Clinical trial NCT04217317
Conditions: Relapsed T-Cell Lymphoma Refractory T-Cell Lymphoma Non Hodgkin Lymphoma
Sponsor: Wake Forest University Health Sciences
Start date: 2020-09-16; Completion date: 2024-07-11
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to determine if it is possible to give CPI-613 with the drug Bendamustine for 2 days every 28 days without causing severe side effects. In addition, this study will also test the safety of CPI-613 when given in combination with Bendamustine.

Detailed description:
Primary Objectives: A pilot Study to evaluate the feasibility, safety and tolerability of a two day course per cycle of Bendamustine plus CPI-613 in patients with relapsed and refractory T cell non-hodgkin lymphoma.

Exploratory Objectives

To evaluate:

* Overall response rate (ORR) and disease control rate (DCR) derived from the Lugano classification.
* Duration of response (DOR) derived from the Lugano classification.
* Progression-Free-Survival (PFS) derived from Lugano classification.
* Overall Survival (OS).
* Single cell transcriptomics from PMBCs pre- and post-treatment; for correlative analyses of blood PBMC (and possibly excess pre-treatment tumor biopsy) cell population diversity and functional states to reveal potential mechanisms of drug treatment with regard to patient response status.

Arms: arm 1: CPI-613 at 2500 mg/m2 is infused intravenously (IV) via a central catheter over 2 hrs on Days 1and 2. Bendamustine at 90 mg/m2 is infused IV over 10 minutes on Days 1 and 2 of each treatment cycle, given immediately after CPI-613 administration.
Interventions: intervention 1: CPI 613 intervention 2: Bendamustine
Intervention descriptions: intervention 1: CPI-613 is to be given as 2-hr IV infusion via a central venous catheter. The starting dose of CPI-613 will be 2500 mg/m2 which was determined to be the MTD in the previous phase I clinical trial. intervention 2: Bendamustine at 90 mg/m2 is infused by IV over 10 minutes on Days 1 and 2 of each treatment cycle. Bendamustine is given immediately after CPI-613 administration.

Protocol documents:
Prot_SAP_001.pdf: 
Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-
Cell Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
ClinicalTrials.gov:  NCT04217317
Protocol version date: 11/29/22 
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Principal Investigator: 
Rakhee Vaidya, M.B.B.S. 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
Biostatistician 
Ralph D’Agostino, PhD. 
Division of Public Health Sciences 
Comprehensive Cancer Center of Wake Forest University 
Research Nurses: 
Kayla Bolin 
Comprehensive Cancer Center of Wake Forest University 
Catalina Gonzalez-Pinzon 
Comprehensive Cancer Center of Wake Forest University 
Study Coordinator: 
Denisse Funes-Valencia 
Comprehensive Cancer Center of Wake Forest University 
Data Manager: 
Sharon McFadden 
Comprehensive Cancer Center of Wake Forest University 
Regulatory / Budget: 
Emily Teal, MA 
Comprehensive Cancer Center of Wake Forest University 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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Investigational Drug: 
CPI-613 and Bendamustine 
 
IND Number: 
 
123218 
 
Drug Sponsor: 
 
Rafael Pharmaceuticals, Inc. 
 
Participating Institutions:       Wake Forest Baptist Comprehensive Cancer Center 
 
 
 
 
 
 
 
 
 
 
 
 
Version Date: 
 
 
11/29/22 
 
 
 
 
 
 
 
 
Proprietary and Confidential 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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SCHEMA 
 
 
 
 
 
 
 
 
Patients with relapsed and/or refractory T-Cell Non-
Hodgkin Lymphoma who may or may not have received 
hematopoietic cell transplant  
Administration of CPI-613 in combination with Bendamustine 
Informed 
consent 
Primary Objectives 
Pilot Study to evaluate the feasibility, safety and tolerability of a two day course 
per cycle of Bendamustine plus CPI-613 in patients with relapsed and 
refractory T cell non-hodgkin lymphoma.     
 
Exploratory Objectives 
To evaluate: 
A. Overall response rate (ORR) and disease control rate (DCR) derived from 
the Lugano classification (Cheson et al. 2014) for PTCL patients and 
Global Response Score for CTCL (MF/SS) patients (Olson et al. 2011). 
B. Duration of response (DOR) derived from the Lugano classification for 
PTCL patients and Global Response Score for CTCL (MF/SS) patients. 
C.  Progression-Free-Survival (PFS) derived from Lugano classification for 
PTCL patients and Global Response Score for CTCL (MF/SS) patients.   
D.  Overall Survival (OS). 
E. Single cell transcriptomics from PMBCs pre- and post-treatment; for 
correlative analyses of blood PBMC (and possibly excess pre-treatment 
tumor biopsy) cell population diversity and functional states to reveal 
potential mechanisms of drug treatment with regard to patient response 
status 
  
 
We recognize that with the limited sample size in this study that these 
rate estimates will only provide initial information about the rates. 
Inclusion at 2500mg/m2 dose of CPI-613 plus 
Bendamustine to capture additional safety and response 
at this dose level 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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Table of Contents 
SCHEMA .............................................................................................................. 3 
Primary Objectives ..................................................................................... 3 
Exploratory Objectives ................................................................................ 3 
1.0 
STUDY POPULATION AND RATIONALE ................................................ 6 
2.0 
STUDY OBJECTIVES ............................................................................... 7 
2.1 
Primary Objectives ........................................................................... 7 
2.2 
Exploratory Objectives ..................................................................... 7 
3.0 
PATIENT ELIGIBILITY CRITERIA ............................................................ 7 
3.1 
Inclusion Criteria .............................................................................. 7 
3.2 
  Exclusion Criteria ........................................................................... 8 
3.3 
 Inclusion of Women and Minorities ................................................. 9 
4.0 
REGISTRATION PROCEDURES ............................................................ 10 
5.0 
Study Outcomes and Study Measures ................................................. 11 
5.1 
Primary Outcome ......................................................................... 11 
5.2 
Secondary Outcomes .................................................................. 11 
6.0 
STUDY PROCEDURES ........................................................................... 12 
6.2.1 Pre-Study Screening Tests ............................................................ 15 
6.2.2 Safety Assessment ........................................................................ 15 
6.2.3 Anti-Tumor Efficacy Assessment ................................................... 15 
6.3 
Specifics of Tests Performed During the Study ............................. 23 
ECOG Performance Status ...................................................................... 23 
7.0 
STUDY DESIGN ...................................................................................... 25 
7.1 
Treatment Cycles ........................................................................... 25 
7.2 
Dosing Delay and Dose Modification ............................................. 26 
7.2.1 Dosage Adjustment for CPI-613 Related Toxicities ....................... 26 
7.2.2 Dosage Adjustment for Bendamustine Related Toxicities ............. 27 
7.4 
Duration of Treatment for Each Patient.......................................... 28 
8.0 
STUDY DRUGS ....................................................................................... 28 
8.1 
Bendamustine ................................................................................ 28 
8.2 
CPI-613 .......................................................................................... 28 
8.3 
 Concomitant Medications and Prophylactic Treatment ................. 33 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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9.0    Adverse Events List and Reporting Requirements ............................... 33 
9.1 
Adverse Event Characteristics ....................................................... 33 
9.2 
Adverse Event Characteristics of CPI-613 ..................................... 35 
9.3 
List of adverse events for Bendamustine ....................................... 35 
9.4 
Definition of DLT and DLT Evaluation Period ................................ 36 
9.5 
STRC SAE Reporting Requirements ............................................. 37 
9.6 
WFUHS IRB AE Reporting Requirements ..................................... 37 
10.0 
Statistical Considerations ..................................................................... 38 
10.1 
Analysis of Primary Objective ........................................................ 38 
10.2 
Exploratory Objectives ................................................................... 38 
10.4 
Power and Sample Size ................................................................. 39 
10.5 
Accrual Rate .................................................................................. 39 
10.6 
Interim Analysis Plan ..................................................................... 39 
11.0 
Data Management .................................................................................. 40 
12.0 
Multi-Institutional Monitoring Plan ....................................................... 40 
12.1.  SAE Reporting ............................................................................... 40 
12.2.  Registration Procedures ................................................................ 41 
12.3.  Study Monitoring ............................................................................ 41 
12.4. Required Documentation ............................................................... 41 
12.5 
Adherence to the Protocol ............................................................. 42 
12.6 
Amendments to the Protocol .......................................................... 42 
12.7 
Record Retention ........................................................................... 42 
12.8  Obligations of Investigators ............................................................ 42 
REFERENCES ................................................................................................... 44 
Appendix A – Subject Eligibility Checklist ..................................................... 47 
Appendix B – Protocol Registration Form ...................................................... 52 
Appendix C Safety and Toxicity Review Committee SOP . Error! Bookmark not 
defined. 
 
 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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1.0 STUDY POPULATION AND RATIONALE 
 
Salvage therapy followed by autologous hematopoietic cell transplant (AuHCT) for 
patients with relapsed or refractory non-hodgkin lymphoma (NHL) is effective only for 
a subset of patients (Hagberg et al. 2006).  For aggressive NHL (i.e., the high-grade B 
and T-cell NHL that often present as tumors in the lymph nodes), the outcome in 
relapsed or refractory disease is less optimistic. Relapsed or refractory T-cell non-
Hodgkin lymphomas have a poor outcome with median PFS and OS of only 3 months 
and 6 months respectively. 
 
CPI-613 is a lipoate derivative that targets the pyruvate dehydrogenase complex and 
has shown activity in hematologic malignancies (Zachar et al. 2011; Pardee et al. 
2013). CPI-613 selectively targets the altered form of mitochondrial energy 
metabolism in tumor cells, causing changes in mitochondrial enzyme activities and 
redox status which lead to apoptosis, necrosis and autophagy of tumor cells (Zachar 
et al. 2011). These activities of CPI-613 involve the catalytic and regulatory functions 
of the pyruvate dehydrogenase complex (PDC), its regulatory kinases (PDKs), and the 
α-ketoglutarate dehydrogenase complex (KGDHC) (Zachar et al. 2011). The anti-
tumor activity of CPI-613 in cell culture of different types of cancer cell lines, animal 
tumor models and clinical trials against diverse cancers have been documented, 
particularly against pancreatic cancer (Zachar et al. 2011; Pardee et al, 2011 & 2012; 
Lee et al. 2011 & 2012; Senzer et al. 2012). CPI-613 is also well-tolerated at doses up 
to 3,000 mg/m2, according to a Phase 1 trial in patients with solid tumors and another 
Phase 1 trial in patients with hematologic malignancies. 
 
Bendamustine has shown single agent activity in the relapsed lymphoma setting with 
response rates of approximately 50% for B and T cell NHL (Vacirca at al. 2013; 
Ghesquieres et al. 2013; Damaj et al. 2013).  
 
A phase I dose-escalation study of CPI-613 with bendamustine was recently 
completed for patients with relapsed or refractory T-cell lymphomas. In this study, 
subjects received the combination of CPI-613 and bendamustine with CPI-613 given 
at escalating doses starting at 2,000mg/m2 over 2 hrs on days 1-4. The study showed 
that this combination was well-tolerated and a maximum tolerated dose (MTD) was 
established at 2500 mg/m2 for CPI-613. However, it was noted that the 4-day dosing 
schedule for CPI-613 on that trial was cumbersome and a barrier to patient enrollment 
and treatment. We propose a pilot study using the MTD of 2500 mg/m2 for CPI-613 in 
combination with bendamustine given over an abbreviated schedule for 2 days every 
28 days in patients with relapsed/and/or refractory T-cell lymphoma. Correlative 
studies including single cell sequencing pre-and post-treatment will be performed for 
marker identification. Results from this pilot study will be used to describe the overall 
response rate of this regimen in the study population and form the basis for a future 
phase II clinical trial. 
 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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2.0 STUDY OBJECTIVES 
 
2.1 
Primary Objectives 
 
Pilot Study to evaluate the feasibility, safety and tolerability of a two day course per 
cycle of Bendamustine plus CPI-613 in patients with relapsed and refractory T cell non-
hodgkin lymphoma.     
 
2.2 
Exploratory Objectives 
 
To evaluate: 
A. Overall response rate (ORR) and disease control rate (DCR) derived from the 
Lugano classification (Cheson et al. 2014) for PTCL patients and Global 
Response Score for CTCL (MF/SS) patients (Olson et al. 2011). 
B. Duration of response (DOR) derived from the Lugano classification for PTCL 
patients and Global Response Score for CTCL (MF/SS) patients. 
C.  Progression-Free-Survival (PFS) derived from Lugano classification for PTCL 
patients and Global Response Score for CTCL (MF/SS) patients.   
D.  Overall Survival (OS). 
E. Single cell transcriptomics from PMBCs pre- and post-treatment; for correlative 
analyses of blood PBMC (and possibly excess pre-treatment tumor biopsy) cell 
population diversity and functional states to reveal potential mechanisms of drug 
treatment with regard to patient response status 
  
 
We recognize that with the limited sample size in this study that these rate estimates will 
only provide initial information about the rates.  
 
3.0 
PATIENT ELIGIBILITY CRITERIA 
 
3.1 Inclusion Criteria 
 
Patients must meet all of the following inclusion criteria before enrollment: 
 
1. Histologically or cytologically confirmed PTCL (all subtypes) or CTCL (mycosis 
fungoides/ sezary syndrome) as defined by 2016 World Health Organization 
(WHO) classification.   
2. For patients with PTCL:   
a. Patients must have relapsed/ refractory disease to one or more systemic 
therapies.   
b. Patients with CD30-positive lymphoma must have received, be ineligible 
for, or intolerant to brentuximab vedotin. 
c. Patients with limited prior exposure to Bendamustine (less than 2 full 
cycles or ≤ 480 mg/m2) may be included, based on PI discretion.   


