Fecal Microbiota Transplantation in Patients Undergoing Chimeric Antigen Receptor T-cell Therapy and Allogeneic Stem Cell Transplant: A Pilot Study
Phase: NA
Conditions: Lymphoma Receiving CAR-T Therapy
Sponsor: University Health Network, Toronto

 
 
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Fecal microbiota transplantation in patients undergoing chimeric antigen receptor T-cell  
therapy and allogeneic stem cell transplant (ORCHID): A pilot study  
 
Protocol Number: FMT-CARTSCT 
 
Ozmosis Protocol Number: OZUHN-038 
 
Protocol Version and Date: v 1.0 17-Dec-2025 
 
Phase of Study: Pilot study  
 
Sponsor:  
 
Abi Vijenthira, MD, SM, FRCPC 
Princess Margaret Cancer Centre 
700 University Avenue, OPG 6-707 
Toronto, Ontario M5G 1X6 
Tel: 416-946-4501 ext. 3377 
Fax: 416-946-4563 
E-mail: abi.vijenthira@uhn.ca 
 
Co-Principal Investigators: 
Abi Vijenthira, MD, SM, FRCPC 
Arjun Law, MD, FRCPC 
Susy Hota, MD, MSc, FRCPC 
Susan Poutanen, MD, MPH, FRCPC 
Bryan Coburn, MD, PhD, FRCPC 
 
Collaborators and other study personnel: 
Tiana Korbachech, MD, PhD 
Erinn McCarthy, BSc 
Terry Johnston, patient partner 
 
Investigational agent: Fecal microbiota transplant (FMT) 
 
Clinical Trial Management Company: 
Ozmosis Research Inc. 
700 University Avenue 
Suite 217-2N, Toronto, ON M5G 1Z5 
Main Line: 416-634-8300 
Fax: 416-634-8333 
 
Protocol History 
Version 1.0, dated 17-Dec-2025 
 
 
 

 
 
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PROTOCOL APPROVAL PAGE 
 
Protocol Number: FMT-CARTSCT 
Version: 1.0 
Version Date: Dec 17, 2025 
 
I have reviewed the protocol. 
 
I agree to conduct the study as detailed in the protocol and in compliance with International Council 
for Harmonisation (ICH) Guidelines E6 (r2): Guideline for Good Clinical Practice (GCP) and all the 
ethical and regulatory considerations stated. 
 
 
 
 
 
_______________________________________ 
 
 
_______________________ 
Dr. Abi Vijenthira 
 
 
 
 
 
 
Date 
 
 

 
 
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STUDY SYNOPSIS 
 
Study Title: 
Fecal microbiota transplantation in patients undergoing 
chimeric antigen receptor T-cell therapy and allogeneic stem 
cell transplant: A pilot study 
Study Sites: 
Princess Margaret Cancer Centre (single site study) 
Study Design: 
This is a single centre, non-randomized, single-arm 
interventional pilot study examining fecal microbiota 
transplantation in patients undergoing CAR-T or allogeneic 
stem cell transplantation (alloSCT) 
 
Duration: 
 
Approximately 2.5 years, including 2 years of recruitment, 
minimum 1 series of FMT treatments and a minimum 6 
months of follow-up  
 
Planned Total Sample 
Size: 
20 eligible patients will be enrolled in this study – 10 
patients with B-cell lymphoma undergoing CAR-T and 10 
patients with AML/MDS undergoing alloSCT 
Investigational Agent: 
Fecal microbiota transplant (FMT) 
Study Objectives: 
Primary Objective 
 To evaluate the feasibility and safety of fecal 
microbiota transplantation (FMT) in patients 
undergoing CAR-T or allogeneic stem cell 
transplantation 
Secondary Objectives 
 In patients undergoing CAR-T: To evaluate the 
incidence of all grade and Grade >3 cytokine release 
syndrome (CRS), and all grade and Grade >3 
immune effector cell-associated neurotoxicity 
syndrome (ICANS) 
 In patients undergoing alloSCT: To evaluate the 
incidence of all grade and Grade >3 acute graft-
versus-host disease (GVHD) including gut GVHD 
 To assess one and three month overall response rates 
after infusion of CAR-T cells or stem cells (alloSCT) 
 To assess progression-free survival at 6 months 
 To assess overall survival at 6 months 
Exploratory Objectives 
 To evaluate baseline and day +30, +90, +180 T-cell 
phenotypic and functional subsets 

 
 
