vaccine administration sites; urticaria) occurring at the frequency of more than 
once in the previous three months, the research participant may choose to delay the semi-annual or 
annual boost vaccination for up to one year after the last vaccine-related response. If the research 
participant chooses to delay the semi-annual or annual vaccinations due to persistent vaccine-
related responses, evaluations to include: research and standard blood samples; clinical evaluation; 
CT scans of the abdomen, chest, and pelvis; and surveys, as described in “Day-28 to Day 0” below 
may be obtained semi-annually or annually.  
 
The research participant may also choose to continue to receive the semi-annual or annual boost 
vaccinations per protocol with evidence of persistent vaccine-related responses. Research 
participants experiencing urticaria must wait at least one month since the last hive before receiving 
another vaccine.  
 
Data and samples may be obtained from Day-28 to Day 0 
1.  A clinical evaluation to include vital signs, ECOG status, weight, review of systems, 
physical examination, and toxicity evaluation. 

 
25
2. CT scans of the abdomen, pelvis, and chest. If the CT scan is not done at Hopkins, the 
research participant must provide the report and a copy of the scans. If the research 
participant is allergic to the CT scan contrast or is contraindicated, a non-contrast CT of the 
chest and a MRI of the abdomen and pelvis will be obtained. 
3. A leukapheresis for in vitro studies will be encouraged. If the research participant refuses a 
leukapheresis, approximately 200 cc of blood will be drawn. As of Amendment #8, research 
bloods are no longer required to be collected. 
4. Blood testing to include CBC/diff, absolute eosinophils, absolute neutrophils, absolute 
lymphocytes, comprehensive chemistry panel including electrolytes, albumin, BUN, 
creatinine, AST,ALT, total bilirubin, and alkaline phosphatase, amylase, and CA 19-9.  
5. Research blood: 20 cc for serum banking. As of Amendment #8, research bloods are no 
longer required to be collected. 
6. Pregnancy test for women of childbearing potential. Urine pregnancy test preferred. 
7.  If not previously enrolled on IRB # NA_00036444 (SKCCC J0248) entitled, Long term 
follow-up of patients who received lethally irradiated allogeneic pancreatic tumor cells 
transfected with the GM-CSF gene, the research participant will be encouraged to join the 
long-term follow-up study. 
 
Day 0   
1. Administration of vaccine (Topical lidocaine-based anesthetic may be placed about 1-2 
hours prior to planned vaccine administration time to the intended vaccine sites.) 
2. Vital signs before and after vaccine administration 
3. Photograph of vaccine sites (if clinically indicated) 
4. Assessment for toxicities 
5. Monitor for 30 minutes after vaccine administration 
6. Tetanus toxoid boost if last tetanus vaccination > 10 years. Tetanus/diphtheria (Td) may be 
substituted if tetanus alone is not available. If both are not available, no tetanus vaccine will 
be administered.  
 
 
Day 28 after Boost Vaccine (-3/ + 14 days) 
1.   A leukapheresis for in vitro studies will be encouraged. If the research participant refuses a 
leukapheresis, approximately 200 cc of blood will be drawn. As of Amendment #8, research 
bloods are no longer required to be collected. 
2. Assessment for toxicities and vaccine site reactions from previous vaccinations, and       
medications. 
3.   Photograph of vaccine sites or reactions (if clinically indicated) 
4.  If not previously enrolled on IRB # NA_00036444 (SKCCC J0248) entitled, Long term 
follow-up of patients who received lethally irradiated allogeneic pancreatic tumor cells 
transfected with the GM-CSF gene, the research participant will be encouraged to join the 
long-term follow-up study.  
 
If the research participant is unable to return to Johns Hopkins for the day 28 after boost visit, 
effort will be made to obtain information for this visit. Data may be obtained regarding toxicity 
and vaccine site reactions by study clinician contact with the research participant, his/her family, 
or health care providers. The surveys may be mailed to the research participant’s home with a 
stamped return envelope. Fax and electronic correspondence for the diaries and surveys is also 

 
26
acceptable. Arrangements may be made for the research samples to be obtained locally and 
shipped to the Hopkins’ Jaffee Lab. 
 
Off-study  
1.  A clinical evaluation to include vital signs, ECOG status, weight, review of systems,        
physical examination, measurement of vaccine sites and toxicity evaluation. 
2. CT scans of the abdomen, pelvis, and chest. If the CT scan is not done at Hopkins, the 
research participant must provide the report and a copy of the scans. If the research 
participant is allergic to the CT scan contrast or the contrast is contraindicated (as in the 
case for renal insufficiency), a non-contrast CT of the chest and a MRI of the abdomen and 
pelvis will be obtained. 
3.  A leukapheresis or approximately 200 cc of peripheral blood will be obtained for in vitro 
studies. As of Amendment #8, research bloods are no longer required to be collected. 
4.  Research blood: 20 cc for serum banking. As of Amendment #8, research bloods are no 
longer required to be collected. 
5. Blood testing to include CBC/diff, absolute eosinophils, absolute neutrophils, absolute 
lymphocytes, comprehensive chemistry panel including electrolytes, albumin, BUN, 
creatinine, AST, ALT, total bilirubin, alkaline phosphatase, and CA 19-9.  
6. Assessment of vaccine sites. This will include: number of sites that have erythema, 
induration, pruritus, and tenderness; and measurement of induration and erythema of largest 
vaccine site. 
7.   Assessment of toxicities (Information may include evaluations made by the local health care 
provider.) 
 
If the research participant is unable to return to Johns Hopkins for the off-study visit, effort will 
be made to obtain medical records that may include laboratory and imaging tests results, 
pathology reports, and health care providers’ notes. Data may also be obtained regarding 
toxicity and disease status by study clinician contact with the research participant, his/her 
family, or health care providers. The surveys may be mailed to the research participant’s home 
with a stamped return envelope. Fax and electronic correspondence for the diaries and surveys 
is also acceptable. Arrangements may be made for the research samples to be obtained locally 
and shipped to the Hopkins’ Jaffee Lab. 
 
If the off-study visit is within 28 days of a protocol-specified visit in which the assessments and 
samples were obtained, the off-study assessments and specimens need not, but may be, repeated. 
 
Research Samples 
 
De-identified samples may be shared with other investigators with written authorization from the 
principal investigator. Additional samples may be collected for research purposes, including, but 
not limited to those obtained through biopsies, surgeries, and autopsies. As of Amendment #8, 
research bloods are no longer required to be collected. 
 
 

 
27
Table 3.       Study schema including toxicity and immune monitoring for Prime Vaccine 
#1 and each Boost Vaccination. 
Assessment 
Day 
01 
Day 1 
Day 2 Day 3 
Day 4 
 
 
 
Day 
282 
Clinical evaluation 
X 
 
 
 
 
 
 
 
 
CT abd/chest/pelvis 
X 
 
 
 
 
 
 
 
 
Vital signs3 
X 
X4 
 
X4 
 
 
 
 
X10 
Toxicity 
assessment/evaluation5 
X 
X4 
 
X4 
 
 
 
 
X5,6, 
Vax site assessment5 
 
X4 
 
X4,6 
 
 
 
 
X5,6 
Heme/ diff/abs.eos 
X 
 
 
 
 
 
 
 
 
Chemistries7 
X 
 
 
 
 
 
 
 
 
CA 19-9 
X 
 
 
 
 
 
 
 
 
Amylase 
X 
 
 
 
 
 
 
 
 
Leukapheresis or PBL 
in vitro studies 8 
X 
 
 
 
 
 
 
 
X 
Research blood: HLA 
typing 
and 
EBV 
testing9 
X 
 
 
 
 
 
 
 
 
Research 
blood: 
Serum banking8 
X 
 
 
 
 
 
 
 
 
Vaccine site biopsy8 
X9 
 
 
 
 
 
 
 
 
Photograph, 
if 
indicated9 
X 
X6 
 
X6 
 
 
 
 
X6 
 
1 May be done up to 28 days prior to Day 0.  Additional leukapheresis may be performed for an 
interesting immunological response. 
2 Day 28 (-3/ +14 days) assessments and samplings are to be done after each vaccination.  
3 Vital signs include temperature, pulse rate, respiration rate, and blood pressure 
4 At first vaccination only. 
5 Assess to resolution.  
6 Information may be obtained by phone, e-mail, fax, and/or through the evaluation by the local 
health care provider, if unable to assess in person. 
7 Chemistries include: electrolytes, albumin, BUN, creatinine, AST, ALT, total bilirubin, and 
alkaline phosphatase 
8 At any time during the study, additional leukapheresis or PBL in vitro studies may be obtained, 
skin biopsies and photographs may be taken of the vaccine sites and rashes, as clinical indicated as 
long as the research participant is in agreement. As of Amendment #8, research bloods are no 
longer required to be collected. 
9 Obtain baseline biopsy, HLA typing and EBV testing prior to the first vaccine only for the vaccine 
naïve cohort only. 
10 Prime vaccine 3 only. 
 
The significant results of all assessments indicated above in Table 3 will be recorded in an 
electronic database. 
 

