A Randomized Placebo-Controlled Clinical Trial of Fecal Microbiota Transplantation in Patients With Acute Myeloid Leukemia and Allogeneic Hematopoietic Cell Transplantation Recipients
Phase: PHASE2
Conditions: Acute Myeloid Leukemia, Allogeneic Hematopoietic Cell Transplantation
Sponsor: Masonic Cancer Center, University of Minnesota

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
March 16, 2022 
Page 1 of 38 
2017LS170 
Masonic Cancer Center 
University of Minnesota 
 
 
 
A Randomized Placebo-Controlled Clinical Trial of Fecal Microbiota 
Transplantation in Patients with Acute Myeloid Leukemia and Allogeneic 
Hematopoietic Cell Transplantation Recipients 
2017LS170 
MT2018-01 
IND# 18607 
 
IND Sponsor/Principal Investigator: 
Shernan G. Holtan, MD 
Division of Hematology, Oncology and Transplantation 
 
 
Co-Investigators: 
Armin Rashidi MD, PhD 
Christopher Staley, PhD* 
Pamala Jacobson, PharmD, FCCP* 
Alexander Khoruts, MD 
*non-clinical, will not consent patients 
 
Biostatistician: 
Qing Cao, MS 
Xianghua Luo, PhD 
 
Medical Monitor: 
Byron Vaughn, MD 
 
Version Date: 
March 16, 2022 
 
 
Confidential 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
 Page 2 of 38 
 
2017LS170 
 
Revision History 
 
Revision # 
Version Date 
Summary of Changes 
Consent 
Change 
n/a 
08/06/2018 
Original submission to CPRC 
n/a 
1 
09/17/2018 
Removed MMF PKs from study; Increased accrual goal to 72 
patients per arm; Updated stopping rules; Updated to note that 
the study will use a REDCap database; added details on 
procedures for patients withdrawing from study; added 
guidance on patients unable to receive additional study drug 
doses; updated sample procurement and processing; minor 
edits for clarity 
n/a 
1A 
11/29/2018 
Per FDA request: updated exclusion criteria, safety follow-up, 
and monitoring; added patient drug reaction diary. 
Yes 
2 
2/11/2019 
Following study start up meeting: clarified eligibility procedures; 
expanded window for subsequent treatments; simplified drug 
administration procedures; removed research blood draws; 
deleted clinical visits; updated AE reporting procedures, added 
to ad hoc DSMC reporting procedures  
Per FDA request: added concomitant medications to patient 
diary  
Administrative changes: Updated to use Oncore database alone 
(removed REDcap) and blood to be stored in the TTL lab; added 
IND number to cover page; updated co-investigator list 
Yes 
2A 
04/19/2019 
Updated event monitoring per FDA request 
No 
3 
04/26/2019 
Table 8.1 Removed KPS score as this it is not done standard of 
care; changed 4 month visit to 4 week visit 
Table 8.2 Simplified table format, removed specification of tube 
size for bloods; moved 4 month research blood draw to 6 
months, deleted clinic visit at 4 month 
Section 12 – added details about the make-up and procedures 
of DSMC 
Removed Appendix III – Karnofsky scale 
Throughout – minor edits for clarity and spelling; clarification of 
Oncore forms used 
Yes 
4 
07/25/2019 
Section 5.2, 7.1.2,6.1, 6.3, Appendix I and II – patients will be 
permitted to co-enroll on other research studies 
Section 6.2 – Removed reference to biostatistician performing 
randomization 
Section 7.2 – Updated study drug administration guidelines to 
allow for patients consuming medications and light snacks 
within 2 hours prior to and post FMT/Placebo administration  
Sections 7.2, 9.1.2, 9.1.3 – Clarified that study product will be 
prepared and administered by trained study staff 
Sections 8.1, 8.2, 11.2, 13.2, schema – Clarified that procedures 
will occur 9 months after randomization 
Sections 8.2, 10.2 – Removed references that specified method 
of stool sample collection 
Section 11.5 – updated reporting to IRB Ethos system 
Throughout protocol – minor edits for punctuation 
Yes 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
 Page 3 of 38 
 
2017LS170 
 
5 
09/18/2019 
Schema, Section 8.2 – reduced amount of blood collected; 
combined week 1 & week 2 stool sample collections into a single 
collection at day 10 
Synopsis, Secondary Objectives, Endpoints – revised first 
secondary objective/endpoint to clarify time frame of 
engraftment 
Yes 
6 
11/06/2019 
Study design, inclusion criteria, eligibility checklist: clarified 
eligibility on Arm A to include any patients receiving 
chemotherapy 
Fixed typo in flow chart  
Yes (AML 
consent only) 
7 
01/15/2020 
Section 4 –clarification that patients will not be enrolled more 
than once on the same protocol 
Section 5.2, Section 6.3, Section 6.4, Section 7, Appendix I, 
Appendix II – minor clarifications to pre-treatment eligibility 
criteria; added allowance for patients to receive antibiotics for 
Pneumocystis carinii prophylaxis 
Section 8.1 – footnote clarification 
Section 8.2 – Added GVHD evaluation; updated footnote to 
allow for more frequent patient contact 
Section 11.1 – removed adverse events related to underlying 
disease process from definition of reportable events 
 
No 
8 
07/07/2020 
Section 5.1, Section 6, Section 6.1, Section 12.6, and Section 15.3 
- Updated consenting procedures to allow for remote 
consenting. 
Yes 
8A 
7/27/2020 
Section 5.1, Section 12.6, and Section 15.3 – Per IRB request, 
clarified documentation for remote consent. 
Yes 
9 
11/11/2020 
Section 8.2 Edited the window around research related sample 
collection 
Seciton 11.5, Section 12.3, Section 14.5 Added additional 
medical monitor to the trial to review stopping rule events. 
No 
10 
05/07/2021 
Section 8.2 research blood sample amount reduced to 6 mL 
Yes 
11 
09/22/2021 
Section 8.2 and Section 11.2 Simplified follow-up, removing 
monthly updates regarding the following potential findings: 
weight gain, or new diagnosis of pre-diabetes, diabetes, 
hypertension, obesity, or autoimmune conditions 
Yes 
12 
3/16/2022 
Change in Primary Principal Investigator/IND Sponsor 
Yes 
 
 
IND Sponsor/Principal Investigator Contact Information: 
Shernan Holtan, MD 
Hematology, Oncology and Transplantation 
Department of Medicine 
420 Delaware Street SE, MMC 480  
Minneapolis, MN 55455 
612-625-8942 (phone) 
612-625-6919 (fax) 
sgholtan@umn.edu (email) 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
 Page 4 of 38 
 
2017LS170 
 
Table of Contents 
 
Abbreviations ............................................................................................................................... 7 
Protocol Synopsis ......................................................................................................................... 8 
Protocol Schema .......................................................................................................................... 9 
Objectives ..................................................................................................................................10 
1.1 
Primary Objective ..........................................................................................................10 
1.2 
Secondary Objectives .....................................................................................................10 
1.3 
Correlative Objectives ....................................................................................................10 
2 
Background .........................................................................................................................10 
3 
Summary and Rationale ........................................................................................................11 
4 
Study Design ........................................................................................................................11 
5 
Patient Selection ..................................................................................................................11 
5.1 
Inclusion Criteria ...........................................................................................................11 
5.2 
Exclusion Criteria ...........................................................................................................12 
6 
Patient Registration ..............................................................................................................12 
6.1 
Study Enrollment ...........................................................................................................12 
6.2 
Randomization ..............................................................................................................12 
6.3 
Timing of initial study treatment .....................................................................................12 
6.4 
Timing of Additional Study Treatments ............................................................................13 
6.5 
Missed Additional Study Treatments ...............................................................................13 
6.6 
Patients Who Do Not Begin Study Treatment ...................................................................13 
7 
Treatment Plan ....................................................................................................................14 
7.1 
FMT/Placebo Administration Criteria ...............................................................................14 
7.2 
Study Drug Administration .............................................................................................14 
7.3 
Management of Selected Expected Toxicities ...................................................................15 
7.4 
Duration of Treatment ...................................................................................................15 
7.5 
Duration of Study Participation .......................................................................................15 
8 
Schedule of Patient Activities .................................................................................................16 
8.1 
Required Clinical Care Activities ......................................................................................16 
8.2 
Research Related...........................................................................................................17 
9 
Study Drug Information .........................................................................................................19 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
 Page 5 of 38 
 