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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d. Patients must have measurable disease (e.g., a tumor mass >1 cm or 
evidence of bone marrow involvement) 
3. For patients with CTCL, stage IB- IVB mycosis fungoides or Sezary syndrome 
are eligible 
a. Patients must have relapsed/ refractory disease to at least one previous 
systemic therapy. Psoralen plus ultraviolet light therapy (PUVA) is not 
considered to be a systemic therapy. 
4. Male and female patients 18 years of age and older  
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 
6. Expected survival >3 months 
7. 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.  
8. Fertile men must practice effective contraceptive methods during the study, 
unless documentation of infertility exists. 
9. At least 2 weeks must have elapsed from prior chemotherapy drugs (other than 
steroids) or radiation 
10. At least 6 weeks must have elapsed from prior autologous stem cell transplant 
and 12 weeks must have elapsed from prior allogeneic stem cell transplant. 
11. Laboratory values ≤2 weeks must be: 
a. Adequate hematological function (absolute neutrophil count [ANC] 
≥1,500/mm3, platelets ≥100,000/mm3). In subjects with known bone 
marrow involvement, ANC must be ≥ 1000/mm3 and platelets 
≥75,000/mm3 
b. Adequate hepatic function (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). 
c. Adequate renal function (serum creatinine 1.5 mg/dL or 133 µmol/L). 
12. No evidence of current infection. 
13. Mentally competent, ability to understand and willingness to sign the informed 
consent form. 
  
 
3.2   
Exclusion Criteria 
 
Patients with the following characteristics are excluded: 
 
1. Known cerebral metastases, central nervous system (CNS) or epidural tumor. 
2. History of prior malignancy and considered to be at greater than 30% risk of 
relapse 
3. Patients receiving 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 treatment with study drugs (steroids are allowed) 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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4. Patients with a history of allogeneic transplant must not have ≥ grade 3 graft-
versus-host disease (GVHD) or any clinically significant GVHD requiring 
systemic immunosuppression. 
5. Serious medical illness that would potentially increase patients’ risk for toxicity. 
6. Pregnant women, or women of child-bearing potential not using reliable means of 
contraception (because the teratogenic potential of CPI-613 is unknown). 
7. Lactating females.   
8. Fertile men unwilling to practice contraceptive methods during the study period. 
9. Any condition or abnormality which may, in the opinion of the investigator, 
compromise the safety of patients. 
10. Unwilling or unable to follow protocol requirements. 
11. Active heart disease including but not limited to symptomatic congestive heart 
failure, symptomatic coronary artery disease, symptomatic angina pectoris, 
symptomatic myocardial infarction or symptomatic congestive heart failure.  
12. Evidence of current infection. 
13. Patients with known HIV infection, hepatitis B, or hepatitis C with positive viral 
load. 
14. Patients who have received cancer immunotherapy of any type within the past 2 
weeks prior to initiation of CPI-613 treatment. 
 
3.3  
Inclusion of Women and Minorities 
 
Men and women of all races and ethnic groups who meet the above-described 
eligibility criteria are eligible to participate in this trial. 
 
 
The study consent form will also be provided in Spanish for Spanish-speaking 
participants. Based on WFBCCC population estimates, we expect approximately 
44.7% of participants to be women. Translating this to our sample size estimate of 
12, we plan to enroll at least 5 women. Similarly, we expect approximately 2.8% of 
study participants to be Hispanic/Latino (N=1). We plan to enroll at least 13% Black 
or African American (N=2), .5% American Indian/Alaska Native (N=0), .9% Asian 
(N=1). Should we not meet or exceed these estimates, the PI will engage the Office 
of Cancer Health Equity to discuss strategies to enhance recruitment in these target 
populations. 
 
 
 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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4.0 
REGISTRATION PROCEDURES 
 
All patients entered on any WFBCCC trial, whether treatment, companion, or cancer 
control trial, must be linked to the study in EPIC within 24 hours of Informed Consent. 
Patients must be registered prior to the initiation of treatment.   
 
You must perform the following steps in order to ensure prompt registration of your 
patient: 
 
1. Complete the Eligibility Checklist (Appendix A) 
2. Complete the Protocol Registration Form (Appendix B) 
3. Alert the Cancer Center 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
 
Protocol Registrar FAX
 
Protocol Registrar E-MAIL 
 
            
*Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday. 
 
4. 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, provide a printout of the 
results. Ensure that the most recent lab values are sent. 
 
To complete the registration process, the Registrar will:   
• assign a patient study number 
• assign the patient a dose 
• randomize the patient 
• other appropriate actions 
• register the patient on the study 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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5.0 
Study Outcomes and Study Measures 
5.1 
Primary Outcome 
 
5.1.1 The primary outcome measure will be feasibility, safety and tolerability of the 2-
day dosing regimen of CPI-613 in combination with bendamustine.  Feasibility 
will be defined as 75% of patients being successfully able to complete 80% of 
their therapy regimens. Toxicity data will be collected on all patients who receive 
at least one dose of treatment on the study. 
5.2 
Secondary Outcomes 
 
The following secondary outcomes will be collected and reported for all patients who 
receive at least one dose of the study medication. 
 
5.2.1 ORR defined as the proportion of patients who achieve a best overall response 
CR or PR during or following study treatment according to the Lugano 
classification (Cheson et al. 2014) for PTCL patients and Global Response Score 
for CTCL (MF/SS) patients (Olson et al. 2011) 
5.2.2 DCR defined as the proportion of patients who achieve a best overall response 
CR, PR, or stable disease (SD). Best overall response of SD must have met the 
response SD criteria at least once ≥12 weeks after start of study treatment. 
5.2.3 DOR will be defined for responders (patients with a best overall response of CR 
or PR). It is the time from the date of the first documented CR or PR until the 
date of the first date of progressive disease, or death due to any cause, 
whichever occurs first. If a patient has not progressed or died by the analysis 
cutoff date, DOR will be censored at the time of the last adequate tumor 
assessment on or before the cutoff date 
5.2.4 PFS defined as the time from the start of study treatment until the first date of 
progressive disease, or death due to any cause, whichever occurs first. If a 
patient has not progressed or died by the analysis cutoff date, PFS will be 
censored at the time of the last adequate tumor assessment on or before the 
cutoff date. 
5.2.5 OS measured from the start of study treatment until death due to any cause. If a 
patient is not known to have died at the date of the analysis cut-off, OS will be 
censored at the last date that: 
5.2.5.1 
Patient is documented to be alive. 
5.2.5.2 
At the time of single cell sequencing. 
 
 
 
 
 
 
 
 
 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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6.0  
STUDY PROCEDURES  
 
Table 6-1 (below) provides an overview of the study procedures for Cycles 1-6. Specifics are described in 
subsequent sections. 
 
Procedures and Assessments 
Pre-
Study 
Screena 
Cycles 1-6 
Follow-Up 
Each cycle is 28 days long 
D1  
D2 
D3 
D4 
Informed consent 
 
 
 
 
 
 
Medical history, medications, evaluation of 
symptoms, physical exam  
 
 b 
 
 
 
 
ECOG Performance Status 
 
 b 
 
 
 
 
Pregnancy test for women of child-bearing 
potential 
 
 
 
 
 
 
Vital signs 
 
 c 
 c 
 
 
 
Clinical chemistry  
 
 d 
  
 
 
 
LDH 
 
 d 
 
 
 
 
CBC with differential 
 
 d 
 
 
 
 
CPI-613 (2500 mg/m2) 
 
 
 
 
 
 
Bendamustine (90 mg/m2) d 
 
 
 
 
 
 
Neulasta 
 
 
 
 f 
 f 
 
Research blood samples 
 
  g 
 g 
 
 
 g 
Adverse Event Evaluation 
 
 
 
 
 
 
Phone contact/EMR Review g 
 
 
 
 
 
 g 
For CTCL (MF/SS) patients only 
Dermatology assessment (mSWAT) 
 
Repeat after cycles 3 and 6   
 
Peripheral blood flow cytometry for Sezary cells 
 
Repeat after cycles 3 and 6 only if 
positive at baseline 
 
PET/CT scan 
 
Repeat after cycles 3 and 6 only if 
positive at baseline 
 
For PTCL patients only 
Bone marrow biopsy 
 
Repeat after cycles 3 and 6 for those 
with marrow involvement at baseline 
that cannot be assessed through 
imaging 
 
PET/CT scan 
i 
Repeat after cycles 3 and 6 
 
Phone contact/EMR Review  
 
 
 
 
 
 h 
MF= Mycosis Fungoides, SS= Sezary Syndrome 
a Pre-study screening tests, which are also enrollment evaluations, must be performed according the following time 
frames prior to treatment start: 
Within 8 weeks:  anti-tumor efficacy assessment.  (Note:  If assessment within this timeframe has already been 
performed prior to participating in this trial, the results from this assessment can be used). Patients should not have 
received any additional chemotherapy except steroids after screening PET/CT.  If additional chemotherapy has 
been given, then PET/CT should be repeated prior to enrollment to the study. 
Within 2 weeks:  medical history, physical exam, vital signs, height, weight, ECOG, evaluation of symptoms and 
medications, clinical chemistry, CBC with differential, LDH. 
Within 1 week:  pregnancy test for women of child-bearing potential. 
b Performed within 5 days prior to each cycle 
c Vital signs are performed immediately after CPI-613 administration in cycle 1  
d These tests are performed within 24 hrs prior to dosing of day 1 of CPI-613 with each cycle.   
e   All study assessments will be the same for patients with limited exposure to Bendamustine.  All patients will receive 
baseline scans and have first efficacy scan after 3 full study cycles of CPI- 613 and Bendamustine. Patients will not 
receive more than 6 total cycles of Bendamustine.  Patients with limited prior exposure to Bendamustine (less than 2 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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cycles ≤480 mg/m2) will receive a total of 6 cycles of Bendamustine both on and off study.  If a patient has had 1 cycle 
(2 doses) of Bendamustine prior to enrolling on this study, the Bendamustine will be held in Cycle 6.  If the patient 
received 2 cycles of Bendamustine prior to enrolling on this study, the Bendamustine will be held in Cycles 5 and 6. 
f  Neulasta should be given on day 3 or day 4 after Bendamustine, per institutional guidelines.   On Body Injector (OBI) is 
allowed. 
g Research blood samples are for possible testing of biomarkers, predictors of biological responses, toxicity, genotype vs. 
drug response relationship, etc. They are to be obtained prior to day 1 and day 2 CPI-613 dosing for each cycle.and at 
disease progression or study termination, whichever occurs earlier. 
h Survival and information related to cancer treatment received after the study and disease status is monitored every 3 
months via telephone contact or EMR review after treatment termination. Medical record review will coincide with 
telephone call to obtain information regarding evidence and of relapse (as documented on CT, PET, biopsy, etc). 
   
 
 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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Table 6-2 (below) provides an overview of the study procedures for maintenance (cycles 7-20).  Specifics 
are described in subsequent sections.
 
 
 
 
Procedures and Assessments 
Cycles 7-20 
Follow up 
(Every 3 
months) 
Each cycle is 28 days long 
 
D1 
D2 
D3 
D4 
 
Medical history, medications, evaluation of 
symptoms 
 a 
 
 
 
 
ECOG Performance Status 
  
 
 
 
 
Vital signs 
  
  
 
 
 
Clinical chemistry 
 b  
 b 
 
 
 
LDH    
  
 
 
 
 
CBC with differential 
 
 
 
 
 
Pregnancy test for women of child-bearing 
potential 
 
 
 
 
 
CPI-613 (2500 mg/m2 dose) 
 
 
 
 
 
For CTCL (MF/SS) patients only 
Dermatology assessment (mSWAT) 
Every 3 months for year 1 of maintenance, then every 6 months 
AND at progression. 
For PTCT patients only  
CT chest/ abdomen/ pelvis 
Every 3 months for year 1 of maintenance, then every 6 months 
AND at progression. 
Bone marrow biopsy 
Only if bone marrow is the primary site of measurable disease at 
baseline and cannot be evaluated using imaging- repeat every 3 
months for year 1 of maintenance, then every 6 months AND at 
progression. 
Adverse Event Evaluation 
  
 
 
 
 
Phone contact/EMR Review c 
 
 
 
 
 c 
 
a  Medical history, vital signs, ECOG performance status, evaluation of symptoms, medications: assessed within 5 days prior to 
each cycle. 
b  Creatinine and BUN to be checked within 24 hours of CPI-613. 
c  Survival and information related to cancer treatment received after the study and disease status is monitored every 3 months 
via telephone contact or EMR review after treatment termination. Medical record review will also be performed to coincide with 
the telephone call to obtain information regarding evidence and of relapse (as documented on CT, PET, biopsy, etc).  


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Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
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6.2 
Intervention Administration 
6.2.1 Pre-Study Screening Tests 
 
Pre-study screening tests must be performed according the following time frames 
prior to treatment start: 
 
Within 4 weeks:  tumor assessments.  (Note:  If assessment within this 
timeframe has already been performed prior to participating in this trial, the 
results from this assessment can be used.) 
 
Within 2 weeks:  medical history, physical exam, vital signs, height, weight, 
ECOG, evaluation of symptoms and medications, clinical chemistry, CBC with 
differential, LDH. 
 
Within 1 week:  pregnancy test for women of child-bearing potential. 
 
