Clinical trial NCT01902381
Conditions: Previously Treated Myelodysplastic Syndromes
Sponsor: Wake Forest University Health Sciences
Start date: 2013-08-01; Completion date: 2018-11-26
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This pilot clinical trial studies 6, 8-bis (benzylthio) octanoic acid (CPI-613) in treating patients with myelodysplastic syndromes who failed previous therapy. Sometimes when chemotherapy or biological therapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to treatment. 6, 8-bis (benzylthio) octanoic acid may interfere with the growth of tumor cells and may be an effective treatment for myelodysplastic syndromes that did not respond to previous therapy.

Detailed description:
PRIMARY OBJECTIVES:

I. To evaluate the safety and anti-cancer activities of CPI-613 in myelodysplastic syndrome (MDS) patients who have failed previous agents (such as decitabine \[Dacogen\], azacitidine \[Vidaza\], growth factors or lenalidomide).

OUTLINE:

Patients receive 6, 8-bis (benzylthio) octanoic acid intravenously (IV) over 2 hours on days 1 and 4 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

Arms: arm 1: Patients receive treatment 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1 and 4 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: 6,8-bis(benzylthio)octanoic acid
Intervention descriptions: intervention 1: Given IV

Protocol documents:
Prot_SAP_000.pdf: 
Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous 
Therapy CCCWFU #29113 
ClinicalTrials.gov  NCT01902381
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Principal Investigator: 
Sub-Investigators: 
Biostatistician: 
Study Nurse: 
CRA/Data Manager:  
Regulatory / Budget: 
Bayard Powell, MD 
Wake Forest School of Medicine 
Section on Hematology and Oncology 
Timothy S. Pardee, MD, PhD 
Wake Forest School of Medicine 
Section on Hematology and Oncology 
Leslie Ellis, MD 
Wake Forest School of Medicine 
Section on Hematology and Oncology 
Rupali Bhave, MD 
Wake Forest School of Medicine 
Section on Hematology and Oncology 
Dianna Howard, MD 
Wake Forest School of Medicine 
Section on Hematology and Oncology 
Scott Isom, MS 
Teresa Brady, RN 
Sheila Staszkiewicz 
Megan Brown 
Participating Institution: 
CCCWFU 
 
Investigational Drug: 
CPI-613 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
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IND Number: 
107800 
 
Date:  
05/26/2017 
CONFIDENTIAL: This document is proprietary property of the Comprehensive Cancer 
Center of Wake Forest University Health Sciences. 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
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SCHEMA 
 
Primary Objective 
To evaluate the response rate (RR) of CPI-613 in MDS patients who have failed previous 
therapy. 
Secondary Objective 
To evaluate the safety, progression-free-survival (PFS), overall survival (OS), and changes in the 
frequency of transfusion associated with treatment with CPI-613 in these patients. 
Histologic diagnosis of 
MDS that is 
refractory/relapsed from 
previous therapy 
Clinical Benefit 
Continue 
treatment and 
evaluate every 2 
cycles until 
disease 
progression 
Informed consent 
Cycle 1 and 2 treatment with CPI-613 
Hematology and 
bone marrow exam 
to determine 
treatment response 
No Clinical 
Benefit 
Discontinue 
treatment 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Table of Contents 
1.0 
BACKGROUND AND STUDY OBJECTIVES ..................................................6 
1.1 
Myelodysplastic Syndrome ..........................................................................6 
1.2 
CPI-613 ........................................................................................................6 
1.2.1 Background ......................................................................................6 
1.2.2 Safety and Anti-Cancer Activities of CPI-613 against MDS ..........7 
2.0 
STUDY DESIGN ..................................................................................................12 
2.1 
Study Objective ..........................................................................................12 
2.2 
Outcome Measures.....................................................................................12 
2.3 
Open-Label, Single-Arm Study Design .....................................................12 
3.0 
PATIENT ELIGIBILITY CRITERIA ..............................................................12 
3.1 
Inclusion Criteria .......................................................................................12 
3.2 
Exclusion Criteria ......................................................................................13 
3.3 
Inclusion of Women and Minorities ..........................................................14 
4.0 
REGISTRATION PROCEDURES ....................................................................14 
5.0 
STUDY PROCEDURES .....................................................................................16 
5.1 
Pre-Study Screening Tests and Safety Assessment ...................................17 
5.1.1 Pre-Study Screening Tests .............................................................17 
5.1.2 Safety Assessment .........................................................................17 
5.1.3 Assessment of Anti-Cancer Activities ...........................................17 
5.2 
Specifics of Tests Performed During the Study .........................................18 
5.2.1 ECOG Performance Status ............................................................18 
5.2.2 Clinical Chemistry, Hematology and Coagulation ........................18 
5.2.3 Bone Marrow Exam .......................................................................19 
6.0 
TREATMENT WITH CPI-613 ..........................................................................19 
6.1 
Sample Size, Dose Levels and Justification of the Dose ...........................20 
6.2 
Dosing Delay and Dose Modification of CPI-613 in the Event of Adverse Events
....................................................................................................................20 
6.3 
Duration of Treatment for Each Patient .....................................................21 
7.0 
STUDY DRUG - CPI-613 ....................................................................................21 
7.1 
Description of CPI-613 Drug Product .......................................................21 
7.2 
Handling of CPI-613 ..................................................................................21 
7.3 
Storage of CPI-613 ....................................................................................22 
7.4 
IV Infusion Sets, Syringes and IV Bags to be used for Administration of CPI-613
....................................................................................................................22 
7.5 
Reconstitution and Administration of CPI-613 .........................................23 
7.6 
Request for CPI-613 ..................................................................................23 
7.7 
Procurement of Investigational Drug .........................................................24 
7.8 
Disposal of CPI-613 ...................................................................................24 
7.9 
Calculation of the Amount of CPI-613 for Each Patient ...........................25 
7.10 
Concomitant Medications and Prophylactic Treatment .............................25 
8.0 
ADVERSE EVENTS LIST AND REPORTING REQUIREMENTS ............26 
8.1 
Adverse Event Characteristics ...................................................................26 
8.2 
STRC SAE Reporting Requirements .........................................................27 
8.3  
WFUHS IRB AE Reporting Requirements ...............................................27 
9.0 
STATISTICAL CONSIDERATIONS ...............................................................28 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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10.0 
Data Management and Reporting Schedule ......................................................28 
Appendix A – REGISTRATION GUIDELINES AND FORMS .................................31 
Appendix B:  STRC SAE REPORTING GUIDELINES .............................................35 
Appendix C – CCCWFU ADVERSE EVENT LOG ....................................................39 
Appendix D – Withdrawal of Participation Form ........................................................40 
Appendix E – Data Collection Form for Bone Marrow Exam ....................................41 
Appendix F – Data Collection Form for Number of Transfusions .............................42 
Appendix G –Pre-Study Data Collection Form ............................................................43 
Appendix H – Response Criteria ....................................................................................44 
Appendix I – Response Evaluation Form ......................................................................46 
 
 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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1.0 
BACKGROUND AND STUDY OBJECTIVES 
 
1.1 
Myelodysplastic Syndrome  
 
Myelodysplastic syndrome (MDS) is a diverse collection of hematological malignancies 
that involve dysplasia of the stem cells in the bone marrow, resulting in disorderly and 
ineffective hematopoiesis. The number and quality of blood-forming cells decline 
irreversibly, further impairing blood production. Patients with MDS often develop severe 
anemia resulting in susceptibility to infection, bleeding, etc., and require frequent blood 
transfusions. In most cases, the disease progresses over time and the patient develops 
cytopenia due to deteriorating bone marrow function. The outlook in MDS is poor, and 
some patients will progress to Acute Myeloid Leukemia (AML) within a few months.  
The median survival varies from years to months, depending on the risk level of the 
disease. 
 
Treatment of MDS is complicated. Although allogeneic bone marrow transplant (BMT) 
is a potential curative treatment for MDS, a match donor is not always available.  
Furthermore, most patients with MDS are older and not appropriate candidates for BMT.  
The prognosis and treatment for MDS vary depending on the patient's International 
Prognostic Scoring System (IPSS) score (Greenberg et al. 1997). Regardless of risk 
category, a patient's age and existing comorbidities are also factored into treatment 
decisions. Patients with a Low/Intermediate-1-Risk score (IPSS 0-1) may live with their 
disease for a number of years. These patients are primarily treated with low-intensity 
supportive care, especially red blood cell transfusions, to treat their symptoms and 
maintain their quality of life. In small subsets of Low/Intermediate-1-Risk MDS patients, 
hematopoietic cytokines or antithymocyte globulin may reduce transfusion requirements.  
The drawbacks to these treatments are high failure rates even with improved predictive 
models, and high cost of cytokines. Patients with higher scores (intermediate-2 and high 
risk; IPSS ≥1.5) are at higher risk of transformation to AML and many will die from their 
disease within 1 year of diagnosis. Treatment of these patients is with intensive therapies 
using hypomethylating agents (decitabine and azacitidine). Unfortunately, these agents 
induce significant toxicities at therapeutic doses. Furthermore, after relapsing from a 
hypomethylating agent, there is essentially no effective treatment for this disease.  
Therefore, additional treatment options for MDS are greatly needed. 
 
1.2 
CPI-613 
 
 
1.2.1 Background 
 
CPI-613 is a novel anti-cancer agent (Zachar et al. 2011). It selectively targets the altered 
form of mitochondrial energy metabolism in tumor cells, causing changes in 
mitochondrial enzyme activities and redox status, which leads to apoptosis, necrosis and 
autophagy of tumor cells (Zachar et al. 2011). CPI-613 selectively acts on the altered 
catalytic and regulatory functions of pyruvate dehydrogenase complex (PDC) and the α-


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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ketoglutarate dehydrogenase complex (KGDHC) in tumor cells (Zachar et al. 2011). Due 
to its novel mechanism of action and the multi-molecular targeting approach, CPI-613 is 
equally effective against multi-drug resistance (MDR) cancer cell lines when compared 
to the parental untreated cancer cell lines, according to in vitro studies (Zachar et al. 
2011). 
 
Based on Phase I dose-escalated trials in patients with various advanced stages of solid 
and hematologic malignancies, CPI-613 has been found to be well-tolerated at doses up 
to 3,000 mg/m2 when infused intravenously over 2 hours. CPI-613 also exhibits anti-
tumor activities in patients with various malignancies (Pardee et al, 2011a and b, & 2012; 
Lee et al. 2011 & 2012; Senzer et al 2012), despite the fact that the Phase 1 patient 
population were those with relapsed or refractory disease. 
 
1.2.2 Safety and Anti-Cancer Activities of CPI-613 against MDS 
 
Preliminary results of CPI-613 against MDS were observed in the Phase I dose-escalation 
trial, entitled “An Open Label, Dose-Escalation Study to Evaluate Safety, Tolerability, 
Maximum Tolerated Dose (MTD), Efficacy & Pharmacokinetics (PKs) of CPI-613 Given 
2x Weekly for 3 Weeks in Patients with Advanced Hematologic Malignancies” (Study# 
CCCWFU 29109). In this Phase 1 trial, study subjects had advanced histologically or 
cytologically documented relapsed or refractory hematologic malignancies for whom 
there is no available therapy known to provide clinical benefit. CPI-613 was administered 
IV. A treatment cycle was 3 weeks of 2x weekly dosing of CPI-613, followed by 1 week 
of rest. The dose of CPI-613 was escalated via a “1-3-6” dose escalation scheme, with the 
initial dose being 420 mg/m2 and the highest dose being 3,780 mg/m2. MTD was found to 
be 2940 mg/m2, infused IV over 2 hrs. 
 
Five of 26 patients in the Phase I dose-escalation trial had a diagnosis of MDS at time of 
enrollment. The demographics, prior therapies, and treatment information of these five 
patients are listed in Table 1.2.2 (below). 
 
