Clinical trial NCT02248597
Conditions: Graft Versus Host Disease Hematopoietic/Lymphoid Cancer
Sponsor: Wake Forest University Health Sciences
Start date: 2015-02-25; Completion date: 2023-01-18
Enrollment: 27 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in treating patients with hematological diseases. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclophosphamide after the transplant may stop this from happening.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine if haploidentical stem cell transplant using post-transplant cyclophosphamide results in 60% or better disease free survival (DFS) at 12 months at our institution.

SECONDARY OBJECTIVES:

I. To determine the rate of acute and chronic graft-versus-host disease (GvHD), non-relapse mortality, and relapse.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) once daily (QD) on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2

TRANSPLANT: Patients undergo stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35.

After completion of study treatment, patients are followed up periodically for 2 years.

Arms: arm 1: PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV QD on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2

TRANSPLANT: Patients undergo stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. Allogeneic hematopoietic stem cell transplantation
Interventions: intervention 1: fludarabine phosphate intervention 2: busulfan intervention 3: cyclophosphamide intervention 4: allogeneic hematopoietic stem cell transplantation intervention 5: tacrolimus intervention 6: mycophenolate mofetil
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Undergo myeloablative or reduced intensity allogeneic stem cell transplant intervention 5: None intervention 6: None

Protocol documents:
Prot_SAP_001.pdf: 
Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD 
Prophylaxis: A Pilot Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
Protocol version date 03-12-21 
 
Page 1 of 30 
 
 
 
Principal Investigator: 
 
 
Dianna Howard, MD 
Department of Internal Medicine 
Section on Hematology and Oncology 
Wake Forest Baptist Health 
Winston-Salem, NC 27157 
 
 
 
Co-Investigator(s):  
 
 
Rakhee Vaidya, MD 
Department of Internal Medicine 
Section on Hematology and Oncology 
Wake Forest Baptist Health 
Winston-Salem, NC 27157 
 
Michael D Gautreaux, PhD 
Department of General Surgery 
Wake Forest Baptist Health 
Winston-Salem, NC 27157 
 
 
Cesar Rodriguez-Valdez, M.D. 
Department of Hematology and Oncology 
Wake Forest Baptist Health 
Winston-Salem, NC 27157 
 
 
Biostatistician: 
Scott Isom, MS 
 
Comprehensive Cancer Center of Wake Forest University 
 
 
 
 
 
Research Nurses: 
 
Vicki Lagerwey 
 
 
 
 
Section on Hematology and Oncology 
 
 
 
 
 
 
 
 
 
 
Karen Rike 
                                               Section on Hematology and Oncology 
 
 
 
 
 
Rebecca Damron  
                                               Section on Hematology and Oncology 
                                                
 
                                               Tong Chen, RN, BSN 
                                               Comprehensive Cancer Center of Wake Forest University 
                                                
 
Regulatory Coordinator: 
Alexandra Bolick, MBA 
 
 
 
 
Clinical Protocol and Data Management 


Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD 
Prophylaxis: A Pilot Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
Protocol version date 03-12-21 
 
Page 2 of 30 
 
 
 
 
 
 
 
Comprehensive Cancer Center of Wake Forest University 
 
 
 
 
 
 
Data Manager: 
 
Ronda Francis 
 
 
 
 
Clinical Protocol and Data Management 
 
 
 
 
Comprehensive Cancer Center of Wake Forest University 
 
 
 
 
 
 
QA Specialist: 
 
Amy Landon, BS, CCRP 
 
 
 
 
Biostatistic Core 
 
 
 
 
Comprehensive Cancer Center of Wake Forest University 
 
 
 
 
 
 
Participating Institution: 
Wake Forest Baptist Health 
 
Version Date: 
03.12.21 
09.11.19 - 11.06.18 - 09.26.18 - 08.23.18 - 05.17.18 - 02.09.18 - 
11.06.17 - 01.18.17 - 03.08.16 
Confidential 
 
 
 


Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD 
Prophylaxis: A Pilot Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
Protocol version date 03-12-21 
 
Page 3 of 30 
 
 
 
Table of Contents 
1.0 
Introduction and Background .......................................................................................... 4 
2.0 
Objectives ...................................................................................................................... 5 
3.0 
Inclusion/Exclusion Criteria ............................................................................................. 5 
4.0 
Registration Procedures ................................................................................................. 6 
5.0 
Study Procedures ........................................................................................................... 8 
6.0 
Adverse Event Monitoring and Reporting ......................................................................10 
7.0 
Response Criteria ..........................................................................................................11 
8.0 
Analytic Plan..................................................................................................................12 
9.0 
Stopping Rules for Safety ..............................................................................................12 
10.0 
Data Management .........................................................................................................13 
References ...............................................................................................................................14 
Appendix A – Eligibility Checklist ..............................................................................................15 
Appendix B - Protocol Registration Form ..................................................................................17 
Appendix C – Mandatory STRC SAE Reporting Requirements .................................................18 
Appendix D – Off-Study Form ...................................................................................................24 
Appendix E – Data Collection Form ..........................................................................................25 
Appendix F – Acute GVHD Clinical Criteria ...............................................................................27 
Appendix G – Survival Form .....................................................................................................29 
Appendix H – Adverse Event Log .............................................................................................30 
 
 
 
 
 
 
 
 
 
 
 
 
 


Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD 
Prophylaxis: A Pilot Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
Protocol version date 03-12-21 
 
Page 4 of 30 
 
 
 
1.0 
Introduction and Background 
 
Hematopoietic stem cell transplantation (HSCT) offers a curative potential for many 
hematological diseases including malignant, nonmalignant, and autoimmune disorders.  
However, the potential benefit of HSCT is directly offset by the risk of severe graft-versus-host 
disease (GvHD), which may lead to significant transplant associated morbidity and mortality. 
The risk of GvHD is directly proportional to the degree of HLA-disparity between the donor and 
recipient. For this reason, HLA-matched sibling transplants are associated with optimal 
outcomes.  
 
Only 25% of patients have an HLA-identical sibling1. As a result, the majority of patients require 
an alternative donor source, usually from an unrelated adult donor. For more than 20 years the 
National Marrow Donor Program (NMDP) has been recruiting volunteer donors for patients 
without HLA identical siblings. However, many patients, especially patients from ethnic minority 
backgrounds, frequently lack a full matched donor. Due to the fact that there are only 600,000 
registered African American adult donors compared to the 8 million white registered donors, 
African Americans are less likely to find HLA-matched unrelated donors2. By current estimates, 
approximately 6% of African Americans have an HLA-matched donor by high resolution 
available in the registry3.  
 