 
6.2.2 Safety Assessment 
 
The safety of CPI-613 and Bendamustine will be assessed based on: 
- 
evaluation of symptoms 
- 
vital signs 
- 
ECOG performance status and survival 
- 
clinical chemistry, CBC with differential 
 
The specifics of the safety tests are described in Section 6.3.  All safety 
assessment tests are performed during screening (performed within 2 weeks 
prior to treatment with CPI-613). Associated with Cycle 1, clinical chemistry, 
hematology are performed within 24 hours prior to dosing CPI-613, and only 
creatinine results are needed before dosing CPI-613. Vital signs are performed 
immediately after CPI-613 administration and re-examined only if clinically 
indicated.  Creatinine and BUN should be checked within 24 hours of every dose 
of CPI-613.  Beyond Cycle 1, physical exam and vital signs, ECOG performance 
status, evaluation of symptoms and medications will be performed within 5 days 
prior to each cycle.  Clinical chemistry, hematology, will be assessed on Day 1 of 
each cycle. 
 
6.2.3 Anti-Tumor Efficacy Assessment 
 
Response assessment for CTCL (MF/SS) patients: 
Skin lesions and erythema will be evaluated using the Modified Severity 
Weighted Assessment Tool (mSWAT). 
Modified Severity Weighted Assessment (mSWAT) Tool 
An mSWAT score is derived by measuring each lesion as a percentage of total 
body surface area (%TBSA) and multiplying it by a severity-weighting factor (1 = 


Comprehensive Cancer Center of Wake Forest University 
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patch, 2 = plaque, 4 = tumor). All individual numbers are then added to produce a 
total score. 
Body region (%BSA)  
Patch*  
Plaque*  
Tumor*  
Head (7%)  
 
 
 
Neck (2%)  
 
 
 
Anterior trunk (13%)  
 
 
 
Arms (8%)  
 
 
 
Forearms (6%)  
 
 
 
Hands (5%)  
 
 
 
Posterior trunk (13%)  
 
 
 
Buttocks (5%)  
 
 
 
Thighs (19%)  
 
 
 
Legs (14%)  
 
 
 
Feet (7%)  
 
 
 
Groin (1%)  
 
 
 
Subtotal of lesion BSA  
 
 
 
Weighting factor  
x1  
x2  
x4  
Subtotal lesion BSA x weighting 
factor  
 
 
 
mSWAT score = summation of each column line above   
 
Patch = any size lesion without induration or significant elevation above the surrounding uninvolved skin: poikiloderma 
may be present.  
Plaque = any size lesion that is elevated or indurated; crusting, ulceration, or poikiloderma may be present.  
Tumor = any solid or nodular lesion ≥1 cm in diameter with evidence of deep infiltration in the skin and/or vertical growth.  
Response Criteria for skin, as assessed by mSWAT scores 
Response  Definition  
CR  
100% clearance of skin lesions  
PR  
50% to 99% clearance of skin disease from baseline without new tumors (T3) in 
patients with T1, T2, or T4 only skin disease  
SD  
<25% increase to <50% clearance in skin disease from baseline without new 
tumors (T3) in patients with T1, T2, or T4 only skin disease  
PDc  
(1) ≥25% increase in skin disease from baseline or  
(2) New tumors (T3) in patients with T1, T2, or T4 only skin disease or  
(3) Loss of response: in those with CR or PR, increase of skin score of greater 
than the sum of nadir plus 50% baseline score  
Relapsea  
Any disease recurrence in those with CR  
a Relapse should be defined as loss of response (as defined for PD) in those with CR, ie, increase of skin score of greater 
than the sum of nadir plus 50% baseline score 
Response Criteria in blood 
Peripheral blood flow cytometry for CD4+CD7- and CD4+CD26- cells will be 
used to assess response in blood. 


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CR  
B0  
PR  
>50% decrease in quantitative measurements of blood tumor 
burden from baseline in those with high tumor burden at baseline 
(B2)  
SD  
Fails to attain criteria for CR, PR or PD  
PD  
(1) 
B0 to B2 or  
(2) 
>50% increase from baseline and at least 5,000 neoplastic 
cells/μL or  
(3) 
Loss of response: in those with PR who were originally B2 at 
baseline, >50% increase from nadir and at least 5,000 neoplastic 
cells/μL  
Relapse  
Increase of neoplastic blood lymphocytes to ≥ B1 in those with 
CR  
CR=complete response; PD=progressive disease; PR=partial response; 
SD=stable disease.  
 
Response Criteria in lymph nodes and viscera 
Visceral and nodal disease in CTCL will be evaluated using PET/CT scan and 
according to the 2014 Lugano Classification as described in Table 6.2.3-2. 
 
Global Overall Response Criteria 
 
The International Society on Cutaneous Lymphomas criteria (Olson et al. 2011) 
will be used to assess response of cutaneous lymphoma patients.  CR, NI, PR, 
PD and SD are defined as shown in Table 6.2.3-1. 
 
 
 
 
 
 
 
 
 


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Table 6.2.3-1 
 
 
 
Response assessment for PTCL patients: 
  
The Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2014) 
will be used to stage the disease. Complete response,(CR), partial response 
(PR),stable disease (SD), and progressive disease (PD) are defined as shown in 
Table 6.2.3-2. Overall response rate (ORR) (the combined rates of CR and PR) 
and disease control rate (DCR) (the combined rates of CR, PR and SD) will also 
be calculated. 
 
 
 


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Table 6.2.3-2:  (Cheson et al. 2014)1 
 
Revised Criteria for Response Assessment adapted from Cheson et al. 2014 
Response and Site 
PET-CT based Response 
CT-Based Response 
Complete 
Complete metabolic response 
Complete radiologic 
response (all of the 
following) 
Lymph nodes and 
extralymphatic sites 
Score 1, 2, or 3_ with or without a 
residual mass on 5PS† 
It is recognized that in Waldeyer’s ring or 
extranodal sites with high physiologic 
uptake or with activation within spleen or 
marrow (eg, with chemotherapy or 
myeloid colony-stimulating factors), 
uptake may be greater than normal 
mediastinum and/or liver. In this 
circumstance, complete metabolic 
response may be inferred if uptake at 
sites of initial involvement is no greater 
than surrounding normal tissue even if 
the tissue has high physiologic uptake. 
Target nodes/nodal masses 
must regress to < 1.5 cm in 
LDi 
No extralymphatic sites of 
disease 
Nonmeasured 
lesion 
Not applicable 
Absent 
Organ enlargement 
Not applicable 
Regress to Normal 
New lesions 
None 
None 
Bone marrow 
No evidence of FDG-avid disease in 
marrow 
Normal by morphology; if 
indeterminate, IHC negative 
Partial 
Partial metabolic response 
Partial remission (all of the 
following) 
Lymph nodes and 
extralymphatic sites 
 
 
 
 
 
Score 4 or 5† with reduced uptake 
compared with baseline and residual 
mass(es) of any size 
At interim, these findings suggest 
responding disease 
At end of treatment, these findings 
indicate residual disease 
 
>50% decrease in SPD of up 
to 6 target measurable nodes 
and extranodal sites 
When a lesion is too small to 
measure on CT, assign 5 mm 
X 5mm as the default value 
When no longer visible, 0 x 0 
mm 
For a node >5 mm X 5mm, 


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but smaller than normal, use 
actual measurement for 
calculation 
 
Nonmeasured 
lesions 
 
Not applicable 
 
Absent/normal, regressed, 
but no increase 
Spleen must have regressed 
by > 50% in length beyond 
normal 
Organ enlargement 
Not applicable 
New lesions 
None 
None 
Bone marrow 
Residual uptake higher than uptake in 
normal marrow but reduced compared 
with baseline (diffuse uptake compatible 
with reactive changes from 
chemotherapy allowed). If there are 
persistent focal changes in the marrow in 
the context of a nodal response, 
consideration should be given to further 
evaluation with MRI or biopsy or an 
interval scan 
Not Applicable 
No response or 
stable disease 
Target nodes/nodal 
masses, 
Extranodal lesions 
No metabolic response 
Score 4 or 5 with no significant change in 
FDG uptake from baseline at interim or 
end of treatment 
 
Stable Disease 
< 50% decrease from 
baseline in SPD of up to 6 
dominant, measurable nodes 
and extranodal sites; no 
criteria for progressive 
disease are met 
Non measured 
lesions 
Not applicable 
No increase consistent with 
progression 
Organ enlargement 
Not applicable 
No increase consistent with 
progression 
New Lesions 
None 
None 
Bone Marrow 
No change from baseline 
Not applicable 
Progressive 
disease 
Progressive metabolic disease 
Progressive disease 
requires at least 1 of the 
following 
Individual target 
nodes/nodal 
Score 4 or 5 with an increase in intensity 
of uptake from baseline and/or 
PPD progression: 


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masses 
Extranodal lesions 
New FDG-avid foci consistent with 
lymphoma at interim or end-of-treatment 
assessment 
 
An individual node/lesion 
must be abnormal with  
LDi >1.5 cm and Increase by  
>50% from PPD nadir and 
An increase in LDi or SDi 
from nadir 
0.5 cm for lesions  < 2 cm 
1.0 cm for lesions > 2 cm 
In the setting of 
splenomegaly, the splenic 
length must 
increase by >50% of the 
extent of its prior increase 
beyond baseline (eg, a 15-cm 
spleen must increase to > 16 
cm). If no prior splenomegaly, 
must increase by at least 2 
cm from baseline 
New or recurrent 
splenomegaly 
Non measured 
lesions 
None 
New or clear progression of 
preexisting non measured 
lesions 
New lesions 
New FDG-avid foci consistent with 
lymphoma rather than another etiology 
(eg, infection, inflammation). If uncertain 
regarding etiology of new lesions, biopsy 
or interval scan may be considered 
Regrowth of previously 
resolved lesions 
A new node >1.5 cm in any 
axis 
A new extranodal site >1.0 
cm in any axis; if < 1.0 cm in 
any axis, its presence must 
be unequivocal and must be 
attributable to lymphoma 
Assessable disease of any 
size unequivocally 
attributable to lymphoma 
Bone marrow 
New or recurrent FDG-avid foci 
New or recurrent involvement 
Abbreviations: 5PS, 5-point scale; CT, computed tomography; FDG, fluorodeoxyglucose; IHC, 
immunohistochemistry; LDi, longest transverse diameter of a lesion;MRI, magnetic resonance 
imaging; PET, positron emission tomography; PPD, cross product of the LDi and perpendicular 


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diameter; SDi, shortest axis perpendicularto the LDi; SPD, sum of the product of the 
perpendicular diameters for multiple lesions. 
*A score of 3 in many patients indicates a good prognosis with standard treatment, especially if 
at the time of an interim scan. However, in trials involving PET where de-escalation is 
investigated, it may be preferable to consider a score of 3 as inadequate response (to avoid 
undertreatment). Measured dominant lesions: Up to six of the largest dominant nodes, nodal 
masses, and extranodal lesions selected to be clearly measurable in two diameters. Nodes 
should preferably be from disparate regions of the body and should include, where applicable, 
mediastinal and retroperitoneal areas. Non-nodal lesions include those in solid organs (eg, liver, 
spleen, kidneys, lungs), GI involvement, cutaneous lesions, or those noted on palpation. 
Nonmeasured lesions: Any disease not selected as measured, dominant disease and truly 
assessable disease should be considered not measured. These sites include any nodes, nodal 
masses, and extranodal sites not selected as dominant or measurable or that do not meet the 
requirements for measurability but are still considered abnormal, as well as truly assessable 
disease, which is any site of suspected disease that would be difficult to follow quantitatively 
with measurement, including pleural effusions, ascites, bone lesions, leptomeningeal disease, 
abdominal masses, and other lesions that cannot be confirmed and followed by imaging. In 
Waldeyer’s ring or in extranodal sites (eg, GI tract, liver, bone marrow), FDG uptake may be 
greater than in the mediastinum with complete metabolic response, but should be no higher 
than surrounding normal physiologic uptake (eg, with marrow activation as a result of 
chemotherapy or myeloid growth factors). 
†PET 5PS: 1, no uptake above background; 2, uptake < mediastinum; 3, uptake > mediastinum 
but < liver; 4, uptake moderately > liver; 5, uptake markedly higher than liver and/or new 
lesions; X, new areas of uptake unlikely to be related to lymphoma. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Comprehensive Cancer Center of Wake Forest University 
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Survival:  Survival (and information related to cancer treatment received after the 
study and disease status) will be obtained every 3 months via telephone contact 
after treatment termination. Medical record review will also be performed to 
coincide with the telephone call to obtain information regarding evidence of relapse 
(as documented on CT, PET, biopsy, etc). 
 
  
6.3 
Specifics of Tests Performed During the Study 
 
Described below are the specifics of the tests performed in this study. 
 
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 6.3.1-1 (below). The higher the 
ECOG score, the worse the prognosis. 
 
Table 6.3.1-1:  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 
 
Clinical Chemistry, Hematology 
 
Clinical chemistry includes: 
 
glucose 
BUN 
creatinine 
AST/serum glutamic-oxaloacetic transaminase (SGOT) 
total protein 
ALT/serum glutamic-pyruvic transaminase (SGPT) 
albumin 
alkaline phosphatase (ALP) 
Na+ 
CO2 
K+ 
total bilirubin 
Cl- 
 
Mg 
 
Ca+2 
 
 
 
 
CBC with differential includes: 
 


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white blood count 
hemoglobin 
differential count 
hematocrit 
platelet count 
 
 
 
Research blood and optional blood and tissue samples 
  
Research blood samples will be collected pre-treatment on day 1 and day 2 of each 
cycle prior to CPI-613 dosing, and at disease progression or study termination, 
whichever occurs earlier.  These samples will be 6 mL of whole blood collected into 
EDTA tubes for single-cell sequencing of peripheral blood mononuclear cells to 
determine biomarkers and predictors of biological responses and toxicity. Single cell 
transcriptomics status pre- and post-treatment; for correlative analyses of blood PBMC 
(and excess pre-treatment tumor biopsy) cell population diversity and functional states 
to reveal potential mechanisms of drug treatment with regard to patient response status.  
Additionally, 6 mL of serum will be obtained and “banked” for possible testing of 
biomarkers in future. 
 