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 To evaluate baseline and day +30, +90 intestinal 
microbiome diversity 
 To evaluate engraftment (Donor and recipient 
intestinal microbiome similarity) 
 To evaluate baseline and day +30, +90 plasma and 
urine bacterial metabolomics 
 To evaluate baseline and day +30, +90  incidence of 
antimicrobial resistant organism (ARO) (MRSA, 
VRE, ESBL, CBE) intestinal colonization by rectal 
swab 
 To evaluate incidence of bacteremia, urinary tract 
infections and/or C. difficile infection by day +30 
 To understand patient perspectives on FMT gathered 
by survey at baseline and on day +90 
Inclusion/Exclusion 
Criteria: 
Inclusion criteria (in brief): 
 
1. Men and women ≥ 18 years of age  
2. Diagnosis of the following:  
a. B-cell lymphoma eligible for standard or care 
CAR-T therapy, or 
b. Patients with AML or high risk MDS with 
indication to undergo reduced-intensity 
conditioning alloSCT and an available 
matched related, unrelated, or haploidentical 
donor  
3. ECOG 0-1 
4. Adequate bone marrow function defined as a 
neutrophil count >1.0 x 109 L, HGB >80 g/L, and 
PLT count >20 x 109 L 
5. Willing and able to participate in all required 
evaluations and procedures in this study.  
6. Ability to understand and the willingness to sign a 
written informed consent.  
 
See section 3.1 for a full list of inclusion criteria.  
 
Exclusion criteria (in brief): 
1. For patients undergoing alloSCT: plan to undergo 
myeloablative conditioning  
2. Use of investigational agents within the last 4 weeks 
before enrollment.  
3. Active or uncontrolled infection 
4. Autoimmune disorder currently being treated with 
disease-modifying therapy or with  >10mg/day 

 
 
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prednisone 
5. Inflammatory bowel disease 
6. History of intestinal perforation 
7. Recent gastrointestinal surgical procedure within the 
past 4 weeks 
8. Pregnant or breast-feeding patients 
9. HIV infection with  CD4 count <200 or detectable 
viral load 
10. Serologic status reflecting active hepatitis B or C 
infection as follows:  
a. Presence of hepatitis B surface antigen 
(HBsAg) or hepatitis B core antibody 
(HBcAb) with detectable hepatitis B virus 
(HBV) DNA. (Note, patients with 
undetectable HBV DNA are permitted to 
enroll if they are on Hepatitis B suppressive 
therapy) 
b. Patients with presence of hepatitis C virus 
(HCV) antibody and HCV RNA detectable  
11. History of infection with antibiotic resistant organism 
in the last two years before enrollment (including 
ESBL, MRSA, VISA, VRSA, VRE, CPE) 
12. Any serious medical condition or abnormality in 
clinical laboratory tests that, in the investigator’s 
judgment, precludes the patient’s safe participation in 
the study  
See section 3.1 for a full list of exclusion criteria.  
Screening Assessments: 
 Informed consent 
 Medical history 
 Review of standard of care blood tests including HIV, 
Hepatitis B and C testing 
 Blood and urine collection for correlative studies 
 Stool Sample 
 Rectal Swab 
 Physical Exam  
 Participant 
questionnaire 
on 
perceptions 
and 
acceptability of FMT 
 Pregnancy Test 
 Disease Response B-cell Lymphoma, MDS, & AML 
Treatment 
and 
Post-
Treatment Assessments: 
 FMT series occurring prior to cellular therapy and 30 
days after cellular therapy treatment 
 Post-treatment assessments will occur at Day +30, 
Day +90, and Day +180 after cellular therapy 
treatment 

 
 
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Response: 
Standard of care disease response assessment per institutional 
guidelines 
Safety Variables & 
Analysis: 
Adverse Events unrelated to infection, CRS, ICANS, and 
GVHD be assessed as per CTCAE version 5.0. Infections 
will be assessed as per Bone Marrow Transplant Clinical 
Trials Network criteria. CRS and ICANS will be assessed as 
per ASTCT criteria. GVHD will be assessed per the Mount 
Sinai Acute GvHD International Consortium (MAGIC) 
criteria.  
 
See Section 7 for further details.  
Statistical Analysis:  
See Statistical Considerations section for details 
 
 
 

 
 
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TREATMENT SCHEMA 
 
 
 
 
 
 

 
 
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TABLE OF CONTENTS 
 
 
 