Haploidentical HSCT is an alternative for patients who do not have a fully HLA-matched donor. 
Almost all patients have an available HLA-haploidentical donor, which may include a parent, 
sibling, or child. However, early attempts at performing T cell–replete haploidentical 
transplantations using conventional preparative regimens have been associated with very high 
rates of graft-versus-host disease (GVHD) and graft rejection.4 Ex-vivo T cell depletion of the 
graft in combination with intensive preparative regimens have been employed to improve 
haploidentical transplant outcomes, but have often been associated high rates of infectious 
complications and non-relapse mortality (NRM).5,6 Recent work has demonstrated that the 
addition of high dose Cytoxan administered early post-transplant improves outcomes for 
patients receiving a haploidentical HSCT, and has been associated with acceptable rates of 
NRM and GVHD in single- and multi institution studies.7-9 Most recently, outcomes after T cell–
replete HLA-haploidentical HSCT using post-transplantation cyclophosphamide have been 
found to be equivalent to those of match-related donor (MRD) and matched unrelated donor 
(MUD) transplantations.10 
 
We propose a pilot study of performing haploidentical HSCT at our institution using post-
transplant cyclophosphamide to prevent GvHD and improve clinical outcomes. This protocol will 
be offered to subjects with hematologic malignancies who are eligible to receive a HSCT for 
curative intent with an available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor. 
A reduced intensity preparative regimen will be used in the protocol. 
 
 
 
 
 
 


Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD 
Prophylaxis: A Pilot Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
Protocol version date 03-12-21 
 
Page 5 of 30 
 
 
 
2.0 
Objectives 
 
2.1 
Primary Objective 
 
2.1.1  To determine if haploidentical stem cell transplant using post-transplant 
cyclophosphamide results in 60% or better disease free survival (DFS) at 12 
months at our institution.   
 
 
2.2 
Secondary Objective 
 
2.2.1 To determine the rate of acute and chronic GvHD, non-relapse mortality, 
and relapse.  
3.0 
Inclusion/Exclusion Criteria 
 
3.1 
Inclusion Criteria 
 
3.1.1 Diagnosis of a hematological malignancy requiring an allogeneic stem cell 
transplant consistent with the standard of care. 
 
3.1.2 Remission of any acute hematologic malignancy or adequate disease 
control for chronic malignancies. 
 
3.1.3 Ages 18-69 years old. 
 
3.1.4 Available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor. 
 
3.2 
Exclusion Criteria 
 
3.2.1 Significant organ dysfunction defined as: 
3.2.1.1 LV EF < 50% (evaluated by echocardiogram or MRI). 
 
3.2.1.2 DLCO or FEV1 < 65% predicted 
 
3.2.1.3 AST/ALT > 2.5 x ULN 
 
3.2.1.4 Bilirubin > 1.5 x ULN 
 
3.2.1.5 Serum Cr > 2mg/dL, dialysis, or prior renal transplant 
 
3.2.2 HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis 
C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from 
participation) 
 
3.2.3 Positive pregnancy test for women of childbearing age. 
 


Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD 
Prophylaxis: A Pilot Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
Protocol version date 03-12-21 
 
Page 6 of 30 
 
 
 
3.2.4 Major anticipated illness or organ failure incompatible with survival form 
transplant. 
 
3.2.5 Severe psychiatric illness or mental deficiency sufficiently severe as to 
make compliance with the transplant treatment unlikely and informed consent 
impossible. 
 
3.3 
Inclusion of Women and Minorities 
 
Men and women of all races and ethnicities who meet the above-described inclusion and 
exclusion criteria are eligible to participate in this study. 
 
3.4 Donor Selection Criteria 
 
3.4.1 Avoid donor specific antibodies (DSA). Select donors with a negative anti-
donor cross-match.  
 
3.4.2 Donor with full haplotype HLA-mismatch will be preferred (4 out of 8 HLA 
match) to maximize GVL. 
 
3.4.3 Male donors will be preferred to avoid reactivity against H-Y minor 
histocompatibility antigens and associated risk of risk of acute GvHD, especially 
grafts from multiparous women. 
 
3.4.4 Younger donors will be preferred.  Younger donor age has been associated 
with better patient survival in the MUD SCT setting. 
 
3.4.5 NIMA, IPA, and NK reactivity will not be included in selection criteria due to 
lack of evidence for impact on clinical outcomes and clinical utility. 
4.0 
Registration Procedures 
 
All patients entered on any CCCWFU trial, whether treatment, companion, or cancer 
control trial, must be registered with the CCCWFU Protocol Registrar or entered into 
ORIS Screening Log within 24 hours of Informed Consent. Patients must be registered 
prior to the initiation of treatment.   
 
In order to ensure prompt registration of your patient, please: 
1. Complete the Eligibility Checklist (Appendix A) 
2. Complete the Protocol Registration Form (Appendix B) 
3. Alert the CCCWFU 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: 


Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD 
Prophylaxis: A Pilot Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
Protocol version date 03-12-21 
 
Page 7 of 30 
 
 
 
Protocol Registrar PHONE (336) 713-6767 
Protocol Registrar FAX (336) 713-6772 
Protocol Registrar E-MAIL (registra@wakehealth.edu) 
              *Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday. 
 
4. Please fax/e-mail the eligibility checklist along with the completed registration form. 
Ensure that the source documents column of the checklist is complete and that the 
form is signed by either the research nurse or CRA. Patients will not be registered if 
forms are incomplete.  
Note: If labs were performed at an outside institution, please provide a printout of the 
results. Please ensure that the most recent lab values are sent. 
 