 
Whole Blood Samples 
•   Samples (6 mL each) will be collected into a lavender top K2-EDTA 13x100/6ml 
vacutainer tube 
•   Invert the tube a minimum of 8 times to mix the anticoagulant (EDTA) 
completely, then keep sample at room temperature. 
•   Do not centrifuge, refrigerate or freeze sample. 
•   Label sample and store at room temperature prior to pick-up by TTPSR 
personnel (Libby McWilliams). 
All optional samples and specimens should be delivered to: 
Dr. Wei Zhang (c/o Liz Forbes) (336) 713-7063 
Wake Forest Baptist Health 
 
 
 
Dept of Cancer Biology: NRC322 
 
 
Serum Sample 
 
•   Collect blood (6 mL) in serum separator tube (6.0 mL, with Polymer gel/Silica 
activator). 
•   Gently invert the tube 8-10 times, and let tube sit in an upright position for at 
least 15-30 minutes at room temperature to allow the blood to clot. 


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•   Within 2 hours from time of collection, spin the tubes at 1000x g using a 
standard room temperature centrifuge for 10-15 minutes. 
• After centrifugation, pipette 1.0 mL aliquots of plasma into each of the 1.8 mL-
size polypropylene screw-capped cryovials. Expect to collect between 3-5 
cryovials each containing 1.0 mL aliquots of plasma. 
• Label the aliquots. 
• Quickly freeze the aliquots by placing them either on dry ice or in a –70°C 
freezer. Store the samples at –70°C or colder. 
 
This sample will be stored in Dr. Kucera’s lab for future studies.  Please notify Libby 
McWilliams, the Tumor Procurement Officer, at 
 when this sample is 
drawn. 
 
7.0 
STUDY DESIGN  
 
7.1 
Treatment Cycles 
 
Each treatment cycle is 4 weeks (see Table 7-1, below). CPI-613 at 2500 mg/m2 is 
infused intravenously (IV) via a central catheter over 2 hrs on Days 1and 2. 
Bendamustine at 90 mg/m2 is infused IV over 10 minutes on Days 1 and 2 of each 
treatment cycle, given immediately after CPI-613 administration. Each patient will be 
treated with as many as 6 cycles, if clinically indicated. 
 
Patients with limited prior exposure to Bendamustine (less than 2 cycles or ≤ 480 
mg/m2) will receive a total of 6 cycles of Bendamustine both on and off study.  If a 
patient has had 1 cycle (2 doses) of Bendamustine prior to enrolling on this study, the 
Bendamustine will be held in Cycle 6.  If the patient received 2 cycles of Bendamustine 
prior to enrolling on this study, the Bendamustine will be held in Cycles 5 and 6. 
 
Patients who have a continued response to 6 cycles of treatment with bendamustine 
and CPI-613 may continue maintenance treatment with CPI-613 alone given on days 1 
and 2 every 28 days until disease progression or unacceptable toxicity.   
 
Table 7.1:  Timing of CPI-613 and Bendamustine in Each 4-Week Treatment Cycle 
 
Day 1 
Day 2 
Week 1 
CPI-613 
Bendamustine 
CPI-613 
Bendamustine 
Week 2 
 
 
Week 3 
 
 
Week 4  
 
 
 
 


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7.2 
Dosing Delay and Dose Modification 
 
7.2.1 Dosage Adjustment for CPI-613 Related Toxicities 
 
The occurrence of Grade 1 toxicity does not generally require dose 
modification for subsequent doses for that patient.  However, if Grade 2 
non-hematologic toxicity (which includes infectious toxicity) develops and 
is attributed to at least probably related to CPI-613, treatment 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% of the dose at which such Grade 2 toxicity occurs.  If Grade 3 or 4 
non-hematologic toxicity (which includes infectious toxicity) develops, 
dosing 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 for a patient who has had 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 to 50% of the 
dose at which such Grade 3 or 4 toxicity occur. If the reduced dose of CPI-
613 results in no toxicity, patients may be dose escalated to the prior dose 
at the discretion of the treating physician. 
 
For adverse events unrelated to serum creatinine elevation or reduction in 
renal function but are possibly 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 
nausea) probably related to CPI-613 develops, 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% of the dose at which such Grade 2 toxicity occurs. Grade 
2 nausea does not require withholding treatment or dose reduction. If 
Grade 3 or 4 toxicity probably 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 to 50% of the dose at which such Grade 3 or 4 toxicity occurs. 
 
For adverse events related to creatinine elevation, reduction in renal 
function or mitochondrial inhibition syndrome that are possibly 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. 
 


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Furthermore, if the toxicity possibly 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, if necessary: 
 
- 
compliance of the study sites and investigators to the study protocol 
- 
evaluation of the appropriateness of the procedures for monitoring 
renal function 
 
Special note for Mitochondrial Inhibition Syndrome. 
A. 
This is a constellation of symptoms that may include high fevers, 
hypotension, lethargy, pancytopenia, altered mental status and 
generalized weakness and lactic acidosis. If this occurs or is suspected 
the recommended treatment until symptoms resolve is: 
a. 
IV L-carnitine 50mg/kg/day in divided doses every 4 hours (i.e. 
8.3mg/kg every 4 hours)  
b. 
Folic acid 1mg daily 
c. 
Thiamine 100mg daily 
 
7.2.2 Dosage Adjustment for Bendamustine Related Toxicities 
 
Administration of Bendamustine should be withheld in the event of ≥Grade 
4 hematologic toxicity or clinically significant Grade 2 non-hematologic 
toxicity.  Once non-hematologic toxicity has recovered to Grade 1, 
Bendamustine can be re-initiated at the discretion of the treating 
physician.  For patients experiencing hematologic toxicity, Bendamustine 
may be re-initiated at the discretion of the treating physician once counts 
have improved (Absolute Neutrophil Count [ANC] 1 x 109/L, platelets 75 
x 109/L).  However, if the patient has low blood counts related to 
underlying disease (i.e. bone marrow involvement or splenic 
sequestration), the Bendamustine can be re-initiated at the discretion of 
the treatment physician prior to blood count improvement.  At that point, 
dose reduction as described below should be considered: 
 
-Hematologic toxicity Grade 4 toxicity:  reduce the dose by 30%. 
-Non-hematologic toxicity for clinically significant ≥Grade 3 toxicity:  
reduce the dose by 30%. 
 
Dose re-escalation in subsequent cycles may be considered at the 
discretion of the treating physician. 
 
 


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7.4 
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 receive an allogeneic stem cell transplant 
- 
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. 
 
8.0 
STUDY DRUGS 
 
8.1 
Bendamustine 
 
Bendamustine at 90 mg/m2 is infused by IV over 10 minutes on Days 1 and 2 of each 
treatment cycle. Bendamustine is given immediately after CPI-613 administration. 
 
8.2 
CPI-613 
 
CPI-613 is to be given as 2-hr IV infusion via a central venous catheter. The starting 
dose of CPI-613 will be 2500 mg/m2 which was determined to be the MTD in the 
previous phase I clinical trial. 
 
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-


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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613 is a clear and colorless solution that is free of any particulate matter.   
 
Handling of CPI-613 
 
CPI-613 is an investigational drug and the 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 excessive light before administration to patients. 
 
Storage of CPI-613 
 
CPI-613 should be stored under refrigeration, at 2˚-8˚C (36˚-46˚F), except when being 
prepared for administration. 
 
Administration Route 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. 
 
CPI-613 can cause leaching of Diethylhexyl Phthalate (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:  Kendall Monoject syringes, all mono-ject 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 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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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  Wolf 
GMBH) syringes 
• 
Becton Dickinson syringes 
• 
Terumo syringes 
• 
Monoject syringes 
• 
Glass syringes 
 
Reconstitution Process and Administration of CPI-613 
 
CPI-613 must be diluted from 50 mg/mL to 12.5 mg/mL with 5% Dextrose Water 
(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 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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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.   
 
Request for CPI-613 
 
CPI-613 must be requested from Rafael 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.  Rafael policy 
requires that CPI-613 be shipped directly to the institution where the patient is to be 
treated.  Rafael does not permit the transfer of CPI-613 between institutions (unless 
with prior written approval from Rafael).  Requests must be submitted to Rafael by 
email to
 
 
The following information must be provided in the request of CPI-613 from Rafael: 
 
- 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 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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- Amount (# vials) requested 
- Date of request 
- Date shipment expected 
- Study Protocol (title and protocol#) for which the requested CPI-613 is to be used 
 
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 Rafael 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 Rafael, or its designee, 
during periodic monitoring visits. 
 
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. 
 
-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. 
 
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 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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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. 
 
8.3 
 Concomitant Medications and Prophylactic Treatment 
 
Patients cannot receive any standard or investigational treatment (except CPI-613 and 
Bendamustine) for their cancer, or any other investigational drugs for any indications, 
while on this study. All concomitant medications (including trade and generic names, 
dosage and dosing schedule) must be recorded. Concomitant use of anti-emetics is 
permitted for patients with disease-related nausea.  If study subjects experience metallic 
taste/taste alteration during CPI-613 infusion, which can sometimes lead to nausea and 
vomiting, patients can take mint candy to minimize the adverse effect.  The use of mint 
candy, and its effectiveness in minimizing metallic taste/taste alteration, should also be 
recorded. 
 
Special note for Mitochondrial Inhibition Syndrome. 
*This is a constellation of symptoms that may include high fevers, hypotension, lethargy, 
pancytopenia, altered mental status and generalized weakness and lactic acidosis. If 
this occurs or is suspected the recommended treatment until symptoms resolve is: 
a. 
IV L-carnitine 50mg/kg/day in divided doses every 4 hours (i.e. 8.3mg/kg every 4 
hours)  
b. 
Folic acid 1mg daily 
c. 
Thiamine 100mg daily 
 
For Bendamustine, prophylactic treatment for drug-related symptoms can be given 
according to Package Inserts of the study drugs and clinical practice.  Supportive 
treatment may include anti-emetic, anti-diarrhea, anti-pyretic, anti-allergic, anti-
hypertensive, analgesics, antibiotics, allopurinol, and others such as blood products and 
bone marrow growth factors.  Patients may use erythropoietin for chronic anemia.  The 
investigator may utilize erythropoietic factors, or blood or platelet transfusions at their 
discretion. 
9.0    Adverse Events List and Reporting Requirements 
9.1 
Adverse Event Characteristics 
 
• 
CTCAE term (AE description) and grade:  The CTEP Active Version of the NCI 
Common Terminology Criteria for Adverse Events (CTCAE 5.0) 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 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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appropriate treatment areas should have access to a copy of the CTEP Active 
Version of CTCAE. 
• 
 
• ‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ for expedited reporting 
purposes only.   
• 
 
• 
Attribution of the AE: 
• 
Definite – The AE is clearly related to CPI-613. 
• 
Probable – The AE is likely related to CPI-613. 
• 
Possible – The AE may be related to CPI-613. 
• 
Unlikely – The AE is doubtfully related to CPI-613. 
• 
Unrelated – The AE is clearly NOT related to CPI-613. 
 
The Wake Integrated Solution for Enterprise Research (WISER) database will be used 
for this study to monitor dose level accrual and toxicity-related data. Built-in features 
within WISER auto-suspend protocol accrual when dose level target accrual is reached 
or when DLTs reach the protocol-defined limit. Suspension is only lifted following PI 
review of all adverse events.  All grade 3, 4, 5 adverse events should be reported on 
flowsheets and in WISER regardless of whether they are on the list in 8.2 and 8.3. 
 
All SAEs which are Serious, Possibly Related and Unexpected are required to be 
reported to Rafael Pharmaceuticals via the provided SAE Reporting Form.  All 
completed forms must be sent to Claudia Moore at Rafael.  Rafael will submit any 
applicable SAEs to the FDA.   
 
SAE reports must be submitted to Rafael by email to:
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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9.2 
Adverse Event Characteristics of CPI-613 
 
Possibly related:  
• Alkaline phosphatase  
• Anorexia  
• ALT (SGPT) 
• AST (SGOT) 
• Bilirubin (hyperbilirubinemia) 
• Calcium (hypercalcemia, hypocalcemia) 
• *Diarrhea 
• Flushing 
• Hemoglobin (anemia) 
• *Injection site Reaction 
• Leukocytes  
• Lymphopenia 
• *Nausea 
• Neutrophils (neutropenia) 
• Platelets (thrombocytopenia) 
• Potassium 
• Sodium 
• *Vomiting 
• Hematuria 
 
Probably related: 
• *Creatinine 
 
Asterisk (*) denotes expected Adverse Events. 
 
9.3 
List of adverse events for Bendamustine 
 
Definitely related:  
• Myelosuppression. 
• Infections (pneumonia, sepsis, septic shock, and death). 
• Anaphylaxis and Infusion Reactions (symptoms include fever, 
chills, pruritus, rash and in rare instances severe anaphylactic 
and anaphylactoid reactions). 
• Tumor Lysis Syndrome. 
• Skin Reactions (rash, toxic skin reactions and bullous 
exanthema). 
• Extravasation injury (erythema, marked swelling, and pain). 
 