2017LS170 
 
9.1 
Fecal Microbiota - lyophilized .........................................................................................19 
9.1.1 
Accountability ........................................................................................................19 
9.1.2 
Handling ................................................................................................................19 
9.1.3 
Ordering ................................................................................................................19 
9.1.4 
Destruction and Return ...........................................................................................19 
9.2 
Fecal Microbiota - lyophilized .........................................................................................20 
9.2.1 
Description ............................................................................................................20 
9.2.2 
Toxicology .............................................................................................................20 
9.2.3 
Supplier.................................................................................................................20 
9.2.4 
Storage and stability ...............................................................................................20 
9.2.5 
Handling, Ordering, Accountability, Destruction and Return. .......................................20 
9.3 
Placebo ........................................................................................................................21 
10 Correlative/Special Studies ....................................................................................................21 
10.1 
Specimen Collection and Transport To Processing Laboratory ............................................21 
10.2 
Initial specimen processing, storage, and shipping ............................................................21 
10.3 
Analytical Method .........................................................................................................22 
11 Event Monitoring, Documentation and Reporting ....................................................................22 
11.1 
Event Terminology ........................................................................................................23 
11.2 
Event Documentation ....................................................................................................24 
11.3 
SAE and Death Documentation .......................................................................................24 
11.4 
Early Stopping Rule Documentation and Reporting ...........................................................24 
11.5 
Expedited Event Reporting .............................................................................................25 
12 Study Data Collection and Monitoring .....................................................................................25 
12.1 
Data Management.........................................................................................................25 
12.2 
Case Report Forms ........................................................................................................26 
12.3 
Data and Safety Monitoring Plan (DSMP) .........................................................................26 
12.4 
Study Monitoring ..........................................................................................................28 
12.5 
Record Retention ..........................................................................................................28 
12.6 
Telephone and Electronic Consent Procedures .................................................................28 
13 Study Endpoints ...................................................................................................................29 
13.1 
Primary Endpoint ..........................................................................................................29 
13.2 
Secondary Endpoints .....................................................................................................29 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
 Page 6 of 38 
 
2017LS170 
 
13.3 
Correlative Endpoints ....................................................................................................29 
14 Statistical Considerations ......................................................................................................29 
14.1 
Study Design .................................................................................................................29 
14.2 
Power Analysis: .............................................................................................................30 
14.3 
Data Analysis Plan: ........................................................................................................30 
14.4 
Sample Size and Accrual .................................................................................................30 
14.5 
Safety Monitoring .........................................................................................................30 
15 Ethical and Regulatory Considerations ....................................................................................31 
15.1 
Good Clinical Practice ....................................................................................................31 
15.2 
Ethical Considerations ....................................................................................................31 
15.3 
Informed Consent .........................................................................................................31 
16 References ..........................................................................................................................32 
Appendix I – Eligibility Checklist for Initial Enrollment ......................................................................35 
Appendix II – Eligibility Checklist for FMT/placebo Administration .....................................................36 
Appendix III – FMT/Placebo Reaction Diary ....................................................................................37 
 
 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
 Page 7 of 38 
 
2017LS170 
 
ABBREVIATIONS 
AE 
Adverse Event 
ALL 
Acute Lymphoblastic Leukemia 
Allo-HCT 
Allogeneic Hematopoietic Stem Cell Transplant 
AML 
Acute Myeloid Leukemia 
ANC 
Absolute Neutrophil Count 
CBC/diff 
Complete Blood Count With Differential 
C. Diff 
Clostridium difficile Infection 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMSO 
Dimethyl Sulfoxide 
DSMP 
Data & Safety Monitoring Plan 
DNA 
Deoxyribonucleic acid 
FDA 
Food and Drug Administration 
FMT 
Fecal Microbiota Transplant 
GVHD 
Graft versus Host Disease 
IND 
Investigational New Drug  
MCT 
Molecular and Cellular Therapeutics facility 
IRB 
Institutional Review Board 
PBMC 
Peripheral Blood Mononuclear Cells 
PHI 
Protected Health Information 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
TTL 
Translational Therapy Lab 
UPIRTSO 
Unanticipated Problems Involving Risks to Subjects or 
Others 
 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
 Page 8 of 38 
 
2017LS170 
 
Protocol Synopsis 
 
 
 
Study Design: 
This is a randomized, double-blind, placebo-controlled clinical trial of Fecal Microbiota 
Transplant (FMT) in 2 independent cohorts (72 acute myeloid leukemia patients 
undergoing chemotherapy and 72 Allo-HCT patients). Participants in each cohort will 
be randomized in a 2:1 ratio to receive up to 3 treatments of FMT vs. placebo after 
each exposure to antibacterial antibiotics until 3 months after randomization. The 
primary endpoint is 4-month all-cause, clinically defined infection rate. Interim safety 
analysis will be performed.   
Primary 
Objective: 
To demonstrate the efficacy of FMT in acute myeloid leukemia patients and stem cell 
transplant recipients, as measured by the number of all infections within 4 months 
after the first study drug administration.  
Secondary 
Objectives: 
• 
To determine FMT engraftment rate at 10 days and 4 weeks post-FMT 
• 
In the Allo-HCT cohort, determine the cumulative incidence of acute grade II-IV 
GVHD until day 180 post-HCT 
• 
In both cohorts, determine the incidence of bloodstream infection (BSI) until 1 
week after each FMT 
• 
In both cohorts, determine the number of bacterial, viral, and fungal infections  
within 4 months after the first study drug administration. 
Inclusion 
Criteria: 
• 
Age≥ 18 years 
• 
Acute myeloid leukemia (AML) undergoing chemotherapy, or  patients 
undergoing Allo-HCT 
• 
For each study treatment: ANC > 1,000, resolution of all acute toxicities to grade 
2 or lower, and at least 2 days post discontinuation of all antibacterial antibiotics 
Exclusion 
Criteria: 
• 
Planned continuation of antibacterial antibiotics after the first neutrophil 
recovery (ANC > 1,000) 
• 
Subjects with severe food allergies 
• 
Subjects with a history of chronic aspiration 
Accrual Goal 
72 subjects in each cohort over 2 years 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 10 of 38 
 
2017LS170 
 
Objectives 
1.1 Primary Objective 
To demonstrate the efficacy of FMT in AML patients and allo-HCT recipients, as measured by 
the number of all infections within 4 months after the first study drug administration. 
1.2 Secondary Objectives 
• To determine FMT engraftment rate at 10 days and 4 weeks post-FMT 
• In the Allo-HCT cohort, determine the incidence of acute grade II-IV GVHD until day 180 
post-HCT 
• In both cohorts, determine the incidence of BSI until 1 week after each FMT 
• In both cohorts, determine the number of bacterial, viral, and fungal infections within 4 
months after the first study drug administration.  
1.3 Correlative Objectives 
• 
To determine the effect of FMT on biomarkers of gut barrier integrity 
2 Background 
Perturbations in gut microbiota ecology and homeostasis play an important role in pathogenesis 
of various disease states [1] [2]. This includes stem cell transplant complications such as acute 
GVHD [3] [4] [5] and bloodstream infections in patients receiving intensive chemotherapy [6] [7]. 
Disruptions of the gut barrier as a result of cytotoxic chemotherapy and/or radiation in the setting 
of anti-leukemic treatment or transplant preparative regimen exposes the host to the gut 
microbiota in a dysregulated fashion. In addition, routine use of prophylactic and therapeutic 
antibiotics in these patients leads to microbiota injury manifested as a reduction in beneficial 
bacteria (e.g., Clostridia) and dominance of a few pathogenic bacteria (e.g., Enterococci) [8]. 
Collectively, these changes result in pathologic cytokine release, deregulation of local and 
systemic immune responses (i.e., the underlying event in acute GVHD), and bloodstream 
infection.  
Microbiota restoration is an active field of research with the overarching goal of preventing 
disease states associated with dysbiosis. One promising such approach is fecal microbiota 
transplantation (FMT) from healthy donors. The safety of this approach is becoming apparent 
even in immunosuppressed patients. The best example is FMT in allo-HCT patients to treat 
steroid-refractory acute GVHD and correct dysbiosis after engraftment, now reported from 2 
independent groups [9] [10]. Stem cell transplant patients, particularly those with acute GVHD, 
represent one of the most severely immunocompromised patients and the demonstrated safety 
of FMT in these patients has made this approach a popular therapeutic strategy in less 
immunosuppressed patient populations.  