To complete the registration process, the Registrar will:   
 
• 
assign a patient study number 
• 
register the patient on the study 


Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
Protocol version date 03-12-21 
 
Page 8 of 30 
 
 
 
 
5.0 
Study Procedures 
 
 
 
Pre-
StudyA 
On-Study 
 
Day 
-3  
Day  
-2  
Day  
0 
Days 
3  
and 4 
Day 
15C 
Day 
30C 
Day 
45C 
Day 
60C 
Day 
100D 
6 months post-
transplantD 
12 months post-
transplantD 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
Cyclophosphamide 
 
 
 
 
X 
 
 
 
 
 
 
 
Stem cell transplant 
 
 
 
X 
 
 
 
 
 
 
 
 
AE CollectionB 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Data Collection 
(Appendix E) 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
A:  Pre-study requirements must be completed prior to registration 
BAE collection of only grade 3+ adverse events 
C:  Visit window is +/- 4 days of listed Day post-transplant. 
D. Visit window is +/- 14 days of listed Day post-transplant 
 
 
 
 
 
 


Protocol Version Date: 03.12.21 
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Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot 
Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
5.1 
Participant Recruitment 
 
The Bone Marrow Transplant Program at Wake Forest University Baptist Medical Center performs 
over 100 stem cell transplants a year, approximately one third of which are allogeneic. Patients will 
be recruited for this protocol after referral to Wake Forest University Baptist Medical Center, and if 
deemed eligible to receive an allogeneic stem cell transplant as standard of care treatment of their 
disease.  
 
5.2 
Transplant Preparative Regimen 
 
A Reduced Intensity Conditioning (RIC) Regimen will be included in this study as follows: 
 
a. Fludarabine 25 mg/m2/dose IV infusion over 30 minutes administered once daily for 3 
doses on Days -5, -4, and -3 (total dose of 75 mg/m2) 
 
b. Total body irradiation (TBI):  600 cGy divided in 4 x 150 cGy fractions, twice daily over 
days -2, -1.  
 
 
5.3 
Stem Cell Transplant Day 0.  
 
On the day of transplant, recipients will receive an infusion of the stem cell product with a target cell 
dose per recipient body weight of 3 - 5 x 106 CD34+ cells/ kg. 
 
 
5.4 
Post-transplant GvHD Prophylaxis.  
1. Cyclophosphamide 50 mg/kg IV will be administered once per day on days 3 and 4 after 
HSCT. 
2. Tacrolimus PO from days 5 to 120 , with a target level of 4 to 8 ng/mL.   
      3.  Cellcept 15 mg/kg PO rounded to the nearest 500 mg and may be adjusted for  therapeutic 
levels as appropriate on days 5 to 35. 
 
5.5 
Infection Prophylaxis.  
1. G-CSF 5 g/kg was administered from day +5 until neutrophil recovery. 
2. PCP, antiviral, and antifungal standard of care prophylaxis will be administered to all patients 
after transplantation. 
 
 
5.6 
Concomitant Medications and Supportive Care 
 
Supportive care will be administered as per the guidelines set forth in Biol Blood Marrow Transplant 
2009;15(10):1143-1238. 
5.6.1 High fevers and rigors commonly are associated with haploidentical immunotherapy. 
Immunosuppressive therapy given after transplant but prior to day + 5 may decrease the effect of 
post-transplant Cytoxan (PTCy) and increase the risk of GVHD.  Therefore, immunosuppressive 
therapy (i.e., steroids) needs to be avoided prior to day + 5 after SCT.  To treat fevers and rigors 
associated with immunotherapy, verify that neutropenic fever protocols are being followed.  May also 
consider the following agents: 
• 
Acetaminophen 
• 
Antihistamines 
• 
Demerol or morphine  for rigors 
• 
Ibuprofen (caution with low platelets.  May need to be accompanied by platelet transfusions.) 
 


Protocol Version Date: 03.12.21 
Page 10 of 30 
Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot 
Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
5.6.2 BK-induced Hemorrhagic Cystitis may occur in most patients receiving BuFlu conditioning, and 
may be treated with: 
• 
Supportive care for symptoms, i.e., pain relief 
• 
Bladder irrigation 
• 
Intravesicular cidofovir 
 
 
5.7 
Duration of Study Participation and Criteria for Removal from Study 
 
 
Participants may remain on study until one of the following criteria applies: 
 
• 
Disease progression 
• 
Intercurrent illness that prevents further administration of treatment 
• 
Unacceptable adverse event(s) 
• 
Patient withdraws consent to participate 
• 
General or specific changes in the patient’s condition render the patient unacceptable for 
further participation in the judgment of the investigator 
6.0 
Adverse Event Monitoring and Reporting 
 
6.1 
Adverse Event List  
 
Potential adverse events include infections, GvHD, toxicity to chemotherapy.  For this study, we will 
capture all Grade 3+ adverse events. Those that can be attributed to Cytoxan by the PI or designee 
will be recorded in the study’s database.  Patients should be followed for Grade 3+ AEs up to 100 
days post-transplant.  After 100 days post-transplant, patients will continue to be monitored only for 
GvHD, Relapse, and/or Death. 
 
 
6.2 
Adverse Event Characteristics 
 
• 
CTCAE term (AE description) and grade:  The descriptions and grading scales found in the 
revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be 
utilized for AE reporting. All appropriate treatment areas should have access to a copy of the 
CTCAE version 4.0. A copy of the CTCAE version 4.0 can be downloaded from the CTEP 
web site (http://ctep.cancer.gov). 
 
• 
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ (see Section 7.1 above) for 
expedited reporting purposes only.   
 
• 
Attribution of the AE: 
 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
 
6.3 
STRC SAE Reporting Requirements 
 


Protocol Version Date: 03.12.21 
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Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot 
Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
The Data Safety Monitoring Committee (DSMC) is responsible for reviewing SAEs for WFBCCC 
Institutional studies as outlined in Appendix B. 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.  
 
6.4 
WFUHS IRB AE Reporting Requirements 
 
Any unanticipated problems involving risks to subjects or others and adverse events shall be 
promptly reported to the IRB, according to institutional policy. Reporting to the IRB is required 
regardless of the funding source, study sponsor, or whether the event involves an investigational or 
marketed drug, biologic or device. Reportable events are not limited to physical injury, but include 
psychological, economic and social harm. Reportable events may arise as a result of drugs, 
biological agents, devices, procedures or other interventions, or as a result of questionnaires, 
surveys, observations or other interactions with research subjects. 
 
All members of the research team are responsible for the appropriate reporting to the IRB and other 
applicable parties of unanticipated problems involving risk to subjects or others. The Principal 
Investigator, however, is ultimately responsible for ensuring the prompt reporting of unanticipated 
problems involving risk to subjects or others to the IRB. The Principal Investigator is also responsible 
for ensuring that all reported unanticipated risks to subjects and others which they receive are 
reviewed to determine whether the report represents a change in the risks and/or benefits to study 
participants, and whether any changes in the informed consent, protocol or other study-related 
documents are required. 
 