Probably related: 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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Other malignancies (pre-malignant and malignant diseases including myelodysplastic 
syndrome, myeloproliferative disorders, acute myeloid leukemia and bronchial carcinoma) 
 
Possibly related:   
• 
Immune/autoimmune events (uveitis, optic neuritis, pleuritis,serum 
sickness with polyarticular arthritis, and vasculitis with rash) 
• Agitation 
• Anorexia 
• Arthritis 
• Conjunctivitis 
• Depression 
• Dyspepsia 
• Edema 
• Hyperkinesia 
• Hypertonia 
• Hypesthesia 
• Hypoglycemia 
• Injection site pain 
• Insomnia 
• Lacrimation disorder 
• Malaise 
• Nervousness 
• Neuritis 
• Neuropathy 
• Paresthesia 
• Somnolence 
• Vertigo 
• Weight decrease 
 
9.4 
Definition of DLT and DLT Evaluation Period 
 
A DLT is defined as follows: 
 
For non-hematological toxicities: 
• 
Any non-hematological toxicity Grade ≥ 3, except for alopecia and 
nausea uncontrolled by medical management. 
• 
Any Grade ≥ 2 toxicity that does not resolve to Grade ≤ 1 by the start 
of the next cycle. 
For hematologic toxicities:  
a. 
Grade 4 neutropenia lasting more than 5 days 
b. 
Febrile neutropenia of any duration (ANC <1.0 x 10 9/L, fever 
>38.5◦C)  
c. 
Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with 
bleeding or any requirement for platelet transfusion 
d. 
Grade 4 anemia, unexplained by underlying disease 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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The DLT evaluation period is through Cycle 1 (4 weeks) for each patient.  
**NOTE: Toxicities must continue to be collected during Cycles 2, 3, 4, 5 and 6 for 
data analysis purposes. This is reiterated on the Adverse Event Form (See Forms 
Packet).** 
9.5 
STRC SAE Reporting Requirements 
 
The Data Safety Monitoring Committee (DSMC) is responsible for reviewing SAEs 
for WFBCCC Institutional studies as outlined in Appendix D. All Adverse Events 
that occur during protocol intervention and are coded as either 1) unexpected 
grade 4, 2) unplanned inpatient hospitalization ≥ 24 hours (regardless of grade), or 
grade 5 (death) must be reported to the DSMC using the using the SAE console in 
WISER.  
 
All WFBCCC Clinical Protocol and Data Management (CPDM) staff members 
assisting a Principal Investigator in investigating, documenting and reporting an 
SAE qualifying for DSMC reporting are responsible for informing a clinical member 
of the DSMC as well as the entire committee via the email notification procedure of 
the occurrence of an SAE.  
 
9.6 
WFUHS IRB AE Reporting Requirements 
 
IRB (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 
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. 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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Any unanticipated problems involving risks to subjects or others occurring at another site 
conducting the same study that has been approved by the WFUHS 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. 
10.0 
Statistical Considerations 
 
10.1 Analysis of Primary Objective 
 
The primary objectives for this pilot study are to assess the feasibility, safety and 
tolerability of administering CPI-613, when used in combination with Bendamustine in 
patients with relapsed and refractory T-cell NHL who have or have not received 
hematopoietic cell transplant and to evaluate further the safety of CPI-613 and 
Bendamustine combination. 
 
For each of these primary objectives we will measure proportions of patients and 
corresponding 95% confidence intervals to gather preliminary estimates of feasibility, 
safety and tolerability and corresponding levels of variability.  Specifically, for the 
feasibility objective, we will consider a patient as completing therapy if they complete 80% 
of proposed treatment regimen.  Using this pilot study, we will estimate this proportion of 
patients, and would consider this regimen “feasible” for future studies if at least 75% of 
patients successfully complete 80% of their therapy regimens.  We will then calculate a 
95% exact Clopper-Pearson confidence interval for this proportion. Next, for the second 
primary objectives of safety and tolerability, we will gather additional toxicity data for 
patients in this trial.  We will examine toxicities by patient and by body system.  We will 
calculate proportions of patients who have specific toxicities and also examine the 
distribution of toxicities by grade across patients.  These estimates will provide further 
useful data for characterizing the safety and tolerability profile of patients taking this 
combination therapy.  
 
 
10.2 Exploratory Objectives 
 
All patients who are enrolled and receive any treatment will be considered evaluable for 
efficacy outcomes in this pilot study regardless of the amount of treatment received.  
 
For these exploratory objectives of evaluating Overall Response Rate (ORR), Disease 
Control Rate (DCR), Duration Of Response (DOR), Progression-Free-Survival (PFS), and 
Overall Survival (OS) we will perform descriptive analyses.  Given the small sample size 
expected for this study, evaluation of each of these secondary objectives will be 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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exploratory in nature.  Descriptive statistics will be calculated to describe each of the 
categorical measures such as Response Rate (RR).  In addition, Clopper-Pearson 95% 
exact confidence intervals will be calculated for each binary outcome.  For time to event 
measures such as OS and PFS Kaplan Meier survival curves will be estimated and 
median times will be estimated from these curves.  Each of these analyses will be 
performed to generate useful pilot data for planning future studies.  The amount of 
treatment received will be examined in these exploratory analyses as well to determine if 
there is any association between this level and any of the efficacy outcomes.  So for the 
response rate measures we will examine whether treatment amount is higher (or lower) 
based on levels of response.  Likewise, for time to event analyses we will examine 
whether treatment amount is associated with outcomes using Cox proportional hazards 
regression.  We recognize that with the small sample size in this pilot study these 
analyses examining associations between treatment amount and efficacy outcomes will 
only provide exploratory data to examine these questions.   
 
Single cell transcriptomic status pre- and post-treatment will be assessed and this data 
will be examining in a descriptive manner.  Correlation of blood PBMC (and possibly 
excess pre-treatment tumor biopsy) cell population diversity and functional states will be 
examined and seen if there is any relationship between these biomarkers and patient 
response status.  For example, for continuous assessments a two-sample t-test will be 
performed to compare measures between responders and non-responders.  Likewise, for 
categorical assessments, Fisher’s exact tests will be performed to compare rates 
between responders and non-responders. 
 
10.4 Power and Sample Size 
 
We expect to screen 20 subjects in this study in order to obtain 12 evaluable 
subjects.  With a sample size of 12 patients, a two-sided 95% exact Clopper Pearson 
confidence interval will have a width of +/- 0.29 if the sample proportion is 0.5.  For 
examining feasibility, we anticipate that the observed rate will be above 75%, so with this 
value the confidence interval would have a width of +/-0.259 (thus the lower bound would 
be 0.43.  Although, these confidence intervals have relatively large widths, it is felt that 
this study will still provide useful information to inform the design of future larger studies.  
 
10.5 Accrual Rate 
 
We anticipate accruing at least one patient every 2 months on this protocol and thus 
expect that accrual for this pilot trial will be completed in ~24-28 months. 
 
10.6 Interim Analysis Plan 
 
There are no interim analyses planned for this study. 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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11.0 
Data Management 
 
Form 
Database 
Informed Consent 
WISER/On Core 
Protocol Registration Form 
REDCap 
Withdrawal of Participation Form 
REDCap 
Telephone Follow-up/Survival Form 
REDCap 
Efficacy Assessment Form/Bone Marrow 
Biopsy 
REDCap 
Adverse Event Log 
REDCap 
Medical Record Review Form 
REDCap 
 
Vitals/ECOG 
REDCap 
12.0 
Multi-Institutional Monitoring Plan 
 
12.1.  SAE Reporting  
 
Each investigator is responsible for submitting SAEs and unexepected AEs to their 
Institutional Review Board/Ethics Committee according to their institutional guidelines. 
Any serious or unexpected event, which occurs to any patient in the course of their 
treatment on this study or within 30 days following cessation of treatment, must be 
reported immediately to the Comprehensive Cancer Center of Wake Forest University 
(WFBCCC) within 24 hours of the investigator learning of its occurrence.  When calling to 
report an event, please clearly state the protocol number (WFBCCC 28314) and the 
patient identification number, along  
with the event description and grade. The 
immediate reports should be followed promptly by detailed, written reports.   
 
A FDA Form 3500 (MEDWATCH) must be sent to WFBCCC for all SAEs which  are 
unexpected, fatal or life-threatening experience and associated with the use of the drug 
within 48 hours.   
 
The patient must be followed up until clinical recovery is complete and/or laboratory 
results have returned to normal. This may mean that follow-up will continue after the 
patient has completed the trial. 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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12.2.  Registration Procedures 
 
All patients must be registered with the WFBCCC Protocol Registrar before enrollment to 
study.  To register a patient, contact the WFBCCC Protocol Registrar  Monday through 
Friday, 8:30AM-4:30PM EST. 
 
12.3.  Study Monitoring 
 
Personnel from the WFBCCC Protocol Office will monitor the trial. Clinical Research 
Associates may periodically visit the investigative site to assure proper conduct of the trial 
and proper collection of the data. The investigators at each site will allow the monitor to 
review all source documents used in the preparation of the case  
reports.  
 
All study forms should be sent to the coordinating site within one week of patient 
completion.   
 
12.4. Required Documentation 
 
Before the study can be initiated at any site, the following documentation must be 
provided to the Protocol Office at Wake Forest University Health Sciences. 
 
A. Written documentation of IRB approval of protocol (identified by title, 
protocol version and date of approval) for each site.  
B. IRB membership list 
C. Current curricula vitae and documentation of professional licensure of 
the Principal Investigator and co-Investigators listed on the 1572.  
D. U.S. Food and Drug Administration (FDA) Form 1572, signed by the 
Principal Investigator at the participating center. The names of any sub-
investigators at the participating center must appear on this form. 
Investigators must also complete all regulatory documentation as 
required by local regulations. This includes any required human subjects 
training required by the site’s local IRB.  
E. Human subject protections documentation (e.g. NIH, CITI) for all 
research personnel (e.g. study coordinators, data managers and other 
research personnel).  
F. IRB approved study informed consent and HIPAA consent form. HIPAA 
consent language can be included within the study informed consent. 
Please note that all informed consent forms should be reviewed and 
approved by the WFU protocol office prior to submission to the site’s 
designated IRB.  
G. Laboratory certifications (CAP, CLIAs) and laboratory reference value 
ranges for each laboratory listed on the site’s 1572.  
H. Executed clinical research contract 
I. Any approval memos from IRB for protocols, continuing reviews, and 
approved informed consents 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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J. Signed WFUHS Conflict of Interest Form 
 
12.5 Adherence to the Protocol 
 
Except for an emergency situation in which proper care for the protection, safety, and 
well-being of the study patient requires alternative treatment, the study shall be conducted 
exactly as described in the approved protocol. Any deviation from the protocol must have 
prior approval by the WFBCCC Principal Investigator and must be recorded and 
explained. 
 
12.6 Amendments to the Protocol 
 
Should amendments to the protocol be required, the amendments will be originated and  
documented by the Principal Investigator at WFBCCC. The written amendment will be 
sent to investigators and must be submitted to the IRB at the investigator's site for 
approval. It should also be noted that when an amendment to the protocol substantially 
alters the study design or the potential risk to the patient, a revised consent form might be 
required. 
12.7 Record Retention 
 
Study documentation includes all Case Report Forms, data correction forms or queries, 
source documents, Sponsor-Investigator correspondence, monitoring logs/letters, and 
regulatory documents (e.g., protocol and amendments, IRB correspondence and approval, 
signed patient consent forms). 
 
Source documents include all recordings of observations or notations of clinical activities 
and all reports and records necessary for the evaluation and reconstruction of the clinical 
research study. 
 
Government agency regulations and directives require that all study documentation 
pertaining to the conduct of a clinical trial must be retained by the study investigator.  In 
the case of a study with a drug seeking regulatory approval and marketing, these 
documents shall be retained for at least two years after the last approval of marketing 
application  in an International Conference on Harmonization (ICH) region.  In all other 
cases, study documents should be kept on file until three years after the completion and 
final study report of this investigational study. 
12.8  Obligations of Investigators 
 
The Principal Investigator is responsible for the conduct of the clinical trial at the site in 
accordance with Title 21 of the Code of Federal Regulations and/or the Declaration of 
Helsinki.  The Principal Investigator is responsible for personally overseeing the treatment 
of all study patients. The Principal Investigator must assure that all study site personnel, 
including sub-investigators and other study staff members, adhere to the study protocol 
and all FDA/GCP/NCI regulations and guidelines regarding clinical trials both during and 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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after study completion. 
 
 
The Principal Investigator at each institution or site will be responsible for assuring that all 
the required data will be collected and entered onto the flowsheet.  Periodically, monitoring 
visits will be conducted and the Principal Investigator will provide access to his/her original 
records to permit verification of proper entry of data. At the completion  
of the study, all 
case report forms will be reviewed by the Principal Investigator and will require his/her final 
signature to verify the accuracy of the data. 
 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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REFERENCES 
 
Brepoels L, Stroobants S, De Wever W, Spaepen K, Vandenberghe P, Thomas J, et al. 
Hodgkin lymphoma: response assessment by revised International Workshop Criteria. 
Leuk Lymphoma. 2007;48:1539-1547. 
 
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, 
Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, 
Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V. Revised Response 
Criteria for Malignant Lymphoma. J Clin Oncol. 2007;25(5):579-586. 
 
Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, 
staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano 
classification. J Clin Oncol. 2014;32(27):3059-3068. 
 
Damaj G, Gressin R, Bouabdallah K et al. Results from a prospective, open-label, phase 
II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. J 
Clin Oncol. 2013;31:104-110. 
 