 
28
3.4.2  Leukapheresis 
 
All research participants will be encouraged to periodically undergo a leukapheresis as outlines in 
the protocol. If the research participant does not agree to the leukapheresis the standard 200 cc of 
peripheral blood will be obtained. In addition, any research participant demonstrating an interesting 
immunological response may be asked to undergo leukapheresis to obtain greater numbers of 
lymphocytes for research purposes. This may include physical responses thought to be related to 
the vaccine (including, but not limited to vaccine site flares) or interesting laboratory responses 
(including, but not limited to mesothelin-specific CD8+T cell responses). There will be at least two 
weeks between additional leukapheresis procedures. As of Amendment #8, research bloods are no 
longer required to be collected. 
 
Prior to the leukapheresis, subjects will be evaluated by the Hematopoietic and Therapeutic Support 
(HATS) Center to determine if their vascular access appears to be adequate for the leukapheresis 
procedure.  
 
If the research participant had a leukapheresis within two weeks (+/- 14 days) of a protocol-
specified research sample collection point, the peripheral blood lymphocyte collection of 200 cc of 
blood and the peripheral blood lymphocyte collection need not be repeated.  
 
3.4.3  Evaluation for Safety and Anticipated Toxicities 
 
Severe toxicities are unlikely, based on information from previous GM-CSF gene vaccine studies 
completed here at Johns Hopkins Hospital trials, including the Phase I and II pancreatic tumor 
vaccine trials.  In experiments involving over 400 mice, use of irradiated GM-CSF secreting tumor 
cells caused only reversible lymphadenopathy and reversible subcutaneous swelling; no ulcerations 
were seen.  In our first phase I trial in patients with renal cell carcinoma, only local erythema and 
swelling were seen following intradermal injections of cell doses up to 4 x 107 GM-CSF modified 
vaccine cells, and up to 4 x 108 unmodified vaccine cells.  
 
At the highest dose level, we predict that initially 45 mcg of total GM-CSF will be secreted locally 
per 24 hours, a level that will diminish as tumor cells are killed by invading inflammatory cells. To 
support hematologic recovery in oncology patients after intensive chemotherapy, subcutaneous or 
intravenous doses of GM-CSF between 5 and 10 ug/kg/day are commonly used (350-700 mcg total 
for a 70 kg individual). At this dose range the following side effects are commonly seen: local or 
generalized skin rashes, bone pain (attributed to stimulation of hematopoietic progenitors), fever, 
and malaise. Although patients in the initial Phase I study of the allogeneic tumor vaccine had 
normal bone marrow function, leukocytosis and toxic levels of serum GM-CSF did not occur with 
the 10 fold lower dose of GM-CSF. The maximum serum GM-CSF level obtained was 14.0 pg/ml 
with dose level four at 48 hours after the first pancreatic tumor vaccine. 
 
The plasmid used to transfect the GM-CSF gene is safe. In contrast to retroviral vectors, it lacks the 
coding sequences that would allow replication and the generation of helper virus. This plasmid 
containing the GM-CSF gene has been sequenced following vector construction to confirm its 
insertion, orientation, and the lack of mutations.  In addition, this vector has been confirmed to 
produce bioactive GM-CSF. 

 
29
 
The risk of generating autoimmune reactions is unknown but is believed to be small. The pancreas 
would be the most likely organ to be involved. Pancreatitis and loss of pancreatic function can be 
supported by the use of exogenous pancreatic enzymes and insulin injections if needed. Other 
organs that may share tissue specific antigens might also be involved, such as the salivary glands 
and other gastrointestinal organs. In the Phase I and II studies there were no evidence of 
autoimmune reactions. 
 
Every patient who has received the vaccine will be evaluated for toxicity.  The research participant 
will be taken off-study if unacceptable adverse events are experienced.  Possible toxicities include 
local swelling, induration, or ulceration at the site of the vaccine, systemic toxicities from paracrine 
secretion of GM-CSF, and induction of autoimmunity.  Patients will be evaluated on days 1 and 3 
by a research nurse following the semi-annual or annual vaccination boosting to monitor for local 
and systemic toxicities. The research participant may be contacted by phone or e-mail or the 
information may be obtained from their local health care providers. The research participant will be 
advised to call the research nurse and/or the principal investigator if there are any new toxicities, 
concerns or questions. 
 
3.4.4  Interval Health Care 
 
The research participant disease status may be evaluated more frequently than twice a year. Patients 
may undergo additional abdomen, chest and pelvis CT scans and blood tests, including CA 19-9 
levels, as recommended by their local oncology, or by the study team as standard of care for 
possible disease recurrence. The results of the CT scans, blood tests, and progress notes will be 
requested from the research participant’s local oncologist. Medical records obtained will be added 
to the oncology outpatient medical records, including electronic forms, when possible. Data related 
to the toxicity and/or disease status assessments will be recorded in the case report form binders 
and electronic data base. 
 
If the research participant is followed at Johns Hopkins, the medical records will be accessed at 
least quarterly, and more frequently, if needed for disease recurrence.  
 
If patient is taken off study, the patient’s medical records will be requested from the health care 
provider providing further care for 28 days after the last research product was administered, or 
longer for resolution of any adverse events related to the research product. After off-study, the 
research participant will be followed annually via the protocol application number NA_00036444, 
entitled, “Long-term follow-up of patients who receive lethally irradiated allogeneic pancreatic 
tumor cells transfected with the GM-CSF gene”, SKCCC J0248, if consent is granted.   
 
 
 
 
 
3.4.5  Continuation of Therapy 
 
Provided there is no radiographic evidence of pancreatic cancer disease recurrence, no dose 
limiting toxicities, and the vaccine is available, the patient will receive an equal mixture of 
allogeneic pancreatic cancer cell lines Panc 10.05 and Panc 6.03 for a total dose of 5 x 108 vaccine 
cells divided equally into six intradermal injections to be given as two in each anterior upper thigh 
and two in the non-dominant upper arm (unless contraindicated) twice every year.  

 
30
In the event that a research participant has evidence of persistent vaccine-related responses 
(including, but not limited to: vaccine site flares such as recurrent erythema, induration, and 
pruritus at previous vaccine administration sites; urticaria) occurring at the frequency of more than 
once in the previous three months, the research participant may choose to delay the semi-annual or 
annual boost vaccination for up to one year after the last vaccine-related response. The research 
participant may also choose to continue to receive the semi-annual or annual boost vaccinations per 
protocol with evidence of persistent vaccine-related responses. Research participants experiencing 
urticaria must wait at least one month since the last hive before receiving another vaccine.  
 
The same study schema (Table 3.) that includes toxicity and immune monitoring will be followed 
with each semi-annual or annual vaccination. 
 
3.4.6  Off-study 
 
Research participants will be discontinued from participating in this study for the following 
circumstances: 
 
 There is radiographic evidence of pancreatic cancer recurrence. 
 Serious vaccine related adverse events occur. 
 The vaccine supply is exhausted. 
 The research participant is noncompliant, is unable to comply with the treatment plan, or 
requests withdrawal. 
 The research participant is receiving concomitant immunotherapy, chemotherapy, radiotherapy, 
or other biological or gene therapy.  
 
If determined to be off-study, the research participant will be followed for 28 days after the 
administration of the last vaccine for toxicities related to the vaccine, or longer, if vaccine-related 
toxicities occur. Whenever possible, the research participant will be asked to have the tests 
indicated for the day 28 visit as the off-study visit, unless this was done within 28 days of the off-
study date.  
 
If the research participant consents there will be a lifelong follow-up through participation in Dr. 
Daniel Laheru’s study, IRB # NA_00036444 (SKCCC J0248) entitled, Long term follow-up of 
patients who received lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-
CSF gene. 
 
3.5  
Management of Toxicities 
 
Local vaccine site reaction may be treated with topical applications of aloe vera or vitamin E gel or 
lotion.  Significant local inflammation that is causing the research participant severe pain or is 
interfering with the activities of daily living may be treated with cold packs and oral analgesics. 
Local toxicities of pruritus at the vaccine sites and systemic pruritus may be treated with topical or 
oral diphenhydramine hydrochloride (Benadryl) or topical aloe vera. If oral diphenhydramine 
hydrochloride is used the recommended dose shall be 25-50 mg every four to six hours as needed 
for pruritus, not to exceed 300 mg/day. Cases of local ulceration should be manageable with local 

 
31
wound care, with or without antibiotics.  Severe local inflammation or significant clinical 
autoimmunity will be managed on a case by case basis. 
 