Any unanticipated problems involving risks to subjects or others occurring at a site where the study 
has been approved by the WFUHS IRB (internal events) must be reported to the WFUHS IRB within 
7 calendar days of the investigator or other members of the study team becoming aware of the 
event. 
 
Any unanticipated problems involving risks to subjects or others occurring at another site conducting 
the same study that has been approved by the WFUHS IRB (external events) must be reported to 
the WFUHS IRB within 7 calendar days of the investigator or other members of the study team 
becoming aware of the event. 
 
Any event, incident, experience, or outcome that alters the risk versus potential benefit of the 
research and as a result warrants a substantive change in the research protocol or informed consent 
process/document in order to insure the safety, rights or welfare of research subjects. 
7.0 
Response Criteria 
 
 
Relapse of disease after transplant will be determined by morphological, cytogenetic,  
and 
molecular testing specific for the hematological malignancy of the patient. 
 


Protocol Version Date: 03.12.21 
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Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot 
Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
 
GvHD will be determined by the clinical criteria set forth in Appendix F and/or histological 
 
grading from biopsy.  
 
 
Disease free survival will be defined as time from registration to death from any cause or 
 
relapse of disease.  
 
 
Non-relapse mortality will be defined as time from registration to death due to anything other than r
 
elapse of hematological malignancy. Patients who relapse will be treated as a competing risk.  
 
 
Overall survival will be defined as time to death due to all causes. 
8.0 
Analytic Plan 
 
Our primary objective is to determine if the twelve month disease free survival probability for patients 
treated with haploidentical stem cell transplant using post-transplant cyclophosphamide is 0.60. We 
will calculate the proportion of subjects alive with no relapse disease at 12 months and the 
corresponding 95% confidence interval using the  normal approximation for binomial proportions.  
With 24 patients, we would need 16 or more patients for the lower bound of the 95% confidence 
interval to be above 0.60. If the  
lower bound of the confidence interval is above 0.6, we can be 
confident that the true proportion is also above 0.60. We will accrue up to two patients per month for 
one year. Once each participant has been in the study for one year, we will test our primary 
hypothesis. Patients will then be followed for an additional two years. We do not  anticipate any drop 
outs.  
 
We will monitor patients continuously throughout the study at regular clinic visits after transplant. If at 
any time six participants experience death or relapse within the first 12 months after transplant, the 
study will stop for futility.  
 
To evaluate our primary objective, we will first consider twelve month disease free survival as a 
binary outcome.   We will calculate the proportion of patients who  experience death or disease 
relapse by one year and construct a corresponding 95% confidence interval using the normal 
approximation for binomial proportions.  Additionally, we will treat disease free survival as a censored 
outcome. The survival function will be estimated and plotted using the method of Kaplan and Meier. 
Additionally, we will calculate the rates of acute and chronic GvHD, overall survival, and relapse (or 
death) in our study population at twelve months. To evaluate relapse-free mortality, we will estimate 
the cumulative incidence function in the presence of relapse.   
 
9.0 
Stopping Rules for Safety  
 
We expect that the rate of non-relapse mortality (NRM) is 20% in this population.  We have 
calculated the following stopping rules for safety that take into account this expected rate using a 
Bayesian design.  The study will stop if the probability of the true NRM rate is greater than the 
anticipated rate (assumed 0.2) is more 0.90.  We use a Beta distribution (alpha=1.0, beta= 1.5) as 
the prior distribution for the probability of non-relapse mortality, and we will start monitoring for safety 
when four deaths are observed.  
 


Protocol Version Date: 03.12.21 
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Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot 
Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Number of 
patients 
Stop if number of 
NRM by day-90 
reaches or 
exceeds 
≤11 
4 
≤15 
5 
≤19 
6 
 
We conducted a simulation study to evaluate the performance of the above stopping rules using 
various probabilities of NRM.  We first sampled 24 independent Bernoulli  trials, each with a 
probability p of NRM.11  Using the above stopping rules, we noted if the study would have stopped 
and how many NRM’s were observed. We repeated this process 100,000 times.  The results for 
several values of p are summarized in the table below.  
 
 
Prob of 
NRM = p 
10% 
20% 
30% 
40% 
50% 
60% 
70% 
Proportion 
of 
Stopped 
Studies 
2.40% 26.43% 66.28% 91.47% 98.93% 99.93% 99.99% 
Average # 
of NRM 
2.70 
4.79 
7.20 
9.60 
12.00 
14.40 
16.80 
 
If the true probability of NRM is very low (10%), the study is unlikely to stop for safety. Under our 
expected rate of NRM, the 26.43% of simulated studies stopped early for  safety. When the true rate 
of NRM is more than twice than our expected rate, the study is very likely to stop.  From the results 
of this simulation, we believe the stopping rules are appropriate. 
10.0 Data Management 
 
Form 
Database 
Informed consent 
WISER 
Registration form 
WISER 
Data collection form 
REDCap 
 


Protocol Version Date: 03.12.21 
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Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot 
Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
References 
 