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 11 of 38 
 
2017LS170 
 
Our primary goal in the present study is to demonstrate the efficacy of our FMT product in allo-
HCT and AML patients upon count recovery. These patients are at risk of dysbiosis-related 
complications such as BSI and GVHD. The freeze-fried encapsulated preparation of fecal 
microbiota was originally developed as a treatment option for patients suffering with the 
recurrent C. diff. infection who have failed multiple attempts to cure the infection with 
antibiotics alone [11]. Overall, 43/49 (88%) of patients achieved a clinical success, defined as no 
recurrence of CDI over 2 months. Analysis of the fecal microbiome demonstrated near 
normalization of the fecal microbial community by 1 month following FMT treatment.  
3 Summary and Rationale 
The adverse effect of dysbiosis in various disease states has been well established. Dysbiosis is 
very common and particularly problematic in the setting of curative treatments for hematologic 
malignancies, partly due to the routine use of antibiotics. Dysbiosis increases complications of 
cancer treatment such as BSI, GVHD, and C. difficile infection. FMT is a promising approach to 
restore the normal composition and diversity of microbiome, and may improve outcomes of 
chemotherapy in patients at high risk for complications.  
4 Study Design 
This is a randomized, double-blind, placebo-controlled clinical trial of Fecal Microbiota Transplant 
(FMT) procedure in 2 independent cohorts (72 Acute Myeloid Leukemia (AML) patients 
undergoing chemotherapy and 72 Allo-HCT patients). Participants in each cohort will be 
randomized in a 2:1 ratio to receive up to 3 treatments of FMT vs. placebo after each exposure 
to antibacterial antibiotics until 3 months after randomization. Patients will not be enrolled more 
than once on this protocol. The primary endpoint is the number of all infections within 4 months 
after the first study drug administration. Interim safety analysis will be performed.  
5 Patient Selection 
Study entry is open to adult patients regardless of gender or ethnic background. While there will 
be every effort to seek out and include women and minority patients, the patient population is 
expected to be no different than that of other leukemia and HCT studies at the University of 
Minnesota. 
5.1 Inclusion Criteria 
• Age≥ 18 years 
• Cohort A: Patients undergoing chemotherapy for acute myeloid leukemia (AML; newly 
diagnosed or relapsed/refractory) 
• Cohort B: Allo-HCT patients  

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 12 of 38 
 
2017LS170 
 
o Any T-replete allogeneic transplant regimen 
• 
Sexually active females of childbearing potential and males with partners of child-bearing 
potential must agree to use adequate birth control until at least six months post-
FMT/placebo 
• 
Voluntary in-person written consent; or, remote consent via phone or electronic system. 
Remote consent will be documented with wet ink signature or  e-signature using a 21 CFR 
Part 11 compliant system such as REDcap before performance of any study-related 
procedure not part of normal medical care. 
5.2 Exclusion Criteria 
• Planned continuation of antibacterial antibiotics (with the exception of antibiotics used 
for Pneumocystis carinii prophylaxis) after the first neutrophil recovery (ANC > 1,000) 
• Subjects with severe food allergies 
• Subjects with a history of chronic aspiration 
• Pregnant or breast feeding. The FDA has not classified this agent into a specified 
pregnancy category. Females of childbearing potential must have a blood test or urine 
study within 14 days prior to registration to rule out pregnancy 
6 Patient Registration 
Registration will occur after the patient has consented and eligibility is confirmed, but before 
any treatment has been administered. To be eligible for registration to this study, the patient 
must meet each criteria listed on the eligibility checklist (found in appendix I) based on the 
eligibility assessment documented in the patient’s medical record.  
6.1 Study Enrollment  
Upon completion of the screening evaluation, eligibility confirmation and obtaining either 
written, telephone, or electronic consent, the Study Coordinator or designee will enroll 
the patient on study in OnCore system. Co-enrollment on other studies is permitted. 
6.2 Randomization  
Patients will be randomized on a 2:1 ratio of FMT versus placebo in OnCore to complete 
enrollment. 
6.3 Timing of initial study treatment 
Patients will be consented before or within 7 days of starting chemotherapy [Cohort A] 
or before transplant Day 0 [Cohort B]. Patients will receive initial study treatment 
(FMT/placebo) either inpatient or outpatient, once their ANC count is greater than 1000. 
Additionally, if all antibacterial antibiotics have been discontinued (with the exception of 
antibiotics used for Pneumocystis carinii prophylaxis) for at least 2 days and all acute 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 13 of 38 
 
2017LS170 
 
toxicities have resolved to grade 2 or lower, study therapy will begin within 7 days after 
discontinuation of antibacterial antibiotics. To receive the study therapy, treatment 
eligibility will be confirmed based on the eligibility assessment (outlined in section 7.1 
below and in appendix II) and documented in the patient’s medical record. Patients will 
be permitted to co-enroll on other studies. 
6.4 Timing of Additional Study Treatments 
If patients are retreated with antibacterial antibiotics within the 3 month period after 
randomization, they may repeat FMT/placebo, up to two additional times, for a total of 
three treatments. Repeat FMT/placebo will begin after completion of each antibacterial 
antibiotic course, once the patient’s ANC count is greater than 1000, antibacterial agents 
(with the exception of antibiotics used for Pneumocystis carinii prophylaxis) have been 
discontinued for at least 2 days, and all acute toxicities have resolved to grade 2 or lower. 
Treatment eligibility must be reconfirmed (using the eligibility assessment in appendix II) 
before each additional study treatment and documented in the patient’s medical record. 
6.5 Missed Additional Study Treatments 
If patients who receive additional antibacterial antibiotics are unable to receive an 
additional study treatment for the following reasons: 
• They are travelling and unable to return to the University of Minnesota clinic in 
the permitted study window. 
• They receive additional antibacterial antibiotics at their home provider clinic and 
are unable to return to the University of Minnesota clinic in the permitted study 
window 
• Additional special prohibitive circumstances are present and discussed with the PI 
the study treatment will be considered skipped, but not a deviation, and patients will 
continue to be followed on study. Patients will be eligible for additional treatments within 
the 3 month period after randomization. 
If patients are unwilling to receive additional study treatments, they will be removed from 
the study, no further labs will be drawn, and no further samples will be collected. 
Further details on study removal are shown in section 7.5. 
6.6 Patients Who Do Not Begin Study Treatment  
If a patient is registered to the study, and is later found not able to begin the study 
treatment, for any reason, the patient will be taken off study. The Study Coordinator or 
designee will update OnCore of the patient’s non-treatment status. The patient will be 
replaced to fulfill enrollment requirements. 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 14 of 38 
 
2017LS170 
 
7 Treatment Plan 
In order to provide optimal patient care and to account for individual medical conditions, 
investigator’s or treating physician’s discretion may be used in the prescribing of all 
supportive care drug therapy (i.e. acetaminophen, diphenhydramine, etc.). 
Each FMT treatment will consist of ~5.0 x 1011 bacteria divided in 4-6 capsules given either 
inpatient or outpatient. Trehalose-containing capsules (excipient alone) will be used as 
placebo. The following administration criteria need to be met: 
7.1 
FMT/Placebo Administration Criteria 
In instances where meeting the criteria for a specific subject is equivocal, the treating 
clinician and PI will collaborate to make a determination. This consultation should be 
documented.  
For each study treatment administration, FMT/placebo capsules shall be administered if 
the following criteria are met: 
7.1.1 Inclusion Criteria 
• Neutrophil recovery: ANC > 1,000, checked within the last 7 days  
• All anti-bacterial antibiotics have been discontinued for at least 2 days. 
(excluding antibiotics used for Pneumocystis carinii prophylaxis) 
• Acute toxicities have resolved to grade 2 or lower 
• Negative pregnancy test result for females of child bearing potential 
7.1.2 Exclusion Criteria 
• Unable to swallow capsules 
• Disease has relapsed/progressed after original consent 
• Active infection  
• [Cohort B]  GVHD on treatment  
Participants who are not eligible to receive the first dose of study product will be taken off 
study and replaced.  
7.2 Study Drug Administration 
The oral capsules of FMT/placebo will be administered to patients directly by trained clinical 
research staff. The protocol for capsule FMT/placebo administration includes: 
1)  Only clear liquids, medications, or light snacks by mouth for at least 2 hours prior 
and 2 hours after FMT/placebo. Crackers or other light snacks to manage nausea or 
other side effects are permitted. 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 15 of 38 
 
2017LS170 
 
2) Swallow capsules with at least one glass of plain tap water. 
3) Remain upright for 2 hours after the capsule administration. 
Patients will be monitored for 15 minutes after taking the first FMT/Placebo.  They will be 
given a study drug reaction diary to log side effects every day for one-week post FMT/placebo 
dose. 
In addition, a member of the study team will contact the patients by telephone 1, 3 (+/-1), 
and 7 (+/- 3) days after each FMT/placebo administration to monitor for adverse events (AEs) 
to include: fever, abdominal pain, diarrhea, constipation, and bloating 
7.3 Management of Selected Expected Toxicities  
1) Fever within 7 days after FMT/placebo: Patients with fever will be evaluated in the 
emergency room or in clinic same day. Standard institutional algorithms for treatment 
fever in immunosuppressed patients will be applied.  
2) Vomiting within 8 hours after FMT/placebo: This will be treated similar to nausea and 
vomiting for other reasons, using medications such as ondansetron or 
prochlorperazine. If not controlled by these measures, the patient will be referred to 
the emergency room.  
7.4 Duration of Treatment 
The FMT/placebo capsule will be administered orally up to 3 total times within the 3 month 
period after randomization either inpatient or outpatient. Patients may receive additional 
treatments (#2 - #3) after each new course of antibacterial antibiotics. Each administration 
will occur at the time of neutrophil recovery (ANC > 1000) as long as antibacterial antibiotics 
(with the exception of antibiotics used for Pneumocystis carinii prophylaxis) have been 
discontinued for at least 2 days and all acute toxicities have resolved to grade 2 or lower.   
7.5 Duration of Study Participation 
Evaluable patients will be followed for 9 months after randomization unless: 
• Consent is withdrawn 
• Routine treatment follow-up is discontinued due to failing health, re-transplant, or 
other reason 
• Patients who fail to comply with receiving additional FMT/placebo after antibacterial 
antibiotics. 
• The treating physician decides at some point that ongoing participation is not in the 
patient’s best interest  
In these cases, patients will be followed for toxicity, but will not have study samples obtained.