4.0  
Statistical Considerations 
 
4.1 
Sample Size 
 
The primary statistical endpoint of this study is to evaluate the safety and feasibility of vaccine 
boosting with lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF 
gene. Among patients who have previously been treated with the vaccine, the cohort is limited to 
those who continue to have no disease recurrence for at least 1 year after treatment.   Currently, 
there are three potentially eligible patients from the original phase I study, and 14 from the phase II 
study. A total of up to 17 previously treated patients will be eligible to continue to receive vaccine 
treatment in the form of semi-annual boosts. The second cohort of vaccine naïve patients who have 
been recurrence free for at least 28 days following adjuvant therapy will be given three priming 
vaccines each a month apart, followed by semi-annual vaccine boosts in order to determine the 
feasibility of administering the vaccination to vaccine naïve patients and to obtain initial estimates 
of the efficacy of such treatment with respect to prolonging disease-free status. As of Amendment 
#9, participants will be switched to annual vaccinations. We will base our determination of 
feasibility by estimating the proportion of patients with a dose limiting toxicity (DLT) within 28 
days of the first vaccine treatment.  Between 20 and 45 vaccine naïve patients will be included.  An 
initial group of 20 patients will be recruited and an interim analysis will be performed in order to 
guard against excessive toxicities relating to treatment.  No DLTs have been observed in neither the 
phase I or II studies.  If there is significant evidence that more than 10% of the vaccine naïve 
patients have dose limiting toxicities within 28 days of the first vaccination, then the trial will be 
halted.   If 6 out of 20 of the initial patients have DLTs, the lower bound of the exact 95% 
confidence interval for the proportion of patients with a DLT is 11.89%.  Therefore, we will halt 
the trial due to excessive toxicity at the interim analysis if 6 or more patients have a DLT within the 
first 28 days of their first vaccine.  Otherwise, an additional 20 vaccine naïve patients will be 
accrued.  If 20 patients are accrued, the maximum width of the 95% confidence interval estimate of 
the proportion of patients with a DLT is 0.438.  If the full cohort of 40 patients is accrued, then the 
maximum width of the 95% confidence interval is 0.309. 
 
The sample size was expanded to include a cohort of up to 45 vaccine-naïve research participants 
and 17 previously vaccinated research participants for a total sample up to 62 research participants. 
 
4.2 
Analysis of Primary Endpoint: Safety and toxicity measurements 
 
The primary endpoint of this study is safety as measured by local and systemic toxicity. These 
toxicities will be characterized according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events, Version 3.0, and can be accessed and downloaded via the website: 
http://ctep.cancer.gov/reporting.  Dermatologic toxicity measurements of the vaccine sites will be 
performed.  For each patient cohort (vaccine naïve and vaccine treated), we will tabulate the 
number, type and degree of toxicities for each round of vaccination.  In addition, we will estimate 
the proportion of individuals who have a DLT within the first 28 days of vaccination for each round 
with an exact 95% confidence interval. 

 
32
 
4.3  
Analysis of Secondary Endpoints 
 
The analysis of the remaining endpoints are primarily descriptive in nature and are intended to be 
used to generate estimates of efficacy and hypotheses to be tested in later trials.  For each endpoint, 
separate analyses will be performed for the vaccine naïve and vaccine treated patients. 
 
4.3.1  Efficacy endpoints 
 
The primary efficacy endpoint of interest is the overall survival (OS) of patients treated with 
vaccine boosts.  The overall survival is defined as the time from the first vaccine boost until death.  
If a patient is lost to follow-up or the study is ended prior to death, the patient will be considered 
censored at their last recorded follow-up.  For each cohort, Kaplan Meier curves will be constructed 
and the median survival estimates will be calculated with 95% confidence intervals using 
Greenwood’s formula.  Since the time between completion of treatment and the initiation of 
vaccine boosts will vary among subjects, we will use a Cox proportional hazards model to adjust 
for this delay in boosts.   
 
We are also interested in investigating the effect of vaccine boosts on recurrence free survival 
(PFS).  Patients who are treated at Johns Hopkins will be followed every 3 months and evaluated 
for recurrence.  However, the standard of care follow-up varies from institution to institution.  In 
order to prevent biasing our results, it is necessary to coarsen the follow-up interval so that every 
individual is evaluated at the same time points regardless of the institution.   For example, if the 
only visits held in common among all patients were the semi-annual exams prior to vaccine 
boosting, it would be necessary to only consider the status of the JH patients at those two time 
points regardless of recurrence information gained from the additional 2 visits.  This coarsening of 
the data may cause an overestimation of PFS.  In order to take into account both potential forms of 
bias, we will perform our analysis of PFS on the entire cohort as well as the subpopulation of 
patients from Johns Hopkins (estimated to be approximately 50% of the research participants). PFS 
will be defined as the time from the first vaccine until evidence of disease recurrence.  If a patient 
withdraws from the study prior to being diagnosed with progressive disease, they will be censored 
at the date of their last follow-up visit.  If an individual dies prior to being diagnosed with 
progressive disease, they will be considered to have progressed at the date of their last follow-up 
visit. This is a conservative estimate if we count the disease recurrence at the next planned visit 
then this will bias the PFS time upward. The PFS will be summarized using Kaplan-Meier curves 
and estimates of median PFS with 95% confidence intervals based upon Greenwood’s formula.  
Due to potential causes of bias discussed earlier, the results will be considered extremely 
preliminary.  If the PFS estimates for patients treated at Johns Hopkins appear to be lower than that 
of the population as a whole and the Johns Hopkins patients are followed at more frequent intervals 
than the other patients, then this indicate that an overestimation of PFS may exist.  No formal 
comparison is planned due to the small sample size.  Such results could affect the future planning 
of follow-up treatment for patients in subsequent trials. 
 
Measurements of immune response include but are not limited to mesothelin, prostate stem cell 
antigen (PSCA) and mutated k-ras-specific T cell responses. Continuous variables will be 
summarized with means and standard deviations. Dichotomous and categorical variables will be 

 
33
summarized using proportions with exact 95% confidence intervals and counts, respectively.   
These summaries will be computed for each patient at two time points around each vaccine boost:  
pre-vaccination and four weeks post vaccination. Plot will be used to show the changes in immune 
response over time both for each individual and for each cohort.  For each vaccine boost, 
comparisons in the pre and post-vaccine responses will be compared using paired t-tests (or 
Wilxcoxon signed rank tests if appropriate) for continuous variables and Fisher’s exact test for 
dichotomous or categorical variables. Associations between immune responses will be explored 
graphically (e.g. scatterplots, boxplots) and numerically (e.g. correlations, 2 tests). 
 
Measurements of antitumor immunity include but are not limited to the measurement of shared 
tumor-specific antigens and k-ras specific antitumor immune responses.  Autologous lymphocytes 
will be obtained from peripheral blood before each vaccination, and at four weeks following each 
vaccinations.  The graphical and numerical analyses of these results will be the same as that 
described for measurements of immune responses and will be carried out for each cohort 
separately. 
 
4.3.2  Relating immune response to clinical response 
 
The relationships between immune and clinical responses will be assessed using a variety of 
statistical techniques.  Preliminary explorations will be graphical in nature (e.g. boxplots, 
scatterplots).   Univariate and multivariate modeling will be used quantify the associations.  In the 
case of a binary clinical outcome (e.g. toxicity), logistic regression will be used.  In the case of a 
time-to-event clinical outcome (e.g. OS), the Cox proportional hazards model will be used. 
 
4.3.3  Longevity of an allogeneic vaccine 
 
Pharmacokinetic studies will be used to evaluate the longevity of the allogeneic vaccine by 
measuring the levels of GM-CSF in the serum.  Serum will be obtained from each research 
participant on days 0 and 3 of treatment.   Pharmacokinetic parameters will be estimated, when 
possible, using standard compartmental models.  Parameter estimates and normal theory standard 
errors will be calculated by fitting using weighted least squares.   Summary statistics (e.g. mean, 
standard deviation) will be presented for each cohort on each day at each vaccine boost.  Plots of 
the means against time will be included to assess the change in the parameters over time.  The 
relationship between pharmacokinetic parameters and clinical outcomes will be assessed using 
logistic regression for binary outcomes (e.g. toxicity) and Cox proportional hazards models for time 
to event outcomes (e.g. OS, PFS). 
  
4.3.4  Psychosocial and symptom profiles 
 
The psychosocial and symptom profiles will be evaluated through the use of a variety of surveys 
and measurement tools.  Surveys will be administered at several time points: day 0 and day 28 of 
the each vaccination. The responses will be measured using 8 techniques described in Section 5.3 
and include topics such as concept of hope, symptom burden, patient satisfaction, and QOL.  
Categorical measurements such as those based upon Likert scales (e.g. Hearth Hope Index) will be 
summarized using counts, medians, ranges and estimates of the probability distributions. 
Continuous variables will be summarized using means and standard deviations. Trends over time 

 
34
will be summarized by plotting the median measurements against time with an estimate of 
variability (e.g. standard deviation, inter-quartile range) for each cohort.  Associations between 
measurements will be evaluated graphically (e.g. boxplots, scatterplots) and numerically (e.g. 
Spearman’s correlation).  Comparisons between time points will be made using non-parametric 
techniques (e.g. Kruskal-Wallis test, 2 test). 
 
5.0  
Response Criteria 
 
5.1 
Evaluation of Clinical Activity 
 
Most patients will have only minimal residual disease at the time of enrollment.  Therefore, there 
will be no evaluable disease to measure at baseline.  Patients will be monitored for disease-free and 
overall survival.  The results from this trial will be compared to historical controls seen at the Johns 
Hopkins Hospital (5).  Patients recently seen at the Johns Hopkins Hospital who can be matched for 
pathologic stage, surgical intervention, and adjuvant combination chemotherapy and radiation 
therapy, are the most accurate group of historical controls since our institution has the largest 
reported experience treating patients with this disease and has recently reported the best survival 
statistics for current interventions (5).  
 