Gallamini A, Fiore F, Sorasio R, Meignan M. Interim positron emission tomography scan 
in Hodgkin lymphoma: definitions, interpretation rules, and clinical validation. Leuk 
Lymphoma. 2009;50:1761-1764. 
 
Ghesquieres H, Stamatoullas A, Casasnovas O et al. Clinical experience of 
bendamustine in relapsed or refractory Hodgkin lymphoma: a retrospective analysis of the 
French compassionate use program in 28 patients. Leuk Lymphoma. 2013;54:2399-2404. 
 
Hagberg H, Gisselbrecht C. Randomised phase III study of R-ICE versus R-DHAP in 
relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-
dose therapy and a second randomisation to maintenance treatment with rituximab or not: 
an update of the CORAL study. Ann Oncol. 2006;17 Suppl 4: iv31-32. 
 
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 Case 
Rep.2011;1(3):137-145. 
 
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 Case Rep. 
2012;2(3):95-101. 
 
Majhail NS, Weisdorf DJ, Defor TE, et al. Long-term results of autologous stem cell 
transplantation for primary refractory or relapsed Hodgkin's lymphoma. Biol Blood Marrow 
Transplant. 2006;12:1065-1072. 
 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin 
Oncol. 1982;5(6):649-655. 
 
Olsen EA, Whittaker S, Kim YH, Madeleine D, Prince HM, Lessin SR, et al. Clinical End 
Points and Response Criteria in Mycosis Fungoides and Sézary Syndrome: A Concensus  
Statement of the International Society for Cutaneous Lymphomas, the United States 
Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the 
European Organisation for Research and Treatment of Cancer. J Clin Oncol. 
2011;29(18):2598-2607. 
 
Pardee T, Lee K, Luddy J, Maturo C, Rodriguez R, Levitan DA, Hurd DD, Ellis LR, Isom 
S, Harrelson R, Manuel M, Dralle S, Lyerly S, Powell BL. A Phase I Study of the Safety, 
Efficacy and Pharmacokinetics of the First in Class Pyruvate Dehydrogenase Complex 
Inhibitor CPI-613 in Patients with Advanced Hematologic Malignancies [abstract]. Blood. 
2013;122(21),486-486.Pardee TS, Levitan DA, Hurd DD. Altered mitochondrial 
metabolism as a target in acute myeloid leukemia [abstract].  J Clin Oncol. 29 (2011). 
 
Pardee TS, DeFord-Watts LM, Peronto E, Levitan D, Hurd D, Kridel SK, Powell B. The 
1st in class tumor specific anti-mitochondrial metabolism agent CPI-613 is well tolerated 
and has activity in several hematologic malignancies [abstract]. J Clin Oncol. 30 (2012). 
 
Study COM-001.  2006.  Compatibility Testing of CPI-613 Drug Product - Infusion Sets. 
 
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 Case Rep. 
2012;2(2):38-45. 
 
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. 
 
Study NCL-027.  Seng J.  2006.  Escalating Dose Toxicology Study of Intravenously 
Administered CPI-613 to Miniature Pigs. 
 
Study NCL-030.  Seng J.  2006.  An Acute Toxicity Study of CPI-613 Administered Via 
the Intravenous (Slow Bolus) Route to Mice. 
 
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. 
 
Study PHO-001 (Covance Study# 7769-101).  Potts B.  2007.  Photostability Testing of 
CPI-613 Drug Product. 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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Study STA-010.  Bhasin R. 2007.  Stability of CPI-613 Injection dosing solutions after 
Dilution with 5% Dextrose (D5W). 
 
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. 
 
Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined 
with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann 
Hematol. 2014;93(3):403-409. DOI: 10.1007/s00277-013-1879-x. Epub 2013 Aug 17. 
 
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 anticancer 
agents in vivo. J Mol Med (Berl). 2011;89(11):1137-1148. DOI: 10.1007/s00109-011-
0785-8. Epub 2011 Jul 19 
 
 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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Appendix A – Subject Eligibility Checklist 
 
IRB Protocol No.    
WFBCCC Protocol No.  WFBCCC 28419 
 
Study Title: Pilot Study of CPI-613 in Combination with Bendamustine in Patients with Relapsed or  
Refractory T-Cell Non-Hodgkin Lymphoma  
Principal Investigator:  Rahkee Vaidya, M.B.B.S. 
 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria 
is met 
Criteria 
is NOT 
met 
Source Used to Confirm 
1.  Histologically or 
cytologically confirmed 
PTCL (all subtypes) or CTCL 
(mycosis fungoides/sezary 
syndrome) as defined by 
2016 World Health 
Organization (WHO) 
classification.   
□ 
□ 
 
2. For patients with PTCL:   
a. Patients must have 
relapsed/ refractory 
disease to one or 
more systemic 
therapies.   
b. Patients with CD30-
positive lymphoma 
must have received, 
be ineligible for, or 
intolerant to 
brentuximab vedotin. 
c. Patients with limited 
prior exposure to 
Bendamustine (less 
than 2 full cycles or ≤ 
480 mg/m2) may be 
included, based on PI 
discretion.   
d. Patients must have 
measurable disease 
(e.g., a tumor mass 
>1 cm or evidence of 
bone marrow 
involvement) 
□ 
□ 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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3. For patients with CTCL, 
stage IB- IVB mycosis 
fungoides or Sezary 
syndrome are eligible 
a. Patients must have 
relapsed/ refractory 
disease to at least 
one previous 
systemic therapy. 
Psoralen plus 
ultraviolet light 
therapy (PUVA) is not 
considered to be a 
systemic therapy. 
□ 
□ 
 
4. Male and female patients 18 
years of age and older  
□ 
□ 
 
5. Eastern Cooperative 
Oncology Group (ECOG) 
performance status 0-2. 
□ 
□ 
 
6. Expected survival >3 months 
□ 
□ 
 
7. 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.  
□ 
□ 
 
8. Fertile men must practice 
effective contraceptive 
methods during the study, 
unless documentation of 
infertility exists. 
□ 
□ 
 
9. At least 2 weeks must have 
elapsed from prior 
chemotherapy drugs (other 
than steroids) or radiation 
□ 
□ 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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10.  At least 6 weeks must have 
elapsed from prior 
autologous stem cell 
transplant and 12 weeks 
must have elapsed from 
prior allogeneic stem cell 
transplant. 
□ 
□ 
 
11. Laboratory values ≤2 weeks 
must be: 
a. Adequate 
hematological 
function (absolute 
neutrophil count 
[ANC] ≥1,500/mm3, 
platelets 
≥100,000/mm3). In 
subjects with known 
bone marrow 
involvement, ANC 
must be ≥ 1000/mm3 
and platelets 
≥75,000/mm3 
b. Adequate hepatic 
function (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). 
c. Adequate renal 
function (serum 
creatinine 1.5 mg/dL 
or 133 µmol/L). 
□ 
□ 
 
12. No evidence of current 
infection. 
□ 
□ 
 
13. Mentally competent, ability 
to understand and 
willingness to sign the 
informed consent form. 
 
□ 
□ 
 
Exclusion Criteria 
(as outlined in study protocol) 
Criteria 
NOT 
present 
Criteria 
is 
present 
Source Used to Confirm 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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1. Known cerebral metastases, 
central nervous system 
(CNS) or epidural tumor. 
□ 
□ 
 
2. History of prior malignancy 
and considered to be at 
greater than 30% risk of 
relapse 
□ 
□ 
 
3. Patients receiving 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 treatment with 
study drugs (steroids are 
allowed) 
□ 
□ 
 
4. Patients with a history of 
allogeneic transplant must 
not have ≥ grade 3 graft-
versus-host disease (GVHD) 
or any clinically significant 
GVHD requiring systemic 
immunosuppression. 
□ 
□ 
 
5. Serious medical illness that 
would potentially increase 
patients’ risk for toxicity. 
□ 
□ 
 
6. Pregnant women, or women 
of child-bearing potential not 
using reliable means of 
contraception (because the 
teratogenic potential of CPI-
613 is unknown). 
□ 
□ 
 
7. Lactating females.   
□ 
□ 
 
8. Fertile men unwilling to 
practice contraceptive 
methods during the study 
period. 
□ 
□ 
 
9. Any condition or abnormality 
which may, in the opinion of 
the investigator, compromise 
the safety of patients. 
□ 
□ 
 
10. Unwilling or unable to follow 
protocol requirements. 
□ 
□ 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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11. Active heart disease 
including but not limited to 
symptomatic congestive 
heart failure, symptomatic 
coronary artery disease, 
symptomatic angina 
pectoris, symptomatic 
myocardial infarction or 
symptomatic congestive 
heart failure.  
□ 
□ 
 
12. Evidence of current 
infection. 
□ 
□ 
 
13. Patients with known HIV 
infection, hepatitis B, or 
hepatitis C with positive viral 
load. 
□ 
□ 
 
14. Patients who have received 
cancer immunotherapy of 
any type within the past 2 
weeks prior to initiation of 
CPI-613 treatment. 
□ 
□ 
 
This subject is      
 eligible / 
 ineligible     for participation in this study.    (continued on next 
page) 
WISER 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, 
please specifically state which document in the medical record was used to assess eligibility. Please 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 
 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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Appendix B – Protocol Registration Form  
 DEMOGRAPHICS 
Patient: Last Name: _____________________ 
First Name: ________________________ 
MRN:          ___ ___ ___ ___ ___ ___ ___ ___ 
DOB (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
Zip Code:  ___ ___ ___ ___ ___ 
SEX:   Male     Female 
Ethnicity (choose one):   Hispanic       
Non-Hispanic 
Race (choose 
all that apply): 
 WHITE     BLACK     ASIAN   PACIFIC ISLANDER    NATIVE AMERICAN 
Height:   ___ ___.___ inches 
Weight: ___ ___ ___.___lbs.(actual) 
Surface Area: ___ ___.___m2   
Primary Diagnosis: ___________________________ 
Date of Diagnosis: ___ ___ /___ ___/___ ___ 
Performance Status : __________ 
Stage of Disease: ______________ 
CURRENT DISEASE STATUS AT REGISTRATION: _________________________________________ 
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 ___________________ 
_______/________ _______________ _____________ 
______________ 
________________ 
 
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 
  
 
 
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 OnCore):   ___ ___ ___ ___ ___ ___ ___ ___ 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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 Appendix C Safety and Toxicity Review Committee SOP 
 
Data and Safety Monitoring 
Committee (DSMC) Serious Adverse 
Event (SAE) Notification SOP 
Date: 02/11/2021 
 
Mandatory DSMC SAE Reporting Requirements in WISER 
This document describes reporting requirements of adverse events from WFBCCC Investigator 
Initiated interventional trials to the Data and Safety Monitoring Committee (DSMC). A trial is 
considered a WFBCCC Investigator Initiated interventional trial if the following criteria are met: 
 
1) The Principal Investigator (PI) of the trial is a member of a department at the Wake Forest 
University Baptist Medical Center. 
2) WFBCCC is considered as the primary contributor to the design, implementation and/or 
monitoring of the trial. 
3) The trial is designated as “Interventional” using the Clinical Research Categories 
definitions provided by the NCI in the Data Table 4 documentation. 
(https://cancercenters.cancer.gov/GrantsFunding/DataGuide#dt4) 
 
There are two distinct types of WFBCCC Investigator Initiated interventional trials based on where 
patient enrollment occurs.  These include: 
 
1) Local WFBCCC Investigator Initiated interventional trials defined as trials where all patients are 
enrolled from one of the WFBCCC sites. These include the main outpatient Cancer Center 
clinics (located in Winston-Salem) as well as WFBCCC affiliate sites located in Bermuda Run 
(Davie Medical Center), Clemmons, Lexington, High Point, or Wilkesboro. 
2) Multi-Center WFBCCC Investigator Initiated interventional trials defined as trials where 
patients are enrolled from other sites in addition to WFBCCC sites.   
There are three types of trials that are included in this category: 
a. Trials sponsored by the NCI Community Oncology Research Program (NCORP) that are 
conducted at multiple sites where the PI is a member of a department at the Wake 
Forest University Baptist Medical Center. 
b. Trials sponsored by Industry that are conducted at multiple sites and the PI is a 
member of a department at the Wake Forest University Baptist Medical Center. 
c. Trials sponsored by WFBCCC that are conducted at multiple sites and the PI is a 
member of a department at the Wake Forest University Baptist Medical Center. 
 
All Adverse Events (AEs) and Serious Adverse Events (SAEs) that occur on any patients enrolled on 
WFBCCC Investigator Initiated Interventional trials must be entered into the WISER system. The only 
exception to this requirement is for patients enrolled on NCORP trials at non- WFBCCC sites. AEs and 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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SAEs for NCORP patients enrolled at WFBCCC sites must be entered into the WISER system. Once these 
AEs and SAEs are entered in WISER, certain actions must be taken regarding the reporting of specific 
Adverse Events to the DSMC. 
 
 
 
All Adverse Events that occur during protocol intervention (defined below) and are coded as either 1) 
unexpected grade 4, 2) unplanned inpatient hospitalization > 24 hours (regardless of grade), or grade 
5 (death) must be reported to the DSMC using the using the SAE console in WISER. 
 
A research nurse or clinical research coordinator when made aware that an adverse event meets one 
of the above criteria has occurred on a WFBCCC Investigator Initiated interventional trial, is responsible 
for informing a clinical member of the DSMC by phone (or in-person) about the adverse event. The 
nurse/coordinator should contact the treating physician prior to calling the DSMC clinical member to 
obtain all details of the SAE, as well as all associated toxicities to be recorded along with the SAE. In 
addition, this nurse or coordinator is responsible for entering the adverse event information into the 
SAE console in WISER.  Once the adverse event has been entered into the SAE console an email 
informing the entire DSMC will be generated. 
 