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
March 16, 2022 
Page 16 of 38 
2017LS170 
8 Schedule of Patient Activities 
8.1 Required Clinical Care Activities 
Below are standard of care evaluations which are performed as part of the parent protocols. Results of these evaluations will be extracted from 
the BMT Database. 
 
Administration 1-3 
 
 
Activity 
 Initial 
Assessment* 
Pre FMT/placebo 
Assessment 
(w/in 7 days) 
¥4 weeks post first FMT /placebo 
(+/- 7 days) 
9 months after randomization 
(+/- 14 days) 
Clinical evaluation 
X 
X 
X 
X 
Weight 
X 
 
X 
X 
Medical history 
X 
X 
X 
X 
Physical exam and 
vital signs 
X 
X 
X 
X 
Medications 
X 
X 
X 
X 
Disease relapse** 
 
X 
 
 
Adverse events 
assessment 
 
X 
X 
X 
¥ Activities are from the time of the most recent FMT/placebo administration. If the patient receives additional FMT/placebo administration, the 
clock will “restart” 
*Prior to consenting 
**No procedures will be done to determine remission/relapse status for this study per se. However, if the existing information shows relapse, the 
patient will not receive further treatment and further samples will not be collected.  
 
 
 
 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 17 of 38 
 
2017LS170 
 
 
8.2 Research Related  
 
 
Administration 1-3¥ 
 
 
 
Prior to Treatment 
(chemotherapy or 
HCT) 
When ANC > 
1000 
¥1 day,  
and 3 (+/- 1 
day)  days 
post 
FMT/placebo 
¥1 week 
post FMT 
/placebo 
(+/- 3 
days) 
¥10 days 
FMT 
/placebo 
(+/- 3 
days) 
¥4 weeks 
post FMT 
/placebo 
(+/- 3 
days) 
 
 9 months 
after 
randomization 
(+/- 14 days) 
Consent 
X (by day 7 of 
chemotherapy or before 
day 0 of transplant) 
 
 
 
 
 
 
 
Eligibility Screening 
X (by day 7 of 
chemotherapy or before 
day 0 of transplant) 
X 
 
 
 
 
 
 
Randomize to FMT or 
Placebo 
X 
(within 3 days after 
consent) 
 
 
 
 
 
 
 
FMT/placebo  
 
X 
 
 
 
 
 
 
Serum pregnancy test 
X 
X  
 
 
 
 
 
 
Stool Sample 
** 
X (by day 7 of 
chemotherapy or before 
day 0 of transplant) 
X (at count 
recovery within 
7 days of 
ANC>1000) 
 
 
X 
X 
 
X  
Serum Sample 
10 ml of serum ( red 
top tube)  
X (by day 7 of 
chemotherapy or before 
day 0 of transplant) 
X (at count 
recovery within 
7 days of 
ANC>1000) ỻ 
 
 
 
Xµ 
 
X 
Blood:  6 mL  (yellow-
top  tubes)  
X (by day 7 of 
chemotherapy or before 
day 0 of transplant) 
X (at count 
recovery within 
7 days of 
ANC>1000) ỻ 
 
 
 
Xµ 
 
X  
GVHD Assessment 
 
 
 
 
 
 
 
X 
Research staff may 
review toxicities/drug 
diary with patients 
either at SOC visits or 
via telephone as per 
most current COVID-19 
guidelines £ 
 
 
Xß 
Xß 
 
X€ 
 
X€ 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 18 of 38 
 
2017LS170 
 
¥ Samples are from the time of the most recent FMT/placebo administration. If the patient receives additional FMT/placebo administration, the 
clock for stool, but not blood/serum, collection will “restart” 
** Sample will be collected only if patient has a bowel movement. Missed samples will not be considered a deviation. 
ß Study staff will review drug reaction diary with patient. If a subject reports an adverse event that warrants further investigation, an 
unscheduled clinic visit will be initiated. 
€ Patients will be asked whether or not they have gained weight or been newly diagnosed with conditions such as pre-diabetes, diabetes, 
hypertension, obesity, or autoimmune conditions 
ỻ Prior to first FMT/placebo only 
µ Only after study drug administration #1, whether or not clock has reset for other study procedures 
£ Telephone calls may be more frequent if clinically indicated 
Research sample collection is tied to the clinical care schedule of events and their associated window for performance. Therefore, if a clinical time 
point does not occur or is altered, the research related time point will be adjusted (or eliminated) as appropriate. It is recognized that with novel 
therapies as used in this study, the timing of protocol directed research samples may miss important patient specific events. For this reason, up to 3 
extra samples for a total of 180 ml of blood may be drawn at additional time points that are not specified above. 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
March 16, 2022 
Page 19 of 38 
2017LS170 
9 Study Drug Information 
Single donor lots of minimally manipulated microbial material in lyophilized form, derived from 
human feces will be provided by the Molecular and Cellular Therapeutics (MCT) facility at the 
University of Minnesota.  
9.1 Fecal Microbiota - lyophilized 
Dosage form: capsules for oral administration  
Concentration or strength: ~1.0 x 1011 per capsule 
Total dosage: ~5 capsules 
Single-use or multiuse container: Single Use 
Manufacturer information: UMN Microbiota Therapeutics Program. FMT capsules 
will be manufactured at the Molecular and Cellular Therapeutics, University of 
Minnesota, 1900 Fitch Avenue, St. Paul, MN 55108 
 
 
The following elements apply: 
9.1.1 Accountability 
UMN Microbiota Therapeutics Program, the manufacturer, will maintain product 
records for the manufacturing process through delivery of the product to the 
sponsor-investigator. The Molecular and Cellular Therapeutics facility will 
maintain product accountability records from receipt through dispensing the 
product to the sponsor-investigator. The sponsor-investigator will record 
administration of the product to each subject.  
9.1.2 Handling 
Qualified personnel, familiar with aseptic technique and procedures that ensure 
the quality of the agent and minimize undue exposure to themselves and the 
environment, should undertake the preparation, handling, and, when applicable, 
safe disposal of the agent. The encapsulated lyophilized product will be 
administered directly to patients for oral use by trained staff. 
9.1.3 Ordering 
UMN Microbiota Therapeutics Program will deliver the lyophilized fecal 
microbiota preparation to the trained study staff for administration to the subject.  
9.1.4 Destruction and Return 
Unused agent will be disposed of according to approved institutional standard of 
practice.  
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 20 of 38 
 
2017LS170 
 
9.2 Fecal Microbiota - lyophilized  
9.2.1 Description 
The lyophilized product is manufactured by diluting the fecal slurry to 2.9-8.6 x 
1010 microbes per milliliter with sterile phosphate buffered saline (PBS) and 
amended with a sterile trehalose solution to a final concentration of 10%. A 35ml 
aliquot of the suspension is distributed to a stainless steel tray and lyophilized.  
The lyophilized powder is manually filled into capsules, which are stored with a 
dessicant at -60°to -80°C in a mechanical freezer. The single dose is defined as 5 x 
1011 bacteria in variable number of capsules (typically 4-6). 
9.2.2 Toxicology 
Thus far, the capsule FMT product has been used exclusively in patients with 
multiply recurrent C. difficile infection who have failed to cure the infection with 
antibiotics alone. No adverse events attributable to the product were noted in the 
initial published experience with 49 patients [11]. This experience has since been 
extended to 108 patients with no adverse events attributable to the product.  
9.2.3 Supplier  
The microbiota capsules and placebo are manufactured by the Microbiota 
Therapeutics Program in accordance with IND 15071 (Sponsor-Investigator is 
Khoruts).  The manufacturing is done in accordance with cGMP protocols in the 
Molecular and Cellular Therapeutics (MCT) building on the St. Paul campus.  The 
capsules are kept in MCT until they are released to Dr. Khoruts in accordance with 
release criteria.  Following release the capsules are kept at -80oC in Dr. Khoruts’ 
Lab freezer in the Wallin Medical Biosciences Building. 
9.2.4 Storage and stability 
Lyophilized preparations will be stored in a desiccated condition at -60°to -80°C 
in a mechanical freezer. 
Stability testing, described in the updated IND 15071, includes microbial cell 
membrane integrity that shows no loss of cell viability various temperatures up to 
6 months. The data includes testing at room temperature for 4 days, which 
suggests no loss of activity is anticipated when the product is taken out of storage 
and brought into clinic. In vivo stability testing was done by clinical potency of the 
product in curing C. difficile infection over at least one year.  
9.2.5 Handling, Ordering, Accountability, Destruction and Return. 
See section 9.1. 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 21 of 38 
 