Patients may undergo standard of care evaluations consisting of abdominal, chest, and pelvis CT 
scans at regular intervals to evaluate for local recurrence and distant metastases.  In addition, any 
patient presenting with symptoms will undergo evaluation for metastases.  Recurrent disease is 
defined as evidence of either local or metastatic recurrence by CT scan. 
 
The serum tumor marker CA19-9 lacks a sufficient sensitivity and specificity to serve as reliable 
indicators of response. The CA 19-9 levels will be followed to evaluate whether large and 
persistent changes might correlate with either in vitro immune responses or with time to clinical 
recurrence. 
 
5.2 
Evaluation of Immune Responses 
 
A central goal of the clinical trial is to identify immunologic changes associated with the vaccine 
therapy that may be markers of potential clinical responses.  The local immune response to vaccine 
will be tested with biopsy and histological analysis.  Specific systemic responses to tumor and to 
normal tissue will be assessed by in vitro assays.   
 
The leukapheresis product or peripheral blood will be obtained from each research participant at 
periodic protocol-specified intervals for the in vitro assays.  In addition, research participants may 
be asked to donate additional lymphocytes by leukapheresis.  Informed consent will be obtained for 
this procedure using the Leukapheresis Informed Consent Form which is a separate document than 
the main vaccine study informed consent form.  
 
De-identified samples may be shared with other investigators with written authorization from the 
principal investigator. Additional samples may be collected for research purposes, including, but 
not limited to those obtained through biopsies, surgeries, and autopsies. 
 

 
35
 
 
5.2.1 In vitro analysis of induction of antitumor immunity 
 
Autologous lymphocytes will be obtained from peripheral blood before the first and each semi-
annual vaccination for in vitro immune monitoring studies. Approximately 200 ml of blood will be 
required at these time points for all of the following immunologic studies.  Studies include the 
analysis of pancreatic adenocarcinomas for:  (1) shared tumor-specific antigens, (2) k-ras specific 
antitumor immune responses. Twenty ml of blood will be obtained prior to each vaccination for 
serum banking.  
 
5.2.2 Biopsy of Vaccine Site 
 
Patients will be observed for signs of local inflammation and induration. If responses in this trial 
are similar to the responses observed in the Phase I and II allogeneic pancreatic tumor vaccine 
studies, marked inflammatory responses will be present between days 1 and 3.  A baseline 3 mm 
punch biopsy will be obtained for vaccine naïve research participants only. Additional skin biopsies 
may be obtained, if clinically indicated. Vaccine sites may be photographed before injections and 
before biopsies. The biopsy sites will be anesthetized with local 1% lidocaine with 1:100,000 
epinephrine. 
 
Half of the biopsy specimen will be formalin fixed for hematoxylin and eosin stains. The other half 
of each biopsy specimen will be snap frozen in OCT for immunohistochemistry stains including; T 
cell staining (antiCD3), macrophage staining (Ham56), dendritic cell staining (S100), B cell 
staining (antiCD20), and cytokeratin staining (for presence of tumor cells). 
 
To semiquantitate the immune infiltration, the slides will be interpreted without knowledge of the 
research participant’s information.  The type of immune cells infiltrating the vaccine site adjacent 
to the vaccine cells will be determined using the immunohistochemical stained slides. In addition, a 
semiquantitative estimate of the proportion of each infiltrating cell type will be determined using a 
grid to count the number of each cell type per number of tumor cells in that field. These methods 
for semiquantitation have been successfully employed in the renal vaccine trial. These results will 
be compared with the biopsy results from our previous vaccine trials. 
 
The biopsy of the vaccine site should not significantly jeopardize any potential therapeutic benefit 
for the patient. The amount of vaccine and the number of responding immune cells removed by this 
biopsy is believed to be small.  
 
5.3  
Evaluation of psychosocial and symptom responses 
 
There is a gap in the literature regarding the psychosocial and symptom profiles of long-term 
cancer survivors. For a cancer, such as pancreatic cancer, that has a dismal prognosis, the 
information gained through intermittent evaluations of research participants’ quality of life, trust, 
hope, social support, decisional control preferences, advance directive preferences, and symptoms 
will be quite valuable. Due to limited research, the data collected through this study may bring forth 
new insights into the quality of life of people who are out living their expected survival time. 

 
36
 
The surveys and measurement tools will be completed at days 0 and 28 while the research 
participant is physically at Johns Hopkins, if possible. On day 0, the goal is to have the forms 
completed prior to vaccination, but in order to minimize subject burden the forms may be 
completed during the monitoring period immediately after vaccination. If the participant has a visit 
scheduled at Hopkins, the day 28 surveys will be completed during the visit. If the participant is 
unable to complete the surveys during the day 0 or 28 visit they will be asked to return the surveys 
when completed. A stamped return addressed envelope will be provided if the participant is unable 
to complete the surveys at the visit, and a deviation from the standard timing will be noted.  
 The psychosocial and symptom responses will be measured through: 
 
EORTC QLQ-C30  
City of Hope Quality of Life, Cancer patient/survivor version, QOL-CA 
Herth Hope Index 
Symptom Distress Scale 
Trust Scale 
Pancreatic Cancer Survivor Survey 
 
The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3 
is a likert-scale evaluation of 30 items that focuses on physical activities, symptoms, overall health 
and overall quality of life.  
The Quality of Life Scale: Patient/Cancer Survivor (QOL-CS) Version   measures the quality of life 
(QOL) in people with cancer through a 41 item interval level scale. This QOL instrument has been 
used extensively in cancer survivorship research studies. It measures an overall QOL that has a 
Cronbach’s alpha coefficient of 0.93, as well as four domains contained within QOL: physical, 
psychological, social, and spiritual well-being with subscale alphas of 0.71, 0.77, 0.81, and 0.89, 
respectively (Ferrell, Hassey-Dow & Grant, 1995, Ferrell, Hassey-Dow, Leigh, Ly, & 
Gulasekaram, 1995).  
The Herth Hope Index is a four-point Likert scale with 12 items related to the concept of hope in 
this instrument developed by Herth (1991, 1992) that provides a score of 12 to 48, with a higher 
value indicating a higher level of hope.  
 
The Symptom Distress Scale is a symptom burden assessment instrument developed by McCorkle 
and Young (1978) that measures the frequency and intensity of nausea and pain (2 items for each 
symptom), and a single measure of appetite, insomnia, fatigue, bowel, concentration, appearance, 
breathing, outlook, and cough on a five point Likert- like scale 
 
The Patient Trust Scale is a 10 item survey strongly related to patient satisfaction and medical care 
(r = 0.68, P < 0.0001). It covers three dimensions: honesty, confidentiality, competency, and 
agency (Kao, Green, Zaslavsky, Koplna, & Cleary, 1998). 
  
The Pancreatic Cancer Survivor Survey Research Participant Baseline Survey is being pilot tested 
in this clinical research study. The survey questions research participants on issues not covered in 
the previous established measurement tools, such as: research participation decision making, 
conflict of interest, informed consent, and advance directives.    
 

 
37
6.0 
Adverse and Problem Event Reporting 
 
6.1. 
Responsibilities 
 
It is the responsibility of the principal investigator to notify the IND sponsor of the vaccine research 
product, Elizabeth Jaffee, M.D., Hopkins Medicine Institutional Review Board, and Hopkins 
Institutional Biosafety Committee of any serious adverse event due to any cause, which occurs 
during the course of this investigation, and is believed to be in any way related to study drug. The 
sponsor will notify the appropriate federal regulatory agencies, including but not limited to the 
Food and Drug Administration. 
 
The Principal Investigator or their designee must notify the IND sponsor, Elizabeth Jaffee, M.D. of 
any Serious Adverse Event (SAE) within 24 hours of the investigator learning that the adverse 
event has occurred.  Events must be documented on the appropriate Johns Hopkins Medicine IRB 
form available at  
 See section 6.3 for IRB reporting guidelines.  
 
All adverse and problem events occurring from day 0 to 28 of each vaccine cycle will be recorded. 
All serious adverse and problem events occurring from day 0 and 28 of each vaccine cycle will be 
reported to the IRB. All serious adverse events related to the vaccine and deaths will be recorded 
and reported to the IRB. Adverse events related to the vaccine will be followed to resolution. 
 
 
Events of interest, including but not limited to, vaccine site flares and urticaria, may occur 
beyond 28 days after the vaccine administration. Immunologic events, such as vaccine site 
flares and urticaria will be recorded regardless of when they occur. These immunologic 
events are not to be considered adverse events, since these reactions may represent desired 
effects from the research product. There are no time restrictions on recording these events, as 
these events have been known to happen a long time after vaccination.  
 
A serious adverse event (SAE) is one that: 
 Results in death 
 Is life threatening 
 Requires inpatient hospitalization or prolongation of an existing hospitalization 
 Results in persistent or significant disability/incapacity 
 Is a congenital anomaly/birth defect in the offspring of an exposed patient 
An important medical event that may not result in death, be life-threatening, or require 
hospitalization, may be considered a serious adverse drug experience when, based upon appropriate 
medical judgment, it jeopardizes the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. 
A life threatening adverse event is defined as any adverse experience that places the patient or 
subject, in the view of the investigator, at immediate risk of death from the reaction as it occurred, 
i.e., it does not include a reaction that, had it occurred in a more severe form, might have caused 
death. 