THESE REPORTING REQUIREMENTS APPLY TO any staff member on the study team for a WFBCCC 
Institutional Interventional trial. Ultimately, the protocol PI has the primary responsibility for AE 
identification, documentation, grading and assignment of attribution to the investigational 
agent/intervention. However, when an AE event as described above is observed, it is the 
responsibility of the person who observed the event to be sure that it is reported to the DSMC. 
 
What is considered during protocol intervention? 
During protocol intervention is considered to be the time period while a patient is on study treatment or 
during the time period within 30 days of last study treatment (even if patient begins a new (non-study) 
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 window can be used 
to identify events. If it is a trial sponsored by Industry and the sponsor requires a longer window for 
monitoring of SAEs, then the longer window of time specified by the sponsor should be followed. 
 
What is considered as an Unexpected Grade 4 event? 
Any grade 4 event that was not specifically listed as an expected adverse event in the protocol should be 
considered as unexpected. A grade 4 adverse event can be considered to be unexpected if it is an event 
that would not be expected based on the treatment being received or if it is unexpected based on the 
health of the patient. In either case, if there is any uncertainty about whether a grade 4 adverse event is 
expected or unexpected it should be reported to DSMC. 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
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DSMC notification responsibilities of the person (e.g., nurse) handling the reporting/documenting of the 
SAE in WISER: 
1. Make a phone call (or speak in person) to the appropriate clinical member of the DSMC 
according to the schedule as listed below (page if necessary). 
2. Enter a new SAE into the SAE module that is located in the Subject>> CRA Console in WISER 
WITHIN 24 HOURS of first knowledge of the event. Information can be entered and saved, but 
the DSMC members will not be notified until a date is entered into the  DSMC Notification Date 
Field. This will ensure that all persons that need to be made aware of the event (i.e., PI, study 
team members and DSMC members) will be notified; remember to file a copy of the 
confirmation. 
3. Document that the appropriate person(s) on the DSMC has been contacted. Indicate the name of 
the DSMC clinician that was contacted and the date and time contacted in the Event Narrative 
field in the SAE console of the particular subject. 
4. Document whether or not the protocol should be suspended based on the discussion with the 
DSMC clinician. This is the major function of the email notification. Enter whether the protocol 
should be suspended in the Event Narrative Field. 
5. Follow up/update the clinical member(s) of DSMC regarding any new developments or 
information obtained during the course of the SAE investigation and reporting process. 
 
Elements needed to complete the SAE form in the Subject Console in WISER (see Screen Shot 3): 
1. Event Date 
2. Reported Date 
3. Reported by 
4. If Grade 5, enter Death Date 
5. If Grade 5, enter Death occurred: within 30 days 
6. Event Narrative: Brief description (include brief clinical history relevant to this event, including 
therapies believed related to event). Begin narrative with the DSMC clinician who was notified and 
Date/Time notified. In addition, state attribution by DSMC clinician as either “Unrelated”, 
“Unlikely”, “Possibly”, “Probably”, or “Definitely”.  Always include the following here: 
i. DSMC clinician name, date/time contacted and comments 
ii. Date of last dose before the event 
iii. Is suspension of the protocol needed? Y/N 
7. Treating Physician comments 
8. PI comments, if available 
9. Protocol Attribution after discussion with DSMC clinician 
10. Outcome (Fatal/Died, Intervention for AE Continues, Migrated AE, Not Recovered/Not Resolved, 
Recovered/Resolved with Sequelae, Recovered/Resolved without Sequelae, Recovering and 
Resolving) 
11. Consent form Change Required? Y/N 
12. SAE Classification *This is required in order for the email notification to be sent* 
13. Adverse Event Details – Enter all details for each AE associated with the SAE. 
a. Course start date 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
- 56 of 59 - 
b. Category 
c. AE Detail 
d. Comments 
e. Grade/Severity 
f. Unexpected Y/N 
g. DLT Y/N 
h. Attributions 
i. Action 
j. Therapy 
k. Click ADD to attach the AE Detail to the SAE. 
14. Enter Date Notified DSMC -- *This is required for the email notification to be sent* 
15. Click Submit. The auto-generated notification email will disseminate within 5 minutes. If you do 
not receive an email within 5 minutes, check that you have entered the “Date Notified DSMC” and 
the “SAE Classification”. If these have been entered and the email still has not been received, take 
a screen shot of the SAE in WISER and immediately email it out to all of the STRC members listed 
in this SOP. In the subject line, indicate that this is a manual transmission of the SAE in lieu of the 
auto-generated email. It is required that a notification goes to the DSMC members immediately so 
that their assessment can be obtained within the 24 hour period requirement. Contact the Cancer 
Center Programmer/Analyst to alert that there is an issue with the auto-generated email. 
 
The Clinical Members of DSMC to Notify by Phone or Page: 
 
Monday 
Tuesday 
Wednesday Thursday 
Friday 
Saturday Sunday 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu Seegars 
 
  
 
 
 
 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
- 57 of 59 - 
 
 
 
Definition of Unavailable: 
As a general guideline if the first clinician that is contacted does not respond to the phone call or page 
within 30 minutes, then initiate contact with the next DSMC clinician listed in the table above on the 
particular day the SAE is being reported. Allow up to 30 minutes for the new DSMC clinician to respond to 
a phone call or page before contacting the next member in the table. These times (30 minutes) are a 
general guideline. Best judgment as a clinical research professional should be used giving considerations 
of 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 the DSMC notification form. It is important to take reasonable 
steps and to document that some type of contact has been initiated to one or more of the clinical 
members of DSMC. 
 
DSMC CLINICAN RESPONSIBILITY: 
It is the responsibility of the DSMC 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 DSMC. 
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. DSMC reserves the right to disagree with the 
Investigator's assessment. If DSMC does not agree with the Investigator, DSMC reserves the right to 
suspend the trial pending further investigation. If there is any immediate danger or harm that could be 
present for a future patient based on the information provided in the DSMC report then an immediate 
suspension of enrollment should be considered. 
 
 
AMENDMENTS TO PREVIOUS REPORTS 
If all pertinent information is unavailable with the initial submission, once the additional information is 
available do not submit a new report. Rather, go to the original email that was sent to the DSMC and 
using that email “reply to all”. Entitle this new email “Amendment for (list date of event and patient ID)” 
this will avoid duplications of the same event. List the additional information being reported. This 
information needs to be entered into WISER as well. To do this, go to the Subject console and click SAEs 
on the left column. Click on the appropriate SAE number that needs updating. Then click Update. This 
will allow additional  information to be added. 
 
 
Acronyms 
AE – Adverse Event 
DSMC-Data and Safety Monitoring Committee 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell Non-Hodgkin 
Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
- 58 of 59 - 
SAE-Serious Adverse Event 
WFBCCC – Wake Forest Baptist Comprehensive Cancer Center 
NCI-National Cancer Institute 
WISER –Wake Integrated Solution for Enterprise Research 
 
Screen Shots: 
 
The following screen shots come from the SAE Console within the Subject Console in WISER. 
Screen Shot 1: 
 
Screen Shot 2:
 
Screen Shot 3: 


Comprehensive Cancer Center of Wake Forest University 
Pilot Study of CPI-613, in Combination with Bendamustine, in Patients with Relapsed or Refractory T-Cell 
Non-Hodgkin Lymphoma WFBCCCWFBCCC #28419 
 
Protocol version date: 11/29/22 
- 59 of 59 - 
 
 
 
Screen Shot 4: 
 
 
 
 

ICF_000.pdf: 
Pilot Study of CPI-613, in Combination With Bendamustine, in Patients With Relapsed or Refractory T-
Cell Non-Hodgkin Lymphoma  
NCT04217317
IRB Approved Date: 3/13/24


Page 1 of 16
Adult Consent Form
Section on Hematology and Oncology
PILOT STUDY OF CPI-613, IN COMBINATION WITH BENDAMUSTINE, IN 
PATIENTS WITH RELAPSED OR REFRACTORY T-CELL NON-HODGKIN 
LYMPHOMA – WFBCCC 28419
Informed Consent Form to Participate in Research
Rakhee Vaidya, MD, Principal Investigator
SUMMARY
You are invited to participate in a research study. The purpose of this research is to determine if  
CPI-613 with the drug Bendamustine on days one and two of a treatment cycle can be given 
without causing severe side effects. In previous studies, both drugs were given on many days. 
You are invited to be in this study because you have non-Hodgkin lymphoma that has either not 
responded (or has returned) despite standard treatment, and/or no further (non-investigational) 
therapies are left. Your participation in this research will involve multiple visits and last until 
your cancer is no longer responding to the medication or you decide to withdraw from the study.
Participation in this study will involve taking the drugs CPI-613 and Bendamustine, as well as 
blood draws.  All research studies involve some risks.  These risks are outlined in the consent 
form below.  There is a possibility that you may benefit from participation in this study.  
Your participation in this study is voluntary.  You do not have to participate in this study if you 
do not want to.  There may be other choices available to you.  Some other choices may include 
participating in another research study, receiving other chemotherapies recommended by your 
oncologist, or receiving comfort care for your cancer.  You will not lose any services, benefits, or 
rights you would normally have if you choose not to participate. 
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions if you need help deciding whether to join the 
study. The person in charge of this study is Dr. Rakhee Vaidya. If you have questions, 
suggestions, or concerns regarding this study or you want to withdraw from the study her contact 
information is: 
.
If you have any questions, suggestions or concerns about your rights as a volunteer in this 
research, contact the Institutional Review Board at 
 or the Research Subject 
Advocate at Wake Forest at 
.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


Page 2 of 16
Adult Consent Form
PILOT STUDY OF CPI-613, IN COMBINATION WITH BENDAMUSTINE, IN 
PATIENTS WITH RELAPSED OR REFRACTORY T-CELL NON-HODGKIN 
LYMPHOMA Informed Consent Form to Participate in Research
Rakhee Vaidya, 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 non-Hodgkin lymphoma that has either not responded (or has returned) 
despite standard treatment, and/or no further (non-investigational) therapies are left. 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.
CPI-613 is thought to kill cancer cells by turning off their mitochondria. Mitochondria are used 
by cancer cells to produce energy and are the building blocks needed to make more cancer cells. 
By shutting off these mitochondria, CPI-613 deprives the cancer 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. 
Bendamustine is a chemotherapy drug that is routinely used for treatment of non-Hodgkin 
lymphoma. A previous study of Bendamustine along with CPI-613 in patients with non-Hodgkin 
lymphomas showed that this combination has activity in non-Hodgkin lymphomas. However, the 
CPI-613 was given over several days with each cycle which was cumbersome. The current study 
is a pilot study, which means only a small number of subjects will participate.  The purpose of 
this study is to determine if it is possible to give CPI-613 with the drug Bendamustine for 2 days 
every 28 days without causing severe side effects. In addition, this study will also test the safety 
of CPI-613 when given in combination with Bendamustine. 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
Approximately 20 people will take part in this study at two research sites.  Approximately 12 
people will take part at Wake Forest Baptist Health.
Section on Hematology and Oncology
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


Page 3 of 16
Adult Consent Form
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. 
Pre-Study Tests
The following tests may be completed over a four week period before receiving the 
investigational drug (CPI-613):

You will undergo an imaging scan known as a PET CT scan. A PET CT scan uses 
computers and x-rays to take detailed pictures of areas inside your body. 

You may undergo a bone marrow biopsy for certain non-Hodgkin lymphoma subtypes

Approximately four teaspoons of blood may be drawn to use for research purposes (only 
with your permission).
The following tests may be completed within two weeks before receiving the investigational 
drug (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 2.5 teaspoons of blood will be drawn for non-research related routine lab 
tests.
The following test must be completed within one week before receiving the investigational drug 
(CPI-613):

Pregnancy test for women who can become pregnant. This must be done within one 
week of starting treatment. 
If the results of these tests show that you are eligible to enroll in this study, your participation on 
the study can begin. 
Study Treatment and Procedures
This clinical research study consists of multiple four-week cycles of treatment with CPI-613 and 
Bendamustine.  A cycle is 4 weeks and includes receiving treatment with CPI-613 and 
Bendamustine on two days during week one, followed by three weeks of rest (no treatment). The 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


Page 4 of 16
Adult Consent Form
number of cycles you receive will be determined by how well your cancer responds to the 
therapy. The maximum number of cycles where you will receive Bendamustine is six.  If your 
cancer responds to the combination of Bendamustine plus CPI-613, you may continue to receive 
CPI-613 alone for two days every 4 weeks after the Bendamustine has been discontinued.
The first table below shows the schedule of the treatment, tests, and procedures you will have 
during cycles 1 through 6. The second table describes the schedule of treatment, tests, and 
procedures if you continue on to the Maintenance portion of the study.
Cycles 1-6
(One Cycle = 4 weeks)
Week 1
Procedures
D1
D2
D3
D4
Treatment with CPI-613


Treatment with Bendamustine 


Neulasta


Vital signs (if clinically indicated)


Blood draw (12 teaspoons) for non-
research related routine lab work


Definitions of abbreviations used in this table:
D1=Day 1; D2=Day 2; D3=Day 3; D4=Day 4
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