1. 
McCullough J, Perkins HA, Hansen J. The National Marrow Donor Program with emphasis on the 
early years. Transfusion. Jul 2006;46(7):1248-1255. 
2. 
Aplenc R, Alonzo TA, Gerbing RB, et al. Ethnicity and survival in childhood acute myeloid leukemia: 
a report from the Children's Oncology Group. Blood. Jul 1 2006;108(1):74-80. 
3. 
Dew A, Collins D, Artz A, et al. Paucity of HLA-identical unrelated donors for African-Americans with 
hematologic malignancies: the need for new donor options. Biology of blood and marrow 
transplantation : journal of the American Society for Blood and Marrow Transplantation. Aug 
2008;14(8):938-941. 
4. 
Beatty PG, Clift RA, Mickelson EM, et al. Marrow transplantation from related donors other than 
HLA-identical siblings. The New England journal of medicine. Sep 26 1985;313(13):765-771. 
5. 
Aversa F, Terenzi A, Tabilio A, et al. Full haplotype-mismatched hematopoietic stem-cell 
transplantation: a phase II study in patients with acute leukemia at high risk of relapse. Journal of 
clinical oncology : official journal of the American Society of Clinical Oncology. May 20 
2005;23(15):3447-3454. 
6. 
Ciceri F, Labopin M, Aversa F, et al. A survey of fully haploidentical hematopoietic stem cell 
transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients 
in remission at transplantation. Blood. Nov 1 2008;112(9):3574-3581. 
7. 
Brunstein CG, Fuchs EJ, Carter SL, et al. Alternative donor transplantation after reduced intensity 
conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or 
unrelated double umbilical cord blood grafts. Blood. Jul 14 2011;118(2):282-288. 
8. 
Kasamon YL, Luznik L, Leffell MS, et al. Nonmyeloablative HLA-haploidentical bone marrow 
transplantation with high-dose posttransplantation cyclophosphamide: effect of HLA disparity on 
outcome. Biology of blood and marrow transplantation : journal of the American Society for Blood 
and Marrow Transplantation. Apr 2010;16(4):482-489. 
9. 
Luznik L, O'Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for 
hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation 
cyclophosphamide. Biology of blood and marrow transplantation : journal of the American Society for 
Blood and Marrow Transplantation. Jun 2008;14(6):641-650. 
10. 
Bashey A, Zhang X, Sizemore CA, et al. T-cell-replete HLA-haploidentical hematopoietic 
transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in 
outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor 
transplantation. Journal of clinical oncology : official journal of the American Society of Clinical 
Oncology. Apr 1 2013;31(10):1310-1316. 
11. 
McIver ZA, Melenhorst JJ, Grim A, et al. Immune Reconstitution in Recipients of Photodepleted HLA-
Identical Sibling Donor Stem Cell Transplantations: T Cell Subset Frequencies Predict Outcome. 
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow 
Transplantation. Dec 2011;17(12):1846-1854. 
12. 
McIver Z, Serio B, Dunbar A, et al. Double-negative regulatory T cells induce allotolerance when 
expanded after allogeneic haematopoietic stem cell transplantation. British journal of haematology. 
Apr 2008;141(2):170-178. 
13. 
Biol Blood Marrow Transplant. 2009;15(10): 1143–1238. doi:10.1016/j.bbmt.2009.06.019. 
 
 
 
 


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Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Appendix A – Eligibility Checklist 
 
 
 
 
 
 
 
IRB Protocol No. IRB00029210 
CCCWFU Protocol No.  97214 
Study Title: Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD 
Prophylaxis: A Pilot Study 
Principal Investigator:  Dianna Howard, MD 
 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria 
is met 
Criteria is 
NOT met 
Source Used to 
Confirm * 
Diagnosis of a hematological malignancy requiring 
an allogeneic stem cell transplant consistent with 
the standard of care. 
□ 
□ 
 
Remission of any acute hematologic malignancy or 
adequate disease control for chronic malignancies □ 
□ 
 
Ages 18-69 years old. 
 
□ 
□ 
 
Available familial haploidentical (4 to 6 out of 8 
HLA loci-matched) donor. 
 
□ 
□ 
 
Exclusion Criteria 
(as outlined in study protocol) 
Criteria 
NOT 
present 
Criteria is 
present 
Source Used to 
Confirm * 
Significant organ dysfunction defined as: 
 
 
 
 
LV EF < 50% (evaluated by echocardiogram or 
MRI). 
 
□ 
□ 
 
DLCO or FEV1 < 65% predicted 
 
□ 
□ 
 
AST/ALT > 2.5 x ULN 
 
□ 
□ 
 
Bilirubin > 1.5 x ULN 
 
□ 
□ 
 
Serum Cr > 2mg/dL, dialysis, or prior renal 
transplant 
□ 
□ 
 
HIV positive (Recipients who are positive for 
hepatitis B (HBV), hepatitis C (HCV) or human T-
cell lymphotropic virus (HTLV-I/II) are not excluded 
from participation) 
□ 
□ 
 
 Positive pregnancy test for women of childbearing 
age. 
□ 
□ 
 
Major anticipated illness or organ failure 
incompatible with survival from transplant. 
□ 
□ 
 
Severe psychiatric illness or mental deficiency 
sufficiently severe as to make compliance with the 
transplant treatment unlikely and informed consent 
impossible. 
 
□ 
□ 
 


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Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
 
This subject is      
 eligible /  ineligible     for participation in this study. 
 
ORIS Assigned PID: __________________  
 
 
 
 
 
 
 
 
Signature of research professional confirming eligibility:_____________________ 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 
 
 
 
 


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Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Appendix B - Protocol Registration Form 
 
DEMOGRAPHICS 
Patient: Last Name: 
_______________________________ 
First Name: 
_________________________________ 
MRN:    ___ ___ ___ ___ ___ ___ ___ ___ 
DOB (mm/dd/yy): __ __ / __ __ / __ __ 
SEX:    Male     Female 
Ethnicity (choose one):   Hispanic  Non-Hispanic 
Race (choose all that apply):   
 WHITE     BLACK       ASIAN     PACIFIC ISLANDER     NATIVE AMERICAN 
Height:   ___ ___.___ inches 
Weight: ___ ___ ___.___lbs.(actual) 
Surface Area: ___ ___.___m2   
Zip Code:  ___ ___ ___ ___ ___ 
Primary Diagnosis: _____________________________________________________ 
Date of Diagnosis: ___ ___ /___ ___/___ ___ 
 
Protocol Registrar can be contact by calling 336-713-6767 between 8:30 AM and 4:00 PM, Monday – Friday. 
Completed Eligibility Checklist and Protocol Registration Form must be hand delivered, faxed or e-mailed to 
the registrar at 336-7136772 or registra@wakehealth.edu. 
 
PROTOCOL INFORMATION 
Date of Registration: 
___ ___ / ___ ___ / ___ ___ 
MD Name (last) : 
______________________       
Date protocol treatment started: 
___ ___ / ___ ___ / ___ ___ 
Informed written consent (consent must be signed prior to registration): 
 YES  NO 
Date Consent Signed: 
___ ___ / ___ ___ / ___ ___ 
 
PID # (to be assigned by ORIS): 
___ ___ ___ ___ ___ ___ ___ ___ 


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CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Appendix C – Mandatory STRC SAE Reporting Requirements  
 
 
 
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 
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. 
 
 
 


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ClinicalTrials.gov;  NCT02248597 
 
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. 
 
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 


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ClinicalTrials.gov;  NCT02248597 
 
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 
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 DSMC members listed 


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Comprehensive Cancer Center of Wake Forest University 
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ClinicalTrials.gov;  NCT02248597 
 
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 
 
Glenn Lesser, MD – Hematology Oncology  
Mercedes Porosnicu, MD-- Hematology Oncology  
Ryan Hughes, MD – Radiation Oncology  
Michael Goodman, MD -- Hematology Oncology  
Daniel Reed, MD -- Hematology Oncology  
Mary Beth Seegars, MD -- Hematology Oncology  
 
 
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. 
 