 
38
An adverse drug reaction (ADR) is a noxious and unintended response to a medicinal product in 
which a causal relationship between a medicinal product and an adverse event is at least a 
reasonable possibility, i.e. that the relationship cannot be ruled out.  
 
6.2. 
Recording of an Adverse Event 
 
The principal investigator is responsible for evaluating all adverse events, obtaining supporting 
documents, and determining that documentation of the event is adequate. The principal investigator 
is responsible for determining the severity and relationship of the adverse event to the 
investigational drug. The principal investigator may delegate these duties to sub-investigators and 
must assure that these sub-investigators are qualified to perform these duties under the supervision 
of the principal investigator. 
 
All adverse events will be recorded in the subject’s Case Report Form and in the study data base. 
The detailed description of the event will include appropriately graded severity of the adverse event 
and its relationship to the study drug. 
 
Severity will be categorized by toxicity grade according to the NCI Common Terminology Criteria 
for Adverse Events version 3.0 available at http://ctep.cancer.gov/reporting/ctc.html 
 
Adverse events not listed in the NCI Common Terminology Criteria for Adverse Events will be 
evaluated using the following criteria: 
 Grade 1, Mild: Awareness of symptom, but easily tolerated; usually transient requiring no 
special treatment; does not interfere with usual status or activities 
 Grade 2, Moderate: May be ameliorated by simple therapeutic measures; may interfere with 
usual activities 
 Grade 3, Severe: Incapacitating, inability to perform usual activities 
 Grade 4, Life-threatening/Disabling: Subject was at risk of death or significant disability at 
the time of the event 
 Grade 5, Death related to AE 
 
Relationship of the adverse event to the investigational drug will be determined by the principal 
investigator, and will be categorized as: 
 Unrelated: The adverse event is clearly related to other factors such as the subject’s clinical 
state, environmental factors, or other modes of therapy or concomitant drugs administered 
to the subject. 
 Unlikely to be related: The adverse event may be related to other factors such as the 
subject’s clinical state, environmental factors, or other modes of therapy or concomitant 
drugs administered to the subject. 
 Possibly related: The adverse event follows a reasonable temporal sequence from 
administration of the study drug, and/or follows a known response pattern to the study drug, 
but could readily have been produced by the subject’s clinical state, environmental factors, 
or other modes of therapy or concomitant drugs administered to the subject. 
 Probably related: The adverse event follows a reasonable temporal sequence from 
administration of the study drug and follows a known response pattern to the study drug, 

 
39
and cannot readily have been produced by the subject’s clinical state, environmental factors, 
or other modes of therapy or concomitant drugs administered to the subject. 
 Definitely related:  The adverse event follows a reasonable temporal sequence from 
administration of the study drug and is clearly a known response pattern to the study drug, 
and cannot readily have been produced by the subject’s clinical state, environmental factors, 
or other modes of therapy or concomitant drugs administered to the subject. 
 
All grade 3 and 4 clinical laboratory results that represent an increase in severity from baseline will 
be reported as adverse events. A grade 1 or 2 clinical laboratory abnormality should be reported as 
an adverse event only if it is considered clinically significant by the investigator. 
 
In the event of death, the cause of death should be recorded as the adverse event. An attempt will 
be made to obtain a copy of the death certificate. Because the long-term effects of gene therapy are 
not known, the National Institutes of Health (NIH) would like an autopsy, in the event of death. If 
an autopsy is performed, a copy of the autopsy report should be obtained. 
 
6.3.  
Reporting Guidelines 
 
We will use the current JHM IRB and FDA guidelines for reporting relevant problems, 
events, adverse events, and adverse drug reactions.  
 
7.0 
Clinical Trial Monitoring 
 
This is a Level II study under the Sidney Kimmel Comprehensive Cancer Center (SKCCC) Data 
Safety Monitoring Plan. Data monitoring of this protocol will occur on a regular basis with the 
frequency dependent on the rate of subject accrual and the progress of the study. On a regular basis, 
the protocol will be internally monitored by the principal investigator, Daniel Laheru, M.D. and the 
study’s sponsor, Dr. Elizabeth Jaffee. External data monitoring will be performed by the SKCCC 
Clinical Research Office Quality Assurance Program (CRO QA).  The Data and Safety Monitoring 
Oversight will be conducted by the SKCCC Data and Safety Monitoring Committee (DSMC). The 
oversight will require no additional reporting from the study staff. Per the SKCCC at Johns 
Hopkins Data and Safety Monitoring Plan, revised on June 16, 2005, the CRO QA Program 
forwards their monitoring and auditing reports to the DSMC for review (section 2.1.6., 2.2.5.4., and 
2.2.6.4). Also, all reportable anticipated and unanticipated protocol events/problems and 
amendments that are submitted to the IRB are also reviewed by the DSMC Chair or designee and 
QA manager without any additional reporting requirements from the study staff (2.2.7.3.) 
 
 

 
40
8.0 
References 
 
Abrams, S.I., Hand, P.H., Tsang, K.Y, et al (1996). Mutant ras epitopes as targets for cancer 
vaccines. Seminars in Oncology, 23, 118-34. 
 
American Cancer Society (2006). Cancer Facts and Figures 2006. Atlanta: Author. 
 
Apostolopolous, V., Karanikas, V., Haurum, J., et al. (1997) Induction of HLA-A2 restricted CTLs 
to the mucin-1 human breast cancer antigen. Journal of Immunology, 159, 5211. 
 
Apostolopoulos, V. & McKenzie, I.F. (1994). Cellular mucins: targets for immunotherapy. Critical  
Review in Immunology, 14, 293-309. 
 
Argani, P., Iacobuzio-Donahue, C., Ryu, B., et al. (2001). Mesothelin is overexpressed in the vast 
majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer 
marker by serial analysis of gene expression (SAGE). Clinics of Canadian Research, 7, 3862-3868. 
 
Billings, B. J., Christen, J. D., Harsmen, W. S., Harrington, J. R., Charie, S. T., Que, F. G. (2005).  
Quality-of-life after total pancreatectomy: Is it really that bad on long-term follow-up? Journal of 
Gastronenterology Surgery, 9,  1059-1067. 
 
Brossart, P., Heinrich, K., & Stuhler, G. (1999). Identification of HLA-A2 restricted T-cell epitopes 
derived from the MUC-1 tumor antigen for broadly applicable vaccine therapies. Blood, 93, 4309-
4317. 
 
Burris, H.A., Moore, M.J., Cripps, M.C., et al. (1997). Improvements in survival and clinical 
benefit with gemcitabine as first-line therapy for patients with advanced pancreatic cancer: A 
randomized trial. Journal of Clinical Oncology, 15, 2403-2413. 
 
Cox, A.L., Skipper, J., Chen, Y., et al. (1994).Identification of a peptide recognized by five 
melanoma specific human cytotoxic T cell lines. Science, 264, 716-719. 
 
Davis, M.P., Dinneen, A.B., Landa, N., et al. (1999). Grover’s disease: clinicopathologic review of  
72 cases. Mayo Clinical Proceedings, 74, 229-234. 
 
Dranoff, G., Jaffee, E.M., Golumbek, P., et al. (1993). Vaccination with irradiated tumor cells 
engineered to secrete murine GM-CSF stimulates potent, specific and long lasting anti-tumor 
immunity. Proceedings of the National Academy of Sciences of the United States of America, 90, 
539-43. 
 
European Organization for Research and Treatment of Cancer (2006). EORTC Quality of Life 
Questionnaires. Retrieved January 19, 2006, from http://www.eortc.be/home/qol/phases.htm  
 
Ferrell, B.R. , Hassey-Dow, K., & Grant, G. (1995). Measurement of the QOL in cancer survivors.  
Quality of Life Research, 4, 523-531. 
 

 
41
Ferrell, B.R., Hassey-Dow, K., Leigh, S. Ly, J., & Gulasekaram, P. (1995). Quality of life in long-            
term cancer survivors. Oncology Nursing Forum, 23, 907-916. 
 
Fitzsimmons, D., George, S., Payne, S., & Johnson, C. D. (1999). Differences in perception of           
quality of life issues between health professional and patients with pancreatic cancer.            
Psycho-oncology, 8, 135-143. 
 
Fitzsimmons D., Johnson, C. D., George, S., Payne, S., Sandberg, A. A., Bassi, C., et al. (1999). 
Development of a disease specific quality of life questionnaire module to supplement the EORTC 
core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. European Journal 
of Cancer, 35, 939-941. 
 
Fitzsimmons, D., Kahl, S., Butturini, M., van Wyk, M., Bornman, P., Bassi, C., et al. (2005). 
Symptoms and quality of life in chronic pancreatitis assessed by structured interview and the 
EORTC QLQ- C30 and QLQ-Pan26. American Journal of Gastroenterology, 100, 918- 
            926. 
 