Table 1.2.2:  Demographics, Prior Therapies and Treatment Responses in Patients with Myelodysplastic 
Syndrome (MDS) from the Phase 1 Dose-Escalated Trial of CPI-613, Study # CCCWFU 29109 
Patient 
 
Prior Therapies 
(start date:  mm/dd/yr) 
CPI-613 Treatment 
 
Response 
Criteriad 
 
# 
 
Sex 
 
Race 
Age 
(yrs) 
KPS 
(%) 
Dose 
(mg/m2) 
# of Cycles 
Completed 
Start 
Date 
004 M Afr 
Am 
48 
80-
90c 
Ara-C/Dauno/VP-16 (3/1/04); HIDAC 
(cons)/ VP-16 (5/1/04); 
HIDAC/Mitoxantrone (12/1/08); 
Bulsulfan/VP-16 (5/1/10) 
840-
2205a 
31 
(ongoing) 
12/6/10 
Complete 
Remission 
010 F Cau 81 
80-
90c 
Azacitidine (4/1/09); Decitabine (10/1/09) 
2,100 
8 
7/18/11 Stable Disease 
011 F Cau 77 
70 
Decitabine (6/8/09) 
1470-
2940b 
12 
8/8/11 Stable Disease 
013 F Cau 57 
80 7+3+3 (9/13/10); 5+2+2 (9/16/10); HIDAC 
cons x2 (11/3/10); unrelated ALLO 
Fludara/Busulfan (3/9/11) 
2,940 
1e 
9/27/11 
NDe 
019 M Cau 68 
80 
Azacytidine for 13 cycles (9/2/2010-
2940 
1f 
4/9/12 
NDf 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
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3/28/2012) 
(infused 
over 1 
hour) 
Afr = African; Am = American; Ara-C = Cytarabine; Cau = Caucasian; Dauno = daunomycin or daunorubicin; F = female; 
HIDAC = high dose Cytarabine; KPS = Karnofsky Performance Status; M = male; ND = Not Determined; yr = year. 
a The dose was 840 mg/m2 for Cycles 1-6, 1,386 mg/m2 for Cycles 7-10, 2,100 mg/m2 for Cycles 11-19, and finally 2,940 mg/m2 
for Cycle 20, via intra-patient dose escalation scheme.  Due to Grade 2 nausea at 2,940 mg/m2, the dose was reduced to 2,205 
mg/m2 from Cycle 21 on. 
b The dose was 2,100 mg/m2 for Cycles 1-7, and was intended to escalate to 2,940 mg/m2 via intra-patient dose escalation 
scheme.  Due to renal adverse event associated with the first dose at 2,940 mg/m2, the dose was reduced to 1,470 mg/m2 from 
Cycle 7 on. 
c Converted from ECOG to KFS according to the scales:  0 being 100; 1 being 80-90, 2 being 60-70, 3 being 40-50; and 4 being 
20-30.
d Response criteria are according to Cheson et al. (2006).
e Off study due to uncontrolled infection, which began prior to CPI-613 treatment, after 1 cycle of treatment.  Response criteria
were not determined.
f Off study after one dose for renal adverse event.
Adverse events (AEs) were observed in Patient 011 and Patient 019. Patient 011was a 77 
year old female with a KPS of 70% at the start of the trial. Patient 011 experienced taste 
alteration (Grade 1) and elevation of creatinine and reduction in glomerular filtration rate 
(both Grade 3) when treated with CPI-613 at 2,940 mg/m2. When the dose was reduced 
to 2,100 mg/m2, patients exhibited diarrhea, low serum bicarbonate and proteinuria (all 
Grade 1). All AEs were reversible upon termination of treatment. Patient 019 was a 68 
year old male with a KPS of 70% at the start of the trial. He experienced acute renal 
failure after receiving one dose of CPI-613 at 2940 mg/m2 infused over 1 hour. His renal 
function recovered following cessation of therapy and returned to close to his baseline. 
While he was deciding if he wanted to resume therapy on protocol his disease progressed 
to AML and he was admitted for induction chemotherapy.  
Anti-cancer activities were observed in all 3 evaluable MDS patients. Specifically, the 
first evaluable MDS patient (Patient 004) was transfusion-dependent prior to treatment 
with CPI-613 because of severe leukopenia and thrombopenia. Upon participation in the 
CPI-613 trial, he was treated with CPI-613 at 840 mg/m2 for Cycles 1-6, 1,386 mg/m2 for 
Cycle 7-10, 2,100 mg/m2 for Cycles 11-19, and 2,940 mg/m2 for Cycle 10, via intra-
patient dose escalation scheme. Due to Grade 2 nausea at 2,940 mg/m2, the dose was 
reduced to 2,205 mg/m2 from Cycles 21 on. The patient did not receive a single 
transfusion starting at 1 cycle of treatment, due to improved white blood and platelet 
counts. He achieved complete remission (CR) after ~8 cycles of treatment in September 
2011, and has maintained CR since then. The patient is currently on the 31th cycle (as of 
May 2013), and disease status continues to be CR. Figure 1.2.2-1a (below) shows the 
improvement in absolute neutrophil count (ANC) during the first ~11 cycles from pre-
treatment level of ~2,000/μL to ~5,000/μL, and platelet counts from ~40,000/μL to 
>120,000/μL.


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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0
50
100
150
200
250
300
350
ANC x1000/µL
0
1
2
3
4
5
6
Cycles 1-12
0
50
100
150
200
250
300
350
Platelet x1000/µL
0
40
80
120
Patient 004 (AML)
CPI-613:  Cycles 1-6 at 840 mg/m2, Cycles 7-12 at 1,386 mg/m2,
and Cycles 13 on at 2,100 mg/m2
 (CPI-613 treatment currently ongoing)
Time (days)
 
 
 
Figure 1.2.2-1b:  7q- or 
monosomy 7 values during 
the treatment with CPI-613 in 
Patient 004.  The 7q- values 
are currently stabilized at 
~50%. 
 
Figure 1.2.2-1c:  Bone marrow 
before and after ~11 cycles of 
CPI-613 in Patient 004.  The 
bone marrow was hypocellular 
prior to CPI-613 treatment (left 
panel), but was healthier with 
more bone marrow cells and 
less fat after CPI-613 treatment 
(right panel). 
Figure 1.2.2-1a:  Absolute neutrophil count 
(ANC, top) and platelet count (bottom) of Patient 
004 pre and during treatment with CPI-613.  The 
dotted line in each plot shows the trend of the 
plot. 
 
The efficacy of CPI-613 was further indicated by the reduction in 7q- (monosomy 7) 
values, an indication of cytogenetic anomaly, from ~50% after Cycle 1 to ~35 % after 
Cycle 5 (Figure 1.2.2-1b, above). Also, the bone marrow prior to CPI-613 treatment was 
hypocellular, exhibiting significant characteristic of advanced AML (Figure 1.2.2-1c, 
above). After ~11 cycles of CPI-613 treatment, the bone marrow was substantially 
healthier and with significantly more healthy bone marrow cells. 
 
The second evaluable patient (Patient 010) is an 82 year old female with “high risk” 
MDS of Refractory Anemia with Excess of Blasts (RAEB)-2 (bone marrow blast cells 
10-19%), who failed both decitabine and azacytidine treatments. She was admitted to 
hospitals 7 times for neutropenic fever during the 2 years prior to CPI-613 treatment.  
Upon treatment with CPI-613 at 2,100 mg/m2, MDS improved to RAEB-1 (bone marrow 
blast cells 5-9%). She was not admitted for neutropenic fever since the start of CPI-613 
treatment. ANC also improved with CPI-613 treatment (Figure 1.2.2-2, below). The 
patient achieved stable disease (SD) according to criteria described by Cheson et al. 
(2006) within a few cycles, and the condition of the disease continued to improve. By 8 
cycles, the disease was close to partial remission (PR). Unfortunately, due to a fall, she 
was taken off the trial in order to received hospice care. CPI-613 treatment stopped and 
the patient passed away shortly after termination of CPI-613 treatment. 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Figure 1.2.2-2:  Absolute neutrophil 
count (ANC, top panel) and platelet 
count (bottom panel) of Patient 010 
before and during the first 4 weeks of 
treatment with CPI-613.  Patient 010 
is an 82 year old female with “high 
risk” Myelodysplastic Syndromes 
(MDS) of Refractory Anemia with 
Excess of Blasts (RAEB)-2, who has 
failed both decitabine and azacytidine. 
 
 
The third and last evaluable patient (Patient 011) is a 77 year old female with MDS. She 
was relapsed from decitabine, which had induced SD temporarily. Her bone marrow blast 
was 0%, and peripheral blast was barely detectable (~100/μL), before CPI-613 treatment.  
The patient has achieved SD with CPI-613 treatment and remained so during CPI-613 
treatment. After 12 cycles of treatment with CPI-613, she was taken off the trial per 
protocol due to fever. 
 
The first non-evaluable patient (Patient 013) was an eighty year old female with MDS.  
She was taken off the study after 1 cycle of treatment due to uncontrolled infection, 
which began prior to CPI-613 treatment. Accordingly, the efficacy of CPI-613 in this 
patient could not be evaluated. In spite of being treated with only 1 cycle (6 doses), 
possible anti-cancer activities were apparent, as reflected by a small upward trend in 
ANC values, without any changes in peripheral blasts, during treatment with CPI-613 
(Figure 1.2.3-3, next page). Bone marrow blast remained to be within normal range of 
2% before and during treatment with CPI-613. There was also no change in platelet 
counts associated with CPI-613 treatment. 
 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Figure 1.2.3-3:  Absolute 
neutrophil count (ANC, 
top) and platelet count 
(bottom) of Patient 013 
before and during 
treatment with CPI-613.  
The dotted line in each 
plot shows the trend of 
the plot.  This patient was 
taken off the study after 
Cycle 1 due to 
uncontrolled infection 
developed prior to CPI-
613 treatment. 
0
5
10
15
20
25
30
ANC x1000/µL
0
2
4
6
0
5
10
15
20
25
30
Platelet x1000/µL
0
5
10
15
20
Patient 013 (MDS)
CPI-613:  Cycle 1 at 2,940 mg/m2
Cycle 1
0
5
10
15
20
25
30
Peripheral Blasts x1000/µL
0
2
4
6
Time (days)
 
In summary, CPI-613 has a novel mechanism of action, is well tolerated, and exhibits 
anti-cancer activities against various types of solid and hematologic malignancies 
(especially MDS), according to a Phase I dose-escalation trial. Accordingly, the safety 
and anti-cancer activities of CPI-613 in MDS patients who have failed hypomethylating 
agents are investigated in the current pilot study. 
 
 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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2.0 
STUDY DESIGN 
 
2.1 
Study Objective 
 
The objective of this study is to evaluate the safety and anti-cancer activities of CPI-613 
in MDS patients who have failed previous agents (such as decitabine [Dacogen®], 
azacitidine [Vidaza®], growth factors or lenalidomide). 
 
2.2 
Outcome Measures 
 
The primary outcome measure is to evaluate the response rate (RR) of CPI-613 in these 
patients. Response rate is defined as the combined rate of complete remission (CR), 
marrow CR, partial remission (PR), or stable disease (SD) as described by Cheson, et al. 
(2006). 
 
The secondary outcome measures are: 
 
• Safety 
• Progression-free-survival (PFS) 
• Overall survival (OS) 
• Changes in the frequency of blood transfusion 
• Hematologic improvement (HI; as defined by Cheson et al . [2006]) 
 
2.3 
Open-Label, Single-Arm Study Design 
 
This is a pilot single-arm open-label study. The investigators and study subjects are not 
blinded to the treatment. Also, the assignment of patients will not be randomized, since 
there is only a single arm in this study. 
 
3.0 
PATIENT ELIGIBILITY CRITERIA 
 
3.1 
Inclusion Criteria 
 
Patients must meet all of the following inclusion criteria before enrollment: 
 
A. 
Histologically or cytologically documented MDS of any risk group that has failed 
previous therapy. (Therapy failure is defined as patients who have been 
sufficiently treated with previous agents without response in the opinion of the 
treating physician, or whose disease has progressed or relapsed while on a 
hypomethylating agent.) 
B. 
ECOG Performance Status of ≤3. 
C. 
Men and women 18 years of age or older. 
D. 
Expected survival >2 months. 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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E. 
Women of child-bearing potential (i.e., women who are pre-menopausal or not 
surgically sterile) must use accepted contraceptive methods (abstinence, 
intrauterine device [IUD], oral contraceptive or double barrier device) during the 
study, and must have a negative serum or urine pregnancy test within 1 week 
prior to treatment initiation.  
F. 
Fertile men must practice effective contraceptive methods during the study, unless 
documentation of infertility exists. 
G. 
Patients must have fully recovered from the acute, non-hematological, non-
infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or 
other anti-cancer modalities. Patients with persisting, non-hematologic, non-
infectious toxicities from prior treatment ≤ Grade 2 are eligible, but must be 
documented as such. 
H. 
Laboratory values obtained ≤2 weeks prior to enrollment must demonstrate 
adequate hepatic function, renal function, and coagulation as defined below: 
• aspartate aminotransferase [AST/SGOT] ≤3x upper normal limit [UNL] 
• alanine aminotransferase [ALT/SGPT] ≤3x UNL (≤5x ULN if liver 
metastases present) 
• bilirubin ≤1.5x UNL 
• serum creatinine ≤1.5 mg/dL or 133 μmol/L 
• Albumin >2.0 g/dL or >20 g/L. 
I. 
Mentally competent, ability to understand and willingness to sign an IRB-
approved written informed consent form. 
J. 
Have access via central line (e.g., portacath). 
 
3.2 
Exclusion Criteria 
 
Patients with the following characteristics are excluded: 
 
A. 
Serious medical illness, such as significant cardiac disease (e.g. symptomatic 
congestive heart failure, unstable angina pectoris, coronary artery disease, 
myocardial infarction within the past 3 months, uncontrolled cardiac arrhythmia, 
pericardial disease or New York Heart Association Class III or IV), or severe 
debilitating pulmonary disease, that would potentially increase patients’ risk for 
toxicity. 
B. 
Patients with active central nervous system (CNS) or epidural tumor. 
C. 
Any active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer 
disease). 
D. 
Any condition or abnormality which may, in the opinion of the investigator, 
compromise his or her safety. 
E. 
Pregnant women, or women of child-bearing potential not using reliable means of 
contraception. 
F. 
Fertile men unwilling to practice contraceptive methods during the study period. 
G. 
Lactating females. 
H. 
Life expectancy less than 2 months. 
I. 
Unwilling or unable to follow protocol requirements. 


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J. 
A history of additional risk factors for torsade de pointes (e.g., heart failure, 
hypokalemia, family history of Long QT Syndrome, etc.) 
K. 
Evidence of active infection or serious infection within the past month. 
L. 
Requirement for immediate palliative treatment of any kind including surgery. 
M. 
Prior illicit drug addiction. 
N. 
Patients with large and recurrent pleural or peritoneal effusions requiring frequent 
drainage (e.g. weekly).  
O. 
Patients with any amount of clinically significant pericardial effusion. 
P. 
Patients with known HIV infection. (Note: Patients with known HIV infection are 
excluded because patients with an immune deficiency are at increased risk of 
lethal infections when treated with marrow-suppressive therapy, and because 
there may be unknown or dangerous drug interactions between CPI-613 and anti-
retroviral agents used to treat HIV infections). 
Q. 
Patients who have received radiotherapy, surgery, treatment with cytotoxic agents 
(except CPI-613), treatment with biologic agents, immunotherapy, or any other 
anti-cancer therapy of any kind, or any other standard or investigational treatment 
for their cancer, or any other investigational agent for any indication, within the 
past 2 weeks prior to initiation of CPI-613 treatment. 
R. 
Patients that have received a chemotherapy regimen with stem cell support in the 
previous 6 months. 
3.3 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for 
participation in this trial. 
 