2017LS170 
 
9.3 Placebo 
The placebo (Trehalose-containing capsules) will be provided by the University of 
Minnesota Microbiota Therapeutics Program. The placebo capsules are 
manufactured by the Microbiota Therapeutics Program in accordance with IND 
15071 (Sponsor-Investigator is Khoruts).  The manufacturing is done in the 
Molecular and Cellular Therapeutics (MCT) building on the St. Paul campus.  The 
capsules are kept in MCT until they are released to Dr. Khoruts in accordance with 
release criteria.  Following release the capsules are kept at -80oC in Dr. Khoruts’ 
Lab freezer in the Wallin Medical Biosciences Building. 
10 Correlative/Special Studies 
10.1 Specimen Collection and Transport To Processing Laboratory 
All participants will undergo stool and blood sample collection for microbiota-
related studies (bacterial DNA sequencing of stool/serum, ELISA of serum for 
citrulline/LPS/I-BABP/I-FABP/Flagellin, patient’s germline genetic variants in 
PBMCs relevant to gut barrier) at the schedule indicated in the Study Activity 
Calendar (Section 8). Samples will be collected in the inpatient setting until the 
patients are discharged from the hospital. Stool samples after discharge from the 
hospital will be collected at home and either brought to clinic or mailed to the lab. 
Note, for patients co-enrolled on biospecimen collection trials, such as MT2017-
12, this trial will have priority on specimens if the sample collection dates overlap.  
10.2 Initial specimen processing, storage, and shipping 
PBMC and serum samples will be stored frozen in the Translational Therapy Lab 
(“TTL”). Stool samples will be stored in Dr. Staley’s lab, in a -800 freezer. The 
samples will be stored for further analyses until no longer needed up to a 
maximum of 10 years from the study’s end. Samples will be de-identified and 
labelled with a bar code. 
While participants are hospitalized, stool specimens are collected by the bedside 
nurse, similar to how stool specimens would be collected for diagnostic purposes. 
For outpatient collections, each participant is given an instruction sheet with 
pictures demonstrating simple but proper technique to collect samples at home. 
Participants are provided with sample collection kits and optional specimen 
pans.  The participants mail their samples to the laboratory (cost covered by study) 
or store them in their home freezer and bring them to the clinic at the time of 
their next visit. Research stool samples are collected only at the time of bowel 
movement and no laxatives will be used to facilitate bowel movements. The 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 22 of 38 
 
2017LS170 
 
participants will record the time and date of collection. Stool samples will then be 
kept in patient’s own freezer until they bring the samples to clinic in a provided 
cooler or picked up by one for the study coordinators. A patient has the right to 
withdraw consent at any time by informing a member of the study staff, their 
treating physician, or by following the instructions provided in the HIPAA 
document. If this occurs, any remaining identifiable research sample(s) will be 
destroyed and no further clinical data will be collected from the medical records 
for this study. 
Samples will be labeled with a Sample ID that can be linked back to the subject, 
study timepoint, and date of collection. Receipt of all samples will be verified by a 
clinical research associate and/or a clinical research nurse. All received, processed, 
and stored stool samples will be logged into the repository database maintained 
by Dr. Staley’s lab. All received, processed, and stored blood samples will be 
logged into the FreezerworksTM database maintained by TTL. 
10.3 Analytical Method 
After DNA extraction, stool samples will undergo 16S rRNA amplicon sequencing 
of the V4 region at the University of Minnesota Genomics Center on Illumina 
MiSeq lane, followed by taxonomic annotation by Dr. Staley (Department of 
Surgery). Samples will be processed and annotated using mothur software, and 
taxonomic classifications will be made based on the Ribosomal Database Project 
[12]. Microbiota engraftment will be determined using SourceTracker software 
[13], as described previously [14] [15]. This software uses a Bayesian modeling 
approach to describe the percent of microbial community similarity in patient 
samples to those of the donor sample based on the presence and distribution of 
shared taxa. PBMCs will be sequenced using PCR probes targeted for genetic 
polymorphisms of interest (e.g., haptoglobin) at the University of Minnesota 
Genomics Center. Serum will be analyzed for biomarkers of gut barrier integrity, 
function, and inflammation (e.g., LPS, flagellin, citrulline, I-FABP, amphiregulin) at 
the Cytokine Reference Laboratory using standard ELISA or Luminex assays.   
11 Event Monitoring, Documentation and Reporting 
Toxicity and adverse events will be classified and graded according to NCI's Common 
Terminology Criteria for Adverse Events V 5.0 (CTCAE) and reported on the schedule below. 
A 
copy 
of 
the 
CTCAE 
can 
be 
downloaded 
from 
the 
CTEP 
home 
page. 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50 ) 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 23 of 38 
 
2017LS170 
 
11.1 Event Terminology 
Adverse Event: Any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
 
Serious Adverse Event: An adverse event is considered “serious” if, in the view of either 
the investigator or sponsor, it results in any of the following outcomes:  
• Death 
• A life-threatening adverse event 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition.  
 
Unexpected Event: An adverse event or suspected adverse reaction is considered 
“unexpected” if it is not listed in the investigator brochure or is not listed at the specificity 
or severity that has been observed; or, if an investigator brochure is not required or 
available, is not consistent with the risk information described in the general 
investigational plan or elsewhere in the current application, as amended.  
 
Major and Minor Clinical (Protocol/Patient) Deviations as defined by the Masonic Cancer 
Center: 
 
Major Deviations: 
A deviation or violation that impacts the risks and benefits of the research; may impact 
subject safety, affect the integrity of research data and/or affect a subject’s willingness to 
participate in the research. Deviations that place a subject at risk, but do not result in 
harm are considered to be major deviations.  
 
Minor Deviations: 
A deviation or violation that does not impact subject safety, compromise the integrity of 
research data and/or affect a subject’s willingness to participate in the research. 
 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 24 of 38 
 
2017LS170 
 
11.2 Event Documentation 
Patients will be monitored for adverse events from the first dose of study treatment 
until nine months after randomization as per the schedule in section 8.2. After that 
time point, events meeting the definition of serious and at least possibly related to 
study treatment will be documented upon knowledge. 
Routine AE reporting will occur via data entry into the study eCRF. AEs reported 
through expedited processes (e.g., reported to IRB, FDA, etc.) must also be reported in 
routine study data submissions.  
Adverse events recorded in the case report forms include: 
• All events considered possibly, probably or definitely related to study agent 
• All events of fever, abdominal pain, diarrhea, constipation, and bloating (for 7 
days after each dose of FMT/placebo). Refer to Appendix III. 
• Grade 3 or higher unsolicited adverse events (for 28 days after each dose of 
FMT/placebo) 
• New-onset chronic medical conditions potentially related to FMT (metabolic 
syndrome, glucose intolerance, autoimmune conditions, and weight gain) until 
9 months after randomization. All serious adverse events. 
 
11.3 SAE and Death Documentation 
Any event meeting the definition of a serious adverse event (SAE) requires 
documentation using the SAE Report Form in OnCore. Refer to section 11.4 for the 
definition of events that must be reported to the FDA, Dr. Alexander Khoruts, and IRB 
in an expedited manner. 
Deaths, including due to disease, during the treatment and 6 month follow-up period 
will be recorded as an SAE. Deaths due to disease should be recorded as a Grade 5 
“Neoplasms benign, malignant and unspecified (including cysts and polyps) – Other 
(Progressive Disease). In addition, the death date and cause must be reported in the 
patient follow-up tab in OnCore using the comment field in the survival status section 
to record the cause. Deaths only need to be reported in an expedited manner if they 
meet the criteria in section 11.5. Otherwise, they are reported at the time of IRB and 
FDA annual reporting. 
11.4 Early Stopping Rule Documentation and Reporting  
The following event counts toward an early study stopping rule and must be reported per 
Section 11.5: 
• bloodstream infection within 1 week after FMT/placebo 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 25 of 38 
 
2017LS170 
 
 
An event that counts toward an early stopping rule does not necessarily constitute a SAE 
and should be reported as such only if they meet the criteria for reporting as defined in 
Section 11.5. 
11.5 Expedited Event Reporting 
12 Study Data Collection and Monitoring 
12.1 Data Management 
This study will collect regulatory and clinical data using University of Minnesota CTSI’s 
instance of OnCore® (Online Enterprise Research Management Environment). The Oncore 
Agency 
Criteria for reporting 
Timeframe 
Form to Use 
Submission 
address/email 
address 
U of MN IRB 
Unanticipated death of a locally enrolled subject(s); 
New or increased risk; Any adverse event that require 
a change to the protocol or consent form – refer to 
the IRB website for complete details  
5 Business Days 
RNI  
 
Ethos 
Clinical deviations per current IRB reporting requirements 
RNI 
Ethos 
 
Unexpected and fatal or unexpected and life 
threatening suspected adverse reaction 
no later than 7 
Calendar Days 
 
 
FDA 
1) Serious and unexpected suspected adverse 
reaction or 
2) increased occurrence of serious suspected adverse 
reactions over that listed in the protocol or 
investigator 
brochure or 
3) findings from other sources (other studies, animal 
or in vitro testing) 
no later than 15 
Calendar-Days 
SAE Report 
Form 
Submit to 
CBER as an 
amendment to 
IND 
 