Heinemann, V., Quietzsch, D., Gieseler, F., et al. (2003). A phase III trial comparing gemcitabine 
plus cisplatin vs. gemcitabine alone in advanced pancreatic cancer. Proceedings ASCO 2003, 22, 
250: Abstract 1003.  
 
Iacobuzio-Donahue, C.A., Maitra, A., Shen-Ong, G.L., et al. (2002). Discovery of novel tumor 
markers of pancreatic cancer using global gene expression technology. American Journal of 
Pathology, 160, 1239-1249. 
 
Institute of Medicine (2005a). From cancer patient to cancer survivor: Lost in transition. Executive 
Summary. Retrieved on January 19, 2006 from http://www.nap.edu/execsumm_pdf/11468.pdf 
 
Institute of Medicine (2005b). Cancer Survivorship Facts and Figures. Retrieved January 19, 2006, 
from http://www.iom.edu/CMS/28312/4931/30869/30886.aspx 
 
Jaffee, E.M., Abrams, R.A., Cameron, J.L., et al. (1998). A phase I trial of lethally irradiated 
allogeneic pancreatic tumor cells transfected with the GM-CSF gene for the treatment of pancreatic 
adenocarcinoma. Human Gene Therapy, 9, 1951-71. 
 
Jaffee, E.M., Dranoff, G., Cohen, L.K., et al. (1993).High efficiency gene transfer into primary 
human tumor explants without cell selection. Cancer Research, 53, 2221-2226 
 
Jaffee, E.M., Hruban, R., Biedrzycki, B., Laheru, D.A., et al. (2001). A Novel Allogeneic GM-CSF 
Secreting Tumor Vaccine for Pancreatic Cancer: A Phase I Trial of Safety and Immune Activation. 
Journal of Clinical Oncology, 19, 145-156. 
 
Kabayashi, H., Terao, T., & Kawashima, Y. (1992). Serum sialyl Tn as an independent predictor of 
poor prognosis in patients with epithelial ovarian cancer. Journal of Clinical Oncology, 10, 95. 
 

 
42
Kawakami, Y., Eliyahu, S., Delgado, C.H., et al. (1994). Cloning of the gene coding for a shared 
human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proceedings of 
the National Academy of Sciences of the United States of America, 91, 3515-3519. 
 
Mehanna, H. M. & Morton, R. P. (2006). Does quality of life predict long-term survival in patients 
with head and neck cancer? Archives of Otolaryngology head and Neck Surgery, 132, 27-             
31. 
 
Schou, I, Ekeberg, O., Sandvik, L., Hjermstad, M.J., & Rulnad, C. M. (2005). Multiple predictors 
of health-related quality of life in early stage breast cancer. Quality of Life Research, 14,             
1813-1823. 
 
Smeenk, H.G., Incrocci, L., Kazemier, G., van Dekken, H., Tran, K.T., Jeekel, J., van Eijck, C.H. 
(2005). Adjuvant 5-FU-Based Chemoradiotherapy for Patients Undergoing R-1/R-2 Resections for 
Pancreatic Cancer. Digestive Surgery, 22, 321-328.  
 
Thomas, A.M., Santarsiero, L.M., Lutz, ER., et al. (2004). Mesothelin-specific CD8+ T cell 
responses provide evidence of in vivo cross priming by antigen presenting cells in vaccinated 
pancreatic cancer patients. Journal of Experimental Medicine, 200, 297-306.  
 
Wenzel, L., DeAlba, I., Habbal, R., Kluhsman, B. C., Fairclough, D., Krebs, L., et al. (2005). 
Quality of life in long-term cervical cancer survivors. Gynecologic Oncology, 97, 310-317. 
 
Yeo, C. J., Cameron, J., L., Sohn, T., Lilliemoe, K. D., Pitt, H., Talamini, M., et al., (1997). Six 
hundred fifty consecutive pancreaticoduodenectomies in the 1990s: Pathology, complications, and 
outcomes. Annals of Surgery, 226, 248-260.   
 
 

 
43
 
Appendices 
 
 
EORTC QLQ-C30 (version 3) 
We are interested in some things about you and your health. Please answer all of the questions yourself by 
circling the number that best applies to you. There are no "right" or "wrong" answers. The information that 
you provide will remain strictly confidential. 
Please fill in your initials:  
Your birthdate (Day, Month, Year):  
Today's date (Day, Month, Year):  
_______ 
Not at            A  
    Quite 
 Very 
All  
      Little  
    a Bit  
Much 
1. Do you have any trouble doing strenuous activities, 
like carrying a heavy shopping bag or a suitcase? 
 1  
 
2 
 
3 
 
 4 
2. Do you have any trouble taking a long walk?   
 1  
 
2  
 
3 
 
 4 
3. Do you have any trouble taking a short walk outside 
of the house?   
 
 
 
 
1  
 
2 
 
3 
 
 4 
4. Do you need to stay in bed or a chair during the day?  1  
 
2  
 
3 
 
 4 
5. Do you need help with eating, dressing, washing 
yourself or using the toilet?  
 
 
 
1  
 
2 
 
 3 
 
 4 
 
During the past week:   
 
 
Not at  
 A  
 
Quite        Very 
All  
 
Little   
a Bit         Much 
6. Were you limited in doing either your work or other 
daily activities?  
 
 
 
 
1 
 
 2  
 
3  
 
4 
7. Were you limited in pursuing your hobbies or other 
leisure time activities?   
 
 
 
1 
 
 2  
 
3 
 
 4 
8. Were you short of breath?  
 
 
 
1 
 
 2 
 
3 
 
 4 
9. Have you had pain?   
 
 
 
1 
 
 2  
 
3 
 
 4 
10. Did you need to rest?  
 
 
 
1 
 
 2  
 
3  
 
 4 
12. Have you felt weak? 
 
 
 
1 
 
 2 
 
3 
 
 4  
13. Have you lacked appetite?   
 
 
1  
 
 2 
 
3 
 
 4 
14. Have you felt nauseated?  
 
 
 
1 
 
 2 
 
3  
 
 4 
15. Have you vomited?   
 
 
 
1  
 
 2 
 
3 
 
 4 
 
During the past week:   
 
 
Not at   
A  
          Quite            Very 
All  
 
Little            a Bit            Much 
16. Have you been constipated?  
 
 
1  
 
2 
 
 3  
 
4 
17. Have you had diarrhea?  
 
 
 
1  
 
2 
 
 3 
 
4 
18. Were you tired?  
 
 
 
 
1  
 
2  
 
 3  
 
4 
19. Did pain interfere with your daily activities?   
1  
 
2 
 
 3  
 
4 
20. Have you had difficulty in concentrating on things, 
like reading a newspaper or watching television?  
1  
 
2 
 
 3 
 
 4 
21. Did you feel tense?   
 
 
 
1  
 
2 
 
 3 
 
 4 
22. Did you worry?  
 
 
 
 
1  
 
2 
 
 3  
 
 4 
23. Did you feel irritable?  
 
 
 
1  
 
2  
 
 3  
 
 4 
24. Did you feel depressed?  
 
 
 
1  
 
2  
 
 3  
 
 4 

 
44
25. Have you had difficulty remembering things?  
1  
 
2 
 
 3 
 
 4 
26. Has your physical condition or medical treatment 
interfered with your family life?  
 
 
1  
 
2  
 
3  
 
4 
27. Has your physical condition or medical treatment 
interfered with your social activities?  
 
 
1  
 
2  
 
3  
 
4 
28. Has your physical condition or medical treatment 
caused you financial difficulties?  
 
 
1 
 
 2  
 
3 
 
 4 
 
For the following questions please circle the number between 1 and 7 that best 
applies to you 
29. How would you rate your overall health during the past week? 
1  
2  
3  
4  
5  
6  
7 
Very poor  
 
 
 
 
 
Excellent 
30. How would you rate your overall quality of life during the past week? 
1  
2 
 3 
 4 
 5 
 6 
 7 
Very poor  
 
 
 
 
 
Excellent 
 
 
© Copyright 1995 EORTC Study Group on Quality of Life. All rights reserved. Version 3.0 
 
 

 
45
City of Hope Quality of Life, Cancer patient/survivor version, QOL-CA 
 
Directions: We are interested in knowing how your experience of having cancer affects your 
Quality of Life. Please answer all of the following questions based on your life at this time. 
 
Please circle the number 0-10 that best describes your experiences: 
 
Physical Well Being 
 
To what extent are the following  a problem for you: 
 
1. Fatigue 
                   no problem   0     1     2     3     4     5     6     7     8     9     10    severe problem 
 
2. Appetite changes 
                    no problem   0     1     2     3     4     5     6     7     8     9     10    severe problem 
 
3. Aches or pain 
                    no problem   0     1     2     3     4     5     6     7     8     9     10    severe problem 
 
4. Sleep changes 
                    no problem   0     1     2     3     4     5     6     7     8     9     10    severe problem 
 
5. Constipation 
                    no problem   0     1     2     3     4     5     6     7     8     9     10    severe problem 
 
6. Nausea 
                    no problem   0     1     2     3     4     5     6     7     8     9     10    severe problem 
 
7. Menstrual changes or fertility 
                    no problem   0     1     2     3     4     5     6     7     8     9     10    severe problem 
 
8. Rate your overall physical health 
                    extremely poor   0     1     2     3     4     5     6     7     8     9     10    excellent 
 
 
Psychological  Well Being 
 
9. How difficult is it for you to cope today as a result of your disease and treatment? 
                   Not at all difficult  0     1     2     3     4     5     6     7     8     9     10    very difficult 
 
10. How good is your quality of life? 
                      Extremely poor   0     1     2     3     4     5     6     7     8     9     10    excellent 
 
 
 

 
46
11. How much happiness do you feel? 
                               None at all  0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
12. Do you feel like you are in control of things in your life? 
      Not at all     0     1     2     3     4     5     6     7     8     9     10    completely 
 
13. How satisfying is your life?  
      Not at all     0     1     2     3     4     5     6     7     8     9     10    completely 
 
14. How is your present ability to concentrate or to remember things? 
Extremely poor   0     1     2     3     4     5     6     7     8     9     10    excellent 
 
15. How useful do you feel? 
        Not at all     0     1     2     3     4     5     6     7     8     9     10    extremely 
 
 
16. Has your illness or treatment caused changes in your appearance? 
        not at all     0     1     2     3     4     5     6     7     8     9     10    extremely 
 
17. Has your illness or treatment caused changes in your self concept (the way you see yourself)? 
        Not at all     0     1     2     3     4     5     6     7     8     9     10    extremely 
 
 
How distressing were the following aspects of your illness and treatment? 
 
18. Initial diagnosis 
       not at all     0     1     2     3     4     5     6     7     8     9     10    very distressing 
      distressing  
 
19. Cancer treatments (i.e. chemotherapy, radiation, or surgery) 
       not at all     0     1     2     3     4     5     6     7     8     9     10    very distressing 
                               distressing  
 
20. Time since my treatment was completed 
       not at all     0     1     2     3     4     5     6     7     8     9     10    very distressing 
                               distressing  
 
21. How much anxiety do you have? 
       not at all     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
22. How much depression do you have? 
       not at all     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
To what extent are you fearful  of: 
 
23. Future diagnostic tests 
           no fear     0     1     2     3     4     5     6     7     8     9     10    extreme fear 

 
47
24.  A second cancer 
           no fear     0     1     2     3     4     5     6     7     8     9     10    extreme fear 
 
25. Recurrence of your cancer 
           no fear     0     1     2     3     4     5     6     7     8     9     10    extreme fear 
 
26. Spreading (metastasis) of your cancer 
           no fear     0     1     2     3     4     5     6     7     8     9     10    extreme fear 
 
Social Concerns 
 
27. How distressing has your illness been for your family? 
       Not at all     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
28. Is the amount of support you receive from others sufficient to meet your needs? 
       Not at all     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
29. Is your continuing health care interfering with your personal relationships? 
       Not at all     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
30. Is your sexuality impacted by your illness? 
       Not at all     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
31. To what degree has your illness and treatment interfered with your employment? 
  No problem     0     1     2     3     4     5     6     7     8     9     10    severe problem 
 
32. To what degree has your illness and treatment interfered with your activities at home? 
   
 
 No problem     0     1     2     3     4     5     6     7     8     9     10    severe problem 
 
33. How much isolation do you feel is caused by your illness or treatment? 
            None     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
 
34. How much financial burden have you incurred as result of your illness and treatment? 
            None     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
Spiritual Well Being 
 
35. How important to you is your participation in religious activities such as praying, going to 
church? 
       Not at all     0     1     2     3     4     5     6     7     8     9     10    very important 
                               important 
 
36. How important to you is other spiritual activities such as meditation? 
       Not at all     0     1     2     3     4     5     6     7     8     9     10    very important 
                               important 
 

 
48
37. How much has your spiritual life changes as a result of cancer diagnosis? 
       Less  
   0     1     2     3     4     5     6     7     8     9     10   more important 
                               important 
 
38. How much uncertainty do you feel about your future? 
Not at all     0     1     2     3     4     5     6     7     8     9     10    very uncertain                      
uncertain 
 
39. To what extent has your illness made positive changes in your life? 
     None at all     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
 
40. Do you sense a purpose/mission for your life or a reason for being alive? 
     None at all     0     1     2     3     4     5     6     7     8     9     10    a great deal 
 
41. How hopeful do you feel? 
Not at all     0     1     2     3     4     5     6     7     8     9     10    very hopeful                      
hopeful 
 
 
 
 

 
49
Herth Hope Index 
 
Listed below are a number of statements. Read each statement and place an [X] in the box that 
describes how much you agree with the statement right now. 
 
Strongly 
Disagree 
Disagree 
Agree 
Strongly  
Agree 
1. I have a positive outlook toward life. 
 
 
 
 
2. I have short and/or long range goals. 
 
 
 
 
3. I feel all alone. 
 
 
 
 
4.  I can see possibilities in the midst  
    of difficulties. 
 
 
 
 
5. I have a faith that gives me comfort. 
 
 
 
 
6. I feel scared about my future. 
 
 
 
 
7. I can recall happy/joyful times. 
 
 
 
 
8. I have deep inner strength 
 
 
 
 
9. I am able to give and receive  
   caring/love. 
 
 
 
 
10. I have a sense of direction. 
 
 
 
 
11. I believe that each day has potential. 
 
 
 
 
12. I feel my life has value and worth. 
 
 
 
 

 
50
Symptom Distress Scale 
Below are 5 different numbered statements. Thin about what each statement says, then 
place a circle around the one statement that most closely indicates how you have been feeling 
lately. The statements are ranked from 1 to 5, where number one indicates no problem and number 
five indicates the maximum amount of problems. Numbers two through four indicate you feel 
somewhere in between the two extremes. Please circle one number on each line. 
 
Degrees of Distress 
Nausea (1) 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
I seldom if ever  
    I have nausea once 
I have nausea fairly                    I have nausea half                I have nausea 
have nausea. 
        in a while. 
 
           often. 
 
     the time at least.   
continually. 
 
 
Nausea (2) 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
When I do have 
       When I do have  
       When I have                          When I have                       When  I have  
nausea, it is very          nausea, it is mildly  
    nausea, I feel pretty  
     nausea, I usually 
  nausea, I am as 
 mild. 
 
            distressing.  
 
sick. 
 
        feel very sick.                     sick as I could  
 
 
 
 
 
 
 
 
 
 
 
       possibly be. 
 
 
Appetite 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
I have my normal            My appetite is  
     I don’t really enjoy                      I have to force                  I cannot stand the 
appetite and enjoy            usually, but not                        my food.                                   myself to eat                     thought of food. 
   good food.                    always, pretty good. 
 
 
 
 
food. 
 
 
Insomnia 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
I sleep as well as I            I occasionally have                I frequently have                        I have difficulty                   It is almost 
always have.                     trouble getting to                    trouble getting to                      getting to sleep and         impossible for me 
        sleep and staying asleep.               sleep.                                staying asleep almost              to get a decent   
 
 
 
 
 
 
 
every night.                       night’s sleep. 
 
 
Pain (1) 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
I almost never                 I have pain once in                  I have pain several                    I am usually in some            I am in some 
have pain.                               a while.                                  times a week.                              degree of pain.               degree of pain 
                                                                                                                                                                                  almost constantly. 
 
 
Pain (2) 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
When I do have pain             When I do have             When I do have                        The pain I have is                The pain I have is 
pain, it is very                       pain, it is mildly           pain, it is usually                              very intense                 almost unbearable. 
Mild.                                        distressing.                    fairly intense.     
 
   
 
          
 

 
51
Fatigue 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
I seldom feel tired         There are periods                     There are periods                 I am usually very                    Most of the time,       
 or fatigued.                   when I am rather                      when I am quite                    tired and fatigued.                  I feel exhausted. 
                                      Tired or fatigued.                      tired and fatigued.  
 
 
Bowel 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
I have my normal            My bowel pattern                 My present bowel                         I am usually in                     I am in almost 
bowel pattern.                  Occasionally causes            pattern occasionally                       considerable                           constant 
                                       me some discomfort.          causes me considerable                   discomfort because                discomfort 
                                                                                      discomfort.                                 of my present bowel              because of my                              
 
 
 
    
                                                                            pattern.   
 
         Bowel pattern. 
 
Concentration 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
I have my normal               I occasionally have               I occasionally have                I usually have                  I just can’t seem 
ability to                                    trouble                                 considerable                         considerable                to concentrate at 
concentrate.                           Concentrating.                              Trouble                               difficulty                                 all. 
                                                                                               Concentraasting.                 concentrating. 
 
 
Appearance 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
My appearance               Occasionally I am                     I am not often                       Most of the time I              The worsening of 
has basically not                concerned about                   concerned that my                   am concerned that                   my physical  
changed.                            The worsening of                       appearance is                         my physical                        appearance is a      
                                          my physical                              worsening.                          appearance is                             constant, 
appearance.  
 
 
 
           worsening.                         preoccupying 
 
 
 
 
 
 
 
           concern. 
 