4.0 
REGISTRATION PROCEDURES   
 
All patients entered on any CCCWFU trial, whether treatment, companion, or cancer control 
trial, must be registered with the CCCWFU Protocol Registrar or entered into the Oncology 
Research Information System (ORIS) Screening Log within 24 hours of informed consent.  
 
Patients must be registered prior to the initiation of treatment. In order to ensure prompt 
registration of your patient, please: 
 
1. Complete the Eligibility Checklist (Appendix A) 
2. Complete the Protocol Registration Form (Appendix A) 
3. Alert the WFUHS registrar by phone, and then send the signed Informed Consent Form, 
Eligibility Checklist and Protocol Registration Form to the registrar, either by fax or e-
mail. 
 
Contact Information: 
 
Protocol Registrar PHONE (336) 713-6767 
Protocol Registrar FAX (336) 713-6772 
Protocol Registrar E-MAIL (registra@wakehealth.edu) 


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(*Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday.) 
 
Please fax/e-mail ALL eligibility source documents with registration.  Patients will not 
be registered without all required supporting documents. 
 
Note: If labs were performed at an outside institution, please provide a printout of the 
results. Please ensure that the most recent lab values are sent. 
 
To complete the registration process, the Registrar will: 
 
• assign a patient study number 
• register the patient on the study 
 
 
 


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5.0 
STUDY PROCEDURES 
Table 5-1 (below) provides an overview of assessments and procedures conducted during the pre-study screen and during each treatment cycle. 
Specifics are described in subsequent sections. 
Table 5-1:  Study Procedures  
 
Assessments 
Pre-study8 
Each Treatment Cycle (1 cycle = 4 weeks) 
Follow-Up 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Medical history 
√ 
 
 
 
 
 
 
Physical exam, height, weight, 
vitals 
√ 
√2 
 
 
 
 
 
Pregnancy test 
√ 
 
 
 
 
 
 
Evaluation of symptoms and vital 
signs 
√ 
√2 
√2 
√2 
√2 
√2 
 
ECOG performance status and 
survival 
√ 
√2 
 
 
 
 
 
Clinical chemistry, hematology and 
coagulation3,6 
√ 
√2 
 
 
 
 
 
BMP 
 
 
√ 
√ 
√ 
√ 
 
CPI-6131 
 
√ 
√ 
√ 
√ 
√ 
 
Assessment of response4,6, 7 
 
Cycles 2, 4, 6 (and every 3 cycles thereafter until disease progression) 
 
Bone marrow exam6 
√ 
Cycles 3 and 6 (and at the discretion of the physician or if peripheral blood criteria for a 
complete remission are met (ie ANC>1000, Platelets >100k and freedom from blood 
transfusions) thereafter until disease progression) 
 
Survival and post-study follow-up5 
 
 
 
 
 
 
√ 
CR = Complete Remission; D1 = day 1; D4 = day 4; ECOG = Eastern Cooperative Oncology Group; hr = hour; min = minute; PR = Partial Remission. 
1 CPI-613 is given as a 2-hr IV infusion via a central venous catheter. 
2 These tests are performed with results available for review within 24 hrs before administration of the anti-tumor agents. 
3 Specific chemistry, hematology and coagulation are listed in section 5.2.2.  Renal function will be assessed utilizing the Cockcroft-Gault formula.  
4 Cycles 2, 4, 6 (and every 3 cycles thereafter until disease progression). 
5 Survival and post-study cancer treatment will be monitored by the treating physician during routine follow-up visits for 5 years or until death. 
6 CR, marrow CR, and PR will be assessed using hematology results from blood work and bone marrow exam results, according to the criteria described by Cheson et al. (2006). 
7 Frequency of transfusion is defined as the number of transfusions received during the previous 8 weeks. The baseline assessment should reflect the number of transfusions 
received in the 8 weeks prior to enrollment. On-treatment assessments should be performed at the end of cycles 2, 4, and 6, and every 3 cycles thereafter until progression) 
8   Pre-study requirements must be performed within the following time frames:  Within 4 weeks:  bone marrow exam; Within 2 weeks:  medical history, physical exam, vital 
signs, height, weight, ECOG, evaluation of symptoms and medications, clinical chemistry, hematology, and coagulation; Within 1 week:  pregnancy test for women of child-
bearing potential and frequency of transfusion. 


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5.1 
Pre-Study Screening Tests and Safety Assessment 
5.1.1 Pre-Study Screening Tests 
 
Pre-study screening tests, which are also enrollment evaluations, must be performed 
according the following time frames: 
 
Within 4 weeks:  bone marrow exam. 
Within 2 weeks:  medical history, physical exam, vital signs, height, weight, ECOG, 
evaluation of symptoms and medications, clinical chemistry, hematology, and 
coagulation. 
Within 1 week:  pregnancy test for women of child-bearing potential and frequency of 
transfusion. 
5.1.2 Safety Assessment 
 
The safety of CPI-613 will be assessed from the first dose to 1 month after last dose of 
CPI-613.  The assessment will be based on: 
 
- evaluation of symptoms 
- vital signs 
- ECOG performance status and survival 
- clinical chemistry (and renal function utilizing the Cockcroft-Gault formula) 
- hematology 
- coagulation 
 
The specifics of the safety tests are described in Section 5.2.  All safety assessment tests 
are performed during screening (performed within 2 weeks prior to treatment with CPI-
613). Additionally, evaluation of symptoms, vital signs, and survival will be assessed on 
each treatment day, with results available for review within 24 hours before 
administrationCPI-613. ECOG performance status will be assessed on Day 1 of each 
course. Clinical chemistry (renal function utilizing the Cockcroft-Gault formula) 
hematology, and coagulation will be performed on Day 1 of each treatment cycle, with 
results available for review within 24 hours before administration CPI-613. 
 
5.1.3 Assessment of Anti-Cancer Activities 
 
Tumor response will be assessed based on RR, PFS, and OS (as described by Cheson et 
al. 2006), as well as changes in the frequency of transfusion from baseline. RR and PFS, 
derived from hematology and bone marrow exam. Hematology will be assessed at 
baseline, during week 4 of every 2 treatment cycles until cycle 6, and then every 3 
treatment cycles thereafter until disease progression. Bone marrow will be assessed at 
baseline, cycle 3 and 6 and then at the discretion of the physician or if peripheral blood 
criteria for a complete remission are met (ie ANC>1000, Platelets >100k and freedom 
from blood transfusions) thereafter until disease progression.    
 
Baseline frequency should be recorded as the number of transfusions received during the 
8 weeks prior to enrollment. Once patients have started protocol treatment, transfusion 


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frequency should be assessed at the end of every 2 treatment cycles. 
 
Survival will be assessed during the study and will be monitored by treating physician 
contact after the patients are taken off the trial. 
5.2 
Specifics of Tests Performed During the Study 
 
Described below are the specifics of the tests performed in this study. 
 
5.2.1 ECOG Performance Status 
 
The ECOG Performance Status scales (Oken et al 1982) will be used to assess how a 
patient's disease is progressing and assess how the disease affects the daily living abilities 
of the patient.  These scales are listed in Table 5.2.1-1 (below).  The higher the ECOG 
score, the worse the prognosis. 
 
Table 5.2.1-1:  Scales Used in ECOG Performance Status 
Grade ECOG 
0 
Fully active, able to carry on all pre-disease performance without 
restriction 
1 
Restricted in physically strenuous activity but ambulatory and 
able to carry out work of a light or sedentary nature, e.g., light 
house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out 
any work activities. Up and about more than 50% of waking 
hours 
3 
Capable of only limited self-care, confined to bed or chair more 
than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally 
confined to bed or chair 
5 
Dead 
 
 
5.2.2 Clinical Chemistry, Hematology and Coagulation 
 
Clinical chemistry assessed includes: 
 
glucose 
albumin 
creatinine 
total protein 
Na+ 
BUN 
K+ 
AST/serum glutamic-oxaloacetic transaminase (SGOT) 
Cl- 
ALT/serum glutamic-pyruvic transaminase (SGPT) 
Mg 
alkaline phosphatase (ALP) 
Ca+2 
lactate dehydrogenase (LDH) 
PO4 
total bilirubin 
CO2 
 
 
 


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Hematology includes: 
complete blood count 
hemoglobin 
differential count 
hematocrit 
platelet count 
Coagulation includes: 
Prothrombin time 
Partial thromboplastin time 
5.2.3 Bone Marrow Exam 
The following parameters from bone marrow exam must be recorded in Appendix E 
(Data Collection Form for Bone Marrow Exam): 
-
Morphology
-
Immunophenotype
-
Cellularity
-
Karyotype (cytogenetics and FISH as applicable)
-
Molecular markers
-
% of bone marrow myeloblasts
-
% of dysplasia
-
IPSS classification
6.0 
TREATMENT WITH CPI-613 
CPI-613 will be administered to patients as shown in Table 6-1 (below). Briefly, a treatment cycle is 4 
weeks, with CPI-613 given on Days 1 through 5 of the first week (i.e., 1-week-on-3-weeks-off).  Patients 
will receive pre-treatment antiemetics and supportive measures as determined by their treating physician. 
The default premedication will consist of odansetron 16mg IV infused 15 min prior to therapy. 
Table 6-1:  Administration of CPI-613 in MDS Patients Who Has Failed Previous Agents 
Treatment Cycles 
Administration of CPI-613 
Week 
Day 
Cycle 1 (4 weeks) 
1 
1 
2-hr IV infusion via a central venous catheter
2 
2-hr IV infusion via a central venous catheter
3 
2-hr IV infusion via a central venous catheter
4 
2-hr IV infusion via a central venous catheter
5 
2-hr IV infusion via a central venous catheter
2 
3 
4 
Cycle 2 (4 weeks) 
1 
1 
2-hr IV infusion via a central venous catheter
2 
2-hr IV infusion via a central venous catheter
3 
2-hr IV infusion via a central venous catheter
4 
2-hr IV infusion via a central venous catheter
5 
2-hr IV infusion via a central venous catheter
2 
3 
4 
Bone marrow biopsy (week 4 of cycles 3 and 


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6, then at the discretion of the physician or if 
peripheral blood criteria for a complete 
remission are met (ie ANC>1000, Platelets 
>100k and freedom from blood transfusions) 
thereafter until disease progression) 
Etc., until termination of treatment as 
described in Section 6.3. 
 
 
 
 
hr = hour; IV = intravenous; min = minutes 
6.1 
Sample Size, Dose Levels and Justification of the Dose 
 
The sample size will be 20 for this pilot trial. 
 
The dose will be the maximum tolerated dose (MTD) determined from CCCWFU 22112, entitled 
“An Open Label, Dose-Escalation Study to Evaluate Safety, Tolerability, Maximum Tolerated 
Dose (MTD), Efficacy, and Pharmacokinetics (PKs) of CPI-613 given with High Dose 
Cytarabine and Mitoxantrone in Patients with Relapsed or Refractory Acute Myeloid Leukemia 
(AML)”, sponsored by Dr. Timothy Pardee. This dose was determined to be 2500mg/m2. 
 
6.2 
Dosing Delay and Dose Modification of CPI-613 in the Event of Adverse Events 
 
For adverse events unrelated to serum creatinine elevation or reduction in renal function but are 
possibly, probably or definitely related to CPI-613, the occurrence of Grade 1 toxicity does not 
generally require dose modification for subsequent doses for that patient. However, if Grade 2 
toxicity (other than diarrhea and nausea) develop, treatment is to be withheld and can resume only 
after the Grade 2 toxicity has been reduced to Grade 1 or below, and the dose level for subsequent 
doses for that patient will be reduced by 25%. Grade 2 nausea and diarrhea do not require 
withholding treatment or dose reduction. If Grade 3 or 4 toxicity related to CPI-613 develops, 
dosing of CPI-613 of that patient will be withheld and the patient shall be monitored for recovery 
from, and reversibility of, such Grade 3 or 4 toxicity. To resume treatment with CPI-613 for a 
patient who has had CPI-613-related Grade 3 or 4 toxicity, the Grade 3 or 4 toxicity must be 
reduced to Grade 1 or below, and the dose level for subsequent doses for that patient will be 
reduced by 50%. Patients can be re-dose-escalated at the discretion of their treating physician as 
long as no recurrence of the toxicity is seen at the reduced dose. 
 
For adverse events related to creatinine elevation or reduction in renal function that are possibly, 
probably or definitely related to CPI-613, dosing of the patient will be withheld even if the 
severity level is Grade 1 or above. Treatment can resume only after the toxicity has been reduced 
to Grade 0. The dose level for subsequent doses for that patient will be reduced by 15% if the 
severity level is of Grade 1, by 25% for Grade 2 toxicity, and by 50% for Grade 3 or 4 toxicity. 
 