 


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Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
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 
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:
 


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Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Screen Shot 3: 
 
 
 
Screen Shot 4: 
 
 
 
 
 
 


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Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Appendix D – Off-Study Form 
 
ORIS Assigned PID:  _____________________  Date:  ___ ___ / ___ ___ / ___ ___ 
 
 
Did the subject meet eligibility criteria for study enrollment?   Yes 
   No 
 
 
 
Reasons for withdrawal: (Check all that apply and provide additional information) 
 
 Patient exhibited progression of disease per PET/CT w/ contrast post-cycle 2 
 
 Unacceptable toxicity  
 
 
Describe:  __________________________________________________________ 
 
 Patient withdrawal of consent 
 
 Investigator’s discretion to withdraw patient from the study because continued participation in 
the study is not in the patient’s best interest 
 
 Undercurrent illness: a condition, injury, or disease unrelated to the intended disease for 
which the study is investigating, that renders continuing the treatment unsafe or regular follow-
up impossible 
 
 General or specific changes in the patient’s condition that renders the patient ineligible for 
further investigational treatment 
 
 Non-compliance with investigational treatment, protocol-required evaluations or follow-up 
visits 
 
 Termination of the clinical trial 
 
 Death 
 
 
 
Date of death:  ___ ___ / ___ ___ / ___ ___ 
 
 
 


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CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Appendix E – Data Collection Form 
 
ORIS-assigned PID:  ______________________ 
Date:  ___ ___ / ___ ___ / ___ ___  
 
Post-transplant visit day:   
 15  
 30  
 45  
 
 
 
 
 60  
 100  
 6 months post-transplant  
 
 
 
 
 12 months post-transplant 
 
 
 
 
 
 
1. Does the patient have clinical evidence of acute GvHD? 
 Yes  
 No 
 
 
If yes: 
 
 
 
What is the patient’s organ stage (as per criteria in Appendix F): 
 
 
 
 
 Stage 0 
 
 
 
 
 Stage 1 
 
 
 
 
 Stage 2 
 
 
 
 
 Stage 3 
 
 
 
 
 Stage 4 
 
 
 
 
What is the patient’s IBMTR grade of acute GvHD (as per criteria in Appendix F): 
 
 
 
 
 Stage 0 
 
 
 
 
 Stage 1 
 
 
 
 
 Stage 2 
 
 
 
 
 Stage 3 
 
 
 
 
 Stage 4 
  
 
 
2. Has the subject relapsed?   
 Yes    
 No 
 
If yes, date of relapse: ____/____/____ 
 
 
 
 
If GVHD is present, answer the following questions: 
 


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ClinicalTrials.gov;  NCT02248597 
 
3. Did the subject experience 50% body surface of skin involvement?  
 Yes    
 No 
 
4. Did the subject experience elevated bilirubin?  
 Yes    
 No 
 
 
Bilirubin value: __________ mg/dL Date of bilirubin lab: ____/____/____ 
 
5. Was there a progressive onset of cGvHD?  
 Yes    
 No 
 
6. Did the subject experience thrombocytopenia? 
 Yes    
 No 
 
 
Platelet value: _____________ mcL   
Date of platelet lab: ____/____/_____ 
 
7. Was there gut involvement?  
 Yes    
 No 
 
8. Karnofsky performance status: 
 
 
 100 Normal no complaints: no evidence of disease. 
 
 90 Able to carry on normal activity: minor signs or symptoms of disease. 
 
 80 Normal activity with effort: some signs or symptoms of disease. 
 
 70 Cares for self: unable to carry on normal activity or to do active work. 
 
 60 Requires occasional assistance, but is able to care for most personal needs. 
 
 50 Requires considerable assistance and frequent medical care. 
 
 40 Disabled; requires special care and assistance. 
 
 30 Severely disabled; hospital admission is indicated although death not imminent. 
 
 20 Very sick: hospital admission necessary; active supportive treatment necessary. 
 
 10 Moribund; fatal processes progressing rapidly. 
 
 0 Dead 
 
9. Was the subject still receiving corticosteroids at the time of cGvHD diagnosis? 
 
 Yes 
No 
 
 
10. Was there an absence of early response to immunosuppression? 
 Yes    
 No 
 
 


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Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Appendix F – Acute GVHD Clinical Criteria 
 
Organ Stages of Acute GVHD 
 
 
Skin 
Liver 
Gut 
Stage 
Percent BSA 
Bilirubin 
Stool Volume 
0 
0 
< 2.0 
< 500 
1 
<25 
2.0 – 2.9 
>500* 
2 
25 – 50 
3.0 – 5.9 
>1000 
3 
>50 
6.0 – 14.9 
>1500 
4 
Bullae 
> 15.0 
>2000† 
*or persistent anorexia, nausea and vomiting 
†or severe abdominal pain with or without ileus 
     
 
Glucksberg et.al. Transplantation 1974; 18:295-304 
Thomas et.al. New Engl J Med 1975; 292:895-902 
Przepiorka et.al. Bone Marrow Transplant 1996; 15: 825-828 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MAGIC Grading of Acute GvHD 


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CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Appendix G – Survival Form 
 
Study Number: ___ ___ ___ ___ ___ PID: ___ ___ ___ ___ ___ ___ ___ ___ 
 
PI: ____________________________ Date (mm/dd/yyyy): ___ ___/___ ___/___ ___ ___ ___ 
 
 
Instructions:  
 
 
1. Last known Survival Status:  
 Alive 
 Dead 
 Lost to Follow-up 
 
2. Expired Date: __/__/____ 
 
Relapse Mortality 
Non-Relapse Mortality 
 GVHD 
 Infection 
 Other: Specify ___________________________________ 
 
 
3. Last known Alive Date: __/__/____ 
 
4. Survival Status source: __________________________________________ 
Instructions: Source can be EMR, obituary, family member etc. Add to comments 
in wiser follow-up section 
 
5. Comment: 
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________ 


Haploidentical Stem Cell Transplant using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot Study 
Comprehensive Cancer Center of Wake Forest University 
CCCWFU # 97214 
ClinicalTrials.gov;  NCT02248597 
 