All other events per CFR 312.33 
Submit as part of 
the IND annual 
report 
Summary 
format 
Submit as part 
of the IND 
annual report 
SAE Coordinator 
Events that meet the definition of an early study 
stopping rule 
At time of reporting 
Event Form 
 
mccsaes@umn.edu 
Ad Hoc DSMC 
SAEs and suspected/confirmed transmission of 
pathogens. 
5 Business Days 
Report Form  
 
Shernan Holtan 
sgholtan@umn.edu, 
Armin Rashidi 
arashidi@umn.edu 
and   
Alexander Khoruts 
khoru001@umn.edu  
Medical Monitor 
Events that meet the definition of an early study 
stopping rule 
 
w/in 24 hours 
 
Event Form 
Byron Vaughn, MD 
bvaughn@umn.edu 
pgr: 612-899-4052 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 26 of 38 
 
2017LS170 
 
database resides on dedicated secure and PHI compliant servers. All relevant AHC IS 
procedures related for PHI compliant servers (as required by the Center of Excellence for 
HIPAA Data) apply to Oncore databases. 
The data will be integrated and extracted to researchers through the CTSI Informatics 
team and will be delivered through secure and compliant mechanisms (e.g. AHC IE data 
shelter, BOX, sftp, etc). If data de-identification is needed, then compliant AHC IE data de-
identification tools will be used. The informatics team will grant the IRB approved study 
team members access to data. 
Additional data about correlative laboratory samples generated by the Masonic Cancer 
Center Translational Therapy Laboratory (TTL) from the protocol-directed correlative 
research samples is stored in their Laboratory Information Management System 
(LIMS).The LIMS database application is also stored on a production server located in the 
UMN datacenter (WBOB) and is managed by the Academic Health Center. Key study 
personnel are trained on the use of OnCore and will comply with protocol specific 
instructions embedded within the OnCore. 
12.2 Case Report Forms 
Participant data will be collected using protocol specific electronic case report forms (e-
CRF) developed within Oncore based on its library of standardized forms. The e-CRF will 
be approved by the study’s Principal Investigator and the Biostatistician prior to release 
for use. The Study Coordinator or designee will be responsible for registering the patient 
into OnCore at time of study entry, completing e-CRF based on the patient specific 
calendar, and updating the patient record until patient death or end of required study 
participation.  
12.3 Data and Safety Monitoring Plan (DSMP) 
The study’s Data and Safety Monitoring Plan will be in compliance with the University of 
Minnesota Masonic Cancer Center's Data & Safety Monitoring Plan (DSMP), which can be 
accessed at http:// z.umn.edu/dmsp. 
 
For the purposes of data and safety monitoring, this study is classified as high risk 
(investigator initiated IND protocol). Therefore, the following requirements will be 
fulfilled: 
 
▪ At least quarterly review of the study’s progress by the Masonic Cancer Center Data 
and Safety Monitoring Council (DSMC). 
▪ The PI will comply with at least twice yearly monitoring of the project by the Clinical 
and Translational Science Institute monitoring services. 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 27 of 38 
 
2017LS170 
 
▪ The PI will oversee the submission of all reportable adverse events per section 11.4 to 
the Masonic Cancer Center’s SAE Coordinator, the University of Minnesota IRB, Dr. 
Khoruts, and the FDA.  
 
In addition, at the time of the continuing review with the University of Minnesota IRB, 
a copy of the report with any attachments will be submitted to the Cancer Protocol 
Review Committee (CPRC). 
 
Additional Monitoring: 
A Data Safety Monitoring Committee (DSMC), consisting of a physician from each of the 
following disciplines: Infectious Diseases (1 individual), Gastroenterology (1 individual), 
and Hematology/Oncology (2 individuals) will meet ad hoc (either in person, or online) 
for SAEs and suspected/confirmed transmission of pathogens. These physicians will not 
be involved in the study other than participating in the DSMC. Assessment by at least 3 of 
these 4 physicians is required for each SAE.  
 
SAEs and deaths will be reported to the DSMC on an ongoing basis; the study will be 
stopped for a safety evaluation by the DSMC if they have any concerns, or if a stopping 
rule is activated.   The DSMC chair will be responsible for recording the summary of its 
various meetings and for reporting findings and/or recommendations to the study 
sponsor and to the funding agency. 
 
The Medical Monitor will serve as the liaison between the DSMC and the Sponsor/ 
Investigator. The actual analyses will be conducted by the Study Biostatistician who will 
ensure that the unblinded analyses are not available to study investigators. 
 
 
Medical Monitoring 
An expert in Gastroenterology and Microbiome research, with specific expertise with 
FMT, will serve as the Medical Monitor. The external Medical Monitor will be separate 
from the Sponsor/Investigator and will not participate in any study procedures (e.g., 
screening of subjects, consenting of subjects, administration of FMT or study follow-up). 
The Medical monitoring will include a regular assessment of each stopping rule event. If 
a stopping rule event is considered to be related to the study agent, the DSMC will be 
notified. 
 
Unblinding Procedures 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 28 of 38 
 
2017LS170 
 
If unblinding the study therapy is necessary to ensure a subject’s safety, this will be done 
by the external medical monitor after review of the clinical events. The 
Sponsor/Investigator must be informed within 24 hours by phone, fax or email of the 
unblinding event, followed by a detailed written narrative within 48 hours of the event. 
 
In other circumstances, the medical monitor may choose to unblind him/herself if there 
is concern based on the safety data that a type of adverse event may be associated with 
FMT treatment; in this case, the medical monitor will inform the study sponsor that 
he/she has unblended him/herself, but not of the treatment assignments. 
 
 
IND Annual Reports  
In accordance with regulation 21 CFR § 312.33, the sponsor-investigator, Dr. Holtan, will 
submit a progress report annually. The report will be submitted within 60 days of the 
anniversary date that the IND went into effect. A copy of the IND annual report will be 
submitted to Dr. Khoruts. 
12.4 Study Monitoring  
The investigator will permit study-related monitoring, audits, and inspections by the 
study’s Principal Investigator/IND sponsor and/or any designees, the local IRB, 
government regulatory bodies, and University of Minnesota compliance groups. The 
investigator will make available all study related documents (e.g. source documents, 
regulatory documents, data collection instruments, study data, etc.). The investigator will 
ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.) will be available for trial related monitoring, audits, or 
regulatory inspections. 
12.5 Record Retention 
The investigator will retain study records including source data, copies of case report form, 
consent forms, HIPAA authorizations, and all study correspondence in a secured facility for 
at least 6 years after the study file is closed with the IRB and FDA.  
12.6 Telephone and Electronic Consent Procedures 
Given current COVID-19 restrictions, remote consent via phone or virtual visit will be 
permitted. Remote consent will be documented with either patients' hand-written 
signature or e-signature using a 21 CFR Part 11 compliant system, such as Redcap to 
minimize patient and staff contact.  All electronic paperwork and health information will 
be securely stored in Redcap, OnCore or password protected files. 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 29 of 38 
 
2017LS170 
 
The REDCap database uses a MySQL database via a secure web interface with data checks 
used during data entry to ensure data quality. REDCap includes a complete suite of 
features to support HIPAA compliance, including a full audit trail, user-based privileges, 
and integration with the institutional LDAP server. The MySQL database and the web 
server will both be housed on secure servers operated by the University of Minnesota 
Academic Health Center’s Information Systems group (AHC-IS). The servers are in a 
physically secure location on campus and are backed up nightly, with the backups stored 
in accordance with the AHC-IS retention schedule of daily, weekly, and monthly tapes 
retained for 1 month, 3 months, and 6 months, respectively. Weekly backup tapes are 
stored offsite. The AHC-IS servers provide a stable, secure, well-maintained, and high-
capacity data storage environment, and both REDCap and MySQL are widely-used, 
powerful, reliable, well-supported systems. Access to the study's data in REDCap will be 
restricted to the members of the study team by username and password. 
13 Study Endpoints 
13.1 Primary Endpoint 
To demonstrate the efficacy of FMT in AML patients and allo-HCT patients, as measured by 
the number of all infections within 4 months after the first study drug administration.  
13.2 Secondary Endpoints 
13.2.1 
FMT engraftment rate at 10 days and 4 weeks post each FMT and 9 months after 
randomization. 
13.2.2 
In the Allo-HCT cohort, the cumulative incidence of acute grade II-IV GVHD 
through day 180 post-HCT 
13.2.3 
The incidence of BSI through 1 week after each FMT 
13.2.4 
In both cohorts, the number of bacterial, viral, and fungal infections within 4 
months after the first study drug administration 
13.3 Correlative Endpoints 
• The effect of FMT on gut barrier biomarkers  
14 Statistical Considerations 
14.1 Study Design  
This is a randomized, double-blind, placebo-controlled clinical trial of Fecal Microbiota 
Transplant (FMT) procedure in 2 independent cohorts (72 AML patients undergoing 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 30 of 38 
 