Furthermore, if the toxicity possibly, probably or definitely related to CPI-613 is acute renal 
failure and the severity level is Grade 3 or 4, further patient enrollment will be temporarily 
suspended in order to enable assessment of the following aspects of the trial and implementation 
of corrective measures or protocol amendment, and if necessary: 
 
- 
compliance of the investigators to the study protocol 
- 
evaluation of the appropriateness of the procedures for monitoring renal function 
 


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6.3 
Duration of Treatment for Each Patient 
Treatment with CPI-613 should be continued as long as the treating physician believes there is 
clinical benefit, unless or until: 
-
Patients exhibit disease progression
-
Unacceptable toxicity from CPI-613 in spite of dose reduction
-
Patient withdrawal of consent
-
Investigator’s discretion to withdraw patients from the study because continued
participation in the study is not in the patient’s best interest.
-
Undercurrent illness: a condition, injury, or disease unrelated to the intended disease for
which the study is investigating, that renders continuing the treatment unsafe or regular
follow-up impossible
-
General or specific changes in the patient's condition that renders the patient ineligible for
further investigational treatment
-
Non-compliance with investigational treatment, protocol-required evaluations or follow-
up visits
-
Termination of the clinical trial by the sponsor of CPI-613
When terminating treatment during this trial, the investigator should make every effort to contact 
the patient and to perform a final evaluation.  Also, the reason(s) for withdrawal from the study 
must be recorded. 
Upon being taken off the trial, patient’s survival and post-study cancer treatment will be 
monitored by follow up physician visits once patients are removed from trial.  All patients will be 
followed for 5 years post treatment, or until death. 
7.0 
STUDY DRUG - CPI-613 
7.1 
Description of CPI-613 Drug Product 
CPI-613 is provided in 10-mL amber glass vials.  Each vial contains 10 mL of CPI-613 at a 
concentration 50 mg/mL, equivalent to 500 mg of CPI-613. The drug product of CPI-613 is a 
clear and colorless solution that is free of any particulate matter.   
7.2 
Handling of CPI-613 
CPI-613 is an investigational drug and its toxicity in humans is not fully understood. All 
necessary precautions in handling potentially toxic chemicals must be strictly adhered to.  Gloves 
and protective clothing must be worn when handling CPI-613. Avoid contact by all modes of 
exposure. If the solution contacts the skin, it must be washed immediately and thoroughly with 
soap and water. If the solution comes in contact with mucous membranes, the membranes must 
be flushed thoroughly with water. Spills should be picked up with absorbent material and the area 
must be washed at least 3 times with ethyl alcohol followed by water. 
CPI-613 drug product is slightly photosensitive (Study# PHO-001). Therefore, after removal of 
CPI-613 drug product from the amber vials, CPI-613 drug product should be protected from 


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excessive light before administration to patients. 
 
7.3 
Storage of CPI-613 
 
CPI-613 should be stored under refrigeration, at 2˚-8˚C (36˚-46˚F), except when being prepared 
for administration. 
 
7.4 
IV Infusion Sets, Syringes and IV Bags to be used for Administration of CPI-613 
 
CPI-613 must be administered IV by infusion, via an IV catheter with D5W running at a rate of 
about 125-150 mL/hr.  To avoid local reactions at and around the site of administration, CPI-613 
should be administered via a central venous catheter.  Subsequent sections describe the 
appropriate types of IV catheters, IV bags, syringes and clinical solutions that can be used in 
mixing and administering CPI-613 to patients.  
 
Leaching of Diethylhexyl Phthalate (DEHP):  CPI-613 can cause leaching of DEHP from IV 
infusion sets and IV bags (Study COM-003). Therefore, DEHP-containing IV infusion sets, IV 
bags or syringes should not be used in mixing or administration of CPI-613.  Examples of the IV 
sets, IV bags and syringes that do not contains DEHP and therefore can be used in the 
administration of CPI-613 are: 
 
Extension Set for Syringe Pump Use:  All extension sets from MED-RX do not contain DEHP. 
 
Syringes:  All Monoject syringes are DEHP free. 
 
IV Infusion Sets:  A compatibility study has been conducted showing that CPI-613 is compatible 
with 4 commonly used IV infusion sets (Study# COM-001).  Therefore, these 4 types of IV 
infusion sets, and IV infusion sets that are made with the same materials, can be used to 
administer CPI-613.  These IV infusion sets are: 
 
• 
PVC material - ADDitIV Primary IV Set with Universal Spike, Backcheck Valve, 2 
Injection Sites, DEHP-Free and Latex-Free, 15 drops/mL, REF V14453, B Braun 
Medical Inc. 
• 
Latex material - Interlink System Secondary Medication Set, 10 drops/mL, 2C7451, 
Baxter Healthcare Corporation 
• 
PVC material - SurshieldTM Safety Winged Infusion Set, 0.19 mL Volume, Latex-Free, 
DEHP-Free, SV*S25BLS, Terumo Medical Products Hangzhou Co. Ltd. 
• 
Polyethylene material - Interlink System Paclitaxel Set by Baxter HealthCare, Non 
DEHP-free:  Polyethylene tubing with a 0.22 microfilter Item # 2C7558 10 drops/mL 
 
Syringes:  Compatibility studies (Studies# COM-001 and COM-002) have shown that CPI-613 
drug product (50 mg/mL), and drug product diluted with D5W to various concentrations (1.6-25 
mg/mL) are compatible with various types of syringes, as listed below. Therefore, any of these 
types of syringes, and syringes that are made with the same materials, can be used to administer 
CPI-613. Also, glass syringes can also be used, since glass (such as glass containers) is 
compatible with CPI-613 drug product. 
 
• 
Norm-Ject, polyethlyene barrel, polyethylene plunger, latex free (Henke Sass 


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Wolf GMBH) syringes 
• 
Becton Dickinson syringes 
• 
Terumo syringes 
• 
Monoject syringes 
• 
Glass syringes 
 
7.5 
Reconstitution and Administration of CPI-613 
 
CPI-613 must be diluted from 50 mg/mL to 12.5 mg/mL with 5% Dextrose Water or D5W (i.e., 1 
portion of CPI-613 diluted with 3 portions of D5W) prior to administration.  The diluted drug 
product should be visually inspected for clarity.  If haziness, precipitate or coloration (other than 
colorless) is observed, do not use the diluted drug product for dosing.  After dilution with sterile 
D5W, the solution is clear and has a pH of 8.4-8.8.  The diluted CPI-613 drug product has been 
found to be stable for 24 hrs at room temperature and refrigeration temperature (Studies STA-
010). 
 
CPI-613 must be administered IV, via an IV catheter that is free flowing and free of air in the 
dead space of the IV catheter, to minimize vascular irritation, inflammation and acute toxicity of 
CPI-613 (Study NCL-049). Accidental co-administration of extra air in the dead space of IV 
catheters during administration of CPI-613 has demonstrated the potential to induce acute toxicity 
of CPI-613 according to animal studies (Study NCL-049).  Also, accidental leakage of CPI-613 
into the perivascular space during IV administration, which prolongs exposure of perivascular 
tissue to CPI-613, can induce significant local inflammation according to animal studies (Studies 
NCL-027 and NCL-030).  To avoid local reactions at and around the site of administration, CPI-
613 must be administered via a central venous catheter.   
 
CPI-613 must not be administered as a bolus, but by infusion, at a rate of ~0.5 mL/min, via a 
central venous catheter with D5W running at a rate of about 125-150 mL/hr.  This is to minimize 
potential acute toxicity of CPI-613, according to animal studies (Study NCL-049). 
 
The following precautions must be taken when administering CPI-613: 
 
A. 
Confirmation of the placement of the IV line to ensure a lack of leakage of CPI-613 into 
the perivascular space. 
B. 
Confirmation that the IV line is free flowing. 
C. 
Confirmation that the IV line is free of dead air space. 
D. 
Dilute CPI-613 drug product with D5W, as instructed in the study protocol. 
E. 
Administer CPI-613 by infusion, not as a bolus. 
F. 
After administration of CPI-613, flush the IV line with ~10 mL of D5W to remove 
residual CPI-613. 
G. 
To avoid local reactions at and around the site of administration, CPI-613 should be 
administered via a central venous catheter.   
 
7.6 
Request for CPI-613 
 
CPI-613 must be requested from Cornerstone by the Principal Investigator (or authorized 
designees). CPI-613 may not be used outside the scope of this protocol, nor can it be transferred 
or licensed to any party not participating in this clinical study. Cornerstone policy requires that 


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CPI-613 be shipped directly to the institution where the patient is to be treated. Cornerstone does 
not permit the transfer of CPI-613 between institutions (unless with prior written approval from 
Cornerstone). Requests must be submitted to Cornerstone by fax or email to the following 
address:  
Ms. Claudia Maturo 
Department of Regulatory and Clinical Affairs 
Cornerstone Pharmaceuticals, Inc. 
25 Health Sciences Drive 
Stony Brook, NY 11790 
Telephone: 631-444-6868 
Telefax: 631-444-6895 
Email:  claudia@cornerstonepharma.com 
The following information must be provided in the request of CPI-613 from Cornerstone: 
- Names of the principal investigator and the requestor (if different)
- Name of the study site
- Name of the pharmacist responsible for receiving and storing CPI-613
- Name of the person and address where CPI-613 is to be shipped to
- Amount (# vials) requested
- Date of request
- Date shipment expected
- Study Protocol (title and protocol#) for which the requested CPI-613 is to be used
7.7 
Procurement of Investigational Drug 
Relevant regulations require investigators to establish a record of the receipt, use and disposition 
of all investigational products.  Investigators may delegate responsibility of drug ordering, 
storage, accountability and preparation to their designees. 
The investigator, or the designee, will be responsible for dispensing and accounting of CPI-613 
provided by Cornerstone and for exercising accepted medical and pharmacy practices. 
Records of inventory, dispensation and disposition (vials received, source and dates) must be 
maintained. In addition, all doses dispensed should be accounted for by recording the date, study 
number and name, patient identification, patient initials, patient medical record number and 
balance forward. These records must be maintained and kept at the study site, and will be 
reviewed by Cornerstone, or its designee, during periodic monitoring visits. 
7.8 
Disposal of CPI-613 
The following procedures are to be taken in disposal of CPI-613: 
-
During the study, store the used CPI-613 vials (which must be separate from the unused
CPI-613 vials) at room temperature in an access-limited area.  Alternatively, destroy the
used CPI-613 vials according to institutional policy after documentation of the number of
used CPI-613 vials and remaining volume in each used vial.


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- 
At the end of the study, deface the label (both used and unused vials) with a permanent 
marking pen. 
-
For used CPI-613 vials (if not already destroyed according to institutional policy), after
documentation of the number of used CPI-613 units and remaining volume in each
container, the used containers should be destroyed at the site according to the institutional
procedures for destroying toxic chemicals.  A certificate documenting the destruction of
used vials must be kept on file.
-
All unused CPI-613 vials must be destroyed according to the policy of the institution.
The destruction of CPI-613, and the quantity destroyed, must be documented.  A copy of
the Certificate of Destruction should be sent to:
Ms. Claudia Maturo 
Department of Regulatory and Clinical Affairs 
Cornerstone Pharmaceuticals, Inc. 
25 Health Sciences Drive 
Stony Brook, NY 11790 
Telephone: 631-444-6868 
Telefax: 631-444-6895 
Email:  claudia@cornerstonepharma.com 
7.9 
Calculation of the Amount of CPI-613 for Each Patient 
The amount of CPI-613 at each dose level is based on the BSA of the patient. The BSA values 
will be calculated based on the height and body weight taken during screening and this BSA 
value is used throughout the study. This is unless there is a >10% change in the body weight from 
baseline during the study. At that point, BSA should be revised based on the new body weight 
and height. The new BSA values will be used from that point on for the remainder of the study, 
unless there is another >10% change in body weight which will require another revision of the 
BSA. 
7.10 
Concomitant Medications and Prophylactic Treatment 
Patients cannot receive any standard or investigational treatment (except CPI-613) for their 
cancer, or any other investigational drugs for any non-cancer indications, while on this study.  All 
otherwise permitted concomitant medications (including trade and generic names, dosage and 
dosing schedule) must be recorded. Treatment of disease-related symptoms (such as nausea) is 
permitted. Medications administered in such instances will be considered concomitant 
medications and should be documented accordingly. Supportive treatment may include 
anti-emetic, anti-diarrhea, anti-pyretic, anti-allergic, anti-hypertensive medications, analgesics, 
antibiotics, allopurinol, and others such as blood products and bone marrow growth factors. 
Patients may use erythropoietin for chronic anemia. The treating physician may utilize 
erythropoietic factors, or blood or platelet transfusions at their discretion. 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
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8.0 
ADVERSE EVENTS LIST AND REPORTING REQUIREMENTS 
8.1 
Adverse Event Characteristics 
•
CTCAE term (AE description) and grade:  The CTEP Active Version of the NCI
Common Terminology Criteria for Adverse Events (CTCAE 4.0) will be utilized for AE
reporting.  The CTEP Active Version of the CTCAE is identified and located on the
CTEP website at
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.  All
appropriate treatment areas should have access to a copy of the CTEP Active Version of
CTCAE.
•
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ (see Section 7.1 above) for
expedited reporting purposes only.
•
Attribution of the AE:
-
Definite – The AE is clearly related to the study treatment.
-
Probable – The AE is likely related to the study treatment.
-
Possible – The AE may be related to the study treatment.
-
Unlikely – The AE is doubtfully related to the study treatment.
-
Unrelated – The AE is clearly NOT related to the study treatment.
List of Adverse Events to be Reported: 
Abdominal pain 
Alkaline phosphatase 
ALT (SGPT) 
Anorexia 
AST (SGOT) 
Bilirubin (hyperbilirubinemia) 
Calcium (hypercalcemia, hypocalcemia) 
Creatinine 
Diarrhea 
Flushing 
Hemoglobin (anemia) 
Injection site reaction 
Leukocytes 
Lymphopenia 
Nausea 
Neutrophils (neutropenia) 
Platelets (thrombocytopenia) 
Potassium 
Sodium 
Vomiting 
All grade 3, 4, 5 adverse events should be reported on flow sheets and in ORIS regardless of 
whether they are on this list.  