Appendix H – Adverse Event Log 
 
 
Appendix G –CCCWFU 97214 Adverse Event Log 
 
 
PI: _________________ 
Subject PID: _________________ 
MRN: ________________ 
Cycle #:  
Cycle Start Date:  
Cycle Start Time: 
Cycle End Date:  
Cycle End Time: 
Adverse Event CTC 
Term 
Lab 
Value 
Grade  
(1-5) per 
CTC 
Start 
Date 
Attribution  
DEF= Definite 
PROB= Probable 
POSS= Possible 
UNLK= Unlikely 
UNRL= Unrelated 
Treating MD 
Initials + 
Date 
End Date 
Expected 
N= No 
Y= Yes 
*Serious Adverse 
Event Detail:    
NO= No 
LT= Life Threatening 
DTH= Death 
DIS= Disability 
HOS= Hospitalization 
CA= Caused 
congenital anomaly 
RI= Required 
intervention to prevent 
impairment 
Dose 
Limiting 
Toxicity 
(DLT)  
N= No 
Y= Yes 
Action Taken 
NO= None 
DR= Dose 
Reduced 
RI= Regimen 
Interrupted 
TD= Therapy 
discontinued 
INTR= Interrupted 
then reduced 
Therapy 
Given 
NO= None 
SYM= 
Symptomatic 
SUP= 
Supportive 
VSUP= 
Vigorous 
Supportive 
Reportable?   
IRB= IRB 
STRC= STRC 
FDA= FDA 
SPON= Sponsor 
(Mark all that 
apply) 
Adverse 
Event 
Report 
(AER) 
filed? 
N= No 
Y= Yes 
Outcome 
R= Recovered 
TX= Still under 
treatment or 
observation 
A= Alive with 
Sequalae 
D= Died 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Serious Adverse Event: Hospitalization; Disability; Birth Defect; Life-threatening; Death. 
 
 
CTCAE Version 4 - http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf 
 
 
STRC = Safety and Toxicity Review Committee 
Version 
10/30/17 

ICF_000.pdf: 
Official Title: Haploidentical Stem Cell Transplant Using Post Transplant Cyclophosphamide 
for GvHD Prophylaxis: A Pilot Study  
IRB-Approved Date: 2/22/2021
NCT02248597


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CCCWFU# 97214
Version 02.11.2019
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HAPLOIDENTICAL STEM CELL TRANSPLANT USING POST 
TRANSPLANT CYCLOPHOSPHAMIDE FOR GVHD 
PROPHYLAXIS: A PILOT STUDY
Informed Consent Form to Participate in Research
Dianna S. Howard, MD, Principal Investigator
INTRODUCTION
You are being invited to participate in a research study. Research studies are designed to gain 
scientific knowledge that may help other people in the future. You may or may not receive any 
benefit from being a part of this study. There may also be risks associated with being part of 
research studies. 
You are being asked to take part in this study because you are a candidate for a procedure called 
Hematopoietic Stem Cell Transplantation (HSCT) and someone in your family has agreed to be 
your donor. Your participation is voluntary. Please take your time to make your decision; your 
study doctor or the study staff will explain any information that you do not understand.
WHY IS THIS STUDY BEING DONE?
Hematopoietic Stem Cell Transplant (HSCT) means that you will be infused (transplanted) with 
stem cells from another person, or donor.  HSCT is a standard treatment option and offers a good 
chance of cure for blood diseases (leukemias.)  However, a side effect of the transplant is Graft 
vs. Host Disease (GvHD), a life-threatening condition where the infused stem cells attack you 
because they do not ‘recognize’ your body’s own cells.  The risk of GvHD gets higher the more 
your donor’s HLA markers do not match yours.  HLA, or Human Leukocyte Antigens, are 
molecules that make up your immune system and are found on your white blood cells.  
Unfortunately, less than 1/3 of all patients who need a stem cell transplant have a fully HLA-
matched donor.  For this reason, a transplant with a half HLA-matched donor is usually 
preferred, and is called a “haplo-identical” transplant. Since your biological mother, father, 
sisters, or brothers share at least half of your genetic information, the best “haplo” donors are 
your family members – this is called “familial haplo-identical” transplant or, more commonly, a 
“half-matched related” transplant. 
This pilot study will explore the effects (good or bad) of familial haplo-identical transplants at 
Wake Forest Baptist Health and see how well it will treat your cancer and improve your 
condition.  You are eligible for this study because your doctor has determined that a half-
matched related transplant is the best treatment option for you. 
To avoid the risks associated with half-matched related transplants, you will be given a drug 
called cyclophosphamide on days 3 and 4 after your transplant. Cyclophosphamide is FDA 
approved to treat many different types of cancers, including hematologic malignancies.  
Treatment with cyclophosphamide immediately after a half-matched related transplant is 
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Institutional Review Board 
IRB Number:IRB00029210
Meeting Date Approved 2/22/2021          
Version Valid Until: 2/21/2022