1. 
BACKGROUND & RATIONALE ............................................................................................... 13 
1.1 Background ............................................................................................................................. 13 
1.2 Investigational Product ........................................................................................................... 14 
2. 
OBJECTIVES AND ENDPOINTS .............................................................................................. 17 
2.1 Primary Objective ................................................................................................................... 17 
2.2 Secondary Objectives .............................................................................................................. 17 
2.3 Exploratory Objectives ........................................................................................................... 18 
3. 
PATIENT SELECTION ................................................................................................................ 20 
3.1 Eligibility criteria .................................................................................................................... 20 
4. 
STUDY PROCEDURES .............................................................................................................. 23 
4.1 Description of Procedures ....................................................................................................... 23 
4.2 Safety Monitoring ................................................................................................................... 26 
5. 
STUDY INTERVENTION ........................................................................................................... 28 
5.1 FMT Preparation ..................................................................................................................... 28 
5.2 FMT Administration ............................................................................................................... 30 
5.3 General Guidelines for Concomitant Medications and Supportive Care ................................ 31 
5.4 Duration of Therapy ................................................................................................................ 31 
5.5 Duration of Follow-Up ........................................................................................................... 31 
5.6 Subject Withdrawal/Discontinuation Criteria ......................................................................... 32 
5.7 Drug Dispensing and Accountability ...................................................................................... 32 
6. 
DOSING DELAYS/DOSE MODIFICATIONS ............................................................................ 33 
7. 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ........................................ 34 
7.1 List of Adverse Events and Reporting Requirements ............................................................. 34 
7.2 Adverse Event Characteristics ................................................................................................ 34 
7.3 Adverse events grading: Events not related to infection, CRS, ICANS, or GVHD: .............. 36 
7.4 Adverse events grading: Infectious events .............................................................................. 37 
7.5 Adverse events grading: CRS, ICANS, and GVHD ............................................................... 43 
7.6 Serious Adverse Event Reporting ........................................................................................... 45 
7.7 Abnormal Laboratory Value Reporting ................................................................................... 47 
7.8 Documentation of Adverse Events .......................................................................................... 47 
7.9 Follow-Up of AEs, AESIs and SAEs ...................................................................................... 47 
7.10 Deaths ..................................................................................................................................... 48 
7.11 Pregnancy ................................................................................................................................ 48 
8. 
CORRELATIVE STUDIES .......................................................................................................... 49 
8.1 Ecological outcomes ............................................................................................................... 49 
8.2 Metabolomic studies ............................................................................................................... 49 
8.3 Immunologic studies ............................................................................................................... 49 
9. 
STUDY CALENDAR................................................................................................................... 50 
DATA REPORTING / REGULATORY REQUIREMENTS ................................................................ 52 
9.1 Compliance with Trial Registration and Results Posting Requirements ................................. 52 
9.2 Patient Protection .................................................................................................................... 52 
9.3 Data Collection and Reporting ................................................................................................ 52 
9.4 Subject Confidentiality and Access to Source Data/Documents ............................................. 52 
9.5 Study Monitoring/Auditing ..................................................................................................... 53 
9.6 Study Monitoring/Auditing ..................................................................................................... 53 
9.7 Quality Control and Quality Assurance .................................................................................. 53 
9.8 Data Management Guidelines ................................................................................................. 54 

 
 
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9.9 REB Composition ................................................................................................................... 54 
9.10 Initial Approval ....................................................................................................................... 54 
9.11 Annual Re-Approvals ............................................................................................................. 54 
9.12 Amendments / Revisions ........................................................................................................ 54 
9.13 REB Refusals .......................................................................................................................... 54 
9.14 Serious Adverse Events, Safety Updates, and Investigator Brochure Updates ....................... 54 
9.15 Informed Consent Document .................................................................................................. 55 
9.16 Consent Process/ Patient Eligibility ........................................................................................ 55 
9.17 Site and Study Closure ............................................................................................................ 55 
10. STATISTICAL CONSIDERATIONS ........................................................................................... 56 
10.1 Study Design/Endpoints .......................................................................................................... 56 
The primary endpoints are feasibility and safety. ............................................................................ 56 
10.2 Sample size/Accrual Rate ....................................................................................................... 56 
10.3 Secondary Endpoints .............................................................................................................. 56 
10.4 Exploratory Endpoints ............................................................................................................ 56 
10.5 Missing Data Handling ........................................................................................................... 57 
11. DOCUMENTATION, RECORD ACCESS AND MAINTENANCE OF STUDY RECORDS ... 58 
11.1 Documentation of Patient’s Participation ............................................................................... 58 
11.2 Regulatory Requirements ........................................................................................................ 58 
11.3 Patient Confidentiality and Access to Source Data/Documents .............................................. 58 
11.4 Confidentiality of the Study .................................................................................................... 59 
11.5 Study Data at the End of Registration of Clinical Trial .......................................................... 59 
11.6 Data Reporting ........................................................................................................................ 59 
11.7 Maintenance of Study Records ............................................................................................... 59 
12. ADMINISTRATIVE PROCEDURES .......................................................................................... 60 
12.1 Amendments to the Protocol ................................................................................................... 60 
12.2 Protocol Deviations and Violations ......................................................................................... 60 
12.3 Premature Discontinuation of the