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All AEs are described in the Investigator’s Brochure, and all of them are considered “expected”. 
All Serious Adverse Events (SAEs) which are Possibly, Probably or Definitively Related to CPI-
613, and Unexpected are required to be reported to Cornerstone Pharmaceuticals via the provided 
SAE Reporting Form within 7 days.  All completed forms must be sent to Ms. Claudia Moore at 
Cornerstone.  Cornerstone will submit any applicable SAEs to the FDA. 
SAE reports must be submitted to Cornerstone by fax or email to the following address: 
Department of Regulatory and Clinical Affairs 
Cornerstone Pharmaceuticals, Inc. 
25 Health Sciences Drive 
Stony Brook, NY 11790 
Telephone: 631-444-6868 
Telefax: 631-444-6895 
Email: claudiamoore2001@yahoo.com 
8.2 
STRC SAE Reporting Requirements 
The Safety and Toxicity Review Committee (STRC) is responsible for reviewing SAEs for 
CCCWFU Institutional studies as outlined in Appendix B. STRC currently requires that all 
unexpected grade 4 and all grade 5 SAE’s on these trials be reported to them for review. This 
procedure is a part of the CCCWFU Data Safety Monitoring Plan that our institution has on file at 
the NCI. All CRM staff members assisting a PI in investigating, documenting and reporting an 
SAE qualifying for STRC reporting are responsible for informing a clinical member of the STRC 
committee as well as the entire committee via the email notification procedure of the occurrence 
of an SAE.  
8.3  
WFUHS IRB AE Reporting Requirements 
Any unanticipated problems involving risks to subjects or others and adverse events shall be 
promptly reported to the IRB, according to institutional policy. Reporting to the IRB is required 
regardless of the funding source, study sponsor, or whether the event involves an investigational 
or marketed drug, biologic or device. Reportable events are not limited to physical injury, but 
include psychological, economic and social harm. Reportable events may arise as a result of 
drugs, biological agents, devices, procedures or other interventions, or as a result of 
questionnaires, surveys, observations or other interactions with research subjects. 
All members of the research team are responsible for the appropriate reporting to the IRB and 
other applicable parties of unanticipated problems involving risk to subjects or others. The 
Principal Investigator, however, is ultimately responsible for ensuring the prompt reporting of 
unanticipated problems involving risk to subjects or others to the IRB. The Principal Investigator 
is also responsible for ensuring that all reported unanticipated risks to subjects and others which 
they receive are reviewed to determine whether the report represents a change in the risks and/or 
benefits to study participants, and whether any changes in the informed consent, protocol or other 
study-related documents are required. 
Any unanticipated problems involving risks to subjects or others occurring at a site where the 


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study has been approved by the WFUHS IRB (internal events) must be reported to the WFUHS 
IRB within 7 calendar days of the investigator or other members of the study team becoming 
aware of the event. 
Any unanticipated problems involving risks to subjects or others occurring at another site 
conducting the same study that has been approved by the WFUHS IRB (external events) must be 
reported to the WFUHS IRB within 7 calendar days of the investigator or other members of the 
study team becoming aware of the event. 
Any event, incident, experience, or outcome that alters the risk versus potential benefit of the 
research and as a result warrants a substantive change in the research protocol or informed 
consent process/document in order to insure the safety, rights or welfare of research subjects. 
9.0 
STATISTICAL CONSIDERATIONS 
This is a pilot study with the primary goal to be able to determine initial estimates of RR, and secondary 
goals to determine PFS and OS.  Data from this trial will also provide additional data concerning the 
safety profile of the CPI-613 therapy.  The anticipated accrual rates, proposed analyses, and sample size 
considerations are described below. 
Accrual Rate 
We anticipate accruing five patients per year for this protocol. Thus, we anticipate that we will reach the 
target sample size of 20 patients treated at MTD within four years.  
Proposed Analyses 
The analyses for this protocol will be primarily descriptive.  With a sample size of 20 treated at MTD, we 
do not expect to see statistically significant effects for the outcomes of interest, however this data will 
provide useful preliminary data on the overall safety and efficacy of CPI-613 and provide useful data to 
predict the variability and likely effect sizes for these outcomes.   
For the primary outcome, we will present the proportion (along with a 95% confidence interval) of 
patients who respond. Response rate (RR) is defined as the combined rate of CR, marrow CR, PR, or SD 
as described by Cheson, et al. (2006). Response criteria are shown in Appendix G. In addition, we will 
determine the number of patients who achieve HI, and a reduction in transfusion requirements. For the 
time-to-event outcomes, we will estimate survival curves for OS and PFS using Kaplan-Meier techniques. 
In addition, we will estimate the 6 month and 1-year OS and PFS rates for these participants.  
We will also examine toxicities by looking at each toxicity identified earlier in the protocol by grade.   
Sample Size Considerations 
Since this is a pilot study we do not anticipate having statistical power to detect specific effects.  However 
with the sample size of 20, we will be able to estimate the response rate using a 2-sided 95% confidence 
interval with an interval that will extend no more than 0.22 from the observed response rate. 
10.0 Data Management and Reporting Schedule 
Tumor response will be assessed based on RR, PFS, and OS (as described by Cheson et al. 2006), as well 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
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as changes in the frequency of transfusion from baseline.  
 
RR and PFS, derived from hematology and bone marrow exam, will be assessed at the following 
specified time points: 
 
• 
Baseline (hematology and bone marrow) 
• 
Hematology: week 4 of every 2 treatment cycles until cycle 6 and then every 3 treatment 
cycles thereafter (i.e., cycle 9, cycle 12, cycle 15, etc) until evidence of disease 
progression. 
• 
Bone marrow week 4 of cycles 3 and 6, and then at the discretion of the physician or if 
peripheral blood criteria for a complete remission are met (ie ANC>1000, Platelets >100k 
and freedom from blood transfusions) thereafter until disease progression 
 
Bone marrow exam results should be documented at each specified time point using the data collection 
form in Appendix E, and then input into the corresponding REDCap database.  
 
Transfusion frequency should be documented at each specified time point using the data collection form 
in Appendix F, and then input into the corresponding REDCap database. 
 
Response form (Appendix I) should be completed for each specified time point.   
 
 
 
Data Collection Forms 
Due By 
Database 
 
 
Pre-Study / 
Registration 
Signed Consent 
At time of registration 
ORIS 
Registration Form 
At time of registration 
ORIS 
 
 
On-Study 
Adverse event log (Appendix C) 
Within one week 
ORIS 
Withdrawal of participation form 
(Appendix D) 
Within one week 
REDCap 
Bone marrow exam form (Appendix E) 
Within one week 
REDCap 
Transfusion data form (Appendix F) 
Within one week 
REDCap 
Response form (Appendix I) 
Within one week 
REDCap 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
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10.0 REFERENCES 
 
1. Cheson BD, et al.  Clinical application and proposal for modification of the International Working 
Group (IWG) response criteria in myelodysplasia.  Blood. 108:419-425, 2006. 
2. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in 
myelodysplastic syndrome. Blood. 1997;89:2079-2088. Abstract. 
3. Lee K, Khaira D, Rodriguez R, Maturo C, O’Donnell K, Shorr R.  Long-Term Stable Disease of 
Stage IV Pancreatic Neuroendocrine Tumors and Without Significant Adverse Effect by CPI-613, an 
Investigational Novel Anti-Cancer Agent.  Case Study and Case Report, 1(3):137-145, 2011. 
4. Lee K, Maturo C, Luddy J, Rodriguez R, Shorr R. Pseudo-progression of metastatic pancreatic cancer 
assessed by imaging studies - a case report.  Case Study and Case Report 2(3): 95-101,2012. 
5. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP.  Toxicity And 
Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982. 
6. Pardee TS, DeFord-Watts LM, Peronto E, Levitan DA, Hurd DD, Kridel S.  Altered lipid and 
mitochondrial metabolism are viable targets in acute leukemia.  American Society of Hematology 
(ASH).  Abstract# 3618.  53rd Annual Meeting and Exposition, 2011a. 
7. Pardee TS, Levitan DA, Hurd DD.  Altered mitochondrial metabolism as a target in acute myeloid 
leukemia.  J Clin Oncol 29: 2011b (suppl; abstr 6590) 
8. Pardee TS, DeFord-Watts LM, Peronto E, Levitan DA, Hurd DD, Kridel S, Harrelson R, Manuel M, 
Lyerly S, Powell BL.  Evaluation of the first-in-class antimitochondrial metabolism agent CPI-613 in 
hematologic malignancies.  J Clin Oncol 30: 2012 (suppl; abstr 6524) 
9. Senzer N, Bedell C, Maturo C, Luddy J, Shorr R, Lee K. CPI-613, an investigational novel anti-
cancer agent, provides long-term stable disease without significant adverse effects in a patient with 
stage IV relapsed hepatocellular carcinoma. Case Study and Case report 2012; 2(2): 38-45,2012. 
10. Study COM-001.  2006.  Compatibility Testing of CPI-613 Drug Product - Infusion Sets. 
11. Study COM-002. Bhasin R. 2008. Compatibility Testing of CPI-613 Drug Product Dosing Solutions 
with Different Types of Syringes. 
12. Study COM-003.  Gupta D.  2009.  Investigation of the Release Behavior of Diethylhexyl Phthalate 
(DEHP) from the Polyvinyl-Chloride Containing Infusion Sets and Bags for Intravenous 
Administration by CPI-613 Drug Product. 
13. Study NCL-027.  Seng J.  2006.  Escalating Dose Toxicology Study of Intravenously Administered 
CPI-613 to Miniature Pigs. 
14. Study NCL-030.  Seng J.  2006.  An Acute Toxicity Study of CPI-613 Administered Via the 
Intravenous (Slow Bolus) Route to Mice. 
15. Study NCL-049.  Moore C, Karnik S, Lee K.  2007.  Preliminary Studies of Comparative Toxicity of 
CPI-613 Administered Intravenously (IV) as Bolus Vs. Infusion, Effects of Air in Dead Space of 
Butterfly IV Infusion Set on Toxicity of CPI-613, and Acute Effects of CPI-613 on Clinical 
Chemistry in Rats. 
16. Study PHO-001 (Covance Study# 7769-101).  Potts B.  2007.  Photostability Testing of CPI-613 
Drug Product. 
17. Study STA-010.  Bhasin R. 2007.  Stability of CPI-613 Injection dosing solutions after Dilution with 
5% Dextrose (D5W). 
18. Study VLD-002 (CR Study# LRH00016LX).  McFarlene J. 2006.  Validation of a High Performance 
Liquid Chromatographic-Mass Spectrometric Method for the Analysis of CPI-613 in K3 and K2 
EDTA Human Plasma. 
19. Zachar Z, Marecek J, Maturo Claudia, Gupta S, Stuart S, Howell K, Schauble A, Lem J, Piramzadian 
A, Karnik S, Lee K, Rodriguez R, Shorr R, Bingham PM:  Non-redox-active lipoate derivates disrupt 
cancer cell mitochondrial metabolism and are potent anti-cancer agents in vivo.  J Mol Med 19 July 
2011 Online. DOI 10.1007/s00109-011-0785-8. 
 


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Appendix A – REGISTRATION GUIDELINES AND FORMS   
The following guidelines have been developed in order to ensure timely registration of your patient. 
 
All patients entered on any CCCWFU trial, whether treatment, companion, or cancer control trial, must 
be linked to a protocol in EPIC within 24 hours of Informed Consent.  Patients must be registered prior to 
the initiation of treatment.   
 
In order to ensure prompt registration of your patient, please: 
 
1. Complete the Eligibility Checklist (attached) 
2. Complete the Protocol Registration Form (attached) 
3. Alert the WFUHS registrar by phone, and then send the signed Informed Consent Form, Eligibility 
Checklist and Protocol Registration Form to the registrar, either by fax or 
 e-mail. 
 
Contact Information: 
Protocol Registrar PHONE (336) 713-6767 
Protocol Registrar FAX (336) 713-6772 
Protocol Registrar E-MAIL (registra@wakehealth.edu) 
(*Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday.) 
 
4. Please fax/e-mail ALL eligibility source documents with registration.  Patients will not be registered 
without all required supporting documents. 
 
Note: If labs were performed at an outside institution, please provide a printout of the results.  Please 
ensure that the most recent lab values are sent. 
 
 


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CCCWFU #    29113                                    Eligibility Checklist                                              
Yes 
No 
N/A 
Inclusion Criteria (All responses must be YES in order to enter study) 
Eligibility 
Confirmation 
(registrar) 
 
 
 
1. 
Does the patient have histologically proven myelodysplastic syndrome 
having failed at least one line of previous therapy? 
 
 
 
 
2. 
Does the patient have an ECOG performance status of < 3? 
 
 
 
 
3. 
Is the patient 18 years of age or older? 
 
 
 
 
4. 
Does the patient have an estimated survival of > 2 months? 
 
 
 
 
5. 
Has the patient recovered from the acute, non-hematological, non-
infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy 
or other anti-cancer modalities? Patients with persisting, non-hematologic, 
non-infectious toxicities from prior treatment < Grade 2 are eligible, but must 
be documented as such. 
 
 
 
 
6. 
If the patient is a woman of child-bearing potential (i.e., pre-menopausal 
or not surgically sterile), does she agree to use accepted contraceptive 
methods (abstinence, intrauterine device [IUD], oral contraceptive or double 
barrier device) during the study, and agree to have a negative serum or urine 
pregnancy test within 1 week prior to treatment initiation? 
 
 
 
 
7. 
If the patient is a fertile man, does he agree to practice effective 
contraceptive methods during the study, unless documentation of infertility 
exists? 
 
 
 
 
8. 
Does the patient have documentation of the following laboratory values? 
• 
aspartate aminotransferase [AST/SGOT] ≤3x upper normal limit [UNL] 
• 
alanine aminotransferase [ALT/SGPT] ≤3x UNL (≤5x UNL if liver 
metastases present) 
• 
bilirubin ≤1.5x UNL 
• 
serum creatinine ≤1.5 mg/dL or 133 µmol/L   
• 
Albumin >2.0 g/dL or >20 g/L. 
 
 
 
 
9. 
Is the patient mentally competent, able to understand and willing to sign 
an IRB-approved written informed consent document?  
 
 
 
 
10. Does the patient have access via a central line (e.g., portacath)? 
 
 
Yes 
No 
N/A 
Exclusion Criteria (All responses must be NO in order to enter study) 
Eligibility 
Confirmation 
(registrar) 
 
 
 
1. Has the patient received radiotherapy, surgery, treatment with cytotoxic 
agents (except CPI-613), treatment with biologic agents, immunotherapy, 
or any other anti-cancer therapy of any kind, or any other standard or 
investigational treatment for their cancer, or any other investigational agent 
for any indication, within the past 2 weeks prior to initiation of CPI-613 
treatment? 
 