Page 5 of 16
Adult Consent Form
Additional Evaluations and Procedures
Within five days before the start of cycles two through six, you will have your vital signs and 
performance status evaluated. You will also be asked about any symptoms you may be 
experiencing and any medications you are taking. 
After you have completed cycle three, you will have another PET CT scan and/or skin evaluation 
(depending on your lymphoma subtype) to determine how well your cancer responded to 
treatment with CPI-613 with Bendamustine. 
If the results of the PET CT scan and/or skin evaluation indicate that your cancer has shrunk or 
has remained a stable size, your doctor may decide that you can have three additional cycles of 
treatment with CPI-613 and Bendamustine. If you receive those additional cycles, you will again 
have a PET/CT scan and/or skin evaluation at the end of cycle six.  
If the results of the PET CT scan and/or skin evaluation indicate your cancer is still responding 
your doctor may recommend continuing maintenance treatments with CPI-613 alone.  
For the positron emission tomography (PET) scan, you will receive an injection in a vein.  The 
injection contains a tracer that will travel through your blood stream.  The tracer can show 
doctors how your body is functioning. This is because the tracer will show brightly in areas that 
have a lot of activity.  Cancer cells are usually very active and the PET scan can show a picture 
of this.
As part of this research study, photographs may be obtained of your skin if your lymphoma 
involves the skin.  These photographs are obtained before initiation of cycle 1 and after cycles 3 
and 6 to evaluate response to treatment.  You understand that you may request the photographs 
be stopped at any time during the course of the research study. You can also withdraw your 
consent to use and disclose the photograph before it is used. 
Please choose one of the following regarding the use and disclosure of the photographs used in 
this research study:
_____ I would like the photographs of me to be destroyed once their use in this study is finished.
____ The photographs of me can be kept for use in future studies provided they are kept secure 
and any future study will be reviewed by an IRB.   I understand that I will not be able to inspect, 
review or approve their future use.
We can send copies of your test results to your personal physician. Even if you do not wish to 
have any of your medical information sent to your physician, you can still participate in this 
research study. 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


Page 6 of 16
Adult Consent Form
Do you request that we send important medical findings from your study tests/exams to your 
personal physician? 
[   ] Yes
[   ] No
___________ Initials
STORAGE OF BIOLOGICAL TISSUE
If you agree to participate in this study, you will have the option to provide blood samples to use 
for future research. If you choose to provide these samples, we will draw about 1.5 teaspoons of 
blood from a vein in your arm at the following time points: up to four weeks before the start of 
treatment with CPI-613, and prior to your dose of CPI-613 on Day 1 and 2 of each cycle. These 
samples will be kept and may be used in future research to learn more about other diseases. Your 
samples will be obtained in the Hematology and Oncology clinic at Wake Forest University 
Baptist Medical Center.  We would also like to draw two teaspoons of blood up to four weeks 
before the start of treatment with CPI-613 to be stored at Wake Forest University Baptist 
Medical Center for future research by Dr. Rakhee Vaidya and we would like your permission to 
obtain samples of tumor tissue at the time of your standard of care biopsies.  This tissue will be 
taken from excess tissue collected from your biopsy and will not require any extra procedures 
beyond standard of care.  It will be given only to researchers approved by Dr. Vaidya. An 
Institutional Review Board (IRB) must also approve any future research study using your 
samples. 
Your blood and tissue samples will be stored with a unique identifier and will not include any 
identifiable information about you such as your name, address, telephone number, social security 
number, medical record number or any of the identifiers outlined in the HIPAA Privacy Rule. 
The unique identifier will be a randomly assigned number and only the principal investigator and 
study staff will have access to the code that links the unique identifier to you. Your name, 
address, social security number, etc., will never be disclosed to future researchers and neither 
will the code that links your identifiers to the sample.
The research that may be performed with your blood and tissue samples is not designed to help 
you specifically. There is no personal benefit to you from taking part in this aspect of the 
research study. It might help people who have diseases at some point in the future, but it is not 
known if this will happen. The results of the research performed with your blood and tissue 
samples will not be given to you or your doctor. The results will not be put in your medical 
record and will not affect your care.
Your blood and tissue samples will be used only for research and will not be sold. The findings 
from this research may result in the future development of products that are of commercial value. 
There are no plans to share any of the profits with you which may occur as a result of the 
research.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


Page 7 of 16
Adult Consent Form
Please choose one of the following to indicate your desire to provide blood and tissue samples 
for use in future research: 
_____ YES, I would like to provide blood samples for use in future research, provided they are 
kept secure and any future study will be reviewed by an IRB. I understand that there is no benefit 
to me from taking part in this aspect of this study.
____  NO, I would not like to provide blood samples for use in future research. I understand that 
there is no penalty for choosing not to provide these samples, and I understand that I can still 
participate in this study and that my decision not to provide the samples will not affect my care.  
_____ YES, I would like to provide tissue samples for use in future research, provided they are 
kept secure and any future study will be reviewed by an IRB. I understand that there is no benefit 
to me from taking part in this aspect of this study.
____  NO, I would not like to provide tissue samples for use in future research. I understand that 
there is no penalty for choosing not to provide these samples, and I understand that I can still 
participate in this study and that my decision not to provide the samples will not affect my care.  
Your blood/tissue sample will be stored with a unique identifier and will not include any 
identifiable information about you such as your name, address, telephone number, social security 
number, medical record number or any of the identifiers outlined in the HIPAA Privacy Rule. 
The unique identifier will be a randomly assigned number and only the principal investigator will 
have access to the code that links the unique identifier to you. Your name, address, social 
security number, etc., will never be disclosed to future researchers and neither will the code that 
links your identifiers to the sample.
In the future, people who do research may need to know more about your health. While the study 
investigator may give reports about your health, he/she will NOT be given your name, address, 
phone number, or any other identifying information about who you are, unless you agree to be 
contacted in the future.
____YES you many contact for future research studies
____NO I do not want to be contacted regarding future research studies.
HOW LONG WILL I BE IN THE STUDY?
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 until it is determined 
that your cancer is no longer responding to treatment with CPI-613. If you have had treatment 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


Page 8 of 16
Adult Consent Form
with Bendamustine in the past, you will receive a maximum of six cycles of treatment with this 
drug (including treatment before this study and during this study).  Once you have had six cycles 
of treatment with Bendamustine, you will only receive treatment with CPI-613 for the remainder 
of the study.
For example, if the PET/CT scan that is performed at the end of cycle three shows that your 
cancer has responded to treatment, you will receive three more cycles of treatment. If the scan 
shows that your cancer has stopped responding, you will not receive any further treatment. 
Once you have finished treatment as part of this study, you will receive a phone call from the 
research nurse once every three months to check and see how you are doing if you do not return 
to the clinic for follow-up. These phone calls will continue long term as long as you give 
permission.
In addition, 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 and Bendamustine can be evaluated.  
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. One goal of this 
study is to learn about the safety and effectiveness of the drug when used together with 
Bendamustine to treat non-Hodgkin lymphoma. 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 and human studies in other cancer types. 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.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


Page 9 of 16
Adult Consent Form
Some common side effects observed in patients taking CPI-613 include:

Allergic reaction at the place where you receive your drug

Vomiting

Diarrhea 

Fatigue

Headache

Constipation

Nausea

Light-headedness

Abdominal pain

worsening liver function

worsening kidney function

Jaundice (yellowing of the skin and eyes)

Too much or too little calcium in the blood

Flushing

Anemia

decrease of white blood cells (blood cells that help fight infection)

decrease of platelets (blood cells that help to form clots)

Electrolyte imbalance

Blood in urine
Rarely, there may be other, more severe side effects, such as inflammation throughout your 
body. In addition, 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 a sudden drop of blood pressure with 
loss of consciousness. It can be life-threatening.
Risks and side effects related to Bendamustine include those that are:
Likely

Lowered white blood cell count (neutrophils) that may lead to infection

Lowered platelets, which may lead to an increase in bruising or bleeding

Lowered red blood cells, which may cause anemia, tiredness or shortness of breath

Fatigue

Nausea 

Vomiting

Infection

Side effects during or shortly after the infusion: fever, chills
Less Likely:  

Diarrhea
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


Page 10 of 16
Adult Consent Form

Constipation

Loss of appetite

Difficulty sleeping or falling asleep

Rash

Dehydration

Heartburn

Irritation or sores in the lining of the throat

Nosebleed

Fever with dangerously low white blood cell count

Blood infection

Pneumonia
Rare but Serious:

Tumor lysis syndrome, a rapid destruction in the number of leukemia/lymphoma cells. 
This may result in kidney failure or chemical imbalances that may have an effect on 
other organs like your heart. If this were to occur, you would receive close monitoring 
and laboratory tests, as well as appropriate medical treatment.

Severe side effects during the infusion or shortly after, or severe allergic reactions 
including shortness of breath, swelling of the throat, and low blood pressure.

Development of a second cancer such as leukemia

A potentially life-threatening condition, affecting less than 10% of the skin, in which 
the skin separates and peels off.

A life-threatening condition, affecting more than 30% of the skin, in which the skin 
separates and peels off.
Other Risks
Certain drugs, when taken together with the study drug, may increase side effects. It is possible 
that CPI-613 could increase the side effects of Bendamustine and other drugs.  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.
You may experience discomfort, bruising and/or bleeding where the needle is inserted. 
Occasionally, some people become dizzy, lightheaded, or feel faint. Infection may occur on rare 
occasions.  
Risks of a central venous catheter placement 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 drugs cause 
severe side effects or if your disease worsens, the study drug will be discontinued. In that case, 
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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.
Pregnancy Risks
 Due to unknown risks and potential harm to the unborn fetus, sexually active women of 
childbearing potential must use a reliable method of birth control while participating in this 
study. Reliable methods of birth control are: abstinence (not having sex), oral contraceptives, 
OrthoEvra patch, NuvaRing, intrauterine devices (IUD), Nexplanon implant, DepoProvera, tubal 
ligation, or vasectomy of the partner (with confirmed negative sperm counts) in a monogamous 
relationship (same partner). An acceptable, although less reliable, method involves the careful 
use of condoms and spermicidal foam or gel and/or a diaphragm with spermicide with Plan B 
used for any noticed condom or diaphragm failures. We encourage you to discuss this issue 
further with your physicians if you have any questions.
Contraceptive Measures for Males
Your participation in this research study may damage your sperm, which could cause harm to a 
child that you may father while on this study. Such harm may be currently unforeseeable. If you 
are sexually active, you must agree to use a medically acceptable form of birth control in order to 
be in this study and for at least 10 weeks afterwards. Medically acceptable contraceptives 
include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide. 
Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are 
not acceptable methods for routine use. You should inform your partner of the potential for harm 
to an unborn child. She should know that if pregnancy occurs, you will need to report it to the 
study doctor, and she should also promptly notify her doctor.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there may 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: sustained 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 chemotherapy medications. These include Pralatrexate,  Romidepsin, Belinostat, 
lenalidomide (which all work by slowing or stopping the growth of cancer cells), or cytotoxic 
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chemotherapy (drugs that enter the bloodstream and are distributed to all parts of the body.  They 
destroy cancer cells by interfering with their ability to divide and grow). All agents carry risk of 
cytopenias (one or more of your blood cell types is lower than it should be), immune 
suppression,,risk for infection, GI toxicity including nausea, vomiting, diarrhea, mouth sores,
organ toxicity and death.
 
•
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 about your health or 
behaviors is considered Protected Health Information. The information we will collect for this 
research study includes:  medical history, medical images, how you respond to study procedures, 
laboratory and other test results, and physical examinations and other personal information.
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. Only the following people or organizations will be granted access to your 
Protected Health Information:
1) The study investigator and his/her staff, or others at Wake Forest University Health 
Sciences who oversee research
2) Other people or laboratories providing services for this research project on behalf of 
Wake Forest University Health Sciences and Wake Forest University Baptist Medical 
Center 
3) The U.S. Food and Drug Administration (FDA); Rafael Pharmaceuticals, Inc.
Monitors, auditors, IRB or other regulatory agencies will be granted direct access to the  
participant’s original medical record for verification of clinical trial procedures or data, without 
violating confidentiality of the participant and to the extent permitted by other applicable laws.
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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. Rakhee Vaidya 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:
Rakhee Vaidya, M.B.B.S
Section on Hematology and Oncology
Wake Forest Baptist Medical Center
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 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 
Sciences and North Carolina Baptist Hospital. These will be kept secure, with access to this 
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Version Valid Until: 3/12/2025


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information limited to individuals with proper authority, but who may not be directly involved 
with this research study.
WHAT ARE THE COSTS?
Rafael Pharmaceuticals, Inc. is providing the investigational drug (CPI-613), for all participants. 
Costs for your regular medical care, including Bendamustine, will be your own responsibility.
WILL YOU BE PAID FOR PARTICIPATING?
You will receive no payment or other compensation for taking part 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.  Rafael 
Pharmaceuticals, Inc. is providing the investigational drug (CPI-613) to Wake Forest University 
Health Sciences to help conduct this study. The researchers do not, however, hold a direct 
financial interest in Rafael Pharmaceuticals, Inc. or the product being studied.  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, at 
.
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 
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Version Valid Until: 3/12/2025


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more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should call Dr. Rakhee Vaidya at 
.
WHAT 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 not in your best medical interest, your condition 
worsened, new information becomes available, you had an unexpected reaction, or because the 
entire study has been stopped. Information that identifies you may be removed from the data or 
specimens that are collected as part of this study and could be used for future research or shared 
with others without additional consent.
Clinically relevant research results will be disclosed to you upon request, once the study results 
are finalized. 
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. Rakhee Vaidya, at 
.
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 at 
.
You will be given a copy of this signed consent form. 
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Institutional Review Board 
IRB Number:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025


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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:IRB00062873
Meeting Date Approved 3/13/2024          
Version Valid Until: 3/12/2025