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regarded as the best way to reduce the risk of GvHD and treat your cancer.  Therefore, another 
goal of this study is to see if giving you cyclophosphamide after your half-matched related 
transplant is safe and effective in treating your cancer and decreasing your chances of getting 
GvHD.
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
Approximately 24 people will take part in this study.
WHAT IS INVOLVED IN THE STUDY?
If you take part in this study, you will provide informed consent and have a medical history 
review.  As part of the research study, you will have your half-matched related stem cell 
transplant at Day 0. Then, on days 3 and 4 after your transplant, you will receive 
cyclophosphamide.  You will be followed up to 2 years from your stem cell transplant to monitor 
your outcome and health.
HOW LONG WILL I BE IN THE STUDY?
You will have follow-up visits as part of the normal standard of care for up to 2 years after your 
transplant.  Therefore you will be in the study for approximately 2 years plus the time it takes to 
set up and receive your half-matched related transplant after signing this consent. 
WHAT ARE THE RISKS OF THE STUDY?
Potential Risks of Stem Cell Transplants
The treatment with blood or bone marrow transplant requires the use of powerful drugs 
(chemotherapy) that have side effects, some potentially very serious.  It will be necessary for you 
to be admitted to the hospital for approximately 6-8 weeks.
In as many as 20-30% of patients undergoing blood or bone marrow transplantation, a 
combination of Graft versus Host Disease (GvHD), treatment thereof, other infections, and side 
effects of chemotherapy may lead to death in the first few months following transplantation.  
Drugs such as cyclosporin, methotrexate, and prednisone are given to try to prevent GvHD and 
many therapies are available to treat GvHD if it should develop.  Specific details of prevention 
and treatment of GvHD will be discussed separately from this consent form.
Potential Risks of Using Cyclophosphamide
Bone Marrow Suppression:  The treatment used to kill cancer cells and the GvHD-causing cells 
after transplant may also kill some normal body cells, especially those that grow rapidly (blood 
cells, hair, cells that line the mouth, stomach and intestines).  Blood cells are made in the bone 
marrow and are responsible for fighting infections (white blood cells), carrying oxygen (red 
blood cells), and causing blood to clot (platelets).  A reduction in the number of these blood cells 
(marrow suppression) can lead to an increased risk of bleeding and infection.  When these effects 
occur, they can be treated with blood products (transfusions) and antibiotics.  Bone marrow 
suppression is an expected side effect after receiving high doses of cancer-killing drugs, and it is 
this serious drug reaction that requires bone marrow transplantation.  
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The transplanted blood or marrow cells will replace the cells damaged by chemotherapy usually 
in 3-5 weeks; however, if the transplant is not successful, recovery of your marrow function may 
not occur and death due to an infection or bleeding is more likely.
In addition, these medications suppress the immune system to allow you to accept the blood or 
marrow cells from your donor.  This suppression of the immune system will, however, also make 
you more susceptible to infections after the blood or marrow transplant.  Even if the bone 
marrow appears to be functioning well, your immune system does not respond normally until at 
least one year after transplantation. 
Heart Failure:  A small number of patients given cyclophosphamide in high doses have 
developed shortness of breath and swollen ankles because of heart weakness.  On rare occasions, 
death due to heart failure can occur.
Lung Damage:  Scarring of the lungs (fibrosis) or inflammation (pneumonitis) may occur 
resulting in cough or shortness of breath and rarely can lead to death due to lung failure.
Liver Irritation:  High doses of chemotherapy may be associated with inflammation of the liver.  
This is usually temporary, but rarely severe liver damage is produced which can be fatal.
Kidney Damage:  Kidney damage is minimized by giving fluids by vein.  Kidney function will 
be monitored with blood tests.  Kidney damage is usually reversible, but may not be or take a 
long time to resolve.
Bladder Irritation:  Cyclophosphamide may produce burning on urination or bloody urine.  You 
should receive by vein at least three liters of fluid (approximately 12 glasses) daily.  Empty your 
bladder frequently.  Bladder irritation is usually reversible, but rarely severe damage occurs 
which can be fatal.  Patients with severe damage may need to have their bladders removed.
Skin Changes:  Many patients who receive high doses of chemotherapy develop a rash.  Later, 
the skin may peel.  A variety of creams may lessen the symptoms.  Sometimes the skin changes 
resemble mild sunburn followed by darkening which may be permanent.
Hair Loss:  Hair will fall out 1-3 weeks after the first dose of chemotherapy but will usually grow 
back several months after chemotherapy is discontinued.  Hair color will not dramatically 
change, but sometimes the hair is darker and curlier. 
Irregular Menstrual Cycle:  The menstrual cycle may usually cease permanently resulting in an 
inability to become pregnant.  Birth control should be practiced for at least 1 year following this 
therapy, if fertility is maintained.
You should tell the research staff about all the medication, vitamins and supplements you take 
and any medical condition you have. This may help avoid side effect, interactions and other 
risks. You should talk to your study doctor about any side effects that you have while taking part 
in the study.
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Institutional Review Board 
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Reproductive Risks: 
The drugs used in this study are known to have risk of causing malformations in an unborn child, 
especially when given in the early part of pregnancy. Therefore, you should not become pregnant 
or father a baby while on this study. For this reason, both men and women will be asked to 
practice an effective method of birth control while you are participating in this study. Also, 
because the risk is unknown to young children, you should not nurse your baby while on this 
study. Ask about counseling and more information about preventing pregnancy.
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, 
intrauterine device (IUD), DepoProvera, Norplant, 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 cervical cap or sponge. We encourage you to discuss this issue further with 
your physicians if you have any questions.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there may or may not be direct benefit to you. We hope the 
information learned from this study will benefit other people in the future. The benefits of 
participating in this study may be: cure of your cancer and prevention of Graft vs Host Disease.  
WHAT OTHER CHOICES ARE THERE?
You do not have to be in this study to receive treatment. You should talk to your doctor about all 
the choices you have. Instead of being in this study, you have these options:

Other chemotherapies 

Comfort care, which is an option if you decide that you do not want any more active 
treatment for your cancer. Comfort care includes pain medication and other types of support. It 
aims to maintain your comfort and dignity rather than cure disease. Usually this care can be 
provided at home. If you think you might prefer comfort care, please discuss this with your 
family, friends, and your doctor.
WHAT ABOUT MY HEALTH INFORMATION?
In this research study, any new information we collect from you about your health or behaviors 
is considered Protected Health Information. The information we will collect for this research 
study includes:  medical history, medical images, how you respond to study procedures, 
laboratory and other test results, and physical examinations.  If this research study involves the 
diagnosis or treatment of a medical condition, then Protected Health Information collected from 
you during this study will be placed in your medical record, and may be used to help treat you, 
arrange payment for your care, or assist with Medical Center operations.
We will make every effort to keep your Protected Health Information private. We will store 
records of your Protected Health Information in a cabinet in a locked office or on a password 
protected computer. Only the following people or organizations will be granted access to your 
Protected Health Information:
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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. 
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. Howard 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:
Dianna S. Howard, MD
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.
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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information limited to individuals with proper authority, but who may not be directly involved 
with this research study.
WHAT ARE THE COSTS?
There are no costs to you for taking part in the research portion of this study.  However, the costs 
for the half-matched related transplant and cyclophosphamide as well as the follow-up office 
visits are considered ‘regular medical care’ procedures and will be billed to you or your 
insurance.
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?
Wake Forest University Health Sciences is sponsoring the conduct of this study. The researchers 
do not, however, hold a direct financial interest in the sponsor or the product and procedures 
being studied.  
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 
more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should call Dr. Howard at 
 
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WHAT ARE MY RIGHTS AS A RESEARCH 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. 
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. Dianna Howard, 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. 
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 (Printed):___________________________
Obtainer Signature:_____________________________ Date:_________ Time:________ am pm
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00029210
Meeting Date Approved 2/22/2021          
Version Valid Until: 2/21/2022