 
 
 
2. Has the patient received a chemotherapy regimen with stem cell support in 
the previous 6 months? 
 
 
 
 
3. Does the patient have a serious medical illness, such as significant cardiac 
disease (e.g. symptomatic congestive heart failure, unstable angina 
pectoris, coronary artery disease, myocardial infarction within the past 3 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
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CCCWFU #    29113                                    Eligibility Checklist                                              
months, uncontrolled cardiac arrhythmia, pericardial disease or New York 
Heart Association Class III or IV), or severe debilitating pulmonary 
disease, that would potentially increase patients’ risk for toxicity. 
 
 
 
4. Does the patient have any active uncontrolled bleeding or bleeding 
diathesis? 
 
 
 
 
5. Is the patient a pregnant woman, or a woman of child-bearing potential 
who is not using reliable means of contraception? 
 
 
 
 
6. Is the patient a lactating female? 
 
 
 
 
7. Is the patient a fertile man who is unwilling to practice contraceptive 
methods during the study period? 
 
 
 
 
8. Is the patient’s life expectancy less than 2 months? 
 
 
 
 
9. Does the patient have an unrelated central nervous system (CNS) or 
epidural tumor? 
 
 
 
 
10. Does the patient have any condition or abnormality which may, in the 
opinion of the investigator, compromise his or her safety? 
 
 
 
 
11. Is the patient unwilling or unable to follow protocol requirements? 
 
 
 
 
12. Does the patient have a history of additional risk factors for torsade de 
pointes (e.g., heart failure, hypokalemia, family history of Long QT 
Syndrome)? 
 
 
 
 
13. Does the patient have evidence of active infection, or serious infection 
within the past month? 
 
 
 
 
14. Does the patient have known HIV infection? 
 
 
 
 
15. Does the patient require immediate palliative treatment of any kind, 
including surgery? 
 
 
 
 
16. Does the patient have a prior history of illicit drug addiction? 
 
 
 
 
17. Does the patient have large and recurrent pleural or peritoneal effusions 
requiring frequent drainage (e.g., weekly)? 
 
 
 
 
18. Does the patient have any amount of clinically significant pericardial 
effusion? 
 
 
This subject is      
 eligible / 
 ineligible     for participation in this study. 
 
ORIS Assigned PID: __________________  
 
 
 
 
 
 
 
 
Signature of research professional confirming eligibility: _______________________ Date: _______________ 
 
Signature of Treating Physician:  _____________________________________ Date:  _______________ 
 
Signature of Principal Investigator**:  _____________________________________ Date:  _______________ 
 
* Examples of source documents include clinic note, pathology report, laboratory results, etc. When listing the 
source, specifically state which document in the medical record was used to assess eligibility. Also include the date 
on the document. Example: “Pathology report, 01/01/14” or “Clinic note, 01/01/14” 
 
**Principal Investigator signature can be obtained following registration if needed 
 
Please send source documentation with Eligibility Form.  
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
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CCCWFU # 29113 
 
 
 Protocol Registration Form                                 
DEMOGRAPHICS 
Patient: Last Name: _____________________ 
First Name: ____________________________ 
MRN:          ___ ___ ___ ___ ___ ___ ___ ___ 
DOB (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
SEX:   
  Male            
  Female 
Ethnicity (choose one):   
 Hispanic 
Non-Hispanic 
Race (choose all that 
apply): 
 WHITE           BLACK            ASIAN 
 PAIFIC ISLANDER                 NATIVE AMERICAN 
Height:   ___ ___.___ inches 
Weight: ___ ___ ___.___lbs.(actual) 
Surface Area: ___ ___.___m2   
 
Zip Code:  ___ ___ ___ ___ ___ 
Primary Diagnosis: _____________________________________________________________ 
Date of Diagnosis: ___ ___ /___ ___/___ ___ 
 
 
 
 
Protocol Registrar can be contact by calling 336-713-6767 between 8:30 AM and 4:00 PM, Monday – 
Friday. 
 
Completed Eligibility Checklist and Protocol Registration Form must be hand delivered, faxed or e-
mailed to the registrar at 336-7136772 or registra@wakehealth.edu. 
 
 
 
 
 
PROTOCOL INFORMATION 
Date of Registration: 
___ ___ / ___ ___ / ___ ___ 
MD Name (last) : 
______________________       
Date protocol treatment started: 
___ ___ / ___ ___ / ___ ___ 
Informed written consent: 
(consent must be signed prior to registration) 
 YES   NO 
 
Date Consent Signed: 
___ ___ / ___ ___ / ___ ___ 
 
PID # (to be assigned by ORIS): 
___ ___ ___ ___ ___ ___ ___ ___ 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
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Appendix B:  STRC SAE REPORTING GUIDELINES   
 
Mandatory STRC SAE Reporting Requirements – Revised 6/05/2012 
 
Safety and Toxicity Review Committee 
(STRC; previously known as CROC)  
Serious Adverse Event (SAE) Notification 
SOP 
     Date: 8/17/2016 
 
 
Mandatory STRC SAE Reporting Requirements  
 
This document describes STRC reporting and use of the electronic submission form that is 
submitted for unexpected grade 4 and any grade 5 (death during protocol intervention) 
SAEs on WFBCCC Institutional interventional trial patients. There are multiple entities that 
require reporting of SAEs. Each entity has different rules for what is reported, and how it is 
reported.  
 
Rules used by other entities (Institutional Review Board (IRB), AdEERS, MedWatch, etc.) 
should NOT be used to evaluate whether an event should be reported to STRC. Only the rules 
for reporting described in this document should be considered. 
 
As defined in the NCI Data Table 4 reporting guidelines, WFBCCC Institutional Interventional 
studies covered by these reporting requirements are defined as: In-house, internally 
reviewed trials, including those collaborative studies conducted with industry 
sponsorship in which the center is a primary contributor to the design, implementation, 
and monitoring of the trial, or participation in a multi-site trial initiated by an institutional 
investigator at another center.  Institutional trials are almost always authored by a researcher 
here at WFBCCC. Institutional protocols are labeled NCI Code=”I” for Institutional on the 
protocol screen in ORIS. Cooperative group protocols are not considered Institutional, but 
Research Base trials are classified as Institutional. 
 
The STRC is responsible for reviewing SAEs for WFBCCC Institutional Interventional studies, 
as defined above. STRC currently requires that unexpected grade 4 and all grade 5 SAEs on 
these trials be reported to the STRC for review. All Clinical Protocol and Data Management 
(CPDM) staff members assisting a PI in documenting and reporting an SAE that qualifies for 
STRC reporting are responsible for informing a clinical member of the STRC by phone (or in-
person), followed by informing the entire committee via the required email notification. 
 
THESE REPORTING REQUIREMENTS APPLY TO any faculty or staff member on the 
study team for a WFBCCC Institutional Interventional trial. Once an event is observed, it 
is the responsibility of the person who observed the event to be sure that it is reported. 
 
What is considered an SAE under this mandatory procedure? 
Any unexpected grade 4 event and all grade 5 events (death during protocol intervention) 
should be reported. These events should be reported if they occur while a patient is on study 
treatment or if they occur within 30 days of last study treatment (even if patient begins a new 
treatment during the 30 days). This window of 30 days should be the standard window to be 
used in all protocols unless a specific scientific rationale is presented to suggest that a shorter 


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window can be used to identify events.  In addition, if it is not clear whether the Grade 4 is 
unexpected it should be reported. 
 
 
Table 1: Summary of STRC Reporting Requirements for Institutional Pilot, Phase 1, 
Phase 2  
and Phase 3 Interventional Trials  
STRC reporting may not be appropriate for specific expected adverse events for protocols. In 
those situations the adverse events that will not require STRC reporting must be specified in 
the text of the approved protocol. 
 
STRC notification responsibilities of the person handling the reporting/documenting of 
the SAE: 
1. Make a phone call (or speak in person) to the appropriate clinical member of the STRC as 
listed below (page if necessary)—see note 2 below 
2. Submit the STRC Notification Form WITHIN 24 HOURS of first knowledge of the event. This 
form is found at either the ORIS main menu page or by going to 
http://ccc.wfubmc.edu/oris/strc.aspx. 
This will ensure that all persons that need to be made aware of the event (i.e., study team 
members and STRC members) will be notified; remember to file a copy of your confirmation. 
(Form instructions will walk you through the required fields, consult the help page for further 
instructions.) 
3. Ensure that you document that the appropriate person(s) on the STRC has been contacted.  
This documentation is placed on the STRC Notification form described above. 
4. Follow up with/update the clinical member(s) of STRC regarding any new developments or 
information obtained during the course of the SAE investigation and reporting process. 
 
Elements to complete the electronic STRC form: 
Please use ‘reply to All’ when responding with one of these terms:  Definite, Probable, 
Possible, Unlikely, or Unrelated 
1. Patient ID (ORIS PID) 
2. Patient Name 
3. Patient MR# 
 
ADVERSE EVENT 
Grade 1, Grade 2, Grade 
3 
 
Grade 4 
Grade 5 
Unexpected Expected 
Unexpected 
Expected 
Unexpected 
Expected 
Unrelated Not 
Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT 
TO STRC 
Unlikely 
Not 
Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT 
TO STRC 
Possible 
Not 
Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT 
TO STRC 
Probable 
Not 
Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT 
TO STRC 
Definite 
Not 
Required 
Not 
Required 
REPORT TO 
STRC 
Not 
Required 
REPORT TO 
STRC 
REPORT 
TO STRC 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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4. WFBCCC(ORIS) Study Number 
5. Title 
6. PI Name 
7. PI Contact Number 
8. PI Comments 
9. STRC Clinician notified by Phone 
10. Notified Date 
11. Notified Time 
12. STRC Clinician Comments 
13. Category [This is the Grade – Either Unexpected Grade 4 or Grade 5 should be entered] 
14. Additional Information (IRB Reporting)(after discussion with PI or STRC Clinician 
i. Is This Event Related to Protocol Treatment? 
ii. Is Suspension of the Protocol Needed? 
iii. Any Changes to Consent or Protocol Needed? 
iv. Was Nature or Severity of Event Unexpected? 
15. Date of the event.  
16. Brief description (include brief clinical history relevant to this event, including therapies 
believed related to event).  
17. Date of Last Dose before event 
18. Relevant tests/labs.  
19. Other Relevant Treatment Information 
20. Other Comments/Notes (include regimen of chemo and dates the patient received them 
if known). 
21. Cc (email) (include treating Physician; separate email list with comma”,”) 
22. Your Name 
23. Your Email 
24. Confirm Your Email 
 
The Clinical Members of STRC to Notify by Phone or Page: 
 
Bayard Powell, MD – Director-at-Large, WFBCCC; Chair, PRC; Section Head, 
Hematology/Oncology.  6-7970 / 6-2701 / Pager 336-806-9308 
Antonius Miller, MD – Hematology Oncology 6-7970 / 6-7414 / Pager 704-637-8384 
Glenn Lesser, MD – Hematology Oncology 6-9527 / 6-7972 / Pager 336-806-8397 
Kathryn Greven, MD – Vice Chair – Radiation Oncology. 3-3600 / 3-6505 / Pager 336-806-
8314 
Marissa Howard-McNatt, MD – General Surgery 6-0545 / 336-806-6438 
Mercedes Porosnicu, MD- Hematology Oncology 6-7980 / 6-0230 / Pager 336-806-9150 
Definition of Unavailable:  
As a general guideline if the first clinician that is contacted does not respond to the phone call or 
page within a reasonable amount of time, then initiate contact with their backup.  Give the back-
up a reasonable amount of time to respond to a phone call or page before contacting another 
member. This is a general guideline.  You must use your best judgment as a clinical research 
professional given the time of day, severity of the SAE, and other circumstances as to when it is 
appropriate to contact backup clinicians.  If the event occurs near the end of day, then leave 
messages (voice or email) as appropriate and proceed with submitting your STRC notification 
form.  The important criteria is that you have taken reasonable steps to notify and document that 
you have initiated some type of contact to one or more of the clinical members of STRC. 
 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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STRC CLINICAN RESPONSIBILITY: 
It is the responsibility of the STRC clinician to review all reported events, evaluate the events as 
they are reported; and communicate a response to the Investigator, event reporter and the 
members of STRC. The review will include but not be limited to the information reported; there 
may be times when additional information is needed in order for an assessment to be made and 
further communication directly with the investigator may be warranted. STRC reserves the right 
to agree with the investigator’s assessment if STRC does not agree with the investigator. STRC 
reserves the right to suspend the trial pending further investigation. 
Is there any immediate danger or harm that could be present for a future patient based on the 
information provided in the STRC report – and if so an immediate suspension of enrollment 
should take place. 
 
AMENDMENTS TO PREVIOUS REPORTS 
If you are not able to supply all pertinent information with the initial submission, once the 
additional information is available do not submit a new report. Go to the original email that 
was received by STRC and others “reply to all” and entitle your email “Amendment for (list date 
of event and patient ID) this will avoid duplications of the same event. List the additional 
information which you are reporting. 
 