2017LS170 
 
chemotherapy and 72 Allo-HCT patients). Participants in each cohort will be randomized to 
receive up to 3 treatments of FMT vs. placebo after each exposure to antibacterial antibiotics 
until 3 months after randomization. The primary endpoint is the number of all infections 
within 4 months after the first study drug administration. Interim safety analysis will be 
performed. Other endpoints are listed in section 13. 
14.2 Power Analysis:  
This is a phase II randomized study aiming for obtaining treatment effect data for further 
phase III study. Nevertheless, the power analysis was conducted for the designed sample sizes 
for two patient groups, the BMT and chemo group, separately. The unbalanced sample size 
between the intervention group (N=48) and the control group (N=24) was chosen in order to 
get reliable estimates for the intervention group for the use of future design of phase III trials. 
The infection rates of the controls in the BMT and chemo groups were estimated based on a 
pilot cohort (17 infectious events per 1440 patient-days, i.e., infection rate=0.013) and 
published data (infection rate=0.009 for days 30-180 post-transplant) [16], respectively. Two-
sided tests for the ratio of two exponential rates [17] with a 120 days’ follow-up were used 
for power calculation with PASS14 (NCSS, LLC). The power for a presumed 50% reduction in 
infection rate for the intervention group (i.e., the infection rate ratio of intervention vs. 
control = 0.5) was calculated.   
14.3 Data Analysis Plan:  
The infection data will be summarized using infection density for each treatment and each 
patient group. The recurrent infection data will be compared between the intervention and 
control using the Lin-Wei-Yang-Ying regression model [18] with intervention as the primary 
covariate, and then adjusting for additional patient/treatment-related characteristics in a 
multivariable regression model. Potentially informative censoring events such as death and 
second transplant will be taken into account with a sensitivity analysis using the method by 
[19]. 
14.4 Sample Size and Accrual 
With ~70 cases of newly diagnosed and ~30 relapsed/refractory AML cases per year, 50% 
consent decline rate, and ~20% probability of being unevaluable after consenting, we expect 
to complete enrollment of the leukemia cohort in ~18-24 months. With ~100 allo-HCT cases 
per year, 50% consent decline rate, and ~20% probability of being unevaluable after 
consenting, we expect to complete enrollment of the HCT cohort in ~18-24 months. 
14.5 Safety Monitoring 
Continuously stopping rules are in place to stop the study in case there are excessive 
complications. In the case that the boundaries are crossed, the Principal Investigator will be 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 31 of 38 
 
2017LS170 
 
notified who will report it to the Masonic Cancer Center Data Safety Monitoring Committee 
and the Medical Monitor. The protocol will be reviewed by the Medical Monitor to determine 
if the protocol should be terminated. The stopping rule was developed using Pocock stopping 
boundaries [20]. The stopping rules will be applied separately for FMT arms in each cohort. 
We do not expect toxicity in placebo arms. Therefore we will not monitor for the two placebo 
arms.  
Excess toxicity will be defined as bloodstream infection within 1 week after FMT. The goal is 
to construct a boundary based on toxicity such that the probability of early stopping is at 
most 10% if the toxicity rate is equal to 30%. Given these parameters, for each of FMT arms, 
the upper stopping boundary for toxicity is 4 out of 4, 5 out of 6, 6 out of 9, 7 out of 11, 8 out 
of 13, 9 out of 16, 10 out of 18, 11 out of 21, 12 out of 23, 13 out of 26, 14 out of 28, 15 out 
of 31, 16 out of 34, 17 out of 36, 18 out of 39, 19 out of 42, 20 out of 44, 21 out of 47, or 22 
at any time. If the true toxicity rate is as high as 60%, the chance of early stopping is 99%; this 
will occur after 13th enrollments. 
15 Ethical and Regulatory Considerations 
15.1 Good Clinical Practice 
The study will be conducted in accordance with the appropriate regulatory 
requirement(s). Essential clinical documents will be maintained to demonstrate the 
validity of the study and the integrity of the data collected. Master files should be 
established at the beginning of the study, maintained for the duration of the study and 
retained according to the appropriate regulations.  
15.2 Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the 
Declaration of Helsinki. The IRB will review all appropriate study documentation in order 
to safeguard the rights, safety and well-being of the patients. The study will only be 
conducted as a single site study where IRB approval has been obtained. The protocol, 
informed consent, written information given to the patients, safety updates, annual 
progress reports, and any revisions to these documents will be provided to the IRB by the 
investigator.  
15.3 Informed Consent 
All potential study participants will be given a copy of the IRB-approved Consent to 
review. The investigator or designee will explain all aspects of the study in lay language 
and answer all questions regarding the study. If the participant decides to participate in 
the study, he/she will be asked to sign and date the Consent document; or consent 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 32 of 38 
 
2017LS170 
 
remotely over the telephone or electronically. Remote consent will be documented with 
either patient’s hand-written signature or e-signatures using a 21 CFR Part 11 compliant 
system such as REDCap. Patients who refuse to participate or who withdraw from the 
study will be treated without prejudice. 
16 References 
 
[1]  NI J, Wu G, Albenberg L, Tomov VT, "Gut microbiota and IBD: causation or correlation?," 
Nat Rev Gastroenterol Hepatol, vol. 14, no. 10, pp. 573-584, Oct 2017.  
[2]  Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold G, Quraishi MN, Kinross J, 
Smidt H, Tuohy KM, Thomas LV, Zoetendal EG, Hart A., "The gut microbiota and host health: 
a new clinical frontier.," Gut, vol. 65, no. 2, pp. 330-9, Feb 2016.  
[3]  Riwes M, Reddy P., "Microbial metabolites and graft versus host disease.," Am J Transplant, 
vol. 18, no. 1, pp. 23-29, Jan 2018.  
[4]  Ying Taur, MD, MPH, Rob Jenq, MD, Carles Ubeda, PhD, Marcel van den Brink, MD, PhD, and 
Eric G. Pamer, MD, "Role of intestinal microbiota in transplantation outcomes.," Best Pract 
Res Clin Haematol, vol. 28, no. 0, pp. 155-161, Jun-Sep 2015.  
[5]  Peled JU, Hanash AM, Jenq RR., "Role of the intestinal mucosa in acute gastrointestinal 
GVHD.," Blood, vol. 128, no. 20, pp. 2395-2402, Nov 2016.  
[6]  Galloway-Peña JR, Smith DP, Sahasrabhojane P, Ajami NJ, Wadsworth WD, Daver NG, 
Chemaly RF, Marsh L, Ghantoji SS, Pemmaraju N, Garcia-Manero G, Rezvani K, Alousi AM, 
Wargo JA, Shpall EJ, Futreal PA, Guindani M, Petrosino JF, Kontoyiannis DP, Shelburne SA., 
"The role of the gastrointestinal microbiome in infectious complications during induction 
chemotherapy for acute myeloid leukemia.," Cancer, vol. 122, no. 14, pp. 2186-96, Jul 2016.  
[7]  Galloway-Peña JR, Smith DP, Sahasrabhojane P, Wadsworth WD, Fellman BM, Ajami NJ, 
Shpall EJ, Daver N, Guindani M, Petrosino JF, Kontoyiannis DP, Shelburne SA, 
"Characterization of oral and gut microbiome temporal variability in hospitalized cancer 
patients.," Genome Med, vol. 9, no. 1, p. 21, Feb 2017.  
[8]  Weber D, Jenq RR, Peled JU, Taur Y, Hiergeist A, Koestler J, Dettmer K, Weber M, Wolff D, 
Hahn J,Pamer EG, Herr W, Gessner A, Oefner PJ, van den Brink MRM, Holler E., "Microbiota 
Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 33 of 38 
 