 
 
 
Breathing 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
 
I usually breathe              I occasionally                           I often have trouble             I can hardly ever                   I almost always 
normally.                          Have trouble                                  breathing.                      Breathe as easily as                   have severe 
                                          breathing.                                                                                    I want.                         Trouble with my 
          breathing. 
 
Outlook 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
I am not worried             I am slightly                           I am worried                         I am very worried                  I am terrified by 
or frightened                    worried but not                    frightened about                          and frightened                     thoughts of the  
about the future.              Frightened about                          things.                                 About things.                                 Future.     
  
 
              Things.   
 
Cough 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
I seldom cough.               I have an                                I often cough.                      I often cough, and                     I often have 
                      occasional cough.                                                                    Occasionally have                     persistent and  
                                                                                                                       severe coughing                    severe coughing 
                                                                                                                               spells.                                      spells. 

 
52
Trust Scale 
 
 
How much do you trust your physician(s) ….. 
 
Completel
y 
Mostly Somewh
at 
A little Not 
at 
all 
1. To put your health and well-being above 
keeping down the health plan’s costs? 
 
 
 
 
 
2. To keep personally sensitive medical 
information private? 
 
 
 
 
 
3. To provide you with information on all 
potential medical options and not just options 
covered by the health plan? 
 
 
 
 
 
4. To refer you to a specialist when needed? 
 
 
 
 
 
5. To admit you to the hospital when needed?  
 
 
 
 
6. To make appropriate medical decisions 
regardless 
of 
health 
plan 
rules 
and 
guidelines? 
 
 
 
 
 
7. Judgment about your medical care? 
 
 
 
 
 
8. To perform necessary medical tests and 
procedures regardless of costs? 
 
 
 
 
 
9. To offer you high-quality medical care? 
 
 
 
 
 
10. To perform only medically necessary 
tests and procedures? 
 
 
 
 
 
 

 
53
Pancreatic Cancer Survivor Survey 
 
Subject ID ____________ 
 
 
 
Date _____________ 
Pancreatic Cancer Survivor Research Participant 
Baseline Survey 
 
1.   When did you decide whether or not you wanted to join the research study?  
Check only one answer. 
 Before arriving at Hopkins 
 During my visit at Hopkins 
 After my first visit at Hopkins 
 Still have not decided 
 
 2. When did you decide whether or not you wanted to join the research study?  
      Check only one answer. 
 As soon as I first heard about it 
 When I first met the study staff (doctor, nurse, assistant) 
 After hearing what the research study was all about  
 After I felt that I really understood the study 
 Still have not decided 
 
3.  Did you know about the research study before you came to Hopkins? 
         Yes 
 
  No     
 
If yes, how did you know about the research study? 
  TV report or news  
    Newspaper 
 
  Magazine 
  Internet search 
 
    Advocacy group     
  Patient    
  Spouse or significant other     Family member  
  Friend 
  Primary or local oncologist    Primary or local general health practitioner 
  Other. Specify type ________________________________________ 
 
4.   What information was most helpful in making the decision about joining the research  
       study? Check only one  answer. 
 Discussion  
 Informed consent form 
 Other. Specify: __________________________________________________ 
 
5.  Who influenced your decision to join the research study? Check all that apply. 
  Study doctor 
 
 
  Study nurse  
 
  Study assistant 
  Informed consent form                     Media 
 
 
  Other patients 
  Spouse or significant other  
  Family member 
 
  Friend 
  Primary or local oncologist   
  Primary or local general health practitioner 
 Cancer center staff other than study doctor, nurse, assistant. List staff’s role, if known  
(for example: registrar, secretary, technician, chaplin, etc.)_________________________ 
  No one 

 
54
If one person helped you to decide more than the other,   
     circle that one person from the above list. 
 
6.  How many people came with you to Hopkins to learn about the research study? 
 Just me 
 
 
 One person  
 
 Two people  
 
 Three people 
 
 Four people  
 
 Five or more people 
 
Subject ID ____________ 
 
 
 
Date _____________ 
 
7.  After you learned all about the research study from the study team at Hopkins, did you  
    discuss the research study with anyone before making the decision? 
         Yes 
    
 
 No   
 
 
If yes, who? Check all that apply. 
 Spouse or significant other      
 Son…….. Check age   less than 16      16-21    22-34   35-49    50 or older 
 Daughter..Check age   less than 16      16-21    22-34    35-49    50 or older 
          Mother 
 
  Father  
     Mother-in law      Father-in-law 
          Sister   
 
  Brother 
     Aunt 
 
   Uncle 
          Close friend  
 Distant friend    Patient with same illness 
          Local oncologist          Local general practitioner                  Local nurse 
    
 
If one person helped you to decide more than the other,   
     circle that one person from the above list. 
 
8.  About how much time did you think about your decision to join the research study? 
  Less than an hour  
 
 1-2 hours 
 
 
 3-4 hours   
  Almost a full day  
 
 1-2 days 
 
 
 3-4 days 
  Almost a full week  
 
 1-2 weeks 
 
 
 3-4 weeks 
 
9. What would have helped to make the decision easier? 
 
________________________________________________________________________ 
 
________________________________________________________________________ 
 
 
10. Did you receive adequate information to make the decision about being in the  
      research study? 
 
 
 
 
 
  Yes     
 
 No   
 
11. Are you satisfied with your decision? 
  
 
  Yes     
 
 No   
 
12. Do you basically understand the research study?   
  Yes     
 
 No   
 
13. Are you aware of any possible conflict of interest within the research study? 
  Yes     
 
 No    
  

 
55
14. What lead you to above response about the possible conflict of interest?  
       Check all that apply. 
 
Information from: 
  Study doctor 
 
 
  Study nurse  
 
  Study assistant 
  Informed consent form                     Media      
  
 
  Other patients 
  Spouse or significant other  
  Family member 
 
  Friend 
  Primary or local oncologist   
  Primary or local general health practitioner 
  Cancer center staff other than study doctor, nurse, assistant. List staff’s role, if known (for 
example: registrar, secretary, technician, chaplin, etc.)_________________________ 
 
15.  Did the informed consent form mention any possible conflict of interest? 
  Yes     
 
 No   
 
Subject ID ____________ 
 
 
 
Date _____________ 
 
16. Do you have other options besides this research study? 
    Yes 
 
  No  
 
If yes, what options are available to you? Check all that apply. 
  Other research studies 
 
 
 
  Standard therapy     
  Additional consultation (2nd or 3rd opinion)    
  No therapy 
  Complementary therapy 
 
 
 
  Hospice care 
              Other __________________________________________________ 
 
17. Do you have any advance directives? 
 
  Yes     
 
  
 
If yes,  
            Do you have a living will? 
  
 
 
 
  Yes     No    
            Do you have a durable power of attorney for health care?    Yes     No   
 
Is this information in your medical records at Hopkins?    
  Yes     No   
 
 No   
 
If no, 
 
Do you know what advance directives are?    
 
   Yes    No 
 
Have you received information about advance directives?       Yes    No  
 
Do you need more information about advance directives?    Yes    No  
 
 
What is the one main reason why you do not have advance directives? 
  Need more information 
 
   Not needed now 
 
 
 
  Too much trouble  
 
   Cannot find the forms 
 
  Too difficult to think about now        Don’t understand the forms 
 
 
  Waste of time 
 
 
    Can’t decide what to do 
               Other____________________________________________________      

 
56
 
Protocol No. 
Participant Number 
Participant Initials 
         Vaccine : ______ 
J-0619 
 
 
 
 
 
 
 
 
Date vaccine administered: 
___/___/___ 
      
RESEARCH PARTICIPANT DIARY - VACCINE REACTIONS 
 
Other Reactions 
Start date 
Stop date 
Describe 
Action Taken 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Call 
 or 
 
 before taking any new medications and if you have any questions.  
 
 
 
     _______________________________________ Research participant’s signature & 
date 
 
 
______________________________________________________________ Reviewer’s signature 
& date 
 
 
Continued on the next page 
Vaccine site 
reactions 
Start date 
Stop date 
Location 
 
Size 
(Example, 
size of a dime, 
etc.) 
Action taken, if any 
(Example, aloe vera, 
vitamin E gel, etc.) 
Redness 
 
 
 
 
 
Swelling 
 
 
 
 
 
Tenderness 
 
 
 
-------------- 
 
Itching 
 
 
 
------------- 
 
 
 
 
 
 
 

 
57
 
HEALTH / MEDICAL COMPLAINTS 
If you experience any health/medical complaints, record this information below.  
Describe what you experienced 
Date 
started 
Date 
stopped 
Actions taken (medications, 
procedures, etc.) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                      MEDICATIONS 
Record any changes in doses and the stop dates of current medications. Record any new 
medications (prescription and/or over-the-counter, including herbal medications and vitamins) 
taken.   
Name of medication, dose and frequency 
 
Reason 
Date  
started 
Date 
stopped 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
________________________________________ Research participant’s signature 
and date 
 
Protocol No. 
Participant Number 
Participant Initials 
         Vaccine : ______ 
J-0619 
 
 
 
 
 
 
 
 
Date vaccine administered: 
___/___/___ 

 
58
_______________________________________________________________ 
Reviewer’s 
signature and date 
 check if this is the last page to record your health/medical complaints and medicines  for this 
cycle.