Acronyms and Definitions 
STRC-Safety and Toxicity Review Committee 
SAE-Serious Adverse Event 
IRB-Institutional Review Board 
WFBCCC-Comprehensive Cancer Center Wake Forest University 
ORIS-Oncology Research Information System 
NCI-National Cancer Institute 
CPDM-Clinical Protocol and Data Management 
Interventional Trials-Therapeutic Level 1 and Level 2 trials 
Therapeutic Level 1-A cancer treatment protocol aimed at directly treating/curing the patient’s 
cancer. 
Therapeutic Level 2-A therapeutic protocol not cancer treatment involves clinical activity to 
treat symptoms, improve the patient’s quality of life, or prevent cancer. 
 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Appendix C – CCCWFU ADVERSE EVENT LOG 
WFBCCC Adverse Event (AE) Log 
PI: _________________ 
 
PID: _________________ 
 
MRN: ________________ 
 
 
 
Cycle Start Date: _____________ 
Cycle End Date: _______________  
Cycle #: __________ 
 
 
 
 
Adverse 
Event CTC 
Term 
Value 
(-5 if non-
numeric) 
Grade  
(0-5) 
per CTC 
Start 
Date 
Attribution 
1=Related 
2=Probably 
3=Possible 
4=Unlikely 
5=Unrelated 
Treating 
MD 
Initials/Da
te 
End 
Date 
Expected 
1=Yes      
0=No 
*Serious 
Adverse 
Event (SAE)   
1=Yes 0=No 
Dose 
Limiting 
Toxicity 
(DLT) 
1=Yes 
0=No 
Action 
Taken 
1=None     
2=Tx 
withheld 
3=Tx D/C   
4=Tx 
adjusted 
5=Other 
Reportab
le?   
1=IRB  
2=STRC  
3=FDA  
4=Spons
or 
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
 
  
  
  
  
 
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Serious Adverse Event: Hospitalization; Disability; Birth Defect; Life-threatening; Death. 
CTCAE Version 4 - http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Appendix D – Withdrawal of Participation Form 
 
ORIS PID _______________________  
 
Date Completed ____ / ____ / ____ 
 
Name of person completing form __________________________ 
Did the subject meet eligibility criteria for study enrollment?   Yes 
   No 
 
 
Reasons for withdrawal: (Check all that apply and provide additional information) 
 Patient exhibited progression of disease 
 Unacceptable toxicity from CPI-613 in spite of dose reduction 
 Patient withdrawal of consent 
 
 For just the primary intervention (CPI-613 administration only) 
 
 For all components of the research study (including follow up in the medical record) 
 Investigator’s discretion to withdraw patient from the study because continued participation in the 
study is not in the patient’s best interest 
 Undercurrent illness: a condition, injury, or disease unrelated to the intended disease for which the 
study is investigating, that renders continuing the treatment unsafe or regular follow-up impossible 
 General or specific changes in the patient’s condition that renders the patient ineligible for further 
investigational treatment 
 Non-compliance with investigational treatment, protocol-required evaluations or follow-up visits 
 Termination of the clinical trial by the clinical sponsor 
 
 
COMMENTS:  ________________________________________________________________ 
____________________________________________________________________________ 
____________________________________________________________________________ 
 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Appendix E – Data Collection Form for Bone Marrow Exam 
 
Study ID:  _________________________________ 
 
Date:  ___ ___ / ___ ___ / ___ ___  
 
Most recent cycle completed:  Baseline   
  
Cycle 3  
 
 
Cycle 6  
 
Other   
___________ 
 
 
Bone Marrow Exam: 
 
Morphology:  __________________________________________________________________ 
 
Cellularity:  ___________________________________________________________________ 
 
Karyotype (cytogenetics and FISH as applicable):  _____________________________________ 
______________________________________________________________________________ 
______________________________________________________________________________ 
 
Molecular markers:  _____________________________________________________________ 
 
% of bone marrow myoblasts:  ___________ % 
 
Revised IPSS Classification:  
 Very Low     
 Low    
 Intermediate    
 High   
 Very High    
 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Appendix F – Data Collection Form for Number of Transfusions 
 
Study ID:  _________________________________ 
 
Date form completed:  ___ ___ / ___ ___ / ___ ___  
 
Time point of assessment: 
Baseline 
 
Cycle 2  
 
Cycle 4  
 
Cycle 6  
 
 
 
 
 
 
Cycle 9  
 
Cycle 12  
 Other ____________   
 
 
Frequency of transfusion is defined as the number of transfusions received during the previous 8 
weeks. The baseline assessment should reflect the number of transfusions received in the 8 
weeks prior to enrollment. On-treatment assessments should be performed at the end of every 2 
treatment cycles. 
 
 
Number of RBC transfusions during period (circle): 0  1   2   3   4   5   6   7   8   9   10 
 
Date range of assessment period:  ___ ___ / ___ ___ / ___ ___ to ___ ___ / ___ ___ / ___ ___ 
 
 
Number of platelet transfusions during period (circle): 0  1   2   3   4   5   6   7   8   9   10 
 
Date range of assessment period:  ___ ___ / ___ ___ / ___ ___ to ___ ___ / ___ ___ / ___ ___ 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Appendix G –Pre-Study Data Collection Form 
 
ORIS PID: ______________________    DATE COMPLETED: (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
The following are required prior to registration: 
CURRENT DISEASE STATUS AT REGISTRATION: _____________________________________________ 
(1ST relapse, 2nd relapse, 3rd relapse, refractory etc., including allo or auto bone marrow transplant) 
 
Prior Therapies/ 
 
Start / End Date of 
Best Response 
Date of  
 
Date of  
 
Duration of  
Protocol # if applicable 
Prior Therapy 
(CR, PR,  
Best Response 
Relapse 
 
Best Response 
 
 
 
 
 
Treatment Failure) 
 
 
 
 
(in Months) 
 
#1 ___________________ 
_______/________ 
_______________ 
_____________ 
______________ 
________________ 
 
#2 ___________________ 
_______/________ 
_______________ 
_____________ 
______________ 
________________ 
 
#3 ___________________ 
_______/________ 
_______________ 
_____________ 
______________ 
________________ 
 
#4 ___________________ 
_______/________ 
_______________ 
_____________ 
______________ 
________________ 
 
#5 ___________________ 
_______/________ 
_______________ 
_____________ 
______________ 
________________ 
 
#6 ___________________ 
_______/________ 
_______________ 
_____________ 
______________ 
________________ 
 
COMMENT:_________________________________________________________________________ 
 
Date of original cancer diagnosis: ___ ___ / ___ ___ / ___ ___ 
 
Date of 1st Remission: ___ ___ / ___ ___ / ___ ___ 
 
Date of 1st Relapse: ___ ___ / ___ ___ / ___ ___ 
 
Date of 2nd Relapse: ___ ___ / ___ ___ / ___ ___ 
 
ECOG Performance Status: 
 
 Score 0 – Fully active, able to carry on all pre-disease performance without restriction 
 Score 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, e.g., light house work, office work 
 Score 2 - Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more 
than 50% of waking hours 
 Score 3 - Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
 Score 4 - Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
CYTOGENETICS: 
Cytogenetics at Diagnosis: 
 
Date of Cytogenetics Report: ___ ___ / ___ ___ / ___ ___ 
 
Risk Category:  
 Good     
 Intermediate    
 Poor    
 
*Enter descriptive text from Cytogenetic Report (3 categories) into REDCap database on Pre-Study Data 
Collection Form. 
 
Revised IPSS Classification:  
 Very Low     
 Low    
 Intermediate    
 High   
 Very High    


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Appendix H – Response Criteria 
 
 
Continued on next page 
 


Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Comprehensive Cancer Center of Wake Forest University (CCCWFU) 
A Pilot Study of CPI-613 in Patients with Myelodysplastic Syndrome Who Have Failed Previous Therapy 
CCCWFU #29113 
 
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Appendix I – Response Evaluation Form 
 
 
MRN: ___________________ 
Patient ID: ______________________ 
Date: ____ ___ / ___ ___ / ___ ___ 
 
Time point of assessment: 
Cycle 2  
 
Cycle 4  
 
Cycle 6  
 
 
 
 
 
 
Cycle 9  
 
Cycle 12  
 Other ____________   
 
 
 
 
Please check the response that applies to this patient. Refer to the response criteria from Cheson 
et al., 2006 described in Appendix G. 
  
       Complete Remission (CR) 
 
Partial Remission (PR)  
 
Marrow Complete Response 
 
Stable Disease  
 
Failure   
 
Relapse after CR or PR 
 
Cytogenetic Response  
 
Disease Progression  
 
Survival 
 
Hematologic Response Criteria: 
 
 
Erythroid Response (pretreatment, <11g/dL) 
  
Platelet Response (pretreatment, < 100 x 109 /L) 
  
Neutrophil Response (pretreatment, <1.0 x 109/L) 
 
Progression or Relapse after (HI) Hematologic Improvement 
 
Treating Physician Signature: ________________________   Date: ___ ___ / ___ ___ / ___ ___ 
 
PI Signature: ____________________________      
   Date: ___ ___ / ___ ___ / ___ ___ 
 

ICF_001.pdf: 
Comprehensive Cancer Center of Wake Forest University (CCCWFU)
CCCWFU 29113
Page 1 of 11
Adult Consent Form
Version: 01/07/2020
Section on Hematology and Oncology
A PILOT STUDY OF CPI-613 IN PATIENTS WITH MYELODYSPLASTIC 
SYNDROME WHO HAVE FAILED PREVIOUS THERAPY 
Informed Consent Form to Participate in Research
Bayard Powell, MD, Principal Investigator
INTRODUCTION
You are invited to be in a research study. Research studies are designed to gain scientific 
knowledge that may help other people in the future. You are being asked to take part in this 
study because you have myelodysplastic syndrome (MDS) and prior treatments have not been 
successful. Your participation is voluntary. Please take your time in making your decision as to 
whether or not you wish to participate. Ask your study doctor or the study staff to explain any 
words or information contained in this informed consent document that you do not understand. 
You may also discuss the study with your friends and family.
WHY IS THIS STUDY BEING DONE?
An investigational drug is one that has not been approved by the U.S. Food and Drug 
Administration (FDA). CPI-613 is an investigational drug that has not been approved by the 
FDA for any type of tumor or cancer, and it is currently being studied for the treatment of cancer 
and related conditions, such as MDS.
The purpose of this study is to test the safety and effectiveness of an investigational drug called 
CPI-613 (“study drug”) when used to treat MDS. In MDS, the blood-forming cells in your bone 
marrow are damaged and have difficulty making new blood cells. If MDS does not respond to 
treatment, it can turn into a type of blood cancer known as acute myeloid leukemia. CPI-613 is 
thought to kill cancer cells by turning off their mitochondria. Mitochondria are used by cells to 
produce energy and are the building blocks needed to make more cells. By shutting off these 
mitochondria, CPI-613 deprives the cells of energy and other supplies that they need to survive 
and grow in your body. In other studies, CPI-613 has been shown to kill cancer cells in some 
types of cancer. We want to find out what effects, good and/or bad, CPI-613 has on MDS. 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
Twenty (20) people at Wake Forest Baptist Health will take part in this study. 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


Comprehensive Cancer Center of Wake Forest University (CCCWFU)
CCCWFU 29113
Page 2 of 11
Adult Consent Form
Version: 01/07/2020
WHAT IS INVOLVED IN THE STUDY?
After your study doctor has answered all your questions about this study and you have given 
written consent by signing this form, several tests will be done to be sure you are able to enter 
this study. Many of the tests are the same as those you have had in the past to diagnose and treat 
your disease. Some of these same tests will also be done during the study to follow your 
progress.
Your participation in this study is divided into different visits:
Pre-Study Screening Tests (To see if you are eligible to participate in this study)
The following tests will be done in order to determine if you are eligible to participate in this 
study. 
Within 4 weeks before receiving CPI-613: You will have a bone marrow biopsy 
Within two weeks before receiving CPI-613.

The study doctor or study nurse will ask you about your medical history, and
obtain a list of all medications that you are currently taking.

The study doctor or study nurse will examine you and determine your
performance status.

A physical examination with your vital signs (heart rate, blood pressure, breathing
rate, and body temperature), height, and body weight will be recorded.

Approximately 10 teaspoons of blood will be drawn for routine lab tests.
Within one week before receiving CPI-613:

Pregnancy test for female subjects who can become pregnant. This must be done
within one week of starting treatment.
Study-Related Treatment Procedure and Tests
This clinical research study consists of treatment with CPI-613. Treatment will be given over a 
4-week period known as a “cycle.” The number of cycles you receive will be determined by how
well your cancer responds to the therapy. The following table shows a schedule of the treatment,
tests and procedures you will have:
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


Comprehensive Cancer Center of Wake Forest University (CCCWFU)
CCCWFU 29113
Page 3 of 11
Adult Consent Form
Version: 01/07/2020
Each Treatment Cycle
Week 
1
Weeks 2-4
Treatment, tests, and procedures
D1
D2
D3
D4
D5
Physical Exam (within 24 hours of 
receiving CPI-613)

Evaluation of symptoms and vital 
signs





Performance status





10 tablespoons of blood drawn for 
routine lab tests

1 teaspoon of  blood drawn to check 
kidney function




Treatment with CPI-613





Bone Marrow Biopsy
1
Definitions of abbreviations used in this table:
D1 = Day 1; D4 = Day 4
1 Week 4 of  cycles 3 and 6 and then as recommended by your doctor until your MDS has failed to 
respond
Additional Evaluations and Procedures
During week 4 of cycle 3, you will undergo a bone marrow biopsy to see if your MDS has 
responded to treatment with CPI-613. If the results show that your MDS has responded, you will 
continue with another 3 cycles of treatment with CPI-613 and having your bone marrow 
examined at the end of cycle 6. If your MDS has failed to respond, you will be removed from the 
study. 
HOW LONG WILL I BE IN THE STUDY?
You will be given CPI-613 5 times each week for 1 week, followed by 3 weeks of rest (a cycle).  
CPI-613 will be given over a 2-hour infusion into your vein through a central venous catheter (a 
catheter that is put into a larger vein in your body and will remain in place for the duration of the 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


Comprehensive Cancer Center of Wake Forest University (CCCWFU)
CCCWFU 29113
Page 4 of 11
Adult Consent Form
Version: 01/07/2020
treatment).The length of participation in this study will vary for each person and will be 
determined by the number of treatment cycles you receive. All participants will be in the study 
for at least 2 months, which is the amount of time required to complete 2 treatment cycles. The 
following details how long you will be in the study based on the total number of cycles you 
receive:

2 cycles: you will be on the study for 8 weeks (2 months)

4 cycles: you will be on the study for 16 weeks (4 months)

6 cycles: you will be on the study for 24 weeks (6 months)

Etc.
You can stop participating at any time. It is important to tell the study doctor if you are thinking 
about stopping so that any risks from CPI-613 can be evaluated by your study doctor. Another 
reason to tell your study doctor that you are thinking about stopping is to discuss what follow-up 
care and testing could be most helpful for you.
WHAT ARE THE RISKS OF THE STUDY?
Being in this study involves some risk to you. You should discuss the risk of being in this study 
with the study staff. 
Risks Related to CPI-613
The study drug is in the very early stages of development for use in humans. The main purpose 
of this study is to learn about the safety and effectiveness of the drug when used to treat MDS. 
Please carefully read the sections on risk and benefits below. Not all of the side effects are 
known at this time. If you choose to take part in this study, it is very important that you let the 
study team know of any symptoms you have.
Some potential risks associated with CPI-613 have been determined from previous animal 
studies. These side effects include vomiting and some temporary heart damage. CPI-613 has also 
caused inflammation around the area where the experimental drug is given, causing swelling, 
redness, and pain. To avoid this potential side effect, CPI-613 will be given to you through a 
central venous catheter. There may be other more severe side effects such as significant 
inflammation throughout your body. The study drug could cause changes in certain chemicals in 
your blood that could indicate liver problems. Significant side effects have also caused some 
deaths in test animals at dose levels that are higher than those to be used in this study. Many side 
effects may go away shortly after being given CPI-613 but in some cases, side effects may be 
severe, long lasting, or may not go away. Although not yet reported in any human subjects, it 
remains possible that CPI-613 might cause your disease to progress or produce a fatal side effect. 
CPI-613 may also cause side effects that we have not yet seen and cannot predict.
Some common side effects observed in patients taking CPI-613 include:

Allergic reaction at the place where you receive your drug

Vomiting
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


Comprehensive Cancer Center of Wake Forest University (CCCWFU)
CCCWFU 29113
Page 5 of 11
Adult Consent Form
Version: 01/07/2020

Diarrhea

Fatigue

Headache

Constipation

Nausea

Light-headedness

Abdominal pain

Changes in liver function

Changes in kidney function

Jaundice (temporary yellowing of the skin and eyes)

Too much or too little calcium in the blood

Flushing

Anemia

Low levels of white blood cells

Low levels of platelets (blood cells that help to form clots)

Electrolyte imbalance

Abnormal heartbeat (changes in heart rhythm that may require placement of a
pacemaker)
There may be other, more severe side effects, such as inflammation throughout your body. The 
study drug could case changes in certain chemicals 
Pregnancy Risks
The effects of CPI-613 on a fetus are unknown. You should not become pregnant or father a 
child while on this study.  If you are able to become pregnant or father a child, BOTH you and 
your partner must use effective birth control methods during the study period.  Effective birth 
control methods are outlined below.
Women subjects who have never been pregnant can use one of the following methods:

Abstinence

A barrier method (diaphragm, cervical cap, sponge, or condom with a spermicidal foam
or jelly) plus hormonal birth control (oral, patch or injectable).

A barrier method (diaphragm, cervical cap, sponge, or condom with a spermicidal foam
or jelly) plus and intrauterine device (IUD).
Women subjects who have previously been pregnant at least once can use one of the following 
methods:

Abstinence

A barrier method (diaphragm or condom with a spermicidal foam or jelly) plus hormonal
birth control (oral, patch or injectable).

A barrier method (diaphragm or condom with a spermicidal foam or jelly) plus and
intrauterine device (IUD).
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


Comprehensive Cancer Center of Wake Forest University (CCCWFU)
CCCWFU 29113
Page 6 of 11
Adult Consent Form
Version: 01/07/2020
Male subjects can use one of the following methods:

Abstinence

Condom with spermicide
For male subjects, you should also advise your partner to use an effective birth control method 
such as those outlined above for women subjects.  
If you suspect that you have become pregnant, you must notify the study doctor immediately.
Female subjects should avoid becoming pregnant for at least 10 weeks following completion of 
the study.  Male subjects should avoid fathering a child for at least 10 weeks following study 
completion.  
Other Risks
It is possible that you could experience an allergic reaction to CPI-613. An allergic reaction can 
be mild, or it can be serious, leading to shock with loss of consciousness, or it can be life-
threatening.
Certain drugs, when taken together with the study drug, may increase side effects. It is important 
that you inform your study doctor of any prescription, over-the-counter, or alternative 
medications you are taking while in this study.
Drawing blood may cause pain, bruising, lightheadedness, or, on rare occasions, infection.
Risks of a central venous catheter may include pain, bleeding, infection, and damage to lungs or 
other tissue.
Your condition may not get better or may become worse during this study.
If you have questions about risks and side effects, ask your study doctor. You should talk to your 
study doctor about any side effects that you have while taking part in this study. The study 
doctor will take steps to try to treat any side effects, if they appear. If the study drug causes 
severe side effects or if your disease worsens, the study drug will be discontinued. In that case, 
your study doctor will discuss treatment options with you.
Taking part in this research study may involve providing information that you consider 
confidential or private. Efforts, such as coding research records, keeping research records secure 
and allowing only authorized people to have access to research records, will be made to keep 
your information safe.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


Comprehensive Cancer Center of Wake Forest University (CCCWFU)
CCCWFU 29113
Page 7 of 11
Adult Consent Form
Version: 01/07/2020
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there may or may not be direct benefit to you. We hope the 
information learned from this study will benefit other people in the future. The benefits of 
participating in this study may be: improvement in your cancer.  
WHAT OTHER CHOICES ARE THERE?
You do not have to be in this study to receive treatment. You should talk to your doctor about all 
the choices you have. Instead of being in this study, you have these options:

Other chemotherapies 

Comfort care, which is an option if you decide that you do not want any more active 
treatment for your cancer. Comfort care includes pain medication and other types of 
support. It aims to maintain your comfort and dignity rather than cure disease. Usually 
this care can be provided at home. If you think you might prefer comfort care, please 
discuss this with your family, friends, and your doctor.
WHAT ABOUT MY HEALTH INFORMATION?
In this research study, any new information we collect from you about your health or behaviors 
is considered Protected Health Information. The information we will collect for this research 
study includes: your health history, bone marrow biopsy information, how you respond to study 
procedures, laboratory and other test results, and physical examinations.
If this research study involves the diagnosis or treatment of a medical condition, then Protected 
Health Information collected from you during this study will be placed in your medical record, 
and may be used to help treat you, arrange payment for your care, or assist with Medical Center 
operations. 
We will make every effort to keep your Protected Health Information private. We will store 
records of your Protected Health Information in a cabinet in a locked office or on a password 
protected computer. 
Some of the people, agencies and businesses that may receive and use your health information
are the research sponsor; representatives of the sponsor assisting with the research; investigators
at other sites who are assisting with the research; central laboratories, reading centers or analysis
centers; the Institutional Review Board; representatives of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital; representatives from government agencies such as 
the Food and Drug Administration (FDA) or the Office of Human Research Protections (OHRP), 
the Department of Health and Human Services (DHHS) and similar agencies in other countries. 
Some of these people, agencies and businesses may further disclose your health information. If
disclosed by them, your health information may no longer be covered by federal or state privacy
regulations. Your health information may be disclosed if required by law. Your health 
information may be used to create information that does not directly identify you. This 
information may be used by other researchers. You will not be directly identified in any 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


Comprehensive Cancer Center of Wake Forest University (CCCWFU)
CCCWFU 29113
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publication or presentation that may result from this study unless there are photographs or 
recorded media which are identifiable. 
If required by law or court order, we might also have to share your Protected Health Information 
with a judge, law enforcement officer, government agencies, or others. If your Protected Health 
Information is shared with any of these groups it may no longer be protected by federal or state 
law.
Any Protected Health Information collected from you in this study that is maintained in the 
research records will be kept for an indeterminate period of time. This authorization does not 
expire. Any research information entered into your medical record will be kept for as long as 
your medical record is kept by the Medical Center. You will not be able to obtain a copy of your 
Protected Health Information in the research records until all activities in the study are 
completely finished. 
You can tell Dr. Bayard Powell that you want to take away your permission to use and share 
your Protected Health Information at any time by sending a letter to this address:
Bayard Powell, MD,
Medical Center Boulevard
Winston-Salem, NC 27157
However, if you take away permission to use your Protected Health Information you will not be 
able to be in the study any longer. We will stop collecting any more information about you, but 
any information we have already collected can still be used for the purposes of the research 
study.
By signing this form you give us permission to use your Protected Health Information for this 
study.
If you choose to participate in this study, your medical record at Wake Forest University Baptist 
Medical Center will indicate that you are enrolled in a clinical trial. Information about the 
research and any medications or devices you are being given as a participant may also be 
included in your medical record. This part of the medical record will only be available to people 
who have authorized access to your medical record. If you are not a patient at this Medical 
Center, a medical record will be created for you anyway to ensure that this important information 
is available to doctors in case of an emergency.
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 Web site at any time. 
Laboratory test results and other medical reports created as a result of your participation in the 
research study may be entered into the computer systems of Wake Forest University Health 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


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Comprehensive Cancer Center of Wake Forest University (CCCWFU)
CCCWFU 29113
Sciences and North Carolina Baptist Hospital. These will be kept secure, with access to this 
information limited to individuals with proper authority, but who may not be directly involved 
with this research study.
A North Carolina Baptist Hospital (NCBH) medical record will be created for all study 
participants. Information about your participation in the study will be placed in the NCBH 
medical record, along with any routine medical test results that were obtained at NCBH as part 
of this study. 
WHAT ARE THE COSTS?
There are no costs to you for taking part in this study. All study costs, including any study 
medications and procedures related directly to the study, will be paid for by the study. Costs for 
your regular medical care, which are not related to this study, will be your own responsibility.
WILL YOU BE PAID FOR PARTICIPATING?
The investigational study drug, CPI-613, is being provided to you at no cost from the 
pharmaceutical company (Cornerstone Pharmaceuticals, Inc.). You will receive no payment for 
your participation in this study.  Parking validation will be provided for all study-related visits.
WHO IS SPONSORING THIS STUDY?
This study is being sponsored by Wake Forest University Health Science.  Cornerstone 
Pharmaceuticals, Inc. is providing the investigational drug (CPI-613) to Wake Forest University 
Health Sciences to help conduct this study. Boris Pasche, MD, the Director of the 
Comprehensive Cancer Center of Wake Forest Baptist Medical Center serves on the board of 
directors for Rafael Holdings, Inc., which owns the manufacturer of the drug that is being 
studied.  Timothy Pardee, MD holds a part-time position as Chief Medical Officer for Rafael 
Pharmaceuticals, Inc, the study drug manufacturer.  Dr. Bayard Powell serves on the Scientific 
Advisory Board for Rafael Pharmaceuticals, Inc.  
.
WHAT HAPPENS IF YOU EXPERIENCE AN INJURY OR ILLNESS AS A 
RESULT OF PARTICIPATING IN THIS STUDY?
Should you experience a physical injury or illness as a direct result of your participation in this 
study, Wake Forest University School of Medicine maintains limited research insurance 
coverage for the usual and customary medical fees for reasonable and necessary treatment of 
such injuries or illnesses. To the extent research insurance coverage is available under this policy 
the reasonable costs of these necessary medical services will be paid, up to a maximum of 
$25,000. Wake Forest University Baptist Medical Center holds the insurance policy for this 
coverage. It provides a maximum of $25,000 coverage for each claim and is limited to a total of 
$250,000 for all claims in any one year. The Wake Forest University School of Medicine, and 
the North Carolina Baptist Hospitals, Incorporated do not assume responsibility to pay for these 
medical services or to provide any other compensation for such injury or illness. Additional 
information may be obtained from the Medical Center’s Director of Risk and Insurance 
Management.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


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Comprehensive Cancer Center of Wake Forest University (CCCWFU)
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If you are injured, the insurer may require information such as your name, social security 
number, and date of birth in order to pay for your care.  This is because the insurer is required by 
law to report any payments made to cover the care of any persons who are members of a 
government insurance plan to the Department of Health and Human Services.
You do not give up any legal rights as a research participant by signing this consent form. For 
more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should call Dr. Bayard Powell.
ARE MY RIGHTS AS A RESEARCH STUDY PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or you may leave the 
study at any time. Refusing to participate or leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. The investigators also have the right to stop your participation in the study 
at any time. This could be because it is in your best interest, you do not follow the study rules, 
the study is stopped, you do not later consent to any future changes that may be made to the 
study plan, or your become pregnant. 
You will be given any new information we become aware of that would affect your willingness 
to continue to participate in the study.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or in the event of a research-related injury, contact the study 
investigator, Dr. Bayard Powell.
The Institutional Review Board (IRB) is a group of people who review the research to protect 
your rights. If you have a question about your rights as a research participant, or you would like 
to discuss problems or concerns, have questions or want to offer input, or you want to obtain 
additional information, you should contact the Chairman of the IRB.
You will be given a copy of this signed consent form. 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022


Comprehensive Cancer Center of Wake Forest University (CCCWFU)
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SIGNATURES
I agree to take part in this study. I authorize the use and disclosure of my health information as 
described in this consent and authorization form.  If I have not already received a copy of the 
Privacy Notice, I may request one or one will be made available to me.  I have had a chance to 
ask questions about being in this study and have those questions answered.   By signing this 
consent and authorization form, I am not releasing or agreeing to release the investigator, the 
sponsor, the institution or its agents from liability for negligence.
Subject Name (Printed):_____________________________
Subject Signature: _________________________________ Date: ________Time:_______ am pm 
Person Obtaining Consent:___________________________ Date:_________ Time:________ am pm
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00024007
Meeting Date Approved 1/25/2021          
Version Valid Until: 1/24/2022