2017LS170 
 
Factor of Outcome after Allogeneic Stem Cell Transplantation.," Biol Blood Marrow 
Transplant, vol. 23, no. 5, pp. 845-852, May 2017.  
[9]  Kakihana K, Fujioka Y, Suda W, Najima Y, Kuwata G, Sasajima S, Mimura I, Morita H, 
Sugiyama D, Nishikawa H, Hattori M, Hino Y, Ikegawa S, Yamamoto K, Toya T, Doki N, 
Koizumi K, Honda K, Ohashi K., "Fecal microbiota transplantation for patients with steroid-
resistant acute graft-versus-host disease of the gut.," Blood, vol. 128, no. 16, pp. 2083-2088, 
Oct 2016.  
[10] DeFilipp Z, Peled J, Li S, Mahabamunuge J, Dagher Z, Slingerland A, Del Rio C, Valles B, 
Kempner M, Smith M, Brown J, Dey B, El-Jawahri A, McAfee S, Spitzer T, Ballen K, Sung A, 
Dalton T, Messina J, Dettmer K, Liebisch G, Oefner P, Taur Y, Pamer E, "Third-party fecal 
microbiota transplantation following allo-HCT reconstitutes microbiome diversity.," Blood 
Advances, vol. 2, pp. 745-753, 2018.  
[11] Staley C, Hamilton MJ, Vaughn BP, Graiziger CT, Newman KM, Kabage AJ, Sadowsky MJ, 
Khoruts A, "Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-
Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study.," Am J Gastroenterol., vol. 
112, no. 6, pp. 940-947, June 2017.  
[12] Cole JR, et al., "The Ribosomal Database Project: improved alignments and new tools for 
rRNA analysis," Nucleic Acids Res, vol. 37, pp. D141-5, 2009.  
[13] Knights D, Kuczynski J, Charlson ES, Zaneveld J, Mozer MC, Collman RG, Bushman FD, Knight 
R, Kelley ST., "Bayesian community-wide culture-independent microbial source tracking.," 
Nat Methods, vol. 8, no. 9, pp. 761-3, July 2011.  
[14] Staley C, et al. , "Community dynamics drive punctuated engraftment of the fecal 
microbiome following transplantation using freeze-dried, encapsulated fecal microbiota.," 
Gut Microbes, vol. 8, no. 3, pp. 276-288, 2017.  
[15] Ridaura VK, et al. , "Gut microbiota from twins discordant for obesity modulate metabolism 
in mice.," Science, vol. 341, no. 6150, p. 1241214, 2013.  
[16] Bejanyan N, Brunstein CG, Cao Q, Lazaryan A, Luo X, Curtsinger J, Mehta RS, Warlick E, 
Cooley SA, Blazar BR, Miller JS, Weisdorf D, Wagner JE, Verneris MR., "Delayed immune 
reconstitution after allogeneic transplantation increases the risks of mortality and chroni 
GVHD," Blood Adv, vol. 2, no. 8, pp. 909-922, Apr 2018.  

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 34 of 38 
 
2017LS170 
 
[17] Zhu H and Lakkis H., "Sample size calculation for comparing two negative binomial rates," 
Statistics in Medicine, vol. 33, no. 3, pp. 376-387, 2014.  
[18] Lin DY, Wei LJ, Yang I, Ying Z., "Semiparametric regression for the mean and rate functions 
of recurrent events," J. R. Statist Soc B, vol. 62, no. 4, pp. 711-730, 2000.  
[19] Wang M-C, Qin J, Chiung CT., "Analyzing recurrent event data with informative censoring," J 
Am Stat Assoc, vol. 96, no. 455, pp. 1057-1065, 2001.  
[20] Ivanova A, Qaqish B, and Schell M., "Continuous toxicity monitoring in phase II trials in 
oncology.," Biometrics, vol. 61, pp. 540-545.  
 
 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 35 of 38 
 
2017LS170 
 
Appendix I – Eligibility Checklist for Initial Enrollment 
A Randomized Placebo-Controlled Clinical Trial of Fecal Microbiota Transplantation in 
Patients with Acute Myeloid Leukemia and Allogeneic Hematopoietic Cell Transplantation 
Recipients 
Eligibility Checklist – page 1 of 1 
Study ID: 17170-UMN-_____ 
 
INCLUSION CRITERIA  
 
A “NO” response to any of the following disqualifies the participant from study entry. 
 
EXCLUSION CRITERION 
A “YES” response to the following disqualifies the participant from study entry. 
 
 
Yes      No 
1. Planned continuation of antibacterial antibiotics (with the exception of antibiotics used 
for Pneumocystis carinii prophylaxis) after the first neutrophil recovery (ANC > 1,000) 
 
 
2. Subjects with severe food allergies 
 
 
3. Subjects with a history of chronic aspiration 
 
 
4. 
Pregnant or breast feeding. The FDA has not classified this agent into a specified 
pregnancy category. Females of childbearing potential must have a blood test or urine 
study within 14 days prior to registration to rule out pregnancy 
 
 
 
Date consent form signed: _______________________________ 
 
 
 
 
Having obtained consent and reviewed each of the inclusion/exclusion criteria, I verify that this 
participant is eligible. 
_________________________________________________________________________________________________ 
Signature of person verifying eligibility  
 
 
 
Date 
 
 
 
Yes      No 
1. > 18 years 
 
 
2. Cohort A: Patients undergoing chemotherapy for acute myeloid leukemia (newly 
diagnosed or relapsed/refractory). 
 
 
NA 
3. Cohort B: Allo-HCT patients  
 
Any T-replete allogeneic transplant regimen  
 
 
NA 
4 
Sexually active females of childbearing potential and males with partners of child-
bearing potential must agree to use adequate birth control until at least six months post-
FMT/placebo 
 
 
5 
Voluntary written consent signed before performance of any study-related procedure 
not part of normal medical care 
 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 36 of 38 
 
2017LS170 
 
Appendix II – Eligibility Checklist for FMT/placebo Administration 
A Randomized Placebo-Controlled Clinical Trial of Fecal Microbiota Transplantation in 
Patients with Acute Myeloid Leukemia and Allogeneic Hematopoietic Cell Transplantation 
Recipients 
Eligibility Checklist – page 1 of 1  
Study ID: 17170-UMN-_____ 
INCLUSION CRITERIA  
 
A “NO” response to any of the following disqualifies the participant from study entry. 
 
EXCLUSION CRITERION 
A “YES” response to the following disqualifies the participant from study entry. 
 
Date consent form signed: 
 
 
 
 
 
Having obtained consent and reviewed each of the inclusion/exclusion criteria, I verify that this 
participant is eligible. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of person verifying eligibility  
 
 
 
 
Date 
 
 
 
 
Yes      No 
1. 
Neutrophil recovery: ANC > 1,000, checked within the last 7 days 
 
2. 
All anti-bacterial agents (with the exception of antibiotics used for Pneumocystis 
carinii prophylaxis) have been discontinued for at least 2 days 
 
 
 
3. 
Acute toxicities have resolved to grade 2 or lower 
 
 
4. 
Negative pregnancy test result for females of child bearing potential 
 
 
 
 
Yes      No 
1. 
Unable to swallow capsules 
 
 
2. 
Disease has relapsed/progressed after original consent  
 
 
3. 
Active infection at the time of screening 
 
 
4. 
[Cohort B] Active GVHD or being treated for GVHD at the time of screening 
 
 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 37 of 38 
 
2017LS170 
 
Appendix III – FMT/Placebo Reaction Diary 
The Diary is to be completed by the patient as a self-assessment for 7 days after each dose of 
FMT/Placebo.  
A new diary must be started for each dose of FMT/Placebo.  
For inpatients, the diary is completed by patient or study personnel. 

2017LS170 FMT for patients with acute leukemia and Allo-HCT 
 
 
 
 
March 16, 2022 
Page 38 of 38 
 
2017LS170 
 
 
Patient Number* 
 
Date of Study Drug  
________/_________/________ 
 
Please answer all questions below daily for 7 days. Be sure to bring back this completed diary to your next clinic visit. 
 
 
Instructions 
Day 1 
Post Study 
Drug 
___/___/____ 
Day 2 
Post Study 
Drug 
___/____/____ 
Day 3  
Post Study 
Drug 
___/____/____ 
Day 4  
Post Study 
Drug 
____/___/____ 
Day 5  
Post Study 
Drug 
___/___/____ 
Day 6  
Post Study 
Drug 
___/___/____ 
Day 7 
Post Study 
Drug 
___/___/_____ 
1. Do you 
have any 
stomach 
pain? 
 
Check the pain 
box if present 
And tell us if 
the pain is mild, 
moderate or 
severe 
 Pain  
Mild 
Mod 
Severe      
 Pain  
Mild 
Mod 
Severe      
 Pain  
Mild 
Mod 
Severe      
 Pain  
Mild 
Mod 
Severe      
 Pain  
Mild 
Mod 
Severe      
 Pain  
Mild 
Mod 
Severe      
 Pain  
Mild 
Mod 
Severe      
2. Do you 
have any 
diarrhea? 
Check: 
Yes  or No 
 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
3. Do you 
have any 
constipation? 
Check: 
Yes  or No 
 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
4. Do you 
have any 
bloating? 
Check: 
Yes  or No 
 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
Yes  No 
5. Record 
your daily 
temperature 
upon waking 
 (do not drink 
anything 5 
minutes 
before taking 
your 
temperature) 
Check: 
Yes  or No 
If your 
temperature is 
101°F for more 
than 24 hours 
notify your 
study doctor or 
research staff. 
Yes  No 
________°F 
 
Time: 
____:____  
AM / PM 
Yes  No 
________°F 
 
Time: 
____:____  
AM / PM 
Yes  No 
________°F 
 
Time: 
____:____  
AM / PM 
Yes  No 
________°F 
 
Time: 
____:____  
AM / PM 
Yes  No 
________°F 
 
Time: 
____:____  
AM / PM 
Yes  No 
________°F 
 
Time: 
____:____  
AM / PM 
Yes  No 
________°F 
 
Time: 
____:____  
AM / PM 
Have you 
taken any 
additional 
medications? 
List medicines, 
including herbal 
supplements 
you have 
taken. 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________ 
____________