A Phase I Trial of IRS-1 HSV C134 Administered Intratumorally in Patients With Recurrent Malignant Glioma
Phase: PHASE1
Conditions: Glioblastoma Multiforme of Brain, Anaplastic Astrocytoma of Brain, Gliosarcoma of Brain
Sponsor: University of Alabama at Birmingham

A Phase I Trial of IRS-1 HSV C134 (IND 17296) Administered Intratumorally in Patients with 
Recurrent Malignant Glioma 
 
Study Protocol & Statistical Analysis Plan  
 
NCT03657576 
 
 
Date of Last Protocol Approval  
17 December 2023  
 
 
James Markert, MD  
University of Alabama at Birmingham  
Birmingham, AL 35294 

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HSV C134 Protocol  
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Comprehensive Cancer Center 
University of Alabama-Birmingham 
Birmingham, Alabama 
 
 
 
 
A Phase I Trial of IRS-1 HSV C134 (IND 17296) Administered Intratumorally in Patients with 
Recurrent Malignant Glioma 
 
Date: 4 Aug 2023 
Version number:  3.0   
 
 
 
 
 
Approval Dates: 
 
 
Review Panel  
 
 
 
Date(s) 
 
 
 
Protocol Version 
CCC Concepts Committee 
 
 
January 26, 2018 
 
 
DRAFT Version 0.2 
Brain Tumor Working Group  
 
February 16, 2018 
 
 
DRAFT Version 0.2 
Clinical Trials Operations Committee  
February 23, 2018 
 
 
DRAFT Version 0.2 
Gene Therapy Panel  
 
 
June 21, 2018  
 
 
DRAFT Version 0.5 
Protocol Review Committee  
 
June 21, 2018  
 
 
DRAFT Version 0.5 
Institutional Biosafety Committee 
 
August 21, 2018 
 
 
DRAFT Version 1.0 
Institutional Review Board 
 
 
September 11, 2018  
 
 
Version 2.0 
Institutional Review Board 
 
 
November 20, 2018  
 
 
Version 2.1 
Institutional Review Board 
 
 
January 30, 2019 
 
 
 
Version 2.2 
Institutional Review Board 
 
 
April 26, 2019  
 
 
 
Version 2.3 
Institutional Review Board 
 
 
November 29, 2019  
 
 
Version 2.4 
Institutional Review Board 
 
 
May 4, 2020  
 
 
 
Version 2.5 
Institutional Review Board 
 
 
April 28, 2021  
 
 
 
Version 2.6 
Institutional Review Board 
 
 
July 29 2022  
 
 
 
Version 2.7 
Institutional Review Board 
 
 
March 22, 2023 
 
 
 
Version 2.8 
Institutional Review Board 
 
 
September 2, 2023 
 
 
 
Version 2.9 
Institutional Review Board 
 
 
 
 
 
 
 
 
Version 3.0 
 
 
 
 
 
Principal Investigators 
 
 
 
Biostatisticians 
James M. Markert, M.D.  
 
 
 
Gary Cutter, PhD 
Kevin A. Cassady, M.D. 
 
 
 
Inmaculada Aban, PhD 
 
 
Research Nurse Coordinator  
 
 
Data Coordinator 
Norma Miller, RN 
 
 
 
 
TBN 
 

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HSV C134 Protocol  
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STUDY SYNOPSIS 
 
 
Objective: 
To obtain safety information in small cohorts of individuals, with cohorts to 
receive escalating doses of IRS-1 HSV C134 (hereafter C134).  Safety will 
be assessed at each dose level before proceeding to the next dose.  
Biologic secondary objectives include characterization of the in situ activity 
of C134 after intratumoral inoculation and of the local and systemic 
immune responses to C134.  As a clinical secondary objective, patients 
will be followed serially by MRI for potential clinical response to C134. The 
clinical strategy takes advantage of the virus’ ability to infect and lyse tumor 
cells and the potential for enhancement of this effect by the induction of an 
anti-tumor immune response. 
Treatment Indication: 
Progressive growth of glioblastoma multiforme, anaplastic astrocytoma or 
gliosarcoma after radiation therapy. 
Clinical Phase: 
Phase 1 (open-label) 
Design: 
 
 
 
 
Single dose of C134 infused through catheters into region(s) of tumor 
defined by MRI. Dosage escalation proceeds only after a minimum of 24 
days of observation, if incidence of Grade III/IV toxicities is acceptable. 
Dose increases or reductions will be determined using a modified 
Continual Reassessment Method (CRM); extent of dose changes for 
subsequent subjects will be increased up to, but not exceeding the next 
higher dose level (1 log). Dose modifications will utilize a modified CRM for 
each successive subject until an MTD or the maximal planned dose is 
reached. 
Study Duration Per 
Patient: 
12 months 
Subject Population: 
4 to 24 patients with recurrent/progressive glioblastoma multiforme, 
anaplastic astrocytoma or gliosarcoma depending on toxicities. 
Study Medication and 
Dosage: 
Dose escalations of up to, but not exceeding the next highest dose level 
(1 log).  Dose escalations from 1 x 106 to 1 x 108 plaque-forming units of 
C134. 
Safety Evaluations: 
Follow-up evaluations using routine laboratory analyses and clinical 
measurements of neurological function and evidence of C134-related 
toxicity. Studies to evaluate the possibility of C134 shedding will also be 
conducted.  Patients will be observed closely during the planned post-
treatment hospitalization period, followed by outpatient evaluations done 
at Day 10 and Day 28, then months 3, 6, and 12, subject to disease 
progression. 
Study Endpoints 
Primary:   CRM-estimated highest safe dose or maximally planned dose 
if no dose-limiting toxicity observed. 
Secondary: Time to progression, survival, biologic assessments. 

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TABLE OF CONTENTS 
1. 
OBJECTIVES ................................................................................................................................. 4 
1.1 
Primary Objective..................................................................................................................... 4 
1.2 
Secondary Objectives .............................................................................................................. 4 
2. 
BACKGROUND .............................................................................................................................. 4 
2.1 
Glioblastoma multiforme. ......................................................................................................... 4 
2.2 
Experimental therapies and conditionally replication competent viruses .................................. 4 
2.3 
Innate antiviral response pathway and viral countermeasures. ................................................ 5 
2.4 
Viral evasion of PKR. ............................................................................................................... 5 
2.5 
134.5 HSV-based therapy. .................................................................................................... 6 
2.6 
Strategies to improve HSV antiglioma therapy ......................................................................... 6 
2.7 
HSV/HCMV chimeric viruses. .................................................................................................. 8 
2.8 
Specific Findings On Safety and Efficacy of C134.................................................................... 8 
3. 
PATIENT SELECTION .................................................................................................................. 14 
3.1 
Eligibility Criteria .................................................................................................................... 14 
3.2 
Exclusion Criteria ................................................................................................................... 15 
3.3 
Inclusion of Women and Minorities ........................................................................................ 16 
4. 
TREATMENT PLAN ...................................................................................................................... 16 
4.1 
C134 Administration ............................................................................................................... 16 
4.2 
Dose-Limiting Toxicity ............................................................................................................ 19 
4.3 
Supportive Care Guidelines ................................................................................................... 19 
4.4 
Duration of Therapy/Study ..................................................................................................... 20 
5. 
EXPECTED ADVERSE EVENTS/DOSE MODIFICATIONS .......................................................... 20 
5.1 
Expected Adverse Events Associated with Malignant Glioma ................................................ 20 
5.2 
Dosing Delays/Dose Modifications ......................................................................................... 21 
5.3 
Study Stopping Criteria .......................................................................................................... 21 
6. 
AGENT FORMULATION AND PROCUREMENT .......................................................................... 22 
6.1 
C134 Formulation and Storage .............................................................................................. 22 
6.2 
C134Dose Preparation .......................................................................................................... 22 
6.3 
Precautions in Handling C134 ................................................................................................ 22 
6.4 
Precautions in Disposal of C134 ............................................................................................ 22 
7. 
CORRELATIVE/SPECIAL STUDIES ............................................................................................ 23 
8. 
STUDY CALENDAR ..................................................................................................................... 24 
9. 
MEASUREMENT OF EFFECT ..................................................................................................... 25 
9.1 
Definitions .............................................................................................................................. 25 
9.2 
Guidelines for Evaluation of Measurable Disease .................................................................. 25 
9.3 
Response Criteria .................................................................................................................. 25 
9.4 
Confirmatory Measurement/Duration of Response................................................................. 26 
9.5 
Progression-Free Survival ...................................................................................................... 27 
10. 
REGULATORY AND REPORTING REQUIREMENTS .............................................................. 27 
10.1 
Expedited Adverse Event Reporting ...................................................................................... 27 
10.2 
Data Reporting ....................................................................................................................... 28 
10.3 
CTEP Multicenter Guidelines:  N/A ........................................................................................ 28 
10.4 
Cooperative Research and Development Agreement (CRADA)/Clinical Trials Agreement 
(CTA):  N/A ....................................................................................................................................... 28 
10.5 Study Monitoring………………………………………………………………………………………...28 
11. 
STATISTICAL CONSIDERATIONS ........................................................................................... 28 
11.1 
Study Design/Endpoints ......................................................................................................... 28 
11.2 
Sample Size/Accrual Rate ..................................................................................................... 29 
11.3 
Stratification Factors .............................................................................................................. 29 
11.4 
Analysis of Secondary Endpoints ........................................................................................... 29 
12. 
REFERENCES/ABBREVIATIONS/APPENDICES ..................................................................... 31 

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Clinical Protocol:  A Phase I Trial of IRS-1 HSV C134 Administered 
Intratumorally in Patients with Recurrent Malignant Glioma 
1. OBJECTIVES 
Lay Abstract: C134  is a next-generation oncolytic herpes simplex virus (oHSV) that is 
conditionally replication competent; that is, similar to G207, a first generation oHSV, it can replicate 
in tumor cells, but not in normal cells, thus killing the tumor cells directly through this process. 
Replication of C134 in the tumor itself not only kills the infected tumor cells, but causes the tumor 
cell to act as a factory to produce new virus. These virus particles are released as the tumor cell 
dies, and can then proceed to infect other tumor cells in the vicinity, and continue the process of 
tumor kill. In addition to this direct oncolytic activity, the virus promotes an immune response 
against surviving tumor cells, which increases the antitumor effect of the therapy.  The virus 
expresses a gene from another virus from the same overall virus family, human cytomegalovirus, 
that allows it to replicate better in the tumor cells than G207. However, the virus has also been 
genetically engineered to minimize the production of any toxic effects for the patient receiving the 
therapy. 
1.1 Primary Objective 
To determine the safety and tolerability of stereotactic intracerebral injections of escalating doses 
of C134 virus, and to determine the maximally tolerated dose (MTD) of C134. 
1.2 Secondary Objectives 
To obtain preliminary information about the potential benefit of C134 in the treatment of patients 
with recurrent malignant gliomas including relevant data on markers of efficacy, including time to 
tumor progression and patient survival. 
2. BACKGROUND  
2.1 Glioblastoma multiforme.  
Malignant gliomas are the most frequently occurring primary brain tumors (1). Glioblastoma 
multiforme, the most malignant of these neoplasms, has also proven to be one of the most fatal 
and refractory cancers (2, 3). Median time to progression and median survival have not 
changed in the past fifty years for these tumors and have thus engendered intensive exploration 
into the study of additional treatment modalities (4).  
2.2 Experimental therapies and conditionally replication competent viruses 
Current molecular therapies for malignant glioma fall into three major groups amongst which there 
is considerable overlap: ligand-based therapies, immunotherapies, and vector-mediated therapies (5). 
While several different modified viruses are under investigation for the treatment of human 
malignancies, this application focuses on conditionally replication competent, 134.5 HSV. 
Oncolytic HSV-1 therapy. Herpes simplex viruses are large, enveloped, DNA viruses with an 
approximately 152 kilobase (kb) pair genome. Genetically modified HSV are attractive as replication-
competent, oncolytic vectors for a number of reasons: 1) procedures for constructing novel HSV are 
well established; 2) multiple genes can be deleted and/or replaced with therapeutic foreign genes 
without affecting the replication capacity of the virus; 3) considerable experience with the biology of 
HSV and its behavior in humans and nonhuman primates exists; and 4) modified herpesviruses retain 
sensitivity to standard antiviral drug therapy as a “built-in” safety feature (5-7).  

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Genes producing neurovirulence of HSV-1 are distinct from 
those that confer oncolytic properties. Deletion of the HSV-1 
neurovirulence gene allows the safe administration of these 
oncolytic vectors to  
mitotically active CNS tumors. Though capable of entry into 
non-dividing normal cells in the CNS, these 134.5 HSV cannot 
replicate efficiently except in actively dividing cells such as tumor 
cells (8-10), and hence are referred to as tumor-selective viruses. 
HSV-1 mutants with deletions of both copies of the 134.5 gene 
have shown significant efficacy for therapy of brain malignancies 
in preclinical animal models, and have been demonstrated to be 
safe in Phase I and II trials in both the United States and Great 
Britain (7, 11, 12). The virus examined in the U.S. trial, G207, 
contains an additional mutation in the viral ribonucleotide 
reductase gene, UL39, as an additional safety feature to limit viral 
growth (1). 
2.3 Innate antiviral response pathway and viral countermeasures.  
Eukaryotic cells contain an innate defense system that targets viral infection (13). A principal 
component of this system is protein kinase R (PKR), which limits viral gene expression and replication in 
human cells (Figure 1) (14). Low levels of this evolutionarily conserved, interferon-inducible kinase are 
present in a non-active form in unstressed cells. However, its producti on is induced by type I interferons 
or double-stranded RNA (dsRNA) produced during viral infection (13). Upon binding dsRNA, the kinase 
activates and phosphorylates itself as well as cellular proteins involved in the antiviral response. The best 
characterized of the substrates is the α subunit of eukaryotic translation initiation factor 2 (eIF-2) (15, 
16). Phosphorylation of eIF-2 prevents recycling of a critical translation initiation factor, thus limiting viral 
and cellular protein synthesis in the infected cell (14).The PKR-mediated host protein shutoff response, 
in addition to serving as an antiviral defense system in the cell, is also involved in cellular homeostasis. 
Consequently, second messenger signaling pathways in the cell and PKR modulate one another’s activity 
in the cell. These pathways can block PKR activation during periods of cellular stress or cellular 
replication. For example, upregulation of mitogen-activated protein kinase (MAPK) activity in the cell 
(mediated by a component of this pathway, MEK) blocks PKR activation during growth factor stimulation 
or following radiation (depicted as “IR” in Figure 1) (17, 18). Likewise, activated PKR has also been 
shown to modulate MAPK function in the cell and is thought to act as a signal integration point between 
the pathways (19). While regulation of protein synthesis initiation is the best characterized of the PKR 
antiviral functions, the kinase also modulates other cellular functions, including: bulk protein degradation 
in the cell (also called autophagy), RNA transcription, and signal transduction in the cell (17, 20-22). 
Viruses have evolved to selectively regulate the cellular responses to infection by targeting different 
components of the PKR pathway. 
2.4 Viral evasion of PKR.   
Efficient viral protein synthesis is essential for viral replication. Consequently, viruses have evolved 
genes whose products specifically target the PKR protein shutoff response. Those relevant to this 
proposal are summarized in the next three subsections. 
2.4.1. The HSV-1 134.5 gene encodes a multifunctional protein that prevents PKR-mediated 
protein shutoff during infection (9, 23). One function allows late viral protein synthesis in infected cells, 
and is encoded within the 3’ gene domain (8). During infection, wild-type HSV-1 produces 
complementary mRNA transcripts that anneal, forming stable dsRNA which triggers the dimerization 
and activation of dsRNA-activated host protein kinase R (PKR). The HSV-1 134.5 protein (ICP34.5) 
overcomes this PKR-mediated host protein shutoff by binding and recruiting a host phosphatase that 
specifically dephosphorylates eIF-2, allowing continued viral protein synthesis (hereafter referred to as 
the HSV wild-type protein synthesis phenotype) in the infected cell (Figure 1) (24, 25). Recombinant 
viruses that lack the 134.5 gene (134.5 HSV) are incapable of maintaining eIF-2 in an 

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unphosphorylated form and therefore are unable to maintain protein synthesis in the infected cell (26). 
Cessation of protein synthesis occurs at the onset of viral DNA synthesis late in infection, essentially 
eliminating bulk synthesis of viral structural proteins necessary for viral capsid formation (26). 
Consequently, 134.5 HSV replicate inefficiently and produce fewer progeny virions in cells with intact 
PKR pathways (27). 
The 134.5 gene also encodes a second function, neurovirulence, enabling efficient viral replication 
in post-mitotic neuronal cells (8-10, 24). Neurovirulence and protein synthesis functions encoded by the 
134.5 gene are discrete and separable. 134.5 HSV are incapable of efficient replication after direct 
inoculation in the CNS and do not produce encephalitis (9). As such, 134.5 HSV vectors have been 
developed as anti-tumor agents for CNS-based malignancies. Whereas 50-100 PFU of wildtype HSV will 
produce encephalitis and death in half of the mice inoculated intracerebrally, more than 1 x 107 PFU are 
required to produce encephalitis and death with a 134.5 HSV recombinant (9).  
2.4.2 Cryptic HSV-1 PKR-evasion genes. 134.5 HSV can develop secondary mutations 
following serial infection in cultured cells that result in improved late viral protein synthesis and restore 
viral evasion of PKR (27, 28). Two mutations have been described. The first mutation results in the earlier 
expression of an HSV-1 RNA-binding protein, Us11 (Us11), and prevents PKR activation and 
dimerization (Figure 1) (28-31). Another suppressor mutant has been described that maps outside of the 
US8-12 domain (27). This suppressor mutant does not alter Us11 kinetic expression, is more virulent than 
the parent virus (LD50 of 4.8 x105) and its anti-PKR activity appears to be mediated by a different 
mechanism which involves PKR dephosphorylation (27).  
2.4.3 HCMV and PKR evasion. HCMV, like HSV, produces complementary mRNA following 
infection and is at risk for forming dsRNA and triggering PKR activation. Two genetically related HCMV 
genes, IRS1 and TRS1, block PKR function in the infected cell (32, 33). The two genes share a common 
5’ sequence but diverge in the 3’ domain. Studies performed by our group and others (32) have shown 
that the IRS1 and TRS1 genes are both capable of PKR-mediated protein shutoff. Child et al. showed 
that the HCMV gene could complement a defective vaccinia virus and described a dsRNA binding domain 
in the N-terminal shared-protein domain (32). Our studies show that the HCMV genes independently 
complemented 134.5 late viral protein synthesis and preliminary data show that the HCMV genes block 
PKR activation by a different mechanism than wild-type or recombinant HSV. In addition to this shared 
function with IRS1, the TRS1 gene encodes a unique function. The TRS1 gene is integral to HCMV viral 
replication in cell culture. In contrast, the IRS1 gene is readily eliminated from the virus without affecting 
growth in cell culture (34, 35).  
2.5 134.5 HSV-based therapy. 
Some tumor cells contain mutations that enable 134.5 HSV late viral protein synthesis and enhance 
replication (36-42). In general, these mutations either occur directly in the PKR/ eIF-2 pathway or they 
indirectly affect PKR function by upregulating MAPK activity (37, 38, 43). In addition to mutations, ionizing 
radiation (IR) has been shown to upregulate MAPK activity, thereby facilitating late viral protein synthesis 
and replication of 134.5 HSV in gliomas (18, 44). Direct damage to the glioma cell by replicating virus 
may represent only one component of HSV based anti-glioma effect. Immunologic response to the virus 
and exposed tumor antigens may also contribute to the mechanism of 134.5 HSV-based therapy in 
gliomas. 
A recently published study, and preliminary studies by our group, indicate that the PKR pathway is 
functionally intact in gliomas susceptible to oncolysis by 134.5 HSV (40). Furthermore, our preliminary 
data indicate that 134.5 HSV do not synthesize late viral proteins or replicate efficiently in malignant 
glioma cell culture monolayers or in in vivo tumor studies (Figure 3A-C and data not shown). Despite 
this inefficient replication, oncolytic HSV improve survival in in vivo tumor studies. While encouraging, 
current 134.5 vectors are unable to consistently eliminate the entire tumor.   
2.6 Strategies to improve HSV antiglioma therapy 
The ultimate goal of oncolytic viral therapy is to achieve maximum tumor cell killing while retaining 
safety in surrounding normal tissue. To achieve this goal, engineered viruses must be able to selectively 

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replicate and spread throughout the tumor bed without affecting adjacent normal tissue. While the 134.5 
recombinants are safe for intracranial administration, these first generation vectors are limited in their 
replication in tumors and ultimately most patients treated with oncolytic HSV have died from their tumor 
(11). To improve 134.5-based therapy, modifications of the virus have focused on improving viral 
replication, spread within the tumor bed, and enhancing bystander damage to uninfected tumor cells.   
2.6.1 Improving Viral Replication. 
2.6.1.1 Irradiation. Initial studies showed that intratumor injection of the 134.5 into U87-MG 
tumors in nude mice, followed by irradiation improved survival of mice over either therapy alone (45). 
Further studies have demonstrated that in multiple tumor models, IR improves the replication of a variety 
of recombinants, including a virus containing a copy of the 134.5 gene (46, 47). Maximal effects seemed 
to occur when IR was administered between 6 and 24 hours after viral dosing, and occurred over a large 
dose range (5-20 Gy). Improved viral protein synthesis and increased viral replication after external beam 
ionizing radiation (IR) accounted for at least part of the mechanism of the increased tumor-specific killing 
(18, 44). Importantly, these results do not appear to be limited to 134.5 HSV vectors, and no increased 
toxicity was noted with this combined treatment.  
2.6.1.2 Second site mutations. Serial passage of 134.5 HSV in tumor cells in culture selects 
for mutations which allow for improved late viral protein synthesis, and improved viral replication in the 
tumor as described in section B.4.2 (28, 31, 48). Initial reports (2001) indicate that the US11 
compensatory mutant was aneurovirulent (LD50>6 x105); however, it was engineered in a more 
neurovirulent strain of HSV-1 which limited maximal LD50 testing. No intracranial tumor studies were ever 
published  with the US11 recombinant and it was developed for treatment of prostate tumors (31, 49).  
2.6.1.3 Tumor targeting of wild-type HSV-1. Another approach is to selectively target wild-type 
HSV to tumors by modification of HSV glycoproteins required for virus entry. Recombinant HSV have 
been constructed that exclusively enter tumor cells through tumor-specific receptors (50, 51). 
Alternatively, expression of the 134.5 from a tumor-specific promoter has also been considered to 
increase replication of these oncolytic HSV vectors (50, 52). 
2.6.1.4 Temozolomide (TMZ) is an oral alkylating agent approved for treatment of GBM. A 
phase III clinical trial demonstrated that TMZ combined with radiation therapy improved patient survival 
(3). Recent studies demonstrated that combinatorial TMZ + G207 HSV therapy resulted in a synergistic 
response and improved survival over either therapy alone in animal studies. While TMZ added to wild-
type HSV-1 exhibited no synergy, it had an additive effect and importantly, was not antagonistic (53). 
There are no data on the effect of TMZ on 134.5 capable of late viral protein synthesis and wild-type 
replication.  
2.6.2 Increasing Viral Spread.  
Viral spread in the tumor has been posited as another limitation of oncolytic virus therapy. Necrotic 
and ischemic regions of the tumor will not support viral replication and are thought to limit spread of the 
virus through the tumor (54). In the phase I clinical trial with G207, patient tumor samples showed virus 
infected tumor separated from uninfected tumor by necrotic regions (J.M. Markert, unpublished data). 
Convection enhanced delivery has been used with adenovirus and AAV to increase the distribution of 
virus through bulk flow in the tumor interstitium (55). Genetic modification such as the insertion of a 
fusogenic glycoprotein has also been used to enhance viral spread (56). Finally, other investigators have 
used multiple injections in the tumor to overcome the limitations posed by necrotic regions in the tumor 
(57). 
2.6.3 Enhancing Bystander Toxicity 
In addition to direct viral damage to the tumor, oncolytic HSV have also been used as a platform 
for anti-glioma gene therapy. HSV has several advantages over other viruses for gene delivery in the 
CNS: i) it is neurotropic and ii) its genome size (152 kb) allows transfer of genes 30 kb or more in size. 
Selection of the correct combination of the engineered HSV construct and gene(s) for transfer should, 
theoretically, allow maximal exploitation of the advantages of each technique (i.e. direct destruction of 
the tumor by virus replication and its cell-to-cell spread within the tumor followed by subsequent foreign 

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gene expression, allowing for the added destruction of any surviving tumor cells). Thus far, 
immunomodulatory genes (IL-12, TNF-, CCL2, IL-4, and IL-10) and prodrug converting enzymes (purine 
nucleoside phosphorylase, or PNP, and cytosine deaminase, or CD), have been expressed from the virus 
(58-61). We have previously demonstrated that a 134.5 HSV-1 expressing murine interleukin 12 (M002) 
prolonged survival of immunocompetent mice in an experimental intracranial murine model of 
neuroblastoma (58).   
2.7 HSV/HCMV chimeric viruses.  
In an effort to define the HCMV genes responsible for PKR-evasion, we performed marker transfer 
studies and constructed a series of 134.5 recombinant viruses containing putative PKR-evasion genes 
from the  herpesvirus HCMV (Figure 2) (33). We hypothesized that the PKR-evasion gene from a 
genetically related virus would selectively complement one function of the HSV-1 134.5 gene, efficient 
late viral protein synthesis. However, because HCMV is only distantly related to HSV, the HCMV PKR 
evasion genes would not restore the neurovirulence function encoded by the HSV 134.5 gene.  We 
predicted that this selective complementation of one 134.5 function (late viral protein synthesis) would 
enable the virus to replicate more efficiently than 134.5 HSV and that this would lead to improved 
secondary cell infection and spread in the tumor. Studies, funded through a developmental project grant 
within the UAB SPORE, are described below in Section 2.8 and show that these HSV/HCMV chimeric 
134.5 recombinant viruses, or chimeric HSV, are superior to first generation 134.5 HSV vectors with 
respect 
to 
replication, 
expression 
of 
late 
viral 
proteins, and enhanced tumor 
specific killing.  
2.8 Specific Findings 
On Safety and 
Efficacy of C134. 
Experimental intracerebral 
therapy with 134.5 HSV-1 is 
safe. However, poor replication 
and spread of the recombinant 
virus threatens to limit therapy. 
Modifications of these vectors 
have 
demonstrated 
improvements in survival in 
pre-clinical models of GBM. 
Preliminary studies have been 
conducted to identify whether 
chimeric viruses that inhibit PKR function replicate and 
spread in the tumor better than 134.5 recombinant, and 
are summarized below. 
2.8.1.The chimeric HSV synthesize late viral 
proteins and replicate like wild-type virus in malignant 
glioma cell lines. We hypothesized that the PKR-
mediated host protein shutoff response is intact in GBM 
cells, thus limiting 134.5 viral replication. To test this 
hypothesis U87 MG cells were infected with 10 plaque 
forming units of virus per cell and at 14 hours post-
infection, incubated with media supplemented with 
radioactive methionine for 1 hour. The pulse labeling 
experiments and follow up immunostaining studies for 
phosphorylated eIF-2 show that 134.5 HSV (C101, 

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C131, C135) triggers PKR-mediated protein shutoff in the infected human glioma cell lines U87MG 
(Figure 3A-C, lanes 2, 4, and 6), U251MG, and D54MG (data not shown). In contrast, the chimeric HSV 
(C130, C134) maintain late viral protein synthesis similar to 
wildtype virus in these cell lines (Figure 3A-C, lanes 1, 3, and 5). 
To identify if viruses capable of synthesizing late viral proteins 
accumulate greater amounts of viral protein, we immunostained for 
viral protein glycoprotein D (gD).  There was more gD in the 
chimeric HSV (C130 and C134) and wild-type HSV infected cells 
than in the 134.5 infected samples (C101, C131, and C135) 
(Figure 3D). To identify if the chimeric HSV with their ability to 
synthesize late viral proteins, would replicate better than a 134.5 
HSV, we performed viral replication studies. Chimeric HSV 
generated 103-105 more virus than   134.5 HSV in multistep 
replication studies (Figure 3E).  
In summary, the PKR antiviral response is functional in 
malignant glioma cell lines tested thus far, and limits 134.5 late 
viral gene expression and replication. In contrast, chimeric HSV 
synthesize late viral proteins, accumulate greater amounts of viral 
proteins, and replicate similarly to wild-type HSV-1. 
2.8.2. Mechanism of TRS1 and IRS1 inhibition of PKR. 
Defining how the HCMV IRS1 and TRS1 genes preclude PKR 
function in the cell is the focus of another proposal. However, some 
of this information is included to demonstrate that the chimeric 
HSVs encode a unique PKR evasion mechanism that may 
contribute to their improved anti-glioma activity.  
IRS1 and TRS1 co-localize 
with the eIF-2 and prevent PKR activation in chimeric HSV infected 
cell lysates.  In reciprocal pull down studies, PKR co-precipitates with 
HCMV genes (data not shown). Confocal microscopy also shows that 
HCMV proteins co-localize with eIF-2 in infected cells (data shown 
for IRS1 Figure 4B). To test the hypothesis that IRS1 and TRS1 
prevented PKR activation in the infected cell, we examined PKR 
phosphorylation status by in vitro kinase assays and immunostaining 
studies. These studies showed, consistent with past published 
results, that PKR was activated in 134.5-infected samples (C101 
C131, and C135), as indicated by both radioactive phosphorous 
labeling and detection of phospho-PKR-T446 by immunoblot (Figure 
4C, D lanes 3, 5, and 7). In contrast, in cells infected with a US11 
recombinant virus, PKR was maintained in its inactive or 
unphosphorylated state (Figure 4C, D lane 8). The novel findings in 
these studies pertain to the chimeric HSV and show that PKR, while 
abundantly phosphorylated in the kinase assay, remains in its 
inactive form, as indicated by its lack of autophosphorylation on 
threonine #446 (Figure 4 C, D lanes 4 and 6). These data indicate 
that TRS1 and IRS1 co-precipitate and co-localize with PKR and eIF-2. The data also show that in the 
C130 and C134 infected cells, PKR remains in its non-activated form. Chimeric HSV apparently utilize a 
different mechanism than the US11 virus to block PKR activation.  
2.8.3. Chimeric viruses exhibit wildtype viral resistance to Interferon  (IFN-).  
The 134.5 gene product is integral to HSV-1 IFN resistance (He, 2004). Type I IFN treatment 
reduces 134.5 replication. To identify if chimeric HSV exhibit wild-type viral resistance to Type I IFN, 
we examined viral replication in the presence or absence of IFN- treatment. Single step replication 

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assays were performed by 
infecting U87-MG with an 
excess of virus (10 PFU/cell) 
and 
evaluating 
a 
single 
round of virus replication. In 
these single step replication 
assays (Figure 5), minimal 
134.5 virus was recovered 
(6 PFU/ml) in interferon-
treated cultures. Chimeric 
recombinants 
replicated 
similarly to wildtype virus, 
generating 105-106 PFU/ml 
of 
virus 
in 
IFN-treated 
samples (Figure 5). 
In summary, chimeric 
HSVs, 
like 
HSV-1(F) 
replicate 
despite 
IFN- 
treatment 
and 
are 
anticipated 
to 
infect 
secondary tumor cells better than 134.5 virus in vivo.    
2.8.4. The chimeric HSV replicate better than 134.5 in intracranial tumors. To determine 
whether chimeric HSV replicated better than 134.5 virus in intracranial tumors, we implanted U87-MG 
tumors in nude mice, treated them with 5 x 105 PFU of virus and examined virus recovery on days 1, 2, 
4, and 8 post-infection. Results showed increased chimeric HSV recovery (~103 PFU higher recovery) 
and a greater duration of viral replication (C134 and C130 >8d vs 134.5 >4d) in U87 xenografts 
compared to an equivalent dose of 134.5 HSV (Figure 6A).  
2.8.5. The chimeric HSV do not exhibit wild-type neurovirulence. The 134.5 gene encodes 
at least three phenotypes pertinent to anti-tumor therapy: (1) evasion of PKR-mediated host protein 
shutoff response, (2) Type I IFN resistance and (3) neurovirulence. As described above, the HCMV TRS1 
and IRS1 genes restore at least two of the 134.5 gene functions, viral evasion of the PKR host protein 
shutoff response and resistance to IFN-.   
To determine if the HCMV TRS1 and IRS1 gene restored neurovirulence, we performed lethal dosage 
measurement (LD50) studies, as described previously (27). As indicated (Figure 6B), introduction of the 
IRS1 gene (C134) into a 134.5 HSV background did not contribute to neurovirulence. The 134.5 
parent virus C101 and the IRS1 expressing chimeric recombinant C134 have identical neurotoxicity 
profiles (>1 x 107). In contrast, insertion of the TRS1 gene (C130) or US11 gene  (C122) into 134.5 
HSV  partially restores neurovirulence, but only approximately 15 fold (C130 LD50 = 6.8 x 105, C122 
LD50=8.3x105). This is within the LD50 range of the 134.5 HSV (HSV 1716) used in Phase I trials (62). 
While chimeric HSV were safe in neurotoxicity studies, it was still possible that they were capable of 
replication and could be producing subclinical CNS damage in the mice. To identify if chimeric HSV 
replicated better than 134.5 HSV in the CNS, we intracranially inoculated mice with equivalent PFU of 
C101 and C130 and found that the two recombinants replicate similarly in non-malignant CNS (Figure 
6C). It is important to note that chimeric HSV retain sensitivity to antiviral therapy with acyclovir (ACV) 
(data not shown).  

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In summary, the HCMV TRS1 or IRS1 genes restore wildtype viral protein synthesis and 
replication in malignant glioma cells, but do not restore wildtype neurotoxicity. Insertion of the HCMV 
TRS1 gene increases virulence of 134.5 chimeric C130 slightly, but C134 (134.5, IRS1) chimeric 
recombinant is as safe as other 134.5 HSV. Both of these chimeric HSV retain susceptibility to ACV 
therapy.  
2.8.6. Chimeric HSV reduce tumor volumes in vivo. To identify if chimeric HSV was more 
effective than 134.5 virus at reducing tumor volume, we induced U251-ffLuc intracranial tumors in scid 
mice (1 x 106 cells), and treated the animals with a chimeric HSV (C130), a 134.5 recombinant (R3616), 
or saline a week later. We then measured luciferase activity over time using a xenogen In Vivo Imaging 
System (IVIS; Figure 7A). The method involved implantation of GBM cells stably expressing firefly 
luciferase enzyme and at selected times post implantation or post-virus administration, intraperitoneal 
administration of a luciferase substrate (beetle luciferin, 2.5mg/mouse) to the hosts. This low molecular 
weight (~1kD) substrate, upon entering cells containing luciferase enzyme, is cleaved into a photo-
emitting chemical by an ATP-dependent process and then is rapidly degraded (63). Llight emitted is 
captured digitally by a Xenogen IVIS CCD camera and quantified. Because luciferase enzyme is not 
present in native animal cells and has a limited half-life at 37oC of about 2 hrs, light emission is limited to 
viable, metabolically active tumor cells (63). The greater the number of viable GBM cells, the greater the 
light production.  Consistent with prior studies, these results showed that 134.5 therapy (R3616) 
reduced tumor volume (based upon relative photon emission) when compared with saline treated 
animals, but that the chimeric HSV (C130) was more effective at reducing tumor volume (Figure 7A).  
2.8.7. Chimeric HSV therapy improves survival in both a GBM xenograft and syngeneic 
murine brain tumor model. Since the chimeric HSV demonstrated both improved replication and protein 
synthesis 
phenotype, 
we 
hypothesized that this would translate 
into improved survival of mice treated 
with either C130 or C134 chimeric 
HSV versus conventional 134.5 HSV 
treatment. To test this hypothesis, 
cohorts of scid mice bearing U87-MG 
intracranial tumors were treated with 
saline 
or 
equivalent 
doses 
(5 × 105 pfu) of 134.5 or chimeric 
HSV. As shown in Figure 7B, direct 
intratumoral injection of C130 and 
C134 chimeric HSV improved survival 
of mice versus treatment of tumors 
with C101 or G207 (P < 0.0001). 
Though C101 statistically improved 
survival over saline treated mice as 
expected, ultimately all of the C101-
treated animals died. In contrast, the 
majority of animals treated with 
chimeric HSV at a matched dose 
survived.  

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Poorly replicating 134.5 HSV-1 derives a greater benefit from dose escalation than chimeric HSVs. 
Administration of a higher dose of C101 significantly improved median survival of the mice (1x107 [45d] 
vs. 5×105 pfu [36.5d], P < 0.0001). Chimeric HSV were even more effective at lower doses than the 
maximum administered dose of the 134.5 virus (5 x 104 PFU of C130 - >50% of the animals survived 
vs 1 x 107 PFU C101- 15% survival, P = 0.0185). A similar benefit was witnessed in the syngeneic 
Neuro2A brain tumor model, where chimeric HSVs (C130 and C134) were superior to 134.5 therapy 
and an Us11 HSV, yielding a 15-20% improvement in median survival (p=0.0039). 
To summarize, chimeric HSV were superior to 134.5 HSV in two separate experimental murine 
brain tumor models. Chimeric HSV significantly improved survival over all 134.5 HSV-treated cohorts 
in the human xenograft brain tumor model. They also improved survival over treatment with 134.5 HSV 
or an US11 recombinant in a syngeneic murine brain tumor model. Due to its high level of efficacy and 
low neurovirulence profile, C134 demonstrates the most advantageous therapeutic ratio, a critical 
determinant for its utility in patients. 
2.8.8. Effect of IR upon HSV replication. Preliminary studies show that administration of 5 Gy 
of IR to the infected tumor bed improves viral replication and survival. Optimal timing of IR is between 6 
and 24 hpi (data not shown). Preliminary data indicate that in a U87-MG xenograft model, irradiation 
(5Gy) of G207 infected tumors improved long term survival from ~15% to 60% when performed 24hpi 
(Figure 8A). Interestingly, administration of IR at 4hpi and 120 hpi did not result in a statistically significant 
improvement in survival (Figure 8A). Preliminary studies have identified a “therapeutic window” between 
6h and 24h post-infection where IR benefits viral replication and leads to a synergistic improvement in 
survival. Importantly, IR administered outside of this therapeutic window, while not enhancing viral 
oncolysis, is not detrimental to viral therapy. Additional studies have shown that the benefit derived by IR 
is not limited to 134.5 viruses. Recombinants encoding a single 134.5 gene replicate better following 
IR. Furthermore, preliminary studies show that 
external beam IR improves HSV-1(F) replication in 
flank tumors (~1 log increase in recovered virus, data 
not shown). Addition of IR to G207 therapy is 
currently in a SPORE-sponsored Phase I clinical trial, 
with 8 patients enrolled thus far (Figure 8B).  
 
In summary, IR enhances viral protein 
synthesis and replication and in an intracranial 
xenograft model has been shown to improve outcome 
when administered within 6-24 hours of G207 
therapy.   
2.8.9. Stability of Optiprep HSV vectors  
Convection 
enhanced 
delivery 
(CED) 
requires prolonged infusion of the virus through a 
catheter into the tumor. To evaluate the stability of 
Optiprep recombinant virus, we placed equivalent 
PFU of virus in catheters at 4oC and at 37oC and 
measured the quantity of virus recovered over time 
by plaque reduction assay. Results showed that Opti-
prep purified HSV is relatively stable at 37oC with a 
calculated half-life of 16.5h (6.8 x 109pfu @ 0h vs 
9x108pfu @ 48h). 

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2.8.10. Similar 
inflammatory 
infiltrates 
are 
detectable in the brains of CBA 
mice infected with chimeric HSV or 
134.5. 
As 
indicated 
in 
the 
BACKGROUND section, the antiviral 
immune response contributes to the 
anti-tumor effect but may also limit 
viral replication and spread. To 
identify if chimeric HSV elicit a greater 
immune 
response 
than 
134.5 
recombinants, we examined immune 
cell infiltrates in brains of CBA mice 
injected 
with 
these 
recombinant 
viruses. Results showed chimeric 
HSV 
and 
134.5 
(R3616) 
recombinants 
elicited 
similar 
inflammatory responses (Figure 9A 
& 
B). 
The 
majority 
of 
CD8+ 
lymphocytes 
in 
the 
CNS 
were 
activated (CD69+), irrespective of 
which recombinant is injected (Figure 
9C & D).  
2.8.11. Monitoring 
tumor 
volume, viral replication/spread, and inflammatory changes in vivo.  
a.Tumor volume. Both direct (histology) and functional measurement (animal survival) of tumor 
volume have been used to monitor response to oncolytic therapy (as shown in Figures 7C, 10C & D). 
These methods involved killing representative animals to 
evaluate interim responses, which increased animal numbers 
required for statistical evaluation. This approach assumes that 
an individual animal will reflect the population as a whole. As 
shown in Figure 7C, measurement of luciferase activity in the 
tumor provides an alternative method to evaluate tumor 
volume noninvasively, allowing longitudinal population-based 
analysis of therapy.  
b.Viral 
detection. 
Viral 
recovery 
and 
immunohistochemistry have been used successfully to monitor 
viral replication and spread in vivo (as demonstrated in 
Figures 6A [replication] and 10A, B [IHC]). Bioluminescent 
and fluorescent protein expression by the virus can also be 
used to indirectly monitor viral replication and spread in the 
tumor as demonstrated using a 134.5 luciferase expressing 
virus (M007) and a wild-type, EGFP expressing virus (M2001) 
in flank tumors (Figure 10C & D). We routinely construct 
recombinant viruses to encode reporter genes (d2EGFP, 
dsRED monomer, or firefly luciferase). These genes not only 
facilitate screening and selection of recombinant viruses in 
vitro but allow indirect monitoring of viral activity in in vivo 
studies.  
2.8.12. Summary. Chimeric HSV evade a principal 
component of the innate immune response, PKR-mediated 

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protein shutoff. They replicate and resist Type I IFN similar to wildtype HSV-1 in malignant glioma cells. 
However, they do not exhibit wildtype neurotoxicity and, in the case of C134, are no more virulent than a 
134.5 HSV. 
Due to its high level of efficacy and low neurovirulence profile, C134 demonstrates the most 
advantageous therapeutic ratio, a critical determinant for its utility in patients. Preliminary in vivo studies 
in a glioma xenograft murine model demonstrate that chimeric HSV significantly improved survival and 
required two to three log lower doses than 134.5 therapy. Chimeric HSV, by virtue of their near-wildtype 
replication, efficiently spread through tumor and reduce tumor burden by direct viral oncolysis, thus 
improving survival. Chimeric HSV, unlike conventional 134.5 HSV recombinants, maintain protein 
synthesis in infected cells. Chimeric HSV exhibit benefits of both an oncolytic agent and gene therapy 
vector by combining improved viral replication with enhanced viral protein expression.  
3. PATIENT SELECTION 
3.1 Eligibility Criteria 
3.1.1 Patients must have histologically or cytologically confirmed recurrent/progressive 
glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma.  
3.1.2 Prior therapy.  Patients must have failed external beam radiotherapy to the brain at least 
4 weeks prior to enrollment. 
3.1.3 Age ≥18 years. Because no dosing or adverse event data are currently available on the 
use of C134 in patients <18 years of age, children are excluded from this study but will be 
eligible for future pediatric phase 1 single-agent trials.   
3.1.4 Karnofsky Performance Status ≥70% (see Appendix A). 
3.1.5 Life expectancy of greater than 4 weeks. 
3.1.6 Patients must have normal organ and marrow function as defined below: 
 leukocytes 
>3,000/ μl 
 absolute neutrophil count 
>1,500/ μl 
 platelets 
>100,000/ μl 
 total bilirubin 
within normal institutional limits 
 AST(SGOT)/ALT(SGPT) 
<2.5 X institutional upper limit of normal 
 Creatinine within normal institutional limits  
                                           OR 
 
creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels 
above institutional normal. 
3.1.7 Residual lesion must be ≥1.0 and < 5.5 cm in diameter without bilateral extension through 
the corpus callosum as determined by MRI as this is a locally delivered treatment. These 
parameters will be re-evaluated on imaging done on the day of catheter implantation and 
if the lesion no longer meets the criteria, the patient will not undergo catheter implantation 
or treatment with C134. 
3.1.8 The effects of C134 on the developing human fetus are unknown.  For this reason, women 
of child-bearing potential and men must agree to use adequate contraception prior to study 
entry and for the first six months after receiving C134.  Because it is currently unknown if 
C134 can be transmitted by sexual contact, a barrier method of birth control should be 
employed.  Should a woman become pregnant while participating in this study, she should 
inform her treating physician immediately. 
3.1.9 Ability to understand and the willingness to sign a written informed consent document. 
3.1.10 Females of childbearing potential must not be pregnant; this will be confirmed by a 
 
negative serum pregnancy test within 14 days prior to starting study treatment. 

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3.1.11 Steroid use is allowed as long as dose has not increased within 2 weeks of scheduled 
 
C134 administration whenever possible, the patient should be on a steroid dose that is 
 
equivalent to a dexamethasone dose of ≤ 2mg daily at the time of treatment. 
 
3.2 Exclusion Criteria 
Patients who have had chemotherapy, cytotoxic therapy, immunotherapy or gene therapy within 
6 weeks prior to entering the study (4 weeks for Temodar/Temozolomide), surgical resection 
within 4 weeks prior to entering the study, or have received experimental viral therapy at any time 
(e.g., adenovirus, retrovirus or herpesvirus* protocol).  Also, those who have not recovered from 
adverse events due to therapeutic interventions administered more than 4 weeks earlier. 
3.2.1  Patients may not be receiving any other investigational agents. 
3.2.2  History of allergic reactions attributed to compounds of similar biologic composition to C134. 
3.2.3 Tumor involvement which would require ventricular, brainstem, basal ganglia, occipital 
lobe, or posterior fossa inoculation or would require access through a ventricle in order to 
deliver treatment. 
3.2.4  Prior history of encephalitis, multiple sclerosis, or other CNS infection. 
3.2.5  Active oral herpes lesion. 
3.2.6  Concurrent therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, 
famciclovir, ganciclovir, foscarnet, cidofovir). 
3.2.7  Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, 
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any 
other medical condition that precludes surgery.  Also, psychiatric illness/social situations 
that would limit compliance with study requirements. 
3.2.8 Required steroid increase within 2 weeks of scheduled C134 administration. When 
possible, the patient should be on a dexamethasone equivalent dose of ≤ 2mg daily at the 
time of treatment. 
3.2.9 Known history of allergic reaction to IV contrast material that is not amenable to pre-
treatment by UAB protocol. 
3.2.10 Have a pacemaker, ferro-magnetic aneurysm clips, metal infusion pumps, metal or 
shrapnel fragments, or certain types of stents. 
3.2.11 Received Bevacizumab (Avastin) therapy within 4 weeks of scheduled C134 
administration. 
3.2.12 Excluded patient groups 
Pregnant women are excluded from this study because C134 is a viral oncolytic therapy 
with unknown potential for teratogenic or abortifacient effects.  Because there is an 
unknown but potential risk for adverse events in nursing infants secondary to treatment of 
the mother with C134  breastfeeding should be discontinued if the mother is treated with 
C134. 
Immune deficient, because patients with immune deficiency will be unable to mount the 
anticipated immune response underlying this therapeutic rationale, HIV-seropositive 
patients are excluded from this study.  Other treatment studies for this disease that are 
less dependent on the patients’ immune response are more appropriate for HIV-
seropositive patients. 
Unwilling/unable to receive required ophthalmologic exams 

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3.2.13 Any other reason the investigator deems subject is unfit for participation in the study 
 
3.3 Inclusion of Women and Minorities 
Both men and women and members of all ethnic groups are eligible for this trial.  The proposed 
study population, assuming the maximum number of patient enrollments occurs, is illustrated in 
the table below. 
 
 
Gender 
Asian or 
Pacific 
 Islander 
American 
Indian or 
Alaskan 
Native  
*Black, not of 
Hispanic Origin 
 
 
 
Hispanic 
White, not of 
Hispanic Origin 
Other or 
Unknown (Non-
white) 
 
 
 
Total 
Female  
1 
1 
8 
 
10 
Male 
 
1 
0 
13 
 
14 
TOTAL 
 
2 
1 
21 
 
24 
4. TREATMENT PLAN 
4.1 C134 Administration 
Treatment will be administered on an inpatient basis.    No investigational or commercial agents 
or therapies other than those described below may be administered with the intent to treat the 
patient’s malignancy. 
Patients will be treated under monitored local anesthesia, or at the surgeon’s discretion, under 
general anesthesia. After placement of the stereotactic frame, the patients will then undergo a 
contrasted MRI scan to determine the site for stereotactic biopsy.  Patients will then undergo 
stereotactic biopsy of their tumor.  While evidence of radiation damage or necrosis may be present 
on the frozen section, inoculation with C134 will only proceed if viable, recurrent glioma is also 
present on the frozen section. The initial dose level of C134 will be 1 x 106 plaque forming units 
(pfu). Dosing modifications will be undertaken by the Continual Reassessment Method outlined 
in 4.1.1. Virus will be inoculated via catheters placed stereotactically in enhancing regions of 
tumor at up to 5 different loci (each injection over 2 minutes). Catheters will be removed directly 
after administration.  
Virus will be thawed and maintained on ice until ready for delivery; a total of 5.25 hours from 
thawing to delivery has demonstrated titer stability (4 hours at 2-8 degrees Fahrenheit followed 
by 1.25 hours at ambient temperature). 
  
 
4.1.1 Continual Reassessment Method 
Dr. Gary R. Cutter and Dr. Inmaculada B. Aban, Professors in the Department of Biostatistics, 
UAB School of Public Health, with expertise in CRM calculations will apply the software 
developed by Dr. Steven Piantadosi, (Cedars-Sinai) who will serve as a clinical trial statistical 
consultant to advise and assist in the implementation of the Continual Reassessment Method in 
determining dose alterations. In addition, Drs. Aban and Cutter, will provide support in clinical 
trial and data management, and data analysis. 
Rationale for the Use of a Modified Continual Reassessment Method: The description of the 
determination of MTD from the CRM that we are employing is adapted from that used previously in a 
Phase I/II study of the poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor BSI-201 in patients with 

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newly diagnosed malignant glioma conducted under the New Approaches to Brain Tumor Therapy 
(NABTT) CNS Consortium. To estimate the MTDs in terms of clinical toxicities, a modified continual 
reassessment method (CRM), based on that described by Piantadosi et al (64)], will be employed. The 
CRM has been shown to be less biased and more efficient for estimating the MTD than traditional 
dose-finding models. The efficiency of the CRM stems from its explicit use of biological knowledge in 
the form of a parametric dose toxicity model. In the CRM, only a starting dose is specified and the dose 
is escalated or deescalated based on the toxicities of the previous cohort.  
This is advantageous because the investigators can choose the next dose level based on all available 
clinical and statistical information rather than on relatively arbitrary predetermined doses. One 
disadvantage of the CRM is uncertainty of the dose levels that will be used in the trials, because the 
specific dose levels are not defined at the start of the trial. 
Details of CRM Design: The primary statistical outcome for this study is the occurrence of serious 
clinical toxicity. Investigators would like to employ a dose of drug that yields approximately a 1/3 chance 
of serious toxicity. In our opinion, this represents the best chance at a beneficial therapeutic ratio for 
this unusually difficult disease to treat. This target probability of toxicity is chosen based on knowledge 
of previous trials of oHSV in glioma, but is fundamentally subjective. The relationship between dose of 
drug and probability of toxicity is assumed to follow a two-parameter logistic model, both before and  
 
during 
the 
dose finding given 
by where β is the “slope” of the curve and d50 the midpoint (or dose that 
yields a 50% response). The parameters β and d50 govern the dose 
finding process, and are estimated, denoted by and, initially by clinical 
judgment and afterwards by the observed data. This represents a second 
subjective component of dose finding designs. Classical dose-ranging 
designs incorporate this component of subjectivity by setting out, in 
advance of the experiment, a set of doses to employ. A strictly Bayesian 
approach to the CRM requires a joint prior probability distribution for the 
parameters β and d50. However, we have found it easier for clinicians to 
render their clinical judgment about β and d50 in the form of pseudo-data. 
Specifically, we ask for two points on the dose toxicity curve: the dose thought to yield a 10% 
probability of toxicity (d10) and the dose thought to yield a 90%probability of toxicity (d90). Two points, 
d10, d90, are required to initiate the fit for a two-parameter model. The exact points chosen are 
arbitrary, but we have found these generally work well or are easily adapted. The d10 point can often 
be discarded after some data have been obtained. The d90 point is necessary to obtain a fit of the 
model, but is usually relatively unimportant because it characterizes a region of the model that does not 
heavily influence prediction of the next dose. In this sense, d90 is a nuisance parameter – necessary 
for model fitting, but relatively uninfluential on the dose escalation. At both d10 and d90, the investigator 
specifies a numerator (number of responses) and denominator (number of subjects treated), such that 
numerator/denominator = 0.1 or 0.9 as the case may be. The denominators are always taken to be 
small numbers, e.g. 1, to represent weak evidence and reduce the influence of these points compared 
to real subject data. Three values for d90 will be chosen in this protocol with weights of one tenth that of 
real subject data. This allows flexibility in the upper end of the dose toxicity curve. This adaptation to 
the CRM came about after subject data demonstrated that d90 was incorrect in previous studies, 
because doses approaching d90 were tried with no toxicities observed. This situation required that d90 
be moved to a higher dose or the fitted dose toxicity curve became too steep and no dose escalations 
resulted. We assume the dose for d10 = 1 x 104 pfu for C134 (Table 1). A set of three values will be 
chosen for d90 =1 x 1015 pfu. These values for d90 spread probability mass over a wider range and 
may eliminate the need to these starting points, our desire is to employ a dose of virus to yield no more 
Eqn. (1) 

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than 33% chance of clinical toxicity. The initial starting dose will be assumed to be 1 x 106 PFU and the 
maximum dose to be tested would be 1 x 108 PFU. Further assumptions would be that the maximum 
number of subjects would be 24 and that the dose cohort size would be 1. Further, the next CRM 
recommended log dose would be rounded to the nearest 0.5 or full dose. Moreover, the number of 
consecutive subjects at the maximum tolerated dose would be 10 or a number until 24 subjects are 
treated, whichever comes first. This will allow us to collect more information of the safety of the MTD. If 
a second toxicity is observed for patients on the highest dose, then the next lower dose is used and 
declared MTD if 10 consecutive subjects on the same dose are toxicity free or if n=24 is reached. If 
more toxicities are found, CRM will be used in the de-escalation of the dose. For each subsequent 
level, the investigators will evaluate the recommended dose-level. It is possible that the model may 
recommend large interval increases in dose level with which the investigators do not feel comfortable. 
In these cases, the investigators will use this information and their best clinical judgment to assign a 
next dose level. We emphasize that the dose levels recommended by the CRM should not be taken 
literally. 
Model based dose escalation methods, especially the CRM, are able to account for ordinal or 
quantitative toxicity assessments, and use this information to guide subsequent dose changes. In 
particular, the binomial likelihood is: 
 
where i indexes the dose level, p is the probability of toxicity (equation 1 above), d is dose, n the 
number of subjects treated at each dose, and r the number of toxicities. While n is constrained to be an 
integer, r does not have to be integral. In particular, r can be taken to be the sum of ordinal or 
quantitative toxicity measures provided that r < n. The maximization of equation 2 with respect to the 
parameters (model fitting) can then proceed in the usual fashion. Furthermore, the ordinal scores need 
not be the same for all types of toxicity. For example, we might not want alopecia to have the same 
effect on dose reduction as neurologic toxicities. 
 
As subjects are treated at doses estimating the true MTD, the recommended subsequent dose levels will 
begin to converge. The criteria to declare the MTD will be when 2 recommended doses are within 10% 
of one another. It is possible that the dose escalation could continue indefinitely and that the MTD is not 
reached. If 10 subjects are treated in the full dose range in this dose-finding study and the MTD has not 
been reached, we will take pause, evaluate the data, and determine whether to continue the dose-
escalation or terminate the Phase I portion of the study. If a MTD is not being reached based on clinical 
toxicities (too many or too few), the biological indicator (increased PFS or OS) may factor in the choice 
of the C134 dose for the ultimate planned phase II trial. A maximum of 10 subjects will be treated at the 
putative MTD to have better estimation of ≤ 33% DLT rate. 
4.1.2 Estimated Number of Patients 
We anticipate as few as four and as many as 24 patients could be enrolled in this trial). If the highest 
planned dose is successfully administered to subjects and an additional 9 subjects will be entered at the 
CRM-estimation of the safe target dose, there could be as few as 16 patients (Table 2: Scenario 1) or as 
Eqn. (2) 

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many as 24 patients treated (Table 2: Scenario 3). If, on the other hand, 
all subjects develop DLTs, the CRM model would de-escalate both 
through the initial and two lower dose levels involving no more than 4 
subjects and the trial would be halted (Section 4.5) with a minimal 
accrual of 4 subjects. Examples of enrollment scenarios following a DLT 
but leading to an MTD dose determination are shown in Table 2: S2-4). 
Please note that while Table 2 suggests that a dose of 109 pfu might 
be considered, this will not be utilized without a revised protocol 
from the FDA as our current IND only permits dosing up to 108 pfu.  
Please note the table and the enrollment scenarios are examples only 
and do not represent all possible scenarios. 
4.2 Dose-Limiting Toxicity 
The Cancer Therapy Evaluation Program (CTEP) has published 
Common Toxicity Criteria for the grading of adverse events experienced 
in clinical trials for anti-neoplastic agents.  As defined by this criteria, any 
Grade 3 or 4 toxicity involving the liver, lungs and heart, or any other 
Grade 4 toxicity, will be considered a dose-limiting toxicity (DLT) if it is 
determined to be possibly, probably, or definitely related to C134.  
Because of the site of C134 inoculation, important additional events that 
will be considered dose-limiting toxicities if they are possibly or probably 
related to C134 include death, stroke, hematoma requiring surgery, 
untreatable neurologic deterioration, unresponsive systemic infection, 
and disseminated HSV infection.  All adverse events will be reported to 
the Data and Safety Monitoring Board (DSMB) for determination of 
attribution and dose-limiting toxicity. 
Management of the above adverse events is outlined in Section 5. 
Dose escalation will proceed according to the CRM scheme, described above. 
The maximally tolerated dose (MTD) is the highest dose level below the maximally administered 
dose when dose escalation decisions are made according to the guidelines above. 
4.3 Supportive Care Guidelines 
There will be a minimum seven-day observation period between each patient enrolled to 
allow for evaluation of potential toxicity. If the incidence of DLT at any given dose level 
meets the criteria for dose escalation, there will be a waiting period of 24 days before dose 
escalation occurs. The Medical Monitor in conjunction with the UAB Comprehensive Cancer 
Center Data Safety Monitoring Panel will evaluate the safety of each dose tested to 
determine whether the protocol may proceed to the next dose level. An independent Data 
and Safety Monitoring Board (DSMB) will be assembled to assess the progress of the C134 
study, the safety data, and critical efficacy endpoints (when appropriate) and provide 
recommendations to the IND investigator sponsor. The DSMB will review study data in a 
cumulative fashion (including but not limited to adverse events) to evaluate safety, conduct 
of the study when appropriate, as well as the scientific validity and data integrity of the 
study. 
Supportive Care Guidelines 
Appropriate supportive care during the duration of the study includes the following: 
 
Steroid administration for neurologic symptoms arising from increased edema or intracranial 
pressure 
 
Proton pump inhibitors or H2 antagonists for control of steroid-induced gastric irritation 

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 
Anti-epileptic medicines for control of partial or generalized seizures 
 
Post-operative neurological intensive care that is routine for the neurosurgical interventions 
involved in the administration of C134  
 
Other than a restriction on medications with anti-HSV activity (to be given only for the 
management of an adverse event), there are not any limitations on concomitant medications 
that patients may receive for other co-morbidities. 
Management of adverse events is discussed in Section 5. 
4.4 Duration of Therapy/Study 
The therapeutic intervention in this trial involves the administration of a single dose of C134.  For 
this reason it is more appropriate to define the duration of the study for each patient rather than 
the duration of therapy.  Following the 12-month study period described in Section 8.0, patients 
administered C134 will be subject to long term follow-up (15 years)via annual examinations to 
detect potential delayed adverse events. 
 
In regard to the evaluations of treatment efficacy or the acceptability of other treatments for the 
malignant glioma, the study will continue as scheduled until one of the following criteria applies: 
 
Disease progression (as defined in Section 9) 
 
Patient withdrawal from the study 
Scheduled post-therapy safety evaluations as indicated in the study schedule will continue for 
every patient regardless of the response to C134.  These evaluations will stop only if one of the 
following criteria applies: 
 
Disease progression (as defined in Section 9) has rendered the patient unevaluable 
 
Patient withdrawal from the study 
5. EXPECTED ADVERSE EVENTS/DOSE MODIFICATIONS 
5.1 Expected Adverse Events Associated with Malignant Glioma 
Subjects in this trial may present with various adverse events due to their underlying disease. 
The table below outlines various expected adverse events. These events will not be considered 
stopping criteria unless the severity is a Grade 4 or higher or unless otherwise indicated. In the 
event the severity is a Grade 4 or higher, the trial will be halted until review by the Data and 
Safety Monitoring Board. The DSMB will make a determination as to the attribution of the 
adverse event to the study drug, study procedure, or underlying disease as well as to whether 
the study may proceed.  
Expected Adverse Events due to Disease 
Asthenia 
Amnesia 
Nausea 
Somnolence 
Leukopenia 
Fever 
Pneumonia 
Death* 
Hemiplegia 
Confusion 
Headache 
Decreased Consciousness 
Anemia 
Cachexia 
Varicella Zoster 
Infection 
Abnormal 
Mentation 
Stroke 
Dysphasia 
Depression 
Deep Vein 
Thrombosis 
Seizure 
Abnormal Erythrocytes 
Urinary 
Tract 
Infection 
Tumor Progression or 
pseudoprogression 
Increase Liver 
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Hematoma 
Encephalitis/Encephalopathy* 
Hepatitis 
Nuchal Rigidity 
Photophobia 
*Occurrence of these events meets stopping criteria and will halt the trial until evaluation by 
the DSMB. 
 
Patients will be observed closely for evidence of any adverse events.  After the delivery of C134 
, patients will initially be observed in the Neurosurgical Intensive Care Unit.  The patients’ vital 
signs (temperature, blood pressure, pulse, respiratory rate) and neurologic function (Glascow 
Coma Scale and limited neurological exam) will be monitored every hour for the first six hours, 
then every two hours overnight for the first 24 hours.  Patients that appear stable will then be 
transferred to the neurosurgery ward or the General Clinical Research Center, during which time 
the frequency of monitoring will be determined by the attending physician(s) based on the medical 
condition of the patient. 
After discharge the patient will continue to be closely followed for evidence of adverse events, 
with outpatient follow-up evaluations scheduled at 1, 3, 6 and 12 months, or more often if 
medically indicated.  The safety evaluation schedule is outlined in detail in Section 8. 
Most adverse events will be managed according to standard conventions.  General or specific 
neurologic worsening observed in the first several days after C134 administration could be due to 
edema, hydrocephalus, hematoma, or encephalitis.  Such problems occurring later may also be 
attributable to tumor progression.  When appropriate, an MRI will be done to help determine the 
cause of the neurologic changes. 
 
Cerebral edema/hydrocephalus: This commonly occurs in tumor patients post-operatively, 
and usually responds to standard measures for the treatment of increased intracranial 
pressure. 
 
Hematoma: PT, PTT, and platelet count will be obtained. A small hematoma may simply be 
watched and the patient treated as above for edema and then rescanned to exclude an 
enlarging lesion. A large hematoma or one associated with progressive neurologic 
deterioration may require operative evacuation. 
 
Encephalitis: Post-operative fever is not uncommon. However, fever >102F (with or without 
seizures) extending in duration >48 hours, in the presence of a waning Glascow Coma 
Scale and an increase in the area of hemorrhagic necrosis extending beyond the borders of 
the tumor on MRI are suggestive of viral encephalitis. If, in the opinion of the PI,  it is safe 
and indicated, a cerebrospinal fluid sample will be obtained and analyzed by polymerase 
chain reaction (PCR) for evidence of HSV-1. Otherwise, or if CSF results are not diagnostic, 
a stereotactic biopsy will be considered. This biopsy will be taken to assess for presence of 
C134 or wild-type HSV-1, as well as for histopathologic evidence of encephalitis. This will 
consist of a minimum of 2-3 needle core biopsies that will undergo standard hematoxylin 
and eosin (H&E) staining as well as immunostaining for HSV-1, leucocyte common antigen, 
and glial fibrillary acidic protein (GFAP) immunostaining.  High-dose antiviral therapy with 
intravenous acyclovir may be implemented in consultation with the Medical Monitor and will 
be administered according to established method. 
5.2 Dosing Delays/Dose Modifications 
Because C134 is delivered as a single dose, there will not be any intra-patient dosing delays or 
dose modifications. 
Inter-patient dosing delays and dose modifications are discussed in Section 4.2. 
5.3 Study Stopping Criteria 

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During the trial, if any unexpected Grade 3 or 4 toxicity involving the liver, lungs and heart, or 
any other Grade 4 toxicity, including grade 5 toxicity, evidence of encephalitis, or disseminated 
HSV infection (viremia and LFT increase) will be considered stopping criteria. In the event 
stopping criteria are observed, the trial will be halted until review by the DSMB. The DSMB will 
make a determination of attribution of the adverse event with the study drug or procedure as 
well as a decision on whether the trial may proceed.   
Adverse events that are expected due to the underlying disease, as outlined in Section 5.1 
above, will not trigger stopping of the trial unless the severity is greater than what is expected 
or if the DSMB determines the event has met stopping criteria. Regardless of attribution to 
study procedure, study drug, or underlying disease any events of encephalitis/encephalopathy 
or death will trigger a halt in the trial for review by the DSMB. 
6.   AGENT FORMULATION AND PROCUREMENT 
6.1 C134 Formulation and Storage 
cGMP C134 has been produced and certified through the NCI-NeXT program (formerly the Rapid 
Access to Investigational Drug - Developmental Therapeutics Program RAID-DTP). In brief, It has 
undergone all of the necessary bio-toxicology, -stability and preclinical safety studies and has 
received both NCI RAC and FDA IND approval for Phase I study for the treatment of patients with 
recurrent malignant glioma.   
The agent has been prepared at a clinical grade and has met the qualification standards.  It was 
manufactured, filtered, filed and labeled by Leidos Biomedical Research Inc. for Frederick 
National Laboratory for Cancer Research on November 30, 2011.  Stability testing has 
demonstrated no apparent trend leading to out of specification results at annual time points since 
that time.  Concentration of the virus is 2 x 108 pfu/ml with a limit of > 3 x 107 pfu/ml required.  It 
is being stored at -70˚.  Clinical material is Lot L1110001, NSC#751997.  The virus is  
tested 
regularly for appearance, virus titer, expression of HCMV gene IRS1 by western blot, 
endotoxins/LAL and sterility and has passed all these tests at annual time points.   
C134 is supplied in sterile, labeled glass vials that have butyl stoppers crimp sealed containing 
0.12 mL of C134 pended in the storage buffer, D-PBS/10% glycerin. The vials should remain 
frozen at -60C or below until use. 
6.2 C134 Dose Preparation 
A single volume of 1.0 mL containing the assigned dose of C134 is prepared for treatment (five 
inoculations, 0.2 ml each). To prepare the dose, the vial containing C134 should be thawed by 
removing it from the controlled access -60C freezer and rubbing the vial gently between gloved 
hands until the last ice crystals have melted.  The vial should then be placed on ice. Care should 
be taken to ensure that all the liquid is at the bottom of the vial before removing the cap. If it is 
suspected that the contents are on the side or top of the vial, the vial can be tapped gently on a 
flat surface. The cap must be removed carefully to avoid spilling or contamination.  The 
appropriate dose level of C134 will be removed from the vial and diluted in sterile saline to the 
total volume of 1.0 mL.  The final diluted C134 should be gently withdrawn into the syringe for 
injection. 
Once thawed and maintained on ice, the dose must be administered to the patient within four 
hours of preparation.  
Complete instructions for dose preparation are described in Appendix B. 
6.3 Precautions in Handling C134  
Sterile technique and Biosafety Level 2 precautions (gown, gloves, mask) will be rigorously 
followed while preparing the dose. The dose preparations will take place in a biosafety hood. 
6.4 Precautions in Disposal of C134  

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All materials that have been in contact with C134 are considered infectious biohazards, and must 
be decontaminated or incinerated prior to disposal. Needles and syringes should be placed into 
a puncture-resistant, leak-proof container containing disinfectant. All materials that have been in 
contact with the vector must be incinerated in an institutionally approved biohazard incinerator 
before disposal. 
7. CORRELATIVE/SPECIAL STUDIES 
To address secondary objectives of the protocol, additional correlative studies will be performed on 
blood/serum, conjunctival secretions, saliva samples and tumor tissue samples. 
Blood samples will be taken and sera extracted to permit detection and quantification of HSV antibody 
titer pre-and post-inoculation via ELISA and leukocyte (WBC) subset analysis by FACS. Intracellular 
lymphocyte interferon γ levels will be assessed by FACS analysis, and lymphocyte transformation 
assays will also be performed to assess aspects of the TH1 response to treatment with C134. 
Conjunctival secretions and saliva will be assessed for HSV shedding. 
 
To determine the tolerability of C134 therapy upon QOL, we will monitor both objective and subjective 
data on C134 treatment when compared to historical studies using the MD Anderson Symptom inventory 
–Brain Tumor specific (MDASI-BT; Appendix C a validated measure for exploring all aspects of quality 
of life in patients with malignant glioma. We will compare these results with those provided in a previously 
published paper that reports these QOL metrics in patients with recurrent malignant brain tumors to 
determine if there is a trend towards improved QOL with C134 therapy. Similarly, hope versus despair is 
a major concern for patients with malignant brain tumors, particularly as their disease progresses. We 
will administer the Hope Herth Index (Appendix D) and compare results for patients treated under our 
study with historic data in the recurrent malignant glioma population that has been previously published 
(65-68). Both the MDASI-BT and the Hope Herth Index are short and easy to fill-out forms, so patients 
will not be unduly taxed by having to perform them at follow up visits.  
Both subjective (MDASI-BT and the Hope Herth surveys and analysis of burden of treatment) and 
objective (Karnofsky Performance Status score) will be recorded pre-treatment and then measured 
serially post-treatment for each patient.   Descriptive methods will be used for analysis of questionnaires. 
Power calculations are not presented for these analyses as the sample size of this Phase I study is 
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8.  STUDY CALENDAR13 
 
Pre- 
Study1 
Day 
012 
Day 
1 
Day 
2 
Day 
3 
Day 
72 
Day 
102 
Day 
142 
Day 
212 
Day 
282 
Month 
33 
Month 
63 
Month 
123 
Informed consent15 
X4 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concurrent meds 
X 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
Complete physical exam 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X5 
X 
X 
X 
 
X 
 
 
X 
 
 
 
KPS 
X 
 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
QOL 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
CBC w/diff, plts 
X 
 
 
X 
 
 
 
 
 
X 
 
 
 
Serum chemistry6, 
PT/INR, PTT 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
HIV serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
EKG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CXR (AP and lateral) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
-HCG 
X7 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis with micro 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event 
evaluation 
 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
MRI8 
 
X16 
 
 
X 
 
 
 
 
X 
X 
X 
X 
Neurologic exam 
X 
X9 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
HSV Ab titer10 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
HSV detection (saliva, 
conjunctival secretions, 
blood)11 
X 
 
X11 
X11 
X11 
 
X11 
 
 
X11 
X11 
X11 
X11 
Blood sample for LTA, 
Elispot, WBC subsets 
X 
 
 
X17 
 
 
X 
 
 
X 
X 
X 
X 
Biopsy 
 
X 
 
 
 
 
 
 
 
 
 
 
 
C134 Administration 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Ophthalmologic 
evaluation 
 
X19 
 
 
 
X18 
 
X18 
X18 
 
 
 
 
1. 
Baseline evaluations are to be conducted within 2 weeks prior to the administration of C134. 
2. 
Acceptable within ±3 days of days 7, 10, 14, and 28. 
3. 
Acceptable within ±12 days of each respective timepoint. 
4. 
Will be obtained prior to study screening procedures. 
5. 
Frequency post-operatively defined by institutional standards and medical need. 
6. 
Includes sodium, potassium, chloride, bicarbonate, glucose, BUN, creatinine, calcium, phosphorus, total protein, uric 
acid, GGT, AST, CK, LDH, alkaline phosphatase, bilirubin, cholesterol, triglyceride 
7. 
Only women of child-bearing potential 
8. 
All MRI scans will consist of axial fast spin echo, axial flair, axial T1 (pre-gadolinium), and axial T1 (post-gadolinium) 
sequences. T1 images will be obtained in axial, coronal and sagittal planes. 30 acquisitions will be obtained. T2 
weighted images will be obtained in the axial planes only. Review of the baseline MRI scans will be necessary to 
determine if the tumor location is such that the patient may be included in the study. This baseline study will be 
obtained a maximum of 30 days prior to the patient’s stereotactic inoculation.  Unscheduled MRI scans may be done 
if needed to evaluate post-administration neurological decline. 
9. 
Neurologic function (Glascow Coma Scale and limited neurological function exam) will be evaluated more frequently 
during the immediate post-operative period as defined by institutional standards and medical need. 
10. By ELISA; neutralizing antibody assays may also be performed 
11. Samples will be evaluated by PCR and culture; quantitative PCR may be performed on positive samples. Samples will 
be taken daily until discharge, at day 28 and Months 3, 6 and 12. Close contacts and family members should refrain 
from direct physical contact until negative shedding data has been recorded.  
12. Prior to biopsy and intratumoral inoculation. 
13. Appendix E includes the CRFs that will be utilized in this study as a more complete guide to detailed study activities; 
these are also listed in the Informed consent (ICF). 
14. Hope Herth and MDASI-BT will only be conducted pre treatment, , 28, months 3, 6, and 12 
15. See Appendix F. 
16. If surgeon feels that the biopsy is best done utilizing a technique that requires day of biopsy MRI (e.g., very small 
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that requires a specific frame type) a prior MRI will be utilized instead. Catheter placement will be performed according 
to the method used for biopsy. 
17. Acceptable up to Day 4 
18. If any HSV Ocular involvement is detected, Acylovir therapy will be immediately initiated.  
19. Optional but should not delay treatment 
 
9. MEASUREMENT OF EFFECT 
Although response is not the primary endpoint of this trial, patients with measurable disease will be 
assessed by standard criteria. 
9.1 Definitions 
Although the Response Evaluation Criteria in Solid Tumors (RECIST) Committee has proposed 
new international criteria for the evaluation of response and progression of solid tumor, 
unidimensional measurements alone have not yet been sufficiently validated for the evaluation of 
malignant gliomas. The iRANO criteria will be used for evaluation of treatment responses (70) 
 
9.1.1 Measurable Disease 
Measurable lesions are defined as those that can be accurately measured in at least one 
dimension (longest diameter to be recorded) as >10 mm with MRI scan.  All intracranial 
malignant glioma is therefore measurable disease.  All tumor measurements must be recorded 
in millimeters (or decimal fractions of centimeters). 
 
9.1.2 Non-measurable Disease 
 
This type of lesion is not applicable in this study. 
 
9.1.3 Target Lesions 
All intracranial lesions that are likely manifestations of the patient’s malignancy will be 
considered target lesions. 
 
9.1.4 Non-target Lesions 
 
This type of lesion is not applicable in this study. 
9.2 Guidelines for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using a ruler or calipers, or 
digitized method.  All screening evaluations should be performed as closely as possible to the 
beginning of treatment and never more than 4 weeks before the beginning of the treatment. 
Because all of the patients enrolled in this study will have received prior radiation therapy, tumor 
lesions that are situated in a previously irradiated area will be considered measurable. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is the only 
means of assessing the antitumor effect of this treatment for this disease.   
9.3 Response Criteria 
The following criteria are based upon the volume changes that correspond to the definitions 
proposed by the iRANO criteria (70).  For the purposes of this study, the objective response of each 
patient’s disease to C134 will be evaluated by the comparison of a baseline MRI scan to follow-up 
MRI.  For those patients receiving intratumoral inoculation, the screening MRI will serve as the 
baseline MRI. Response will be evaluated on follow-up scans completed at Day 28, Month 3, Month 
6, and Month 12. Additionally, an MRI will be done on Day 3 to evaluate for any early toxicity. To 
prevent the introduction of observer bias, a software package which determines tumor areas and 
volumetrics via assessment of pixel intensity will be utilized to compare pre-and post-treatment 
images. 
 
9.3.1 Evaluation of Target Lesions 
 
“Response” is defined as follows: 
Complete Response (CR) - Disappearance of all treated enhancing tumor on MRI scan, off 
steroids, and neurologically stable or improved. 

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Partial Response (PR) - greater than 50% reduction in the treated enhancing tumor on MRI scan, 
stable or reduced steroid dose, and neurologically stable or improved. 
Progressive Disease (PD) - greater than 25 % increase in the treated enhancing tumor on MRI 
scan, stable or increased steroid dose, and neurologically stable or worse. 
 
Stable Disease (SD) - all other situations 
Some patients on this trial may be taking dexamethasone and/or bevacizumab. Those who have 
decreased the dose of one of these medications to one lower than that utilized at the time of the 
previous MRI AND this dose decrease has occurred within two weeks of the MRI shall not be 
determined to have progressed even if the MRI meets the criteria for PD above, but rather that MRI 
shall be considered non-evaluable. Similarly, should an increase in steroid dosage or bevacizumab 
dosage occur within two weeks of an MRI compared to the prior MRI, the patient will not be eligible 
for consideration of a CR or PR but instead that MRI will be considered non-evaluable. 
Note that since this is considered an immunotherapy trial, the appearance of lesion(s) does not 
necessarily indicate PD. 
 
9.3.2 
Evaluation of Non-target Lesions 
Because all intracranial lesions will be considered target lesions, this assessment is not applicable 
to this study. 
 
9.3.3 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).  The patient's best response assignment will 
depend on the achievement of both measurement and confirmation criteria (see section 9.3.1). 
Note: In some circumstances, it may be difficult to distinguish residual disease from normal tissue.  
When the evaluation of complete response depends on this determination, it is often recommended 
that the residual lesion be investigated (biopsy) before confirming the complete response status.  
Because this disease  would require a brain biopsy in this situation, with potential increased risk to 
the patient, patients with an ambiguous complete response status will only undergo histological 
confirmation if deemed necessary for additional treatment interventions.  If tumor is not the 
predominant feature of biopsy specimen, e.g., if only necrosis is present, or inflammation or gliosis 
are prominent, then progression will not be deemed to have occurred ( Immunotherapy Response 
Assessment in Neuro-Oncology (iRANO) guidelines(70). 
 
9.3.4 
Pseudoprogression 
Pseudoprogression is a well-known entity in oncolytic viral therapy of glioma. We will utilize the 
iRANO criteria to address this phenomenon in this trial: If tumor appears to enlarge or demonstrates 
increased enhancement by MRI consistent with PD, patients will undergo repeat imaging and 
clinical assessments at 3 months to determine whether the changes demonstrate true progression 
or pseudoprogression (70). Note that the investigator may obtain an MRI prior to this 3 month 
interval as indicated. Should significant neurologic deterioration occur that cannot be ascribed to 
tumor or pseudoprogression related events such as seizures or medication changes (e.g., steroid 
tapers) the patient will be considered to have progressed. During the interval, the patient may be 
watched or treated with bevacizumab and/or dexamethasone at the discretion of the investigators. If 
the patient improves with bevacizumab (to be used preferentially at a suggested dose of 10mg/kg 
IV, every two weeks, for three months; previous tumor progression on bevacizumab does not 
preclude its use herein) and/or additional steroid administration (to be used if bevacizumab is 
contraindicated or insufficient) and the MRI changes in lesion size/and or enhancement also 
improves, the patient will be determined to have not progressed but to have suffered 
pseudoprogression, and will continue follow-up within the trial under the previously defined 
schedule. Should neurologic symptoms and/or imaging changes progress despite steroid 
administration on follow-up imaging, the patient will be determined to have progressed and the date 

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of progression shall be assigned to the date of the initial scan that demonstrated findings consistent 
with PD as defined above.  
9.4 Confirmatory Measurement/Duration of Response 
 
9.4.1 Confirmation 
To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by the 
next scheduled MRI after the criteria for response are first met.  In the case of SD, follow-up 
measurements must have met the SD criteria at least once after study entry at a minimum interval 
of 12 weeks. 
 
9.4.2 Duration of Overall Response 
The duration of overall response is measured from the time measurement criteria are met for CR or 
PR (whichever is first recorded) until the first date that recurrent or progressive disease is 
objectively documented (taking as reference for progressive disease the smallest measurements 
recorded since the treatment started).  The duration of overall CR is measured from the time 
measurement criteria are first met for CR until the first date that recurrent disease is objectively 
documented. 
 
9.4.3 
Duration of Stable Disease 
Stable disease is measured from the start of the treatment until the criteria for progression are met, 
taking as reference the smallest measurements recorded since the treatment started. 
9.5  Progression-Free Survival 
 Because this study is a non-randomized phase 1 trial that will enroll relatively few patients, 
progression-free survival will be reported as a secondary endpoint. 
10. REGULATORY AND REPORTING REQUIREMENTS 
10.1 Expedited Adverse Event Reporting 
Adverse events (AE) will use the descriptions and grading scales found in the revised NCI 
Common Toxicity Criteria (CTC). This study will utilize the CTCAE 4.0 for adverse event 
reporting.  All appropriate treatment areas will have access to a copy of the CTCAE 4.0.  A 
table showing the expected adverse events associated with the underlying disease of the 
subjects can be found in Section 5.1. 
 
 Expedited Adverse Event Reporting (AE; formerly known as Adverse Drug Reaction) 
10.1.1 Expedited Reporting Guidelines – Phase 1 studies with investigational agents: 

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UNEXPECTED EVENT 
 
EXPECTED EVENT 
 
GRADES 2 – 3 
Attribution of 
Possible, Probable 
or Definite 
 
GRADES 4 and 5 
Regardless of 
Attribution 
 
GRADES 1 - 3 
 
GRADES 4 and 5 
Regardless of 
Attribution 
 
Grade 2 - Expedited 
report within 10 
working days. 
 
Grade 3 - Report by 
phone to IDB within 
24 hrs. Expedited 
report to follow within 
10 working days. 
(Grade 1 – Adverse 
Event Expedited 
Reporting NOT 
required.) 
 
Report by phone to 
IDB within 24 hrs. 
Expedited report to 
follow within 10 
working days. 
 
This includes deaths 
within 30 days of the 
last dose of treatment 
with an investigational 
agent. 
 
Adverse Event 
Expedited Reporting 
NOT required. 
 
Report by phone to 
IDB within 24 hrs.  
Expedited report to 
follow within 10 
working days. 
 
This includes deaths 
within 30 days of the 
last dose of 
treatment with an 
investigational 
agent. 
 
For grade 2-3 unexpected events, the investigator will be unbiased in assessing the 
relationship of the event and test article and discuss the possible relatedness to 
treatment with the Medical Monitor. 
 
Adverse event and IND safety reports will be filed in a timely manner with institutional 
authorities (IRB, IBC) as well as with the FDA and NIH/ORDA  
 
All serious adverse events (Grade 3 or 4 toxicities will be reported by fax, e-mail or 
phone within 24 hours and a written expedited report filed within ten days. Additionally, 
unexpected Grade 2 or Grade 3 toxicities will require a written expedited report within 
ten days and Grade 3 unexpected adverse events will also require a fax, email, or 
phone call to the the UAB IRB, the UAB CCC DSMP, FDA, and OBA within 24 hours. 
 A list of disease-specific expected adverse events can be found in Section 5.1. 
 Any adverse event requiring an expedited report will also be reported immediately to 
the Medical Monitor and the investigator’s Institutional Review Board (IRB). 
 Patients administered C134 will be subject to long term follow-up (15 years) to detect 
potential delayed adverse events. 
10.1.2 Forms 
1. Although C134 will not be obtained from the NCI, the standard DCTD Form for Reporting AEs Occurring 
with Investigational Agents will still be used.  This form can be downloaded from the CTEP home page 
(https://ctep.cancer.gov/forms/docs/34-adeers_v3-0_sat_11-21-00.pdf). 
10.1.3 Secondary Malignancies 
Investigators are required to report secondary malignancies occurring on or following 
treatment on NCI-sponsored protocols using the form noted above.  Exception:  Cases 
of secondary AML/MDS are to be reported using the NCI/CTEP Secondary AML/MDS 
Report Form. 
 
10.2 Data Reporting 
This study will be conducted under the oversight of the UAB Comprehensive Cancer Center for 
which a Data and Safety Monitoring Plan has been established. 

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10.3 CTEP Multicenter Guidelines:  N/A 
10.4 Cooperative Research and Development Agreement (CRADA)/Clinical Trials Agreement 
(CTA):  N/A 
10.5 Study Monitoring: 
CTNMO will be responsible for the monitoring of study patient data and records. 
All monitoring reports will be kept by the UAB CTNMO to ensure that all reports are contained in 
a central study file. A final monitoring report will be generated and issued to the site and will be 
kept in the central study file by the UAB CTNMO. The staff of the UAB CTNMO will notify the 
participating site of any data queries and manage the overall data quality of the study. 
All data will be substantiated by clinical source documents organized within a patient research 
record. ICH Good Clinical Practices are to be followed. 
  
The study will be subject to a yearly internal audit via the UAB CCC Quality Assurance 
Committee at a minimum and audits may occur more frequently at the request of the QA 
Committee. 
 
11. STATISTICAL CONSIDERATIONS  
11.1 Study Design/Endpoints 
This study is an open-label, dose escalating phase 1 study of the safety of intracranial 
administration of C134, an IRS1-chimeric HSV1, a genetically engineered HSV-1 expressing 
CMV IRS1.  For this reason, the primary endpoint of this study is to determine the safety and 
tolerability of a single stereotactic intracerebral injection of escalating doses of C134 virus, 
and to determine the maximally tolerated dose (MTD).  The dose escalation scheme and the 
definition of the MTD are found in Section 4.1.  Because C134 is administered as a single 
dose intrapatient dose escalations will not be feasible. 
Demographic Analysis: Demographic and baseline characteristics will be summarized for 
each cohort using the statistics of number, mean, median and range for continuous variables 
and for discrete factors, values will be tabulated.    
Safety Analysis: Descriptive statistics will be used in the reporting of adverse events. Adverse 
events will be tabulated and frequencies of events will be determined. All events with a toxicity 
of Grade 3 or above will be tabulated by event, as well as tabulations for all events (where 
toxicity is defined by the Common Toxicity Criteria). Laboratory analyses (chemistries, 
hematology, urinalysis, serological/immunological analyses, WBC and differential) will consist 
of measurements of change from baseline over time by patient and overall, with plots of actual 
values compared to normal values for patients by dose group. Logarithmic transformations 
may be applied as necessary. Group means and standard errors will be calculated for the 
various laboratory parameters. Concurrent Illnesses will be listed and examined by univariate 
and multivariable analysis as possible confounders in the treatment response relationship. 
Concurrent medications will also be listed. Effects of previous treatments for cancer will also 
be examined by univariate and multivariable analysis, and any potential related side effects 
will be analyzed and discussed. 
11.2 Sample Size/Accrual Rate 
Because the number of patients enrolled at each dose level depends on observed toxicities, 
it is not possible to state a definite sample size that will be accrued. The dose escalation plan 
does allow for a minimum of 2 4 patients to be enrolled (if the first two patients enrolled 
experienced dose-limiting toxicity, then 2 dose de-escalations occur with a single patient 
enrolled at each level) and a maximum of 24 patients to be enrolled. It is expected that the 
actual enrollment will fall well between these two extremes. It is expected that this study will 
accrue approximately 10 patients per year. 

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11.3 Stratification Factors 
This study will not stratify patients according to any baseline factors. 
11.4 Analysis of Secondary Endpoints 
 
 
 
11.4.1 Characterization of the in situ activity of C134 after intratumoral inoculation. 
 
Durability and replication of C134 in the resected tumor will be evaluated by the 
presence or absence of HSV DNA and RNA. 
 
In situ ability of C134 to induce an inflammatory TH1-type response will be assessed 
by ELISA for interferon-. 
 
Each of these binomial responses will be summarized by frequencies for each cohort 
and overall. 
 
 
 
11.4.2 Delineation of the local and systemic immune response to C134 administration. 
 
Virus reactivation and shedding will be detected by PCR and culture of serial serum 
and saliva samples. 
 
Immunogenecity of C134 will be evaluated by the use of ELISA to detect HSV antibody 
titers in serial serum samples. 
 
Local inflammatory infiltrate at the site of C134 intratumoral inoculation will be 
characterized by use of immunohistochemistry when possible and systemic response 
evaluated by leukocyte subset analysis via FACS analysis. 
 
Each of these binomial responses will be summarized by frequencies for each cohort 
and overall. 
  
 
 
 
11.4.3 Gather preliminary information about the potential benefit of C134 in the treatment 
of patients with recurrent malignant gliomas. 
 
The percentage of patients experiencing complete response, partial response, stable 
disease and progressive disease will be reported by cohort and overall based on 
follow-up radiographic imaging. 
 
Changes in clinical disease status and steroid administration will be considered when 
reviewing changes in tumor volumetric size. 
 
All changes in tumor volume will also be analyzed with consideration of any other anti-
tumor cancer therapies (either prior to C134 administration or following C134 failure) 
and the timeframes in which they were administered. 
 
Quality of life response: A Karnofsky Performance Status (KPS) score will be recorded 
pre-treatment and then measured serially post-treatment for each patient. Time to KPS 
<60 will be measured for each patient by the Kaplan-Meier analytical method. 
 
11.4.4 Remnant tumor specimens’ studies 
 
Remnant tumor specimens from the trial will be studied for evidence of C134 and antitumor 
responses via molecular testing. Such tests will include RNAseq, Nanostring, Spatial 
transcriptomic analysis, nucleic acid analyses, proteinomics and other protein analyses, 
cytokine and chemokine analyses 
 
 

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of the RANO working group. Lancet Oncol. 2015;16(15):e534-e42. doi: 10.1016/S1470-2045(15)00088-
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ABBREVIATIONS USED: 
Chimeric Virus (short form “chimeric”): A genetically-engineered virus with one or more genes from at 
least two different parent viruses 
CMV, HCMV: Human Cytomegalovirus 
DLT: Dose Limiting Toxicity 
G207-oHSV initially studied in the U.S. in patients with recurrent malignant glioma that is a 134.5 but 
also has another deletion in the viral ribonucleotide reductase gene that renders the virus markedly 
debilitated.   
GBM: Glioblastoma multiforme 
HSV: Herpes Simplex Virus Type 1 
oHSV: oncolytic Herpes Simplex Virus Type 1 
134.5: HSV1 gene responsible for neurovirulence, shutdown of host protein synthesis, and other 
functions. 
134.5 HSV or HSV-1: Viruses deleted for the 134.5 gene 
IRS-1:  A CMV gene that is responsible for antagonizing protein kinase R (PKR) to increase the replication 
of CMV. IRS-1 is closely related to TRS-1 
PKR: Protein Kinase R, a protein expressed by cells involved in innate cellular resistance to viral infection. 
When a DNA virus infects the cell, PKR acts to interfere with viral replication within the cell. 
TRS-1: A CMV gene that is responsible for antagonizing protein kinase R (PKR) to increase the 
replication of CMV. TRS-1 is closely related to IRS-1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

UAB 1814 
HSV C134 Protocol  
Version: 3.0 [21NOV2023] 
37
 
APPENDIX: 
 
Appendix A: 
Karnofsky Performance Score (KPS) 
 
 
 
 
Page 38 
Appendix B: 
Virus Preparation  
 
 
 
 
 
 
 
Page 39 
Appendix C: 
MDASI Quality of Life measurement  
 
 
 
 
Page 40-41 
Appendix D: 
Hope Herth Index Quality of Life measurement  
 
 
 
Page 42-45 
Appendix E: 
C134 CRFs   
 
 
 
 
 
 
 
Page 46-119 
Appendix F: 
C134 Informed Consent Form (ICF)   
 
 
 
 
Page 120-136 
 

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
C134 
Month 3 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
KARNOFSKY PERFORMANCE SCALE 
Percent 
Description 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self, unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his/her needs. 
50 
Requires considerable assistance and frequent medical care. 
40
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. Death not imminent. 
20 
Very sick, hospitalization indicated. Death not imminent. 
10
Moribund, fatal processes progressing rapidly.
0
Dead.
Karnofsky Performance Scale:  
% 
COMPLETE NEUROLOGICAL EXAM 
Level of 
☐ Alert 
☐Sleepy, but easily aroused 
☐Somnolent/difficult to arouse 
☐Not arousable 
Consciousness: 
Orientation: 
Oriented to time: 
☐Yes 
☐ No 
Oriented to place: 
☐Yes 
☐ No 
Oriented to self, person and others: 
☐Yes 
☐ No 
0 = None 
1 = Trace 
Right Arm:   
Right Leg: 
Muscle Strength: 
2 = Gravity eliminated 
(enter corresponding number) 
3 = Against gravity 
4 = Against resistance 
Left Arm: 
Left Leg:   
5 = Normal 
Gait 
☐ Normal 
☐ Mildly ataxic 
☐ Requires a cane 
☐Non-ambulatory 
☐Unable to evaluate 
Evaluation: 
Cranial Nerves: 
Left: 
II    III    IV    V   VI    VII   VIII    IX    X   XI   XII 
Are any cranial 
☐ Yes 
☐ No 
nerves affected? 
Right:  II    III   IV   V   VI VII    VIII    IX    X   XI   XII 
Sensory Exam: 
☐ Yes_ 
Are there abnormalities present? 
(performed as relevant to tumor location/signs/ symptoms) 
☐ No 
Other Neurological Findings: 
Comments: 
APPENDIX A
Protocol Version 2.2 [9JAN2019]
38

Appendix B Table: Dose Preparation Guide 
Dose Range 
1x10e6 ‐ 1x10e8 
Total Infusion Volume:   
1 ml
 Concentration
(PFU/ml)
Vol (ml)
Virus (PFU)
C134 Samples
3.13E+08
0.3
93900000
Desired Dose and Concentration
For <1x10e7 samples prepare a diluted sample of C134 ( 5x10e7/ml) in the glass vial containing the stock virus
Target conc
Starting virus
Volume of virus
Diluent (ml)
Final Conc C134
5.00E+07
3.13E+08
0.3
1.6
4.94E+07
Dose (PFU)
Concentration 
(PFU/ml)
*Diluted Virus
(4.94x10e7 
PFU/ml)
Diluent (ml)
Concentration 
(PFU/ml
1.00E+06
1.00E+06
0.2
9.6
1.01E+06
3.33E+06
3.33E+06
0.6
8.2
3.37E+06
1.00E+07
1.00E+07
1
3.8
1.03E+07
3.33E+07
3.33E+07
2
1
3.29E+07
Dose (PFU)
Concentration 
(PFU/ml)
Stock Virus 
(3.18e8 PFU/ml)
Diluent (ml)
Concentration 
(PFU/ml)
Target conc
Present in bottle
Add to bottle
Final Conc C134
1.00E+08
1.00E+08
0.3
0.7
9.39E+07
 
Protocol Version 2.2 [9JAN2019]
39

- ---- -
Date: ITl I rn I ITl 
(day) 
Subject Initials: I I I I 
Study Name: ________ _ 
Protocol#: -----------
PI: ------------------------
MD Anderson # i I I I I I I PDMS # { I I I I 
M. D. Anderson Symptom Inventory - Brain Tumor (MDASI - BT} 
Part I. How severe are your symptoms? 
People with cancer frequently have symptoms that are caused by their disease or by their treatment. We 
ask you to rate how severe the following symptoms have been in the last 24 hours. Please fill in the 
circle below from 0 (symptom has not been present) to 10 (the symptom was as bad as you can imagine 
it could be) for each item. 
Not 
Present 
0 
1 
' 2 
3 
4 
5 
6 
7 
1. Your pain at its WORST? 
0 
0 
0 
0 
0 
0 
0 
0 
2. Your fatigue (tiredness) at 
0 
0 , 0 
0 
0 
0 
0 
0 
its WORST? 
3. Your nausea at its WORST? 
0 
0 
0 
0 
0 
, 
0 
1.. 
" 
4. Your disturbed sleep at its 
0 
0 
0 
WORST? 
5. Your feeling of being distressed 
0 
0 
..... .:\< 0 
0 
0 
0 
(upset) at its WORST? 
6. Your shortness of breath at its 
0 
0 
0 
WORST? 
7. Your problem with rememberino 
' > 
0 
0 
0 
0 
0 
0 
things at its WORST? 
( 
...-...;-' 
8. Youc pmblem with lack of a .:..Vet 
at its WORST? 
0 
0 
0 
0 
0 
0 
0 
9. Your feeling drowsy (sleepy) at 
0 
0 
0 
0 
0 
0 
0 
0 
its WORST? 
10. Your having a dry mouth at its 
0 
0 
0 
0 
0 
0 
0 
0 
WORST? 
11. Your feeling sad at its WORST? 
0 
0 
0 
0 
0 
0 
0 
0 
12. Your vomiting at its WORST? 
0 
0 
0 
0 
0 
0 
0 
0 
13. Your numbness or tingling at 
0 
0 
0 
0 
0 
0 
0 
0 
its WORST? 
14. Your weakness on one side of 
0 
0 
0 
0 
0 
0 
0 
0 
the body at its WORST? 
15. Your difficulty understanding at its 0 
0 
0 
0 
0 
0 
0 
0 
WORST? 
16. Your difficulty speaking (finding the 0 
words) at its WORST? 
0 
0 
0 
0 
0 
0 
0 
Page 1 of 2 
Copyright 2000 The University of Texas M. D. Anderson Cancer Center 
All rights reserved. 
As Bad As You 
Can Imagine 
8 
9 
10 
0 ' 0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
' 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
---·-
Appendix C
Protocol Version 2.2 [9JAN2019]
40

Date: l(mLtJ I Q.J I W 
Study Name: 
Protocol#: 
PI: 
Subject Initials: 
MD Anderson # i I I I I I I PDMS# 
I I I I 
Not 
As Bad As You 
Present 
Can Imagine 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
17. Your seizures at its WORST? 
0 
0 
o , 0 
0 
0 
0 
0 
0 
0 
0 
18. Your difficulty concentrating at 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
its WORST? 
19. Your vision at its WORST? 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
20. Your change in appearance 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
at its WORST? 
21. Your change in bowel pattern 
0 
0 
0 , 0 
0 
0 
0 
0 
0 
0 
0 
(diarrhea or constipation) at its 
WORST? 
22. Your irritability at its WORST? 
0 
0 
0 
0 
0 
0 
0 
0 
Part II. How have your symptoms 
Symptoms frequently interfere with ( ,..,'-.We 
How much have your symptoms interfered 
with the following items in the t:: 
1 
2 
3 
4 
5 
6 
7 
23. General activity? 
0 
0 
0 
0 
0 
0 
0 
0 
24. Mood? 
0 
0 
0 
0 
0 
0 
0 
0 
25. Work (including work around 
0 
0 
0 
0 
0 
0 
0 
0 
the house)? 
26. Relations with other people? 
0 
0 
0 
0 
0 
0 
0 
0 
27. Walking? 
0 
0 
0 , 0 
0 
0 
0 
0 
28. Enjoyment of life? 
0 
0 
0 
0 
0 
0 
0 
0
, 
Page 2 of2 
Copyright 2000 The University of Texas M. D. Anderson Cancer Center 
All rights reserved. 
Interfered 
Completely 
8 
9 
10 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
Protocol Version 2.2 [9JAN2019]
41

Page 1 
C:\Program Files\Adobe\Acrobat 4.0\Acrobat\plug_ins\OpenAll\Transform\temp\Herth Hope Index.doc 
TNEEL-NE 
                2001 D.J. Wilkie & TNEEL Investigators                                       Well Being: Hope
Hope 
 
Herth Hope Index 
© 1988 Kaye Herth. Reprinted with permission of Kay Herth. 
Study No.______  
HERTH  HOPE  SCALE 
Listed below are a number of statements regarding hope. Read each statement and decide 
whether it applies to you personally. There are no right or wrong answers. Place a check [X] in 
the appropriate box indicating how often the statement has applied to you in the past week or 
two. 
Never 
applies  
to me 
Seldom 
applies 
to me 
Sometimes 
applies 
to me 
Often  
applies 
to me 
1.
I am looking forward to the future.
2.
I sense the presence of loved ones.
3.
I have deep inner strength.
4.
I have plans for the future.
5.
I have inner positive energy.
6.
I feel scared about my future.
7.
I keep going even when I hurt.
8.
I have a faith that gives me comfort.
9.
I believe that good is always possible.
10. I feel at a loss, no where to turn.
11. I feel time heals.
12. I have support from those close to me.
13. I feel overwhelmed and trapped.
14. I can recall happy times.
Appendix D
Protocol Version 2.2 [9JAN2019]
42

 
Page 2 
C:\Program Files\Adobe\Acrobat 4.0\Acrobat\plug_ins\OpenAll\Transform\temp\Herth Hope Index.doc 
TNEEL-NE 
                2001 D.J. Wilkie & TNEEL Investigators                                       Well Being: Hope 
15. I just know there is hope. 
 
 
 
 
 
 
 
 
 
 
 
16. I can seek and receive help. 
 
 
 
 
 
17. I am immobilized by fears and doubts. 
 
 
 
 
 
18. I know my life has meaning and 
purpose. 
 
 
 
 
 
19. I see the positive in most situations. 
 
 
 
 
 
20. I have goals for the next 3-6 months. 
 
 
 
 
 
21. I am committed to finding my way. 
 
 
 
 
 
22. I feel all alone. 
 
 
 
 
 
23. I have coped well in the past. 
 
 
 
 
 
24. I feel loved and needed. 
 
 
 
 
 
25. I believe that each day has potential. 
 
 
 
 
 
26. I can’t bring about positive change. 
 
 
 
 
 
27. I can see a light even in a tunnel. 
 
 
 
 
 
28. I have hope even when plans go astray. 
 
 
 
 
 
29. I believe my outlook affects my life. 
 
 
 
 
 
30. I have plans for today and next week. 
 
 
 
 
 
HERTH  HOPE  SCALE 
© 1988 Kaye Herth. Reprinted with permission of Kay Herth.  
 
 
 
Protocol Version 2.2 [9JAN2019]
43

 
Page 3 
C:\Program Files\Adobe\Acrobat 4.0\Acrobat\plug_ins\OpenAll\Transform\temp\Herth Hope Index.doc 
TNEEL-NE 
                2001 D.J. Wilkie & TNEEL Investigators                                       Well Being: Hope 
 
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 that 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. 
 
 
 
 
© 1989 Kaye Herth.  1999 items 2 & 4 reworded.  Reprinted with permission of Kay Herth. 
 
Protocol Version 2.2 [9JAN2019]
44

 
Page 4 
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TNEEL-NE 
                2001 D.J. Wilkie & TNEEL Investigators                                       Well Being: Hope 
SCORING INFORMATION FOR THE HERTH HOPE SCALE (HHS) 
 
 
Scoring consists of summing the ratings for the subscales and for the total scale. Subscales are 
based on the three factors (see Table 2 in 1991 publication). Total possible points on the total scale is 90 
points. The higher the score the higher the level of hope.  
 
 
Note the following items need to be reversed scored: 6, 10, 13, 17, 22, 26. Score items as 
follows: 
 
 
 
 
 
Never applies to me = 0 
 
 
 
 
Seldom applies to me = 1 
 
 
 
 
Sometimes applies to me  = 2 
 
 
 
 
Often applies to me = 3 
 
 
 
HHS has been translated into Chinese, Spanish, Swedish, Tai, Norwegian and German. 
 
 
Herth, K. (1991).  Development and refinement of an instrument to measure hope. Scholarly 
Inquiry for Nursing Practice: An International Journal, 5(1), 39-51. 
 
 
SCORING INFORMATION FOR THE HERTH HOPE INDEX (HHI) 
 
 
Scoring consists of summing the points for the subscale and for the total scale. Subscales are 
based on the three factors (see Table 2 in 1992 publication). Total possible points on the total scale is 48 
points. The higher the score the higher the level of hope. 
 
 
Note the following items need to be reversed scored: 3, 6. Score items as follows: 
 
 
 
 
 
Strongly Disagree = 1 
 
 
 
 
Disagree = 2 
 
 
 
 
Agree = 3 
 
 
 
 
Strongly Agree = 4 
 
 
 
HHI has been translated into Swedish, Japanese, Norwegian, Spanish and German. 
 
 
Herth, K. (1992). Abbreviated instrument to measure hope: Development and psychometric 
evaluation. Journal of Advanced Nursing, 17, 1251-1259. 
 
 
Protocol Version 2.2 [9JAN2019]
45

CASE REPORT FORM 
A Phase I Trial of IRS-1 HSV C134 Administered Intratumorally in Patients 
with Recurrent Malignant Glioma 
CLINICAL TRIAL SITE: UAB 
PRINCIPAL INVESTIGATOR:  
James M. Markert, MD 
Subject Initials: 
Subject Number: 
Enrollment Date: 
I am confident that the information supplied in this case record form is complete and accurate data.  I confirm 
that the study was conducted in accordance with the protocol and any 
protocol amendments and that written informed consent was obtained prior to the study. 
Investigator’s Signature: 
Date of signature: 
d d 
mm m  
 
yyy y 
Appendix E
Protocol Version 2.2 [9JAN2019]
46

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
 
INCLUSION CRITERIA 
Yes 
No*
 
1 
Does the subject have histologically or cytologically confirmed glioblastoma multiforme,  
anaplastic astrocytoma, or gliosarcoma? 
 
 
 
 
 
 
 
 
 
 
 
 
 
  ☐ 
☐ 
 
 
2 
Has the subject failed external beam radiotherapy ≥5,000 cGy to the brain, and if eligible and 
tolerated, undergone appropriate treatment with temozolomide chemotherapy? 
(All radiation and additional chemotherapies must have been completed at least 4 weeks prior to 
☐ 
☐
enrollment. Prior therapy with nitrosoureas must have been completed at least 6 weeks prior to 
enrollment.) 
3 
Is subject’s age ≥19 years? 
☐ 
☐ 
4 
Is subject’s Karnofsky Performance Status ≥70%? 
☐ 
☐ 
5 
Is subject’s life expectancy greater than 4 weeks? 
☐ 
☐ 
 
 
 
 
 
 
 
 
6 
Does subject have normal organ and marrow function as defined below: 
 
leukocytes……………………...≥3,000/μl 
☐ 
☐
 
absolute neutrophil count….…..≥1,500/μl 
☐ 
☐
 
platelets………………………...≥100,000/μl 
☐ 
☐
 
total bilirubin…………………….within normal institutional limits 
☐ 
☐
 
AST(SGOT)/ALT(SGPT)……..≤2.5 X institutional upper limit of normal 
☐ 
☐
 
 
creatinine……………………….within normal institutional limits 
OR 
☐ 
☐
creatinine clearance…………...≥60 mL/min/1.73 m2 for patients with creatinine levels 
above institutional normal. 
7 
Is subject’s residual lesion ≥1.0 cm in diameter as determined by MRI? 
☐ 
☐ 
 
 
 
8 
Does subject (women of child-bearing potential and men) agree to use adequate contraception 
(barrier method) prior to study entry and for the first six months after receiving C134, to avoid 
intimate contact with pregnant women, infants and young children and individuals with decreased 
☐ 
☐
immunity (ability to fight infection) for two weeks after receiving C134, and to refrain from 
donating blood during the trial? 
 
9 
Does subject have the ability to understand and the willingness to sign a written informed consent
document? 
☐ 
☐ 
 
10 
Females of childbearing potential must not be pregnant: Has this been confirmed by negative 
serum pregnancy test within 14 days prior to starting study treatment?  
 
 
 
 
 
 
  ☐ 
☐ 
*If any inclusion criteria are checked “No” then the patient is not eligible for the study. 
Protocol Version 2.2 [9JAN2019]
47

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
☐
☐
☐
☐
☐
☐
☐
☐
☐
☐
☐
☐
 
 
EXCLUSION CRITERIA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   Yes*  No 
1. Has subject had chemotherapy, cytotoxic therapy, immunotherapy within 4 weeks prior to entering the 
study (6 weeks for nitrosoureas), surgical resection within 4 weeks prior to entering the study, or have 
received experimental viral therapy or gene therapy at any time (e.g., adenovirus, retrovirus or  
herpes virus protocol)?  (However, this does not preclude re-treatment with C134 at a later date.)  
 ☐ 
☐ 
2. Has subject not recovered from adverse events due to therapeutic interventions administered more than 
4 weeks earlier?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. 
Is subject receiving any other investigational agents? 
☐ ☐ 
4. Does subject have a history of allergic reactions attributed to compounds of similar biologic 
composition to C134? 
5. Does subject have tumor involvement which would require ventricular, brainstem, basal ganglia, or 
posterior fossa inoculation or would require access through a ventricle in order to deliver treatment? 
6. Does subject have a prior history of encephalitis, multiple sclerosis, or other CNS infection? 
☐ ☐ 
7. Has subject required steroid increase within 2 weeks of scheduled C134 administration? 
☐ ☐ 
8. Does subject have any active herpes lesions? 
☐ ☐ 
9. Is subject receiving concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, 
penciclovir, famcyclovir, gancyclovir, foscarnet, cidofovir)? 
10. Does subject have any uncontrolled intercurrent illness including, but not limited to ongoing or active  
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, any other  
medical condition that precludes surgery or psychiatric illness/social situations that would limit  
compliance with study requirements? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    ☐ ☐ 
11. Is Subject: 
 
A pregnant woman (excluded from this study because C134 is a viral oncolytic therapy with 
    ☐ ☐ 
unknown potential for teratogenic or abortifacient  effects)? 
 
Breastfeeding (there is an unknown but potential risk for adverse events in nursing infants  
secondary to treatment of the mother with C134)?  
 
 
 
 
 
 
 
 
 
    ☐ ☐ 
 
Immune deficient (will be unable to mount the anticipated immune response underlying this 
 therapeutic rationale, HIV-seropositive patients are excluded from this study)? 
 
12. Does subject have a known history of allergic reaction to IV contrast material that is not amenable to 
pre-treatment by UAB protocol? 
 
13. Does subject have a pacemaker, ferro-magnetic aneurysm clips, metal infusion pumps, metal or 
shrapnel fragments, or certain types of stents? 
14 
Has subject received Gliadel Therapy? 
☐ ☐ 
Has subject received Bevacizumab (Avastin) therapy within 4 weeks of scheduled C134 administration? 
15. (Receipt of Bevacizumab (Avastin) greater than 4 weeks of scheduled C134 administration does not 
☐ ☐ 
exclude patient.) 
 
* If any exclusion criteria are checked “Yes” then the patient is not eligible for the study. 
 
 
Protocol Version 2.2 [9JAN2019]
48

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
 
INFORMED CONSENT 
Does subject meet all inclusion/exclusion criteria? 
☐ Yes 
☐ No 
Has the subject freely given written informed consent? 
☐ Yes 
☐ No 
 
Date signed (ddmmmyyy):   
 
Time (24 hour clock):   
 
 
 
DEMOGRAPHICS 
 
Age (yrs.):   
 
Date of Birth (ddmmmyyyy):   
 
 
 
Gender: 
☐ Female 
☐ Male 
Race: 
☐ Black 
☐White 
☐Asian 
☐Other 
Ethnicity:  Hispanic 
☐Yes 
☐ No 
 
PREVIOUS MEDICAL HISTORY 
Is there any relevant medical history in the following systems? 
System 
Yes 
No 
Comments 
Onset Date 
Ongoing 
(ddmmmyyy) 
Cardiovascular 
☐ 
☐ 
 
☐ Yes  ☐ No 
Respiratory 
☐ 
☐ 
 
☐ Yes  ☐ No 
Hepatobiliary 
☐ 
☐ 
 
☐ Yes  ☐ No 
Gastrointestinal 
☐ 
☐ 
 
☐ Yes  ☐ No 
Genitourinary 
☐ 
☐ 
 
☐ Yes  ☐ No 
Endocrine 
☐ 
☐ 
 
☐ Yes  ☐ No 
Hematological 
☐ 
☐ 
 
☐ Yes  ☐ No 
Musculoskeletal 
☐ 
☐ 
 
☐ Yes  ☐ No 
Neurological 
☐ 
☐ 
 
☐ Yes  ☐ No 
Psychological 
☐ 
☐ 
 
☐ Yes  ☐ No 
Immunological 
☐ 
☐ 
 
☐ Yes  ☐ No 
Dermatological 
☐ 
☐ 
 
☐ Yes  ☐ No 
Allergies 
☐ 
☐ 
 
☐ Yes  ☐ No 
 
HEENT 
☐ 
☐ 
 
☐ Yes  ☐ No 
 
Other 
☐ 
☐ 
 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
49

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
 
MEDICATIONS 
Is the subject currently or previously taking any medications including prescription, OTC, 
vitamins and/or supplements? 
☐ Yes 
☐ No 
*Record all medication on Concomitant Medications CRF* 
 
VITAL SIGNS 
 
Height (cm):   
.  
 
Weight (kg):   
._  
 
 
 
Blood Pressure:   
/  
 
Heart Rate:   
 bpm 
 
 
Respiratory Rate:   
 
Temperature:   
_.  
 °C 
 
 
PHYSICAL EXAMINATION 
 
System 
Normal 
Abnormal 
Not 
Done 
Describe if abnormal or give reason not 
completed 
 
General Appearance 
☐ 
☐ 
☐ 
 
 
HEENT 
☐ 
☐ 
☐ 
 
 
Cardiovascular 
☐ 
☐ 
☐ 
 
 
Pulmonary 
☐ 
☐ 
☐ 
 
Abdomen 
☐ 
☐ 
☐ 
 
Musculoskeletal 
☐ 
☐ 
☐ 
 
Extremities 
☐ 
☐ 
☐ 
 
Lymph Nodes 
☐ 
☐ 
☐ 
 
Dermatology 
☐ 
☐ 
☐ 
 
Other, Specify 
 
☐ 
☐ 
☐ 
 
 
Other, Specify 
 
☐ 
☐ 
☐ 
Protocol Version 2.2 [9JAN2019]
50

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
 
 
 
Level of 
Consciousness: 
Orientation: 
COMPLETE NEUROLOGICAL EXAM 
☐ Alert      ☐Sleepy, but easily aroused      ☐Somnolent/difficult to arouse      ☐Not arousable 
 
Oriented to time:                                                       ☐Yes      ☐ No 
Oriented to place:                                                      ☐Yes      ☐ No 
Oriented to self, person and others:                          ☐Yes      ☐ No 
0 = None 
 
Muscle Strength: 
(enter corresponding number) 
1 = Trace 
2 = Gravity eliminated 
3 = Against gravity 
4 = Against resistance 
5 = Normal 
Right Arm:   
 
 
Left Arm:   
 
Right Leg:   
 
 
Left Leg:   
 
Gait 
Evaluation: 
 
Cranial Nerves: 
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires a cane 
☐Non-ambulatory 
☐Unable to evaluate 
 
 
Left: II    III    IV    V   VI    VII   VIII    IX    X   XI   XII 
Are any cranial 
nerves affected? 
 
Sensory Exam: 
☐ Yes 
 
Right:  II    III   IV   V   VI VII    VIII    IX    X   XI   XII 
 
☐ Yes_ 
☐ No 
Are there abnormalities present? 
(performed as relevant to tumor location/signs/ symptoms) 
 
☐ No 
 
Other Neurological Findings: 
 
 
Comments: 
 
KARNOFSKY PERFORMANCE SCALE 
Percent 
Description 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self, unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his/her needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. Death not imminent. 
20 
Very sick, hospitalization indicated. Death not imminent. 
10 
Moribund, fatal processes progressing rapidly. 
0 
Dead. 
 
Karnofsky Performance Scale:    
% 
 
PREGNANCY STATUS 
 
Date of procedure (ddmmmyyy):    
 
Pregnancy test-serum 
☐ Positive** 
☐ Negative 
☐ NA 
**Unable to participate in this study 
Protocol Version 2.2 [9JAN2019]
51

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
 
 
 
CHEST X-RAY (AP and Lateral) 
 
Date of  procedure (dd/mmm/yyyy) :    
 
 
Is the X-ray: 
☐ Normal 
☐ Abnormal ** 
**Description: 
  
 
 
 
EKG 
 
Date of procedure (ddmmmyyyy) :    
 
 
Is the EKG: 
☐ Normal 
☐ Abnormal ** 
 
**Description: 
  
 
 
 
MRI 
 
Date of procedure (ddmmmyyyy):    
 
Does the MRI meet eligibility requirements (≥ 1 cm): 
☐ Yes 
☐No 
 
Measurement: 
  
 cm 
 
 
LABORATORY ANALYSIS 
 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 
15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
52

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
 
 
 
LABORATORY ANALYSIS 
 
CBC with diff, plts (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Monocytes 
o 
4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 
0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 
0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
 
Serum Chemistry 
Date drawn (ddmmmyyyy):  
 
 
 
 
 
 
 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
53

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
 
 
 
LABORATORY ANALYSIS 
 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 - 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
54

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
 
Urinalysis 
Date collected (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
 
Color 
o Yellow, Straw, Amber 
 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Clarity 
o Clear 
 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Specific Gravity 
o 1.003 – 1.035 
 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
pH 
o 4.6 – 8.0 
 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Protein 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Glucose 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Ketones 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Nitrite 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
 
LABORATORY ANALYSIS 
 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Human Immunodeficiency virus type 1&2 
(HIV 1 / 2 antibody) 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Retain signed and dated report in the plastic sleeve at back of CRF Folder 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Version 2.2 [9JAN2019]
55

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
Urinalysis (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Leukocyte estimate 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bilirubin 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Urobilinogen 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
If Dipstick Analysis is clinically significant, please perform the following microscopic exam 
☐ NA
 
 
White blood cells (WBC) 
o 0 – 5 hpf 
  
 hpf 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Red blood cells (RBC) 
o 0 – 2 hpf 
  
 hpf 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Squamous epithelial cells 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Non-squamous epithelial cells 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Yeast 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Amorphous cells 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mucous in urine 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Casts 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Crystals 
o Negative 
☐ Negative 
☐ Positive 
☐ Normal 
 
☐ Not done 
☐ Yes  ☐ No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Version 2.2 [9JAN2019]
56

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
 
C134 
Pre-Study 
(Enrollment Visit) 
 
Date:   
    
   
 
dd 
mmm 
yyyy 
Subject 
Initials: 
Subject 
Number: 
 
 
 
 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy):    
 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
 
RESEARCH SAMPLES 
Date drawn (ddmmmyyyy):    
 
Test 
Yes 
No 
Comments 
 
HSV Antibody Titer 
☐ 
☐  
 
LTA, Elispot-blood 
☐ 
☐  
 
IFN Gamma Assay 
☐ 
☐  
 
Blood for future research 
☐ 
☐  
Protocol Version 2.2 [9JAN2019]
57

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 0 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
 
 
DAY 0 
Date: 
 
 
ddmmmyyyy 
 
VITAL SIGNS (Pre-surgery) 
 
Weight (kg):   
_._  
 
 
 
Blood Pressure:   
/  
 
Heart Rate:   
 bpm 
 
 
Respiratory Rate:   
 
Temperature:   
.  
°C 
 
 
 
 
 
Level of 
Consciousness: 
Orientation: 
COMPLETE NEUROLOGICAL EXAM 
 
☐ Alert      ☐Sleepy, but easily aroused      ☐Somnolent/difficult to arouse      ☐Not arousable 
 
Oriented to time:                                                       ☐Yes      ☐ No 
Oriented to place:                                                      ☐Yes      ☐ No 
Oriented to self, person and others:                          ☐Yes      ☐ No 
 
0 = None 
 
Muscle Strength: 
(enter corresponding number) 
1 = Trace 
2 = Gravity eliminated 
3 = Against gravity 
4 = Against resistance 
5 = Normal 
Right Arm:   
 
 
Left Arm:   
 
Right Leg:   
 
 
Left Leg:   
 
 
Gait Evaluation: 
☐ Normal 
☐ Mildly ataxic 
☐ Requires a cane 
☐Non-ambulatory 
☐Unable to evaluate 
 
Cranial Nerves: 
Are any cranial 
nerves affected? 
 
Sensory Exam: 
 
☐ Yes 
 
Left: II    III    IV    V   VI    VII   VIII    IX    X   XI   XII 
Right:  II    III   IV   V   VI VII    VIII    IX    X   XI   XII 
☐ Yes_ 
 
☐ No 
Are there abnormalities present? 
(performed as relevant to tumor location/signs/ symptoms) 
 
☐ No 
 
 
Other Neurological Findings: 
 
 
Comments: 
 
 
 
ADVERSE EVENTS 
 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Events CRF* 
 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
 
*Record all medications on Concomitant Medications CRF* 
Protocol Version 2.2 [9JAN2019]
58

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 0 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
 
 
 
DAY 0 (cont.) 
 
 
MRI 
 
Was Stereotactic MRI completed? 
☐ Yes 
☐No  Why?:  
 
 
 
 
PRELIMINARY PATHOLOGY REPORT 
 
Biopsy confirms diagnosis of recurrent/progressive glioblastoma, 
anaplastic astrocytoma or gliosarcoma 
☐ Yes 
☐No 
 
 
 
 
 
Number of catheters placed:    
 
CATHETERS 
 
 
 
 
RESEARCH SAMPLES 
Date drawn: 
dd/mmm/yyyy 
Test 
Yes 
No 
Comments 
 
Blood for future research – post-op 
☐ 
☐  
Protocol Version 2.2 [9JAN2019]
59

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 0 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
 
 
DAY 1 
Date:   
 
ddmmmyyyy 
 
CT 
Was CT completed prior to study drug administration? 
☐ Yes 
☐No   Comment:_  
 
Date completed (dd/mmm/yyyy):     
 
 
Are all catheters in proper position? 
☐ Yes 
☐No   Comment:_  
 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
*Record all Adverse Events on Adverse Events CRF* 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
*Record all medication on Concomitant Medications CRF* 
 
PHYSICAL EXAMINATION 
 
 
System 
 
Normal 
Abnormal 
Not Done 
Describe if abnormal or give reason not completed 
General Appearance 
☐ 
☐ 
☐ 
 
 
HEENT 
☐ 
☐ 
☐ 
 
 
Cardiovascular 
 
☐ 
☐ 
☐ 
 
 
Pulmonary 
 
☐ 
☐ 
☐ 
 
 
Abdomen 
 
☐ 
☐ 
☐ 
 
 
Musculoskeletal 
 
☐ 
☐ 
☐ 
 
 
Extremities 
 
☐ 
☐ 
☐ 
 
 
Lymph Nodes 
 
☐ 
☐ 
☐ 
 
 
Dermatology 
 
☐ 
☐ 
☐ 
 
 
Wound Assessment 
☐ 
☐ 
☐ 
 
 
Other, Specify 
 
☐ 
☐ 
☐ 
 
 
VITAL SIGNS 
See Vital Signs CRF for Days 1-3 
 
COMPLETE NEUROLOGICAL EXAM 
See Neurological Exam CRF for Days 1-3 
 
STUDY DRUG ADMINISTRATION 
See Catheter CRF 
Protocol Version 2.2 [9JAN2019]
60

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 0 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
Normal 
Abnormal 
Not Done 
Describe if abnormal or give reason not completed 
☐ 
☐ 
☐ 
 
 
 
DAY 2 
Date:   
 
ddmmmyyyy 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Events CRF* 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
 
*Record all medication on Concomitant Medications CRF* 
 
VITAL SIGNS 
 
See Vital Signs CRF for Days 1-3 
 
COMPLETE NEUROLOGICAL EXAM 
 
See Neurological Exam CRF for Days 1-3 
 
WOUND EXAMINATION 
 
 
Wound Assessment 
 
 
LABORATORY ANALYSIS 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Resilts 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
61

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 0 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
 
 
 
DAY 2 (cont.) 
 
LABORATORY ANALYSIS 
CBC with diff, plts  (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Monocytes 
o 4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
LABORATORY ANALYSIS 
Serum Chemistry 
Date drawn (ddmmmyyyy): 
 
 
 
 
 
 
 
 
 
 
 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
62

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 0 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
 
 
DAY 2 (cont.) 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 - 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
63

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 0 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
 
 
 
DAY 2 (cont.) 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy):  
 
 
 
 
 
 
 
 
 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
RESEARCH SAMPLES 
Date drawn (ddmmmyyyy):    
 
Test 
Yes 
No 
Comments 
 
LTA, Elispot-blood 
☐ 
☐  
 
IFN Gamma Assay 
☐ 
☐  
 
Blood for future research 
☐ 
☐  
Protocol Version 2.2 [9JAN2019]
64

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 0 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
 
Normal 
Abnormal 
Not Done 
Describe if abnormal or give reason not completed 
☐ 
☐ 
☐ 
 
 
 
 
DAY 3 
Date:   
 
ddmmmyyyy 
 
 
MRI 
 
Date of procedure (ddmmmyyyy):    
 
Was MRI completed prior to discharge? 
☐ Yes 
☐No   Why?   
 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Events CRF* 
 
MEDICATIONS 
 
Have there been any changes to medications? 
☐ Yes 
☐ No 
 
*Record all medication on Concomitant Medications CRF* 
 
VITAL SIGNS 
 
See Vital Signs CRF for Days 1-3 
 
WOUND EXAMINATION 
 
 
 
Wound Assessment 
 
 
COMPLETE NEUROLOGICAL EXAM 
 
See Neurological Exam CRF for Days 1-3 
 
 
KARNOFSKY PERFORMANCE SCALE 
Percent 
Description 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self, unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his/her needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. Death not imminent. 
20 
Very sick, hospitalization indicated. Death not imminent. 
10 
Moribund, fatal processes progressing rapidly. 
0 
Dead. 
 
Karnofsky Performance Scale:    
% 
Protocol Version 2.2 [9JAN2019]
65

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 0 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
 
 
 
DAY 3 (cont.) 
 
LABORATORY ANALYSIS 
 
HSV Detection 
Date collected (ddmmmyyyy):    
 
Test 
Results 
Clinically Significant 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
RESEARCH SAMPLES 
Date drawn (ddmmmyyyy):    
 
Test 
Yes 
No 
Comments 
 
LTA, Elispot-blood 
☐ 
☐  
 
IFN Gamma Assay 
☐ 
☐  
 
Blood for future research 
☐ 
☐  
 
 
 
 
 
 
 
I am confident that the information supplied in this case record form is complete and accurate data.  I 
confirm that the Day 0 to Day 3 visits were conducted in accordance with the protocol and any 
protocol amendments and that written informed consent was obtained prior to the start of the study 
procedures. 
 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
66

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
 
C134 
Day 1 to Day 3 
Subject Initials:  ___  ___  ___ 
Subject Number:  ___  ___  ___ 
 
 
 
 
 
Vital Signs 
 
Date 
dd/mmm/yyy 
Time 
24 hour clock 
BP 
HR 
bpm 
 
RR 
Temp 
°C 
Pre-study drug 
administration 
 
 
 
 
 
 
 
1 hour 
 
 
 
 
 
 
 
2 hours 
 
 
 
 
 
 
 
3 hours 
 
 
 
 
 
 
 
4 hours 
 
 
 
 
 
 
 
5 hours 
 
 
 
 
 
 
 
6 hours 
 
 
 
 
 
 
 
7 hours 
 
 
 
 
 
 
 
8 hours 
 
 
 
 
 
 
 
9 hours 
 
 
 
 
 
 
 
10 hours 
 
 
 
 
 
 
 
11 hours 
 
 
 
 
 
 
 
12 hours 
 
 
 
 
 
 
 
14 hours 
 
 
 
 
 
 
 
16 hours 
 
 
 
 
 
 
 
18 hours 
 
 
 
 
 
 
 
20 hours 
 
 
 
 
 
 
 
22 hours 
 
 
 
 
 
 
 
24 hours 
 
 
 
 
 
 
 
28 hours 
 
 
 
 
 
 
 
32 hours 
 
 
 
 
 
 
 
36 hours 
 
 
 
 
 
 
 
40 hours 
 
 
 
 
 
 
 
44 hours 
 
 
 
 
 
 
 
48 hours 
 
 
 
 
 
 
 
 
Protocol Version 2.2 [9JAN2019]
67

  
 
COMPLETE NEUROLOGICAL EXAM 
 
 
 
 
Date/Time 
(ddmmmyyyy/ 
24 hr clock) 
 
 
 
Level of Consciousness 
Orientation To 
Muscle Strength 
(enter corresponding 
number) 
0 = None 
1 = Trace 
2 = Gravity eliminated 
3 = Against gravity 
4 = Against resistance 
5 = Normal 
 
 
Gait Evaluation 
 
 
Cranial Nerves 
Are any cranial nerves 
affected? 
(If yes, please circle which are 
affected) 
Sensory Exam 
(performed as relevant to 
tumor location/signs/ 
symptoms) 
Are there abnormalities 
present? 
(if yes, describe) 
 
 
Other Neuro- 
logical findings 
Adverse 
Event(s) 
 
*If yes, 
record on 
AE page 
 
Time 
 
Place 
 
Self, person & 
others 
 
 
Pre-study 
drug 
admin 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
1 hour 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
2 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
3 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
4 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
5 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
C134 
 
Day 1 to Day 3 
Subject Initials: 
  
   
 
Subject Number: 
  
 
 
 
 
 
 
 
 
Protocol Version 2.2 [9JAN2019]
68

  
 
COMPLETE NEUROLOGICAL EXAM (cont.) 
 
 
 
 
Date/Time 
(ddmmmyyyy/ 
24 hr clock) 
 
 
 
Level of Consciousness 
Orientation To 
Muscle Strength 
(enter corresponding 
number) 
0 = None 
1 = Trace 
2 = Gravity eliminated 
3 = Against gravity 
4 = Against resistance 
5 = Normal 
 
 
Gait Evaluation 
 
 
Cranial Nerves 
Are any cranial nerves 
affected? 
(If yes, please circle which are 
affected) 
Sensory Exam 
(performed as relevant to 
tumor location/signs/ 
symptoms) 
Are there abnormalities 
present? 
(if yes, describe) 
 
 
Other Neuro- 
logical findings 
Adverse 
Event(s) 
 
*If yes, 
record on 
AE page 
 
Time 
 
Place 
 
Self, person & 
others 
 
 
 
6 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
7 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
8 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
9 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
10 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
11 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐ NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐ NA 
 
C134 
 
Day 1 to Day 3 
Subject Initials: 
  
   
 
Subject Number: 
  
 
Protocol Version 2.2 [9JAN2019]
69

  
 
COMPLETE NEUROLOGICAL EXAM (cont.) 
 
 
 
 
Date/Time 
(ddmmmyyyy/ 
24 hr clock) 
 
 
 
Level of Consciousness 
Orientation To 
Muscle Strength 
(enter corresponding 
number) 
0 = None 
1 = Trace 
2 = Gravity eliminated 
3 = Against gravity 
4 = Against resistance 
5 = Normal 
 
 
Gait Evaluation 
 
 
Cranial Nerves 
Are any cranial nerves 
affected? 
(If yes, please circle which are 
affected) 
Sensory Exam 
(performed as relevant to 
tumor location/signs/ 
symptoms) 
Are there abnormalities 
present? 
(if yes, describe) 
 
 
Other Neuro- 
logical findings 
Adverse 
Event(s) 
 
*If yes, 
record on 
AE page 
 
Time 
 
Place 
 
Self, person & 
others 
 
 
 
 
 
 
 
 
12 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
14 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
16 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
18 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
20 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
22 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
C134 
 
Day 1 to Day 3 
Subject Initials: 
  
   
 
Subject Number: 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐ NA 
 
 
 
 
 
 
 
 
 
 
 
 
☐ NA 
 
 
 
 
 
 
☐ NA 
Protocol Version 2.2 [9JAN2019]
70

  
 
 
COMPLETE NEUROLOGICAL EXAM (cont.) 
 
 
 
 
Date/Time 
(ddmmmyyyy/ 
24 hr clock) 
 
 
 
Level of Consciousness 
Orientation To 
Muscle Strength 
(enter corresponding 
number) 
0 = None 
1 = Trace 
2 = Gravity eliminated 
3 = Against gravity 
4 = Against resistance 
5 = Normal 
 
 
Gait Evaluation 
 
 
Cranial Nerves 
Are any cranial nerves 
affected? 
(If yes, please circle which are 
affected) 
Sensory Exam 
(performed as relevant to 
tumor location/signs/ 
symptoms) 
Are there abnormalities 
present? 
(if yes, describe) 
 
 
Other Neuro- 
logical findings 
Adverse 
Event(s) 
 
*If yes, 
record on 
AE page 
 
Time 
 
Place 
 
Self, person 
& others 
 
 
 
24 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
28 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
32 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
36 hours 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
40 hours 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
 
44 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
 
 
C134 
 
Day 1 to Day 3 
Subject Initials: 
  
   
 
Subject Number: 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐ NA 
 
 
 
 
 
 
☐ NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☐ NA 
Protocol Version 2.2 [9JAN2019]
71

  
 
 
 
C134 
 
Day 1 to Day 3 
Subject Initials: 
  
   
 
Subject Number: 
  
 
 
COMPLETE NEUROLOGICAL EXAM (cont.) 
 
 
 
 
Date/Time 
(ddmmmyyyy/ 
24 hr clock) 
 
 
 
Level of Consciousness 
Orientation To 
Muscle Strength 
(enter corresponding 
number) 
0 = None 
1 = Trace 
2 = Gravity eliminated 
3 = Against gravity 
4 = Against resistance 
5 = Normal 
 
 
Gait Evaluation 
 
 
Cranial Nerves 
Are any cranial nerves 
affected? 
(If yes, please circle which are 
affected) 
Sensory Exam 
(performed as relevant to 
tumor location/signs/ 
symptoms) 
Are there abnormalities 
present? 
(if yes, describe) 
 
 
Other Neuro- 
logical findings 
Adverse 
Event(s) 
 
*If yes, 
record on 
AE page 
 
Time 
 
Place 
 
Self, person & 
others 
 
 
 
48 hours 
 
 
☐ Alert 
☐ Sleepy, but easily aroused 
☐ Somnolent/difficult to arouse 
☐ Not arousable 
 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
 
☐Yes 
☐No 
Right Arm:    
 
Right Leg:     
 
 
Left Arm:    
  
Left Leg:    
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires cane 
☐ Non-ambulatory 
☐ NA 
Left:  ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII      IX      X      XI     XII 
Right: ☐Yes  ☐No 
II     III     IV     V     VI      VII 
VIII     IX 
X      XI     XII 
☐Yes    
 
 
 
 
☐No 
 
 
☐Yes* 
☐No 
Protocol Version 2.2 [9JAN2019]
72

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 1 to Day 3 
 
Subject Initials: 
  
   
 
Subject Number: 
  
    
 
 
 
CATHETER/PUMP STATUS 
(Record time using 24 hour clock) 
 
Date (ddmmmyyyy):   
 
 
Cohort/dose (pfu):    ☐ 1x106 
☐ 3x106 
☐ 1x107 
☐ 3x107 
☐ 1x108 
Other:  
 
 
Catheter/Pump A 
 
Catheter/Pump B 
Catheter/Pump C 
Catheter/Pump D 
Staff 
Initials 
Flush (35 minutes): 
Start Time:    
 
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
Start Time:    
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
Start Time:    
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
Start Time:    
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
 
First Infusion: 
Start Time:    
 
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
Start Time:    
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
Start Time:    
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
Start Time:    
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
 
Was the total amount of Study Drug C134 Administered 1.2 ml? 
☐ Yes 
☐ No 
 
If No, explain:  
 
 
 
Was the total rate of administration 0.4 ml? 
☐ Yes 
☐ No 
If No, explain:  
 
Second Infusion: 
Start Time:   
 
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
Start Time:    
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
Start Time:   
 
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
Start Time:    
☐ N/A 
Stop Time:   
 
 
Amt. Infused:   
ml 
 
Rate:   
ml/hour 
 
Was the total amount of Study Drug C134 Administered 1.2 ml? 
☐ Yes 
☐ No 
 
If No, explain:  
 
 
 
Was the total rate of administration 0.4 ml? 
☐ Yes 
☐ No 
If No, explain:  
 
 
Was total dose of 2.4 ml of Study Drug C134 administered? 
☐ Yes 
☐ No 
 
If No, explain:  
 
 
 
Was Study Drug C134 given per protocol? 
☐ Yes 
☐ No 
If No, explain:  
 
 
 
 
Protocol Version 2.2 [9JAN2019]
73

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 10 (± 3 days) 
Subject 
Initials: 
Subject 
Number: 
 
DAY 10 (± 3 days) 
Date:   
 
ddmmmyyyy 
 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Events CRF* 
 
 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
 
*Record all medication on Concomitant Medications CRF* 
 
 
 
VITAL SIGNS 
 
Weight (kg):   
.  
 
 
Blood Pressure:   
/  
 
Heart Rate:   
 bpm 
 
Respiratory Rate:   
 
Temperature:   
_.  
 °C 
 
 
 
 
PHYSICAL EXAMINATION 
 
 
System 
 
Normal 
Abnormal 
Not Done 
Describe if abnormal or give reason not completed 
General Appearance 
☐ 
☐ 
☐ 
 
HEENT 
☐ 
☐ 
☐ 
 
Cardiovascular 
☐ 
☐ 
☐ 
 
 
Pulmonary 
☐ 
☐ 
☐ 
 
Abdomen 
☐ 
☐ 
☐ 
 
Musculoskeletal 
☐ 
☐ 
☐ 
 
 
Extremities 
☐ 
☐ 
☐ 
 
Lymph Nodes 
☐ 
☐ 
☐ 
 
 
Dermatology 
☐ 
☐ 
☐ 
 
 
Wound Assessment 
☐ 
☐ 
☐ 
 
 
Other, Specify 
 
☐ 
☐ 
☐ 
Protocol Version 2.2 [9JAN2019]
74

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 10 (± 3 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
 
 
Level of 
Consciousness: 
Orientation: 
COMPLETE NEUROLOGICAL EXAM 
☐ Alert      ☐Sleepy, but easily aroused      ☐Somnolent/difficult to arouse      ☐Not arousable 
 
Oriented to time:                                                       ☐Yes      ☐ No 
Oriented to place:                                                      ☐Yes      ☐ No 
Oriented to self, person and others:                          ☐Yes      ☐ No 
0 = None 
 
Muscle Strength: 
(enter corresponding number) 
1 = Trace 
2 = Gravity eliminated 
3 = Against gravity 
4 = Against resistance 
5 = Normal 
Right Arm:   
 
 
Left Arm:   
 
Right Leg:   
 
 
Left Leg:   
 
Gait 
Evaluation: 
 
Cranial Nerves: 
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires a cane 
☐Non-ambulatory 
☐Unable to evaluate 
 
 
Left: II    III    IV    V   VI    VII   VIII    IX    X   XI   XII 
Are any cranial 
nerves affected? 
 
Sensory Exam: 
☐ Yes 
 
Right:  II    III   IV   V   VI VII    VIII    IX    X   XI   XII 
 
☐ Yes_ 
☐ No 
Are there abnormalities present? 
(performed as relevant to tumor location/signs/ symptoms) 
 
☐ No 
 
Other Neurological Findings: 
 
Comments: 
 
 
 
 
 
KARNOFSKY PERFORMANCE SCALE 
Percent 
Description 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self, unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his/her needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. Death not imminent. 
20 
Very sick, hospitalization indicated. Death not imminent. 
10 
Moribund, fatal processes progressing rapidly. 
0 
Dead. 
 
Karnofsky Performance Scale:    
% 
Protocol Version 2.2 [9JAN2019]
75

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 10 (± 3 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
 
LABORATORY ANALYSIS 
 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Monocytes 
o 4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
76

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 10 (± 3 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
LABORATORY ANALYSIS 
Serum Chemistry 
Date drawn (ddmmmyyyy):  
 
 
 
 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 - 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
77

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 10 (± 3 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy):    
 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
RESEARCH SAMPLES 
Date drawn (ddmmmyyyy):    
 
Test 
Yes 
No 
Comments 
HSV Antibody Titer 
☐ 
☐  
LTA, Elispot-blood 
☐ 
☐ 
IFN Gamma Assay 
☐ 
☐ 
Blood for future research 
☐ 
☐  
 
I am confident that the information supplied in this case record form is complete and accurate data.  I 
confirm that the Day 10 Study Visit was conducted in accordance with the protocol and any protocol 
amendments and that written informed consent was obtained prior to the start of the study procedures. 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
78

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 28 (± 4 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
DAY 28 (± 4 days) 
Date:   
 
ddmmmyyyy 
 
MRI 
 
Date of procedure (ddmmmyyyy):    
 
Was MRI completed? 
☐ Yes 
☐No 
 
If no, why?   
 
 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
*Record all Adverse Events on Adverse Events CRF* 
 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
*Record all medication on Concomitant Medications CRF* 
 
VITAL SIGNS 
 
Weight (kg):   
.  
 
 
Blood Pressure:   
/  
 
Heart Rate:   
 bpm 
 
Respiratory Rate:   
 
Temperature:   
_.  
 °C 
 
 
PHYSICAL EXAMINATION 
 
System 
Normal 
Abnormal 
Not Done 
Describe if abnormal or give reason not completed 
General Appearance 
☐ 
☐ 
☐ 
 
 
HEENT 
☐ 
☐ 
☐ 
 
Cardiovascular 
☐ 
☐ 
☐ 
 
 
Pulmonary 
☐ 
☐ 
☐ 
 
Abdomen 
☐ 
☐ 
☐ 
 
Musculoskeletal 
☐ 
☐ 
☐ 
 
 
Extremities 
☐ 
☐ 
☐ 
 
Lymph Nodes 
☐ 
☐ 
☐ 
 
 
Dermatology 
☐ 
☐ 
☐ 
 
Other, Specify 
 
☐ 
☐ 
☐ 
Protocol Version 2.2 [9JAN2019]
79

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 28 (± 4 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
KARNOFSKY PERFORMANCE SCALE 
Percent 
Description 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self, unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his/her needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. Death not imminent. 
20 
Very sick, hospitalization indicated. Death not imminent. 
10 
Moribund, fatal processes progressing rapidly. 
0 
Dead. 
 
Karnofsky Performance Scale:    
% 
 
 
 
 
 
 
 
 
Level of 
Consciousness: 
Orientation: 
COMPLETE NEUROLOGICAL EXAM 
 
☐ Alert      ☐Sleepy, but easily aroused      ☐Somnolent/difficult to arouse      ☐Not arousable 
 
Oriented to time:                                                       ☐Yes      ☐ No 
Oriented to place:                                                      ☐Yes      ☐ No 
Oriented to self, person and others:                          ☐Yes      ☐ No 
0 = None 
 
Muscle Strength: 
(enter corresponding number) 
1 = Trace 
2 = Gravity eliminated 
3 = Against gravity 
4 = Against resistance 
5 = Normal 
Right Arm:   
 
 
Left Arm:   
 
Right Leg:   
 
 
Left Leg:   
 
Gait 
Evaluation: 
 
Cranial Nerves: 
 
☐ Normal 
☐ Mildly ataxic 
☐ Requires a cane 
☐Non-ambulatory 
☐Unable to evaluate 
 
 
Left: II    III    IV    V   VI    VII   VIII    IX    X   XI   XII 
Are any cranial 
nerves affected? 
 
Sensory Exam: 
☐ Yes 
 
Right:  II    III   IV   V   VI VII    VIII    IX    X   XI   XII 
 
☐ Yes_ 
☐ No 
Are there abnormalities present? 
(performed as relevant to tumor location/signs/ symptoms) 
 
☐ No 
 
Other Neurological Findings: 
 
 
Comments: 
Protocol Version 2.2 [9JAN2019]
80

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 28 (± 4 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
LABORATORY ANALYSIS 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 
15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Monocytes 
o 
4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 
0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 
0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
81

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 28 (± 4 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
LABORATORY ANALYSIS 
Serum Chemistry 
Date drawn (ddmmmyyyy): 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 - 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
82

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Day 28 (± 4 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy):    
 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
RESEARCH SAMPLES 
Date drawn (ddmmmyyyy):    
 
Test 
Yes 
No 
Comments 
HSV Antibody Titer 
☐ 
☐  
LTA, Elispot-blood 
☐ 
☐  
IFN Gamma Assay 
☐ 
☐  
Blood for future research 
☐ 
☐  
I am confident that the information supplied in this case record form is complete and accurate data. I confirm 
that the Day 28 Study Visit was conducted in accordance with the protocol and any protocol amendments and 
that written informed consent was obtained prior to the start of the study procedures. 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
83

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 2 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
MONTH 2 (± 12 days) 
Date: 
 
 
ddmmmyyyy 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Event CRF* 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
 
*Record all medication on Concomitant Medications CRF* 
 
LABORATORY ANALYSIS 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 
15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Monocytes 
o 
4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 
0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 
0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
84

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 2 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
CBC with diff, plts (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
Serum Chemistry 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
85

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 2 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 - 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy):    
 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
I am confident that the information supplied in this case record form is complete and accurate data.  I 
confirm that the Month 2 Study Visit was conducted in accordance with the protocol and any protocol 
amendments and that written informed consent was obtained prior to the start of the study procedures. 
 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyy 
Protocol Version 2.2 [9JAN2019]
86

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 3 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
MONTH 3 (± 12 days) 
Date: 
 
 
ddmmmyyyy 
 
MRI 
 
Date of procedure (ddmmmyyyy):    
 
 
Was MRI completed? 
☐ Yes 
☐No 
 
If no, why?   
 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Event CRF* 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
*Record all medication on Concomitant Medications CRF* 
 
VITAL SIGNS 
 
Weight (kg):   
.  
 
 
Blood Pressure:   
/  
 
 
Respiratory Rate:   
 
Heart Rate:   
 bpm 
 
Temperature:   
_.  
 °C 
 
 
PHYSICAL EXAMINATION 
 
 
System 
 
Normal 
Abnormal 
Not Done 
Describe if abnormal or give reason not completed 
General Appearance 
☐ 
☐ 
☐ 
 
HEENT 
☐ 
☐ 
☐ 
 
Cardiovascular 
☐ 
☐ 
☐ 
 
 
Pulmonary 
☐ 
☐ 
☐ 
 
Abdomen 
☐ 
☐ 
☐ 
 
Musculoskeletal 
☐ 
☐ 
☐ 
 
 
Extremities 
☐ 
☐ 
☐ 
 
Lymph Nodes 
☐ 
☐ 
☐ 
 
 
Dermatology 
☐ 
☐ 
☐ 
 
Other, Specify 
 
☐ 
☐ 
☐ 
Protocol Version 2.2 [9JAN2019]
87

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 3 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
KARNOFSKY PERFORMANCE SCALE 
Percent 
Description 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self, unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his/her needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. Death not imminent. 
20 
Very sick, hospitalization indicated. Death not imminent. 
10 
Moribund, fatal processes progressing rapidly. 
0 
Dead. 
 
Karnofsky Performance Scale:    
% 
 
 
 
COMPLETE NEUROLOGICAL EXAM 
Level of 
☐ Alert 
☐Sleepy, but easily aroused 
☐Somnolent/difficult to arouse 
☐Not arousable 
Consciousness: 
 
Orientation: 
Oriented to time: 
☐Yes 
☐ No 
Oriented to place: 
☐Yes 
☐ No 
Oriented to self, person and others: 
☐Yes 
☐ No 
0 = None 
1 = Trace 
Right Arm:   
 
Right Leg:   
 
Muscle Strength: 
2 = Gravity eliminated 
(enter corresponding number) 
3 = Against gravity 
4 = Against resistance 
Left Arm:   
 
Left Leg:   
 
5 = Normal 
Gait 
☐ Normal 
☐ Mildly ataxic 
☐ Requires a cane 
☐Non-ambulatory 
☐Unable to evaluate 
Evaluation: 
Cranial Nerves: 
Left: 
II    III    IV    V   VI    VII   VIII    IX    X   XI   XII 
Are any cranial 
☐ Yes 
☐ No 
nerves affected? 
Right:  II    III   IV   V   VI VII    VIII    IX    X   XI   XII 
Sensory Exam: 
☐ Yes_ 
Are there abnormalities present? 
(performed as relevant to tumor location/signs/ symptoms) 
☐ No 
 
Other Neurological Findings: 
 
Comments: 
Protocol Version 2.2 [9JAN2019]
88

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 3 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
 
LABORATORY ANALYSIS 
 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 
15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Monocytes 
o 
4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 
0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 
0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
89

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 3 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
Serum Chemistry 
Date drawn (ddmmmyyyy): 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 – 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
90

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 3 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy):    
 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
RESEARCH SAMPLES 
Date drawn (ddmmmyyyy):    
 
Test 
Yes 
No 
Comments 
HSV Antibody Titer 
☐ 
☐  
LTA, Elispot-blood 
☐ 
☐  
IFN Gamma Assay 
☐ 
☐  
Blood for future research 
☐ 
☐ 
I am confident that the information supplied in this case record form is complete and accurate data. I 
confirm that the Month 3 Study Visit was conducted in accordance with the protocol and any protocol 
amendments and that written informed consent was obtained prior to the start of the study procedures. 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
91

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 4 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
MONTH 4 (± 12 days) 
Date: 
 
 
ddmmmyyyy 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Event CRF* 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
 
*Record all medication on Concomitant Medications CRF* 
 
LABORATORY ANALYSIS 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 
15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Monocytes 
o 
4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 
0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 
0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
92

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 4 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
CBC with diff, plts (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
 
Serum Chemistry 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
93

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 4 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 – 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy):    
 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
I am confident that the information supplied in this case record form is complete and accurate data.  I 
confirm that the Month 4 Study Visit was conducted in accordance with the protocol and any protocol 
amendments and that written informed consent was obtained prior to the start of the study procedures. 
 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyy 
Protocol Version 2.2 [9JAN2019]
94

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 5 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
MONTH 5 (± 12 days) 
Date: 
 
 
ddmmmyyyy 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Event CRF* 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
 
*Record all medication on Concomitant Medications CRF* 
 
LABORATORY ANALYSIS 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 
15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Monocytes 
o 
4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 
0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 
0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
95

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 5 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
CBC with diff, plts (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
 
Serum Chemistry 
Date drawn (ddmmmyyyy):   
 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
96

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 5 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 - 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy):    
 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
I am confident that the information supplied in this case record form is complete and accurate data.  I 
confirm that the Month 5 Study Visit was conducted in accordance with the protocol and any protocol 
amendments and that written informed consent was obtained prior to the start of the study procedures. 
 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyy 
Protocol Version 2.2 [9JAN2019]
97

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 6 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
MONTH 6 (± 12 days) 
Date: 
 
 
ddmmmyyyy 
 
MRI 
 
Date of procedure (ddmmmyyyy):    
 
 
Was MRI completed? 
☐ Yes 
☐No 
 
If no, why?   
 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Event CRF* 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
*Record all medication on Concomitant Medications CRF* 
 
VITAL SIGNS 
 
Weight (kg):   
.  
 
 
Blood Pressure:   
/  
 
 
Respiratory Rate:   
 
Heart Rate:   
 bpm 
 
Temperature:   
_.  
 °C 
 
PHYSICAL EXAMINATION 
 
 
System 
 
Normal 
Abnormal 
Not Done 
Describe if abnormal or give reason not completed 
General Appearance 
☐ 
☐ 
☐ 
 
HEENT 
☐ 
☐ 
☐ 
 
Cardiovascular 
☐ 
☐ 
☐ 
 
 
Pulmonary 
☐ 
☐ 
☐ 
 
Abdomen 
☐ 
☐ 
☐ 
 
Musculoskeletal 
☐ 
☐ 
☐ 
 
 
Extremities 
☐ 
☐ 
☐ 
 
Lymph Nodes 
☐ 
☐ 
☐ 
 
 
Dermatology 
☐ 
☐ 
☐ 
 
Other, Specify 
 
☐ 
☐ 
☐ 
Protocol Version 2.2 [9JAN2019]
98

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 6 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
 
COMPLETE NEUROLOGICAL EXAM 
Level of 
☐ Alert 
☐Sleepy, but easily aroused 
☐Somnolent/difficult to arouse 
☐Not arousable 
Consciousness: 
 
Orientation: 
Oriented to time: 
☐Yes 
☐ No 
Oriented to place: 
☐Yes 
☐ No 
Oriented to self, person and others: 
☐Yes 
☐ No 
0 = None 
1 = Trace 
Right Arm:   
 
Right Leg:   
 
Muscle Strength: 
2 = Gravity eliminated 
(enter corresponding number) 
3 = Against gravity 
4 = Against resistance 
Left Arm:   
 
Left Leg:   
 
5 = Normal 
Gait 
☐ Normal 
☐ Mildly ataxic 
☐ Requires a cane 
☐Non-ambulatory 
☐Unable to evaluate 
Evaluation: 
Cranial Nerves: 
Left: 
II    III    IV    V   VI    VII   VIII    IX    X   XI   XII 
Are any cranial 
☐ Yes 
☐ No 
nerves affected? 
Right:  II    III   IV   V   VI VII    VIII    IX    X   XI   XII 
Sensory Exam: 
☐ Yes_ 
Are there abnormalities present? 
(performed as relevant to tumor location/signs/ symptoms) 
☐ No 
 
Other Neurological Findings: 
Comments: 
 
 
 
 
 
KARNOFSKY PERFORMANCE SCALE 
Percent 
Description 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self, unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his/her needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. Death not imminent. 
20 
Very sick, hospitalization indicated. Death not imminent. 
10 
Moribund, fatal processes progressing rapidly. 
0 
Dead. 
 
Karnofsky Performance Scale:    
% 
Protocol Version 2.2 [9JAN2019]
99

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 6 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
LABORATORY ANALYSIS 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 
15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Monocytes 
o 
4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 
0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 
0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
100

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 6 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
LABORATORY ANALYSIS 
Serum Chemistry 
Date drawn (ddmmmyyyy): 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 - 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
101

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 6 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy):    
 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
RESEARCH SAMPLES 
Date drawn (ddmmmyyyy):    
 
Test 
Yes 
No 
Comments 
HSV Antibody Titer 
☐ 
☐  
LTA, Elispot-blood 
☐ 
☐  
IFN Gamma Assay 
☐ 
☐  
Blood for future research 
☐ 
☐  
I am confident that the information supplied in this case record form is complete and accurate data. I confirm 
that the Month 6 Study Visit was conducted in accordance with the protocol and any protocol amendments and 
that written informed consent was obtained prior to the start of the study procedures. 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
102

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 9 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
MONTH 9 (± 12 days) 
Date: 
 
 
ddmmmyyyy 
 
MRI 
 
Date of procedure (ddmmmyyyy):    
 
 
Was MRI completed? 
☐ Yes 
☐No 
 
If no, why?   
 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Event CRF* 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
*Record all medication on Concomitant Medications CRF* 
 
VITAL SIGNS 
 
Weight (kg):   
.  
 
 
Blood Pressure:   
/  
 
 
Respiratory Rate:   
 
Heart Rate:   
 bpm 
 
Temperature:   
_.  
 °C 
 
PHYSICAL EXAMINATION 
 
 
System 
 
Normal 
Abnormal 
Not Done 
Describe if abnormal or give reason not completed 
General Appearance 
☐ 
☐ 
☐ 
 
HEENT 
☐ 
☐ 
☐ 
 
Cardiovascular 
☐ 
☐ 
☐ 
 
 
Pulmonary 
☐ 
☐ 
☐ 
 
Abdomen 
☐ 
☐ 
☐ 
 
Musculoskeletal 
☐ 
☐ 
☐ 
 
 
Extremities 
☐ 
☐ 
☐ 
 
Lymph Nodes 
☐ 
☐ 
☐ 
 
 
Dermatology 
☐ 
☐ 
☐ 
 
Other, Specify 
 
☐ 
☐ 
☐ 
Protocol Version 2.2 [9JAN2019]
103

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 9 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
COMPLETE NEUROLOGICAL EXAM 
Level of 
☐ Alert 
☐Sleepy, but easily aroused 
☐Somnolent/difficult to arouse 
☐Not arousable 
Consciousness: 
 
Orientation: 
Oriented to time: 
☐Yes 
☐ No 
Oriented to place: 
☐Yes 
☐ No 
Oriented to self, person and others: 
☐Yes 
☐ No 
0 = None 
1 = Trace 
Right Arm:   
 
Right Leg:   
 
Muscle Strength: 
2 = Gravity eliminated 
(enter corresponding number) 
3 = Against gravity 
4 = Against resistance 
Left Arm:   
 
Left Leg:   
 
5 = Normal 
Gait 
☐ Normal 
☐ Mildly ataxic 
☐ Requires a cane 
☐Non-ambulatory 
☐Unable to evaluate 
Evaluation: 
Cranial Nerves: 
Left: 
II    III    IV    V   VI    VII   VIII    IX    X   XI   XII 
Are any cranial 
☐ Yes 
☐ No 
nerves affected? 
Right:  II    III   IV   V   VI VII    VIII    IX    X   XI   XII 
Sensory Exam: 
☐ Yes_ 
Are there abnormalities present? 
(performed as relevant to tumor location/signs/ symptoms) 
☐ No 
 
Other Neurological Findings: 
Comments: 
 
 
KARNOFSKY PERFORMANCE SCALE 
Percent 
Description 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self, unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his/her needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. Death not imminent. 
20 
Very sick, hospitalization indicated. Death not imminent. 
10 
Moribund, fatal processes progressing rapidly. 
0 
Dead. 
 
Karnofsky Performance Scale:    
% 
Protocol Version 2.2 [9JAN2019]
104

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 9 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
LABORATORY ANALYSIS 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 
15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Monocytes 
o 
4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 
0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 
0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
105

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 9 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
LABORATORY ANALYSIS 
Serum Chemistry 
Date drawn (ddmmmyyyy): 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 - 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
106

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 9 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy): 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
RESEARCH SAMPLES 
Date drawn (ddmmmyyyy):    
 
Test 
Yes 
No 
Comments 
HSV Antibody Titer 
☐ 
☐  
LTA, Elispot-blood 
☐ 
☐  
IFN Gamma Assay 
☐ 
☐  
Blood for future research 
☐ 
☐  
I am confident that the information supplied in this case record form is complete and accurate data. I 
confirm that the Month 9 Study Visit was conducted in accordance with the protocol and any protocol 
amendments and that written informed consent was obtained prior to the start of the study procedures. 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
107

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 12 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
MONTH 12 (± 12 days) 
Date: 
 
 
ddmmmyyyy 
 
MRI 
 
Date of procedure (ddmmmyyyy):    
 
 
Was MRI completed? 
☐ Yes 
☐No 
 
If no, why?   
 
 
ADVERSE EVENTS 
Has the subject experienced any adverse events since last visit? 
☐Yes 
☐ No 
 
*Record all Adverse Events on Adverse Event CRF* 
 
MEDICATIONS 
Have there been any changes to medications? 
☐ Yes 
☐ No 
*Record all medication on Concomitant Medications CRF* 
 
VITAL SIGNS 
 
Weight (kg):   
.  
 
 
Blood Pressure:   
/  
 
 
Respiratory Rate:   
 
Heart Rate:   
 bpm 
 
Temperature:   
_.  
 °C 
 
PHYSICAL EXAMINATION 
 
 
System 
 
Normal 
Abnormal 
Not Done 
Describe if abnormal or give reason not completed 
General Appearance 
☐ 
☐ 
☐ 
 
HEENT 
☐ 
☐ 
☐ 
 
Cardiovascular 
☐ 
☐ 
☐ 
 
 
Pulmonary 
☐ 
☐ 
☐ 
 
Abdomen 
☐ 
☐ 
☐ 
 
Musculoskeletal 
☐ 
☐ 
☐ 
 
 
Extremities 
☐ 
☐ 
☐ 
 
Lymph Nodes 
☐ 
☐ 
☐ 
 
 
Dermatology 
☐ 
☐ 
☐ 
 
Other, Specify 
 
☐ 
☐ 
☐ 
Protocol Version 2.2 [9JAN2019]
108

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 12 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
COMPLETE NEUROLOGICAL EXAM 
Level of 
☐ Alert 
☐Sleepy, but easily aroused 
☐Somnolent/difficult to arouse 
☐Not arousable 
Consciousness: 
 
Orientation: 
Oriented to time: 
☐Yes 
☐ No 
Oriented to place: 
☐Yes 
☐ No 
Oriented to self, person and others: 
☐Yes 
☐ No 
0 = None 
1 = Trace 
Right Arm:   
 
Right Leg:   
 
Muscle Strength: 
2 = Gravity eliminated 
(enter corresponding number) 
3 = Against gravity 
4 = Against resistance 
Left Arm:   
 
Left Leg:   
 
5 = Normal 
Gait 
☐ Normal 
☐ Mildly ataxic 
☐ Requires a cane 
☐Non-ambulatory 
☐Unable to evaluate 
Evaluation: 
Cranial Nerves: 
Left: 
II    III    IV    V   VI    VII   VIII    IX    X   XI   XII 
Are any cranial 
☐ Yes 
☐ No 
nerves affected? 
Right:  II    III   IV   V   VI    VII    VIII    IX    X   XI   XII 
Sensory Exam: 
☐ Yes_ 
Are there abnormalities present? 
(performed as relevant to tumor location/signs/ symptoms) 
☐ No 
 
Other Neurological Findings: 
Comments: 
 
 
 
KARNOFSKY PERFORMANCE SCALE 
Percent 
Description 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self, unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of his/her needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. Death not imminent. 
20 
Very sick, hospitalization indicated. Death not imminent. 
10 
Moribund, fatal processes progressing rapidly. 
0 
Dead. 
 
Karnofsky Performance Scale:    
% 
Protocol Version 2.2 [9JAN2019]
109

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 12 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
LABORATORY ANALYSIS 
 
CBC with diff, plts 
Date drawn (ddmmmyyyy):    
 
 
Test 
Results 
Clinically 
Significant 
 
Red blood cell count (RBC) 
o M:  4.40 – 5.80 x 106/cmm 
o F:   3.80 – 5.20 x 106/cmm 
  
 x 106/cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hemoglobin (Hgb) 
o M:  13.5 – 17.0 g/dL 
o F:   11.3 – 15.2 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Hematocrit (Hct) 
o M:  39 – 50% 
o F:   33 – 45% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Platelet count (PLT) 
o 150- 400 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
White blood cell count (WBC) 
o 4.0 – 11.0 x 103/cmm 
3 
  
 x 10 /cmm 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Neutrophils 
 
35 – 73% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Lymphocytes 
o 
15 – 52% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Monocytes 
o 
4 – 13% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Basophils 
o 
0 – 2% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Eosinophils 
o 
0 – 5% 
  
_% 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular haemoglobin (MCH) 
o 27 – 33 pg 
  
 pg 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Mean corpuscular haemoglobin concentration 
(MCHC) 
o 32 – 36 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Mean corpuscular volume (MCV) 
o 80 – 96 fL 
  
 fL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
110

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 12 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
 
LABORATORY ANALYSIS 
Serum Chemistry 
Date drawn (ddmmmyyyy): 
 
Test 
Results 
Clinically 
Significant 
 
 
Sodium (Na) 
o 133 – 145 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Potassium (K) 
o 3.1 – 5.1 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Chloride (Cl) 
o 97 – 108 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Bicarbonate (CO2) 
o 22 – 32 mEq/L 
  
 mEq/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Glucose 
o 70 – 100 mg/dL (fasting) 
o 70 – 200 mg/dL (non-fasting) 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Blood urea nitrogen (BUN) 
o 5 – 22 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatinine 
o M:  0.7 – 1.3 mg/dL 
o F:   0.4 – 1.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Calcium (Ca) 
o 8.4 – 10.2 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Phosphorus 
o 2.4 – 5.0 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total protein 
o 6.0 – 8.3 g/dL 
  
 g/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Uric acid 
o M:  3.9 – 8.1 mg/dL 
o F:   2.0 – 6.9 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Gamma-glutamyl transferase (GGT) 
o 0 – 65 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Aspartate aminotransferase (AST) 
o 12 – 39 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alanine aminotransferase (ALT) 
o 7 - 52 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
Creatine kinase (CK) 
o M:  35 – 250 Units/L 
o F:   25 – 190 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Protocol Version 2.2 [9JAN2019]
111

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Month 12 (± 12 days) 
Subject 
Initials: 
Subject 
Number: 
 
 
LABORATORY ANALYSIS 
Serum Chemistry (cont.) 
 
Test 
Results 
Clinically 
Significant 
 
 
Lactate dehydrogenase (LDH) 
o 120 – 240 Units/L 
  
 IU/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Alkaline phosphatase (Alk Phos) 
o 39 – 117 Units/L 
  
 Units/L 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Total bilirubin 
o 0.3 – 1.4 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Cholesterol (Chol) 
o 100 – 200 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Triglycerides (TG) 
o 40 – 150 mg/dL 
  
 mg/dL 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Prothrombin time/INR (PT/INR) 
o 12.0 - 14.5 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
 
Partial thromboplastin time (PTT) 
o 25.0 – 35.0 seconds 
  
 seconds 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
LABORATORY ANALYSIS 
HSV Detection 
Date collected (ddmmmyyyy): 
Test 
Results 
Clinically Significant 
Saliva 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Conjunctival 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
Blood 
☐ Negative 
☐ Positive 
☐ Normal 
☐ Abnormal 
☐ Not done 
☐ Yes  ☐ No 
 
RESEARCH SAMPLES 
Date drawn (ddmmmyyyy):    
 
Test 
Yes 
No 
Comments 
HSV Antibody Titer 
☐ 
☐  
LTA, Elispot-blood 
☐ 
☐  
IFN Gamma Assay 
☐ 
☐  
 
Blood for future research 
☐ 
☐  
I am confident that the information supplied in this case record form is complete and accurate data. I 
confirm that the Month 12 Study Visit was conducted in accordance with the protocol and any protocol 
amendments and that written informed consent was obtained prior to the start of the study procedures. 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
112

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
 
Study Termination 
 
Subject Initials: 
  
   
   
 
Subject Number: 
  
    
   
 
 
 
STUDY TERMINATION 
Date:   
 
(ddmmmyyyy) 
 
 
 
Did the subject complete the study? 
☐ No, check all reasons below 
☐ Yes 
 
 
1.   ☐ Adverse Events 
Date of event: 
 
 
(ddmmmyyyy) 
 
2.   ☐ Death 
Date of event: 
 
 
(ddmmmyyyy) 
 
3.   ☐ Lost to Follow-up 
 
 
4.    ☐ Administrative reason, specify:    
 
 
 
5.    ☐ Protocol violation/deviation, specify:    
 
 
 
6.   ☐ Patient noncompliance (refusal or inability to adhere to study requirements) 
 
 
7.   ☐ Sponsor terminated the study 
 
 
8.   ☐ Disease Progression 
 
 
9.    ☐ Other, specify:    
 
 
 
 
 
 
Specify the code number for the primary reason for termination:    
 
 
 
 
 
 
 
 
I have carefully examined all Case Report Forms for this subject and certify that all of the information entered 
on the case report forms are, to the best of my knowledge, correct and complete. 
 
 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
113

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
SURVIVAL 
FOLLOW-UP 
 
Subject Initials: 
Subject Number: 
 
 
 
 
SURVIVAL FOLLOW-UP 
 
 
 
 
Patient status as of: 
 
(ddmmmyyyy) 
 
☐ Alive 
 
 
☐ Dead: Date of death: 
 
 
(ddmmmyyyy) 
 
If Dead, please specify cause of Death:    
 
 
 
☐ Lost to follow-up: Date last known alive: 
 
 
(ddmmmyyyy) 
 
 
 
 
 
Is disease progression observed? 
☐ Yes 
☐ No 
 
If Yes, date of progression: 
 
(ddmmmyyyy) 
 
 
 
 
 
 
 
 
Signature of Person Completing Follow-up 
Date (ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
114

CRF 
Version: 1.1.6  Date: 17 Jun 2016 
  
 
 
 
C134 
SURVIVAL 
FOLLOW-UP 
 
Subject Initials: 
Subject Number: 
 
 
 
 
 
Patient status as of: 
 
(ddmmmyyyy) 
 
☐ Alive 
 
 
☐ Dead: Date of death: 
 
 
(ddmmmyyyy) 
 
If Dead, please specify cause of Death:    
 
 
 
☐ Lost to follow-up: Date last known alive: 
 
 
(ddmmmyyyy) 
 
 
 
 
 
Is disease progression observed? 
☐ Yes 
☐ No 
 
If Yes, date of progression: 
 
(ddmmmyyyy) 
Protocol Version 2.2 [9JAN2019]
115

  
 
 
 
C134 
 
Adverse Event Log 
Subject Initials: 
  
 
Subject Number: 
  
 
 
☐Check if none 
 
 
AE 
# 
 
 
Adverse Event 
Present 
Pre- 
C134 
Onset Date 
dd/mmm/yyyy 
Resolution Date 
dd/mmm/yyyy 
 
Grade/Severity 
 
 
Serious 
Relationship 
to study drug 
 
Frequency 
 
Action taken 
 
Outcome 
 
 
SAE? 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
 
☐ Yes 
☐ No 
 
 
 
 
 
 
 
 
☐ Yes 
☐ No 
 
1 = Mild 
2 = Moderate 
3 = Severe 
4 = Life- 
threatening 
5 = N/A 
1 = Fatal 
2 = Life- 
threatening 
3 = Significant 
disability 
4 = Persistent or 
requires or 
prolongs 
hospitalization 
5 =  Congenital 
anomaly 
6 = Requires 
medical or 
surgical 
interventions 
7 = Not serious 
1 = Definitely 
2 = Probably 
3 = Possibly 
4 = Unlikely 
5 = Not related 
1 = Single 
2 = Continuous 
3  = Intermittent 
1 = None 
2 = Study drug 
discontinued 
3 = Dose adjusted 
4 = Study drug 
stopped/restarted 
5 = Treatment 
required 
6 = Hospitalization 
or prolongation of 
7 = Other 
1 = Ongoing 
2= Grade 
change 
3 = Resolved 
4 = Death 
5 = Unk/Lost to 
follow-up 
 
I have carefully examined all Adverse Events for this subject and certify that all of the information entered above are, to the best of my knowledge, correct 
and complete. 
 
 
PI or Co-PI Signature 
Date (dd/mmm/yyyy) 
 
Page   
 of   
 
Protocol Version 2.2 [9JAN2019]
116

  
 
 
 
 
Medication 
 
 
Start Date 
dd/mmm/yyyy 
 
Stop Date 
dd/mmm/yyyy 
 
Dose 
(mg, g, 
ml, etc.) 
Route 
 
1 = PO 
 
3 = IM 
4 = SQ 
5 = Other 
Frequency 
 
1 = QD 
2 = BID 
3 = TID 
4 = QID 
5 = PRN 
6 = Every   
 hrs 
 
 
 
Indication 
AE# 
(if applicable) 
 
Ongoing 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
 
 
 
 
 
 
□ 
 
 
C134 
 
Concomitant Medications 
Subject Initials: 
  
 
  
 
Subject Number: 
  
 
  
 
 
Check if none 
Record generic name except for combination drug products where brand name can be recorded. Record date medication is started and stopped for each change in dose, route, frequency or 
indication. 
 
 
 
 
2 = IV 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I have carefully examined all Concomitant Medications for this subject and certify that all of the information entered above are, to the best of my 
knowledge, correct and complete. 
 
 
PI or Co-PI Signature 
Date (dd/mmm/yyyy) 
 
 
Page   
 of   
 
Protocol Version 2.2 [9JAN2019]
117

  
 
 
 
C134 
 
Death Report 
Subject 
Initials: 
Subject 
Number: 
 
 
DEATH REPORT 
 
 
 
Date of report:   
 
(ddmmmyyyy) 
 
 
 
 
Date of Death:    
 
(ddmmmyyyy) 
 
 
 
 
Primary cause of death: 
 
Please report on Adverse Event and Serious Adverse Event CRF’s 
 
 
 
 
Relationship of Death to C134 (check one): 
 
☐ Not related 
☐ Unlikely 
☐ Possibly related 
☐ Probably related 
☐ Definitely related 
 
 
 
Relationship of Death to Disease (check one): 
 
☐ Not related 
☐ Unlikely 
☐ Possibly related 
☐ Probably related 
☐ Definitely related 
 
 
Autopsy Performed?   ☐ No 
☐ Yes 
If YES, attach a copy of autopsy report 
 
Is autopsy report attached? 
☐ No 
☐ Yes 
 
 
 
 
 
I am confident that the information supplied in this death report form is complete and accurate data. 
 
 
 
 
 
 
PI or Co-PI Signature 
Date (ddmmmyyyy) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Version 2.2 [9JAN2019]
118

  
 
 
 
C134 
MacDonald Response 
Criteria 
Subject                 
      
 
Initials: 
Subject Number: 
 
MACDONALD RESPONSE CRITERIA 
 
 
Date of Assessment (ddmmmyyyy):   
 
Visit:   
 
MRN:   
 
 
Measurements:    
 mm 
X 
  
 mm 
 
 
Location of tumor 
Right 
Left 
 
 
Frontal 
 
 
 
Parietal 
 
 
 
Occipital 
 
 
 
Temporal 
 
 
 
Cerebellum 
 
 
 
Brainstem 
 
 
 
Corpus Callosum 
 
 
 
Lateral Ventricle 
 
 
 
3rd or 4th Ventricle 
 
 
 
Basal ganglia or thalamus 
 
 
 
Other, specify: 
 
 
 
 
“Response” is defined as follows: 
 
 
□ Complete Response (CR) 
Disappearance of all treated enhancing tumor on MRI scan, off 
steroids, and neurologically stable or improved. 
 
 
□ Partial Response (PR) 
Greater than 50% reduction in the treated enhancing tumor on MRI 
scan, stable or reduced steroid dose, and neurologically stable or 
improved. 
 
 
□ Progressive Disease (PD) 
Greater than 25% increase in the treated enhancing tumor on MRI 
scan, stable or increased steroid dose, and neurologically stable or 
worse. 
 
□ Stable Disease (SD) 
 
All other situations. 
 
 
 
 
 
 
Protocol Version 2.2 [9JAN2019]
119

 
Page 1 of 17 
Version Date: 8/4/23 
 
INFORMED CONSENT 
 
Title of Research: 
A Phase I Trial of IRS-1 HSV C134 Administered Intratumorally 
in Patients with Recurrent Malignant Glioma. 
 
UAB IRB Protocol #: 
IRB-300000571 
 
Principal Investigator: 
James Markert, M.D.; L. Burton Nabors, M.D. 
 
Sponsor: 
The Gateway for Cancer Research 
 
National Institutes of Health (NIH)  
 
Purpose of the Research 
You have been asked to participate in this research study because you have a malignant brain 
tumor that has not responded to standard treatment. This document will tell you about the 
purpose, risks, and benefits of this study.  You should provide your consent only after you have 
received all the necessary information and have had enough time to decide whether you wish 
to participate.  Please feel free to ask any questions before you agree to take part in this study.   
 
The purpose of this study is to determine how safe and how well-tolerated the experimental 
study drug, C134 is when administered into the brain where the tumor is located.  This is a 
Phase I study and is being conducted by Dr. James Markert at the University of Alabama at 
Birmingham. The purpose of a Phase I study is to establish a safe dose range based on side 
effects of the study drug being tested, in this case, C134. All the patients who take part in this 
study will receive the same type of experimental treatment, although some people will receive 
higher doses than other people. There is no “placebo” in this study. Varying doses of C134 will 
be administered in this study and the dose you receive will be determined by the number of 
participants given the drug before you and their response to the medication. Anywhere from 4 
to 24 patients are expected to take part in the study; the final number will depend on the safety 
results.  
 
Background 
C134 is a genetically engineered herpes simplex virus or "HSV" (the virus that usually causes 
cold sores and rarely, a severe infection of the brain). It has been known that viruses may kill 
tumor cells. When tumor cells are mixed with certain viruses in the laboratory, the tumor cells 
die. The DNA of the (HSV) virus has been modified so that tumor cells may be killed when 
infected by C134. The changes made to the virus (HSV) should help prevent the (C134) virus 
from infecting normal brain tissue. Extensive testing in both mice and monkeys has 
demonstrated that C134 is not able to cause HSV when injected directly into the brain. C134 
may also be able to help kill tumor cells because it can prevent tumor cells from killing it more 
effectively than other, similar viruses can. This allows it to infect and kill more brain tumor cells. 
More than 40 patients with malignant brain tumors have been treated by injecting an earlier 

 
Page 2 of 17 
Version Date: 8/4/23 
 
version of this HSV virus into their tumors and surrounding brain tissues without producing any 
serious side effects. Based on laboratory testing, C134 may be more effective against your brain 
tumor than the earlier virus. 
 
Explanation of Procedures 
This study is divided into the following sections, also called phases: the Screening Phase, the 
Treatment Phase and the Follow-up Phase. Before you can participate in the study, tests will be 
performed to make sure that you qualify for the study. This is called the Screening Phase. If you 
qualify for the study you will then enter the Treatment Phase which is the phase where you 
receive the study drug and then enter the Follow-up Phase. 
 
Screening Phase (approximately 2 weeks prior to Treatment Phase):  
The total length of this visit will be approximately 2-4 hours.  If you agree to participate in the 
study, you will come in for a screening visit.  The following will take place during this visit: 
 
• Informed consent will be signed before any study-related procedures are performed. 
• You will be asked questions about your medical history, medications you are taking, and 
how you feel. 
• You will have a complete physical examination, and your pulse, blood pressure, 
respiratory rate, temperature, height and weight will be checked. All exams and data are 
being collected for research purposes. 
• You will have a neurological (nervous system) examination for research purposes to 
check your general nervous system function and muscle strength. 
• Routine lab tests will be performed to confirm that it is safe for you to undergo surgery. 
• A blood sample will be collected for research purposes and tested to evaluate the 
general state of your health, look at your immunity (including HIV status) and test for 
the presence of the herpes virus.  Special research blood tests to monitor the body’s 
ability to send signals to the immune system to target the tumor will also be done; these 
will include a special genetic test done on white blood cells. This testing will tell 
investigators what kind of immune responses against the tumor might be present 
before C134 treatment. 
•  The blood samples will be obtained by inserting a needle into a vein in your arm 
(venipuncture). The blood tests will require that approximately 10 teaspoons of blood 
be drawn, a total of approximately 1 cup over the course of this study. 
• Samples of conjunctival (eye) secretions will be collected by gently touching separate 
sterile cotton tipped swabs to the corner of each eye. This test is done for research 
purposes and will test for the presence of the herpes virus, to see if you have any herpes 
simplex virus in your saliva. This will determine if any HSV was present in your eye 
secretions before C134 was given.  
• Saliva will be collected by placing one sterile cotton tipped swab into the mouth. This 
test is done for research purposes and will test for the presence of the herpes virus, to 

 
Page 3 of 17 
Version Date: 8/4/23 
 
see if you have any herpes simplex virus in your saliva. This will determine if any HSV 
was present in your saliva before C134 was given.   
• A routine urine pregnancy test for women capable of bearing children will be collected. 
All women will have additional urine pregnancy tests during the study, if needed. In 
addition, men and women must have been using an effective method of birth control 
before receiving the study drug. You must also agree to continue to use "barrier" birth 
control (condoms) during the study and for six (6) months following the administration 
of the study drug. 
• An electrocardiogram (ECG) will be performed for research purposes to check the 
electrical activity of your heart. 
• A routine chest x-ray will be performed to check for any signs of infection at baseline. 
The data from the chest x-ray will be evaluated for research. 
• Brief Quality of Life assessment will be made for research purposes. This Brief Quality of 
Life assessment consists of 2 surveys (Herth Hope Index and MD Anderson Symptom 
Inventory-Brain Tumor) and a physician assessment (Karnofsy Performance Scale) will 
be made for research purposes. These 3 assessments are hereafter collectively referred 
to as Quality of Life or QoL assessment. 
 
Treatment Phase:  
The total length of this phase (Day 0-Day 3) will be approximately 4 days.  If the results of the 
screening visit indicate you are eligible, you will be enrolled into the study.  You will be 
hospitalized for a total of approximately 4 days. The first night in the hospital is routine care 
and the additional days are research related. As part of this research study, you will have the 
surgical procedure described in the Study Procedures section below to place the small tube 
called a “catheter” into various parts of the tumor, and the drug, C134, will be injected into the 
brain tumor. The catheter is slightly larger than a pencil lead and will be used to deliver C134 
into various regions of the tumor and then will be removed and the surgical wound will be 
closed with sutures. The total time required to inject the tumor is expected to be 90-120 
minutes. Following the surgery, you will be monitored closely in the Neuro-Intensive Care Unit 
overnight, and then be transferred to the Neurosurgery unit and/or Clinical Research Unit when 
your doctor feels you are stable enough. As part of the research study, your temperature, blood 
pressure, breathing and heart rate ("vital signs") and nervous system checks will be performed 
frequently after surgery and the administration of C134 to monitor your progress.  The nervous 
system checks may include all or some of the following: walking, measures of alertness, muscle 
strength and any changes in movement. You will be discharged when your doctor feels you are 
stable enough to leave the hospital. 
 
Day 0 (biopsy and catheter placement)  
• If able, an ophthalmologic evaluation may be performed. This is an optional evaluation 
and should not delay your treatment 
• You will be admitted to the hospital, as routine care, for biopsy surgery and if eligible, 
catheter placement for research purposes. 

 
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• You will be asked questions about medications you are currently taking and any changes 
to your health since last visit. 
• Vital signs (pulse, blood pressure, respiratory rate and temperature) will be obtained 
prior to surgery.  
• You will have a neurological (nervous system) examination for research purposes to 
check your general nervous system function and muscle strength. 
• An additional research-only MRI may be performed to determine exact location of the 
tumor for the biopsy and catheter placement if the surgeon determines it to be 
necessary.   
• As part of routine care, you will also be given medication into a vein (intravenous) to 
help you relax and feel sleepy before the procedure. You will also receive medication to 
minimize any pain (local anesthesia) before the surgery. 
• The research surgical procedure is called stereotactic (stereo-tactic) surgery because of 
the way all the areas of the brain are identified using the MRI scan and other images and 
a special delivery system explained below. This surgery involves using a special 
removable frame that can be connected to the skull with small screws or pins. The 
frame is used to guide the tubing used for injecting C134 in a precise location so that the 
study drug can be administered directly into the tumor. 
• Before the study drug is injected, as part of routine care, your doctor will take a small 
sample of tissue (biopsy) to check for tumor cells and confirm the diagnosis of brain 
cancer. A thin, long needle connected to the stereotactic frame will be guided to the 
tumor. This procedure is routinely performed in participants for whom a brain biopsy is 
needed. If the diagnosis of recurrent tumor is confirmed, then the surgical procedure 
will proceed to prepare for the delivery of the drug. 
• The tumor will eventually undergo genetic testing to look for abnormal proteins on the 
surface of the tumor cells that might allow C134 to cause an antitumor immune 
response, like a vaccine. Another kind of genetic testing will be done to determine if 
there are certain subtypes of tumors that respond either better or less well to C134 
treatment. 
• After verification of tumor recurrence has been confirmed from the biopsy report, the 
administration of C134 will be done in the operating room. 
• You will be assigned to receive one of the five pre-determined doses of C134 through 
the catheters. The study drug will be injected directly through a needle and tube into 
your tumor. The catheter will be moved as needed and the virus injected in up to 5 
different locations. 
• After the surgery, you will be admitted to the Neurosurgery Intensive Care where your 
vital signs will be monitored frequently and frequent neurological exams will be 
performed  
• Participants should avoid contact with infants and young children, individuals with 
decreased immunity (ability to fight infection), and pregnant women (including intimate 
contact). Participants should also refrain from donating blood during the trial. 

 
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• Close contacts and family members should refrain from direct physical contact until HSV 
detection results in a negative shedding.  
  
Day 1 (all evaluations are for research purposes): 
• Your medications will be reviewed and updated 
• A physical exam will be performed and your wound will be examined. 
• Your vital signs will be monitored frequently 
• Neurological exams will be performed frequently 
• You will be monitored for any signs of adverse events or reactions to the drug 
• Samples conjunctival (eye) secretions, blood, and saliva will be collected to see if you 
have any herpes simplex virus in your eye secretions, blood or saliva after C134 was 
given. 
 
Day 2 (all evaluations are for research purposes): 
• A repeat of evaluations from Day 1 
• Samples conjunctival (eye) secretions and saliva will be collected, to see if you have any 
herpes simplex virus in your eye secretions or saliva. This will determine if any HSV was 
present in your eye secretions after C134 was given. 
• A blood sample will be collected. Special research blood tests, including some genetic 
tests that monitor the body’s ability to send signals to the immune system to target the 
tumor will also be done. ( Acceptable up to Day 4) 
• Samples conjunctival (eye) secretions, blood, and saliva will be collected to see if you 
have any herpes simplex virus in your eye secretions, blood, or saliva after C134 was 
given. 
 
Day 3 (all evaluations are for research purposes): 
• A repeat of evaluations from Day 1.   
• An MRI scan will be performed 
• You will be discharged if your doctor feels you are stable enough to leave the hospital. 
• Samples conjunctival (eye) secretions and saliva will be collected to see if you have any 
herpes simplex virus in your eye secretions, blood, or saliva after C134 was given. 
 
Follow-up Phase 
You will return to the clinic for eight (8) follow-up visits.  All of these follow-up visits are due to 
your involvement in this research study.  
 
In addition to the MRI completed to qualify you for the study, MRIs will also be performed 
during the first week and then later on day 28, and at three months, six months and twelve 
months after surgery. The MRIs performed during the first week and on Day 28 are specifically 
for the study and not considered standard of care. The remaining MRI scans are considered 
standard of care but will also be used for research purposes in your case. A total of 6-7 MRI 
scans will be performed on you throughout the study period to monitor your tumor. If there are 

 
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signs or symptoms that the tumor has become larger, additional MRIs may be performed if your 
doctor feels they are necessary for your routine care. It is also possible that your doctor may 
need to take a biopsy sample of the brain to determine the cause of any increase in signs or 
symptoms you may be having. If this is the case, your doctor will discuss this with you at the 
time and explain details of the procedure to you.  
 
Day 7 (± 3 days) - Total length of this visit will be approximately 1 hour 
• A ophthalmologic exam will be performed 
 
Day 10 (± 3 days) - Total length of this visit will be approximately 2 hours. 
• Your medications will be reviewed and updated  
• You will be asked about any changes to your health since your last visit. 
• A physical exam will be performed. 
• Your vital signs will be monitored  
• Neurological exams will be performed 
• A blood sample will be collected  
• Samples conjunctival (eye) secretions and saliva will be collected to see if you have any 
herpes simplex virus in your eye secretions or saliva. This will determine if any HSV was 
present in your eye secretions after C134 was given. 
• All activities and exams on Day 10 visit are for research purposes 
 
Day 14 (± 3 days) - Total length of this visit will be approximately 1 hour 
• A ophthalmologic exam will be performed 
 
Day 21 (± 3 days) - Total length of this visit will be approximately 1 hour 
• A ophthalmologic exam will be performed 
 
Day 28 (± 4 days) - Total length of this visit will be approximately 3-4 hours. 
• A repeat of evaluations from Day 10 
• A research-only MRI scan will be performed 
• Brief Quality of Life assessments will be made 
• All activities and exams on Day 28 visit are for research purposes. 
• Samples conjunctival (eye) secretions, blood and saliva will be collected to see if you 
have any herpes simplex virus in your eye secretions or saliva. This will determine if any 
HSV was present in your eye secretions, blood, or saliva after C134 was given. 
 
Months 3, 6, and 12 - Total length of this visit will be approximately 3-4 hours. 
• A repeat of evaluations from Day 10 
• A routine MRI scan will be performed 
• Brief Quality of Life assessments will be made for research purposes. 

 
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• Samples conjunctival (eye) secretions, blood, and saliva will be collected to see if you 
have any herpes simplex virus in your eye secretions or saliva. This will determine if any 
HSV was present in your eye secretions, blood or saliva after C134 was given. 
 
Risks and Discomforts 
Blood Draws  
There may be some temporary pain, bruising, bleeding or rarely, infection at the site where 
blood samples are drawn from your arm. Although rare, some individuals may become faint 
during blood drawing procedures. These complications are rarely severe.  
 
MRI Scans  
Magnetic Resonance Imaging (MRI) scans are a painless imaging procedure and are very safe 
for most people. Some discomfort may be experienced since you must lie flat and remain as still 
as possible in a long plastic cylinder for approximately 30-45 minutes. Some people also 
experience anxiety due to fear of being in close spaces. You will be closely observed at all times 
and can be assisted, if necessary by the hospital staff performing the procedure. You may be 
moved out of the machine at your request or, if you are experiencing severe anxiety, you may 
be given anti-anxiety medication prescribed by your doctor to make you less anxious. If you 
would like, ear plugs are available to you to decrease the knocking noise you hear that is made 
by the machine. Pillows will be placed under your knees to make you comfortable and you will 
be covered with a sheet or blanket to keep you warm, if needed.  
 
For a portion of the MRI, a needle will be placed into your vein (intravenous line or  
"IV") and dye will be injected into your vein. This dye helps to give a better picture of the brain 
tumor and surrounding brain. 
 
Participants who are at risk for injury from MRI such as former welders or those with pace 
makers, aneurysm clips, (metal clips on the wall of a large artery), metal infusion pumps, or 
metal and/or shrapnel fragments, will not be entered into the study. 
 
Risk of MRI contrast (dyes) 
 
A small number of people may develop brief reactions during administration of the 
dye used in MRI testing, including nausea, a bad aftertaste, headaches, hot flashes and 
heart palpitations (heart skipping a beat). A smaller group of participants may also be 
allergic to the dye and may develop a rash, itching, hives, breathing difficulties, kidney 
problems, and in extreme cases, death. You will be closely monitored throughout the 
procedure and if an allergic reaction develops, you will be treated promptly. We are 
unable to determine the specific MRI contrast drugs that will be utilized, but it is likely 
that we will use one of the top two agents, gadoteridol and gadoterate meglumine. 
The risks are particularly uncommon in the two MRI dyes planned for use in the 
research portion of this study. Other dyes might be used if you have a previous 

 
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sensitivity to one of these two dyes. These other dyes generally have a similar side 
effect profile to the two mentioned; significant differences will be discussed with you 
prior to the test. 
Also, there is a very small risk of nephrogenic systemic fibrosis (NSF) with the dye used for MRIs 
scans. NSF is an extremely rare condition that has been seen in patients with decreased kidney 
function who receive the MRI dye (gadolinium). It can cause hardening of the skin, the tissue 
under the skin, muscle tissue hardening, scarring around internal organs and in very rare 
occasion, death.  Even in the absence of NSF, the dye could cause problems with kidney 
function or an allergic reaction resulting in a rash, itching, hives, breathing difficulties and in 
extreme cases, death.   
 
There is also a risk of gadolinium staying in the brain after this dye is given during the MRIs. 
Currently, there are no known toxic effects of this deposition, but long-term studies have not 
been reported. The FDA currently does not feel there are safety issues with the gadolinium dyes 
currently in use. 
 
Surgery/Catheter Placement and Removal  
The surgical risks of the stereotactic procedure you will depend on your condition before the 
surgery and the location and size of your tumor. Risks known to be associated with brain 
surgery, involving catheter placement include:  
• 
Hemorrhage (bleeding)  
• 
Deterioration of nervous system function such as:  
˗ weakness in the arm and or leg  
˗ loss of sensation over parts of your body  
˗ partial or complete loss of function related to communication, such as speech 
and comprehension 
˗ other functions related to intellectual capacity, such as memory  
• 
Infection and death 
• 
Mild Pain or Discomfort (Catheter removal requires placement of a new suture to close 
the skin and prevent infection and this is usually done while you are under anesthesia. 
This may cause some mild pain or discomfort. Pain medicine will be available to 
minimize your discomfort during this portion of the procedure should you wish it.)  
 
The relative risks of these procedures, considering your condition, will be discussed with you by 
your doctor.  
 
Risks of Herpes Simplex Virus-C134  
Herpes simplex virus is the virus that usually causes cold sores and rarely, a severe brain 
infection. It can also infect other tissues such as skin and the mucous membranes of the mouth, 
eyes and urinary tract.  
 

 
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This research study will involve the injection of a modified herpes simplex virus into the brain. 
Based on laboratory studies done in mice and monkeys, the modification should allow the C134 
virus to infect and kill tumor cells but not normal brain tissue. This, however, cannot be assured 
in humans. Of the first 10 participants enrolled in this study, one participant with extremely 
advanced tumor experienced the modified virus producing widespread inflammation in the 
brain around the tumor, which altered their mental status and cognition severely and another 
participant experienced the modified virus moving from the tumor into the eye, which resulted 
in partial visual loss that was permanent. Mandatory ophthalmologic exams will be performed 
at Day 7, Day 14, and Day 21 to monitor for any eye issues and treatment will be given as 
needed. The purpose of this study is to find out which dose of the virus can be given without 
any toxic effects.   
 
Based on prior studies with related viruses, we do not expect these risks to occur with any 
significant frequency. However, this is a Phase I study and it is unknown currently whether 
there will be any increase in risks with escalating dose levels for severity, frequency or 
reversibility of these risks. 
 
The potential risks of C134 include, but are not limited to:  
• 
Inflammation of the liver (hepatitis) that could cause death (very rarely)   
• 
Wide-spread viral infection with effects ranging from flu-like symptom to more severe 
reactions  
• 
Allergic reaction to the virus causing symptoms ranging from itching and hives to severe 
cases, difficulty breathing.  
• 
Infection of the brain (encephalitis), which may cause high fevers, confusion, loss  of 
consciousness 
• 
Neurologic difficulties, seizures and even death  
 
The virus in this study has been modified to prevent the development of infection of normal 
brain cells. However, if you should develop an infection of the brain, you will be treated with 
the standard medical therapy that is very effective in treating and eliminating this kind of 
infection. This therapy to destroy the virus uses medications to fight the virus (anti-viral drugs). 
Should this anti-viral therapy be needed, it would require that you be hospitalized and receive 
daily intravenous infusion of the anti-viral drug acyclovir or similar drug for 14-21 days. With 
early treatment, anti-viral drugs like acyclovir and others are likely to halt progression of herpes 
simplex viral infection. Your doctor may need to perform tests to help determine if there is such 
an infection. These might include a biopsy of brain tissue or testing of the fluid surrounding the 
spinal cord and the brain called cerebrospinal fluid (CSF). 
  
Your doctor will discuss these procedures with you if it becomes necessary to perform them. 
The risks of a brain biopsy include the possibility of bleeding, infection or low grade fever, and 
in rare cases, deterioration in nervous system functioning. If a sample of CSF is needed, a small 
needle will be placed in the small of the back into the space around the spinal cord (lumbar 

 
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puncture) and a sample of fluid removed. This can result in headache and in rare cases, 
worsening of nervous system functioning.  
 
There is also a risk that the tumor itself may swell as a result of virus injection, causing 
headache, lethargy (sleepiness and tiredness), nausea, vomiting, seizures, neurological deficits 
or even death. Should tumor swelling develop, you will receive treatment with steroids (drugs 
that decrease inflammation and swelling) for as long as it is necessary. If nervous system 
deficits persist despite steroid treatment, there is a chance that your doctor would recommend 
surgery to remove some or all of the swollen tumor and ease the pressure on the surrounding 
brain.  
 
You will be monitored closely throughout the trial for signs and symptoms of infection so that 
you can be treated promptly.  
 
Most people in the United States have already been exposed to herpes simplex virus and have 
antibodies against the virus. If you do not have antibodies against the virus, it is possible that 
you will develop them after receiving C134. These antibodies help fight infection from the 
herpes simplex virus and are not harmful.  
 
Based upon the risks of brain biopsy, we know that rarely-occasionally (from 0-20 out of 100 
patients), a significant episode of bleeding into the brain, infection or low grade fever, seizure, 
or neurologic problem can occur, sometimes serious. 
  
Since C134 has not been used in people before, it is impossible to estimate the rate of side 
effects from it and these are really unknown. However, based upon results from prior studies 
with other viruses, we estimate that the risks of headaches, lethargy, nausea, vomiting, seizures 
and mild and temporary neurologic deficits including possible problems with speech, weakness, 
vision or numbness after C134 administration may occur occasionally (between 4 and 20 people 
out of 100). Rarely, these could be serious enough to warrant an increase in the duration of 
hospitalization or a new hospitalization. We estimate the risk of brain infection (encephalitis), 
liver inflammation (hepatitis), severe allergic reaction, and widespread viral infection or death 
to be rare and severe permanent neurologic problems to be rare (fewer than 3 out of 100 
people treated). 
 
Seizure medications (Anticonvulsants) 
Because there may be an increased risk of seizures after C134 administration, for about one 
month during and after patients will be placed on an anti-seizure medication (or a second anti-
seizure medication if they are already on one). Since the anti-seizure drug to be added will be 
individualized per patient history, allergies, other medications, etc., no obvious prediction can 
be made of which drug might be utilized-for this reason. Common risks of frequently used 
seizure medications include sleepiness/fatigue, insomnia, dizziness, personality changes, double 
or blurred vision, tingling sensations, tremors balance or memory problems; nausea, vomiting, 
diarrhea, liver problems, or other GI problems; infection or influenza; headache or pain, , 

 
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decreased blood counts; birth defects;  and mild allergic reactions like cough, rash or itching. 
Rare risks include severe allergic reactions leading to blood pressure or breathing problems or 
even death, or suicide. Should you be concerned about any side effects of a seizure medication, 
please discuss these with your doctor so another medication may be substituted as quickly as 
possible. At that time, your doctor can discuss any significant differences in side effect risks of 
the new medicine with you. 
 
Risk of Immune Activity in the Brain  
The risk of C134 therapy in the brain is unknown, but could potentially include permanent 
damage to neurologic function due to swelling or even the development of an autoimmune 
response in which the body’s infection fighting cells perceive normal brain as infection and 
attack it. This could potentially produce problems similar to Multiple Sclerosis (MS). Other, 
unknown effects could also occur including but not limited to stroke, bleeding, dangerously low 
blood pressure, damage to liver or kidney function, or even death.  
 
Data Safety/Confidentiality Breach 
Information obtained about you for this study will be kept confidential to the extent allowed by 
law. However, research information that identifies you may be shared with the UAB 
Institutional Review Board (IRB) and others who are responsible for ensuring compliance with 
laws and regulations related to research, including the Office for Human Research Protections 
(OHRP). The information from the research may be published for scientific purposes; however, 
your identity will not be given out. 
 
If you are a patient, and if any part of this study takes place at University of Alabama Hospital, 
this consent document may be placed in your file at that facility. The document may become 
part of your medical record chart. Further, information relating to this study, including your 
name, medical record number, date of birth and social security number, may be shared with 
the billing offices of UAB and UAB Health System affiliated entities so that the costs for clinical 
services can be appropriately paid for by either the study account or by the patient/patient’s 
insurance. 
 
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it 
illegal for health insurance companies, group health plans, and some employers to discriminate 
against you based on your genetic information. This law generally will protect you in the 
following ways: 
• Health insurance companies and group health plans may not request your genetic 
information that we get from this research. 
• Health insurance companies and group health plans may not use your genetic 
information when making decisions regarding your eligibility or premiums. 
• Employers with 15 or more employees may not use your genetic information that we 
get from this research when making a decision to hire, promote, or fire you or when 
setting the terms of your employment. 
  

 
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Be aware that this new federal law does not protect you against genetic discrimination by 
companies that sell life insurance, disability insurance, or long-term care insurance, nor does it 
protect you against genetic discrimination by all employers. 
  
All specimens are coded and stored in freezers in locked laboratories with limited access. All 
data is coded in a password- and firewall-protected database kept in a secure office. You or a 
member of your family may still voluntarily release information about yourself or your 
involvement in this research. 
 
Unknown Risks  
C134 administration into tumor is new and it is possible that despite our extensive efforts, 
unforeseen problems may occur including the possibility of unknown and possible disabling 
effects or death.  
 
Information for Women of Childbearing Potential, Nursing Mothers, and/or Men Capable of 
Fathering a Child 
We do not know if the study drug will affect mother’s milk or an unborn fetus. Therefore, 
breast-feeding and pregnant women are not allowed to take part in the study. If you are 
pregnant or become pregnant, there may be risks to the embryo or fetus that are unknown at 
this time. Women who can become pregnant must take a pregnancy test before the start of the 
study. 
 
You should not father a child while on this study as the treatment may indirectly affect an 
unborn child. If you are sexually active and are at risk of causing a pregnancy, you and your 
female partner(s) must use a birth control method to avoid pregnancy that works well or you 
must not have sex. 
 
Unless you cannot have children because of surgery or other medical reasons, you must have 
been using an effective form of birth control before you start the study. Because it is currently 
unknown if C134 can be transmitted by sexual contact, you must also agree to continue to use 
an effective form of  barrier birth control for 6 months after taking the study drug. Effective 
barrier birth control includes condoms and abstinence. 
 
Benefits  
There may be no direct benefit to you from this study. While it is also possible that this 
experimental treatment may kill some of your tumor cells, there may still be no beneficial effect 
on the course of your illness. Because of your participation in this study, we may learn more 
about potential ways to treat brain tumors. This information may prove useful in the future 
treatment of patients with brain tumors.  
 
Alternatives 

 
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You are being offered the opportunity to participate in this study after your tumor recurred, 
despite appropriate standard therapies for your disease. Other therapy options have been 
explained to you, including:  
• 
Gliadel®, a wafer that releases a chemotherapy agent that is implanted into the area of 
the brain tumor  
• 
Radiation therapy to the brain 
• 
Additional surgery, to remove tumor 
• 
Other Chemotherapy  
 
There are no other standard treatments that have been shown to have significant effects in 
patients with your disease. A variety of experimental studies for the treatment of brain tumors 
are conducted in medical centers around the world, but the benefit of their approaches is yet 
unknown. In addition, you may decline any further treatment for your disease.  
 
If at any time after receiving C134, there are signs or symptoms indicating growth of the tumor, 
your doctor will again discuss alternative therapies that may be of benefit to you. If you are 
treated with alternative therapies after receiving C134, you will still be permitted to continue 
on the study and be monitored for effects of C134.  
 
Confidentiality  
Information obtained about you for this study will be kept confidential to the extent allowed by 
law. However, research information that identifies you, such as your date of birth and initials, 
may be shared with people or organizations for quality assurance or data analysis, or with those 
responsible for ensuring compliance with laws and regulations related to research. They 
include: 
• UAB Institutional Review Board (IRB). An IRB is a group that reviews the study to protect 
the rights and welfare of research participants. 
• The Gateway for Cancer Research, funding agency for this trial 
• National Institutes of Health (NIH), funding agency for this trial 
• Food and Drug Administration (FDA) 
• Office for Human Research Protections (OHRP) 
• UAB Comprehensive Cancer Center 
• Data Safety and Monitoring Board for this study 
 
The information from the research may be published for scientific purposes; however, your 
identity will not be given out. 
 
Your consent form will be placed in your medical record at UAB Health System. This may 
include either a paper medical record or electronic medical record (EMR). An EMR is an 
electronic version of a paper medical record of your care within this health system. Your EMR 
may indicate that you are on a clinical trial and provide the name and contact information for 
the principal investigator. 

 
Page 14 of 17 
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If you are receiving care or have received care within this health system (outpatient or 
inpatient) and are participating in a research study, results of research tests or procedures (i.e. 
laboratory tests, imaging studies and clinical procedures) may be placed in your existing 
medical record. 
 
If you have never received care within this health system (outpatient or inpatient) and are 
participating in a research study, a medical record will be created for you to maintain results of 
research tests or procedures. 
 
All information within your medical record can be viewed by individuals authorized to access 
the record. 
 
If you have questions about clinical trial billing at a UAB Health System location, contact the 
Office of Clinical Billing Review at fap@uab.edu. For more on UAB’s Fiscal Approval Process 
requirements, go to FAP - Site Minder Processes that can be located online at 
http://www.uab.edu/research/administration/offices/CBR/Pages/Processes.aspx.   
 
Information relating to this study, including your name, medical record number, date of birth 
and social security number, may be shared with the billing offices of UAB and UAB Health 
System affiliated entities, so that the costs for clinical services can be appropriately paid for by 
either the study account or by your insurance. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This website will not include information that can identify you. At most, the 
website will include a summary of the results. You can search this website at any time. 
 
Voluntary Participation and Withdrawal  
Whether or not you take part in this study is your choice.  There will be no penalty if you decide 
not to be in the study. If you decide not to be in the study, you will not lose any benefits you 
are otherwise owed.  
 
You are free to withdraw from this research study at any time.  Your choice to leave the study 
will not affect your relationship with this institution.  You should return to see the study doctor 
for safety reasons so you can be taken off the study drug and referred for follow-up care.  
 
If you end the study early, you will be asked to have blood tests and the same physical and 
nervous system exams you previously had. It is also possible your doctor will request an MRI at 
this time.  
 
You may be removed from the study without your consent if the sponsor ends the study, if the 
study drug is approved by the FDA, if the study doctor decides it is not in the best interest of 
your health, or if you are not following the study rules. 

 
Page 15 of 17 
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Cost of Participation in Research  
There will be no cost to you for taking part in the research portion of this study. All drugs (for 
example C134, additional anti-seizure medication) exams ( for example, the MRI Day 3 and Day 
28), hospital Day 2 and Day 3  and medical care related to this study will be provided to you at 
no cost during the 12 month study period. 
   
The costs of your standard medical care which relate to the biopsy, including the biopsy itself 
and first night of hospitalization, as well the MRI scans that would be obtained whether or not 
you were in the trial (screening, Biopsy/Day 0 and Day 1, Month 3, Month 6 and Month 12) and 
other similar expenses (pain medications, physical therapy, etc.)  will be billed to you and/or 
your insurance company in the usual manner.  
 
If you are in Medicare Advantage (Medicare managed care plan), you should contact someone 
at your plan before you start a clinical trial. They can provide more information about 
additional costs you could incur from participating in clinical trials. 
Payment for Participation in Research  
No compensation is available for taking part in this research study.  
 
Payment for Research Related Injuries  
UAB, Gateway for Cancer Research, and NIH have not provided for any payment if you are 
harmed as a result of taking part in this study. If such harm occurs, treatment will be provided. 
However, this treatment will not be provided free of charge. 
 
Significant New Findings  
Any significant new findings that develop during the course of the study, which may affect your 
willingness to continue in the research, will be provided to you by Dr. James Markert or his 
staff.  
 
Optional Studies 
As part of this study, we would like to store some of the blood and tissue specimens collected 
from you for future research on malignant glioma. The future research may be conducted by 
the study doctor or by other researchers that obtain IRB approval for their research. The 
specimens will be labeled with a code that only the study doctor can link back to you. Results of 
any future research will not be given to you or your doctor. The specimens obtained from you 
in this research may help in the development of a future commercial product. There are no 
plans to provide financial compensation to you should this occur. You do not have to agree to 
allow your specimens to be stored in order to be part of this study. 
 

 
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You may request at any time that your specimens be removed from storage and not be used for 
future research. If you decide you want your specimens removed, you may contact the study 
doctor. Once the request is received, and if your specimens have not already been used for 
other research, they will be destroyed. If you do not make such a request, your specimens will 
be stored indefinitely or until used. 
 
Initial your choice below: 
 
___ I agree to allow my specimens to be kept and used for future research on malignant 
glioma. 
 
___ I do not agree to allow my specimens to be kept and used for future research. 
 
Questions  
If you have any questions, concerns, or complaints about the research or a research-related 
injury including available treatments, please contact the study doctor. You may contact Dr. 
James M. Markert at 205-996-2461 or after hours by paging him at 205-934-3411 (pager 5562). 
 
OR 
 
You may also call Dr. Burt Nabors at 205-934-1432. He may also be reached after hours calling 
the Department of Neurology, Division of Neuro-oncology after hour service number 205-934-
3411 
 
If you have questions about your rights as a research participant, or concerns or complaints 
about the research, you may contact the UAB Office of the IRB (OIRB) at (205) 934-3789 or toll 
free at 1-855-860-3789. Regular hours for the OIRB are 8:00 a.m. to 5:00 p.m. CT, Monday 
through Friday. 
 
Legal Rights 
You are not waiving any of your legal rights by signing this consent form. 
 
Signatures 
Your signature below indicates that you agree to participate in this study. You will receive a 
copy of this informed consent.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Participant or Legally Authorized Representative 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Person Obtaining Consent 
 
 
 
 
 
Date

 
Page 17 of 17 
Version Date: 8/4/23 
 
University of Alabama at Birmingham 
AUTHORIZATION FOR USE/DISCLOSURE OF 
PROTECTED HEALTH INFORMATION (PHI) FOR RESEARCH 
 
Participant Name:    
                                       
 
 UAB IRB Protocol Number:  IRB-300000571 
Research Protocol:  A Phase I Trial of IRS-1 HSV C134 Administered 
Intratumorally in Patients with Recurrent Malignant Glioma 
 Principal Investigator:  James M. Markert, MD 
 Sponsor:  Gateway for Cancer Research, NIH 
 
What is the purpose of this form?  You are being asked to sign this form so that UAB may use and release your protected health 
information for research.  Participation in research is voluntary.  If you choose to participate in the research, you must sign this 
form so that your protected health information may be used for the research. 
 
Why do the researchers want my protected health information?  The researchers want to use your protected health information 
as part of the research protocol listed above and as described to you in the informed consent. 
 
What protected health information do the researchers want to use?  All medical information, including but not limited to 
information and/or records of any diagnosis or treatment of disease or condition, which may include sexually transmitted diseases 
(e.g., HIV, etc.) or communicable diseases, drug/alcohol dependency, etc.; all personal identifiers, including but not limited to your 
name, social security number, medical record number, date of birth, dates of service, etc.; any past, present, and future history, 
examinations, laboratory results, imaging studies and reports and treatments of whatever kind, including but not limited to 
drug/alcohol treatment, psychiatric/psychological treatment; financial/billing information, including but not limited to copies of 
your medical bills, and any other information related to or collected for use in the research protocol, regardless of whether the 
information was collected for research or non-research (e.g., treatment) purposes. 
 
Who will disclose, use and/or receive my protected health information?  All Individuals/entities listed in the informed consent 
documents, including but not limited to, the physicians, nurses and staff and others performing services related to the research 
(whether at UAB or elsewhere); other operating units of UAB, HSF, UAB Highlands, Children’s of Alabama, Eye Foundation Hospital, 
and the Jefferson County Department of Health, as necessary for their operations; the IRB and its staff; the sponsor of the research 
and its employees and agents, including any CRO; and any outside regulatory agencies, such as the Food and Drug Administration, 
providing oversight or performing other legal and/or regulatory functions for which access to participant information is required. 
 
How will my protected health information be protected once it is given to others?  Your protected health information that is given 
to the study sponsor will remain private to the extent possible, even though the study sponsor is not required to follow the 
federal privacy laws. However, once your information is given to other organizations that are not required to follow federal privacy 
laws, we cannot assure that the information will remain protected. 
 
How long will this Authorization last?  Your authorization for the uses and disclosures described in this Authorization does not 
have an expiration date. 
 
Can I cancel this Authorization?  You may cancel this Authorization at any time by notifying the Principal Investigator, in writing, 
referencing the research protocol and IRB Protocol Number. If you cancel this Authorization, the study doctor and staff will not  
use any new health information for research. However, researchers may continue to use the protected health information that was 
provided before you cancelled your authorization. 
 
Can I see my protected health information?  You have a right to request to see your protected health information. However, to 
ensure the scientific integrity of the research, you will not be able to review the research information until after the research 
protocol has been completed. 
 
Signature of participant:   
 
 
 
 
 
 
 
Date:  
 
 
or participant's legally authorized representative:  
 
 
 
 
 
Date:  
 
 
Printed Name of participant’s representative:  
 
 
 
 
 
 
Relationship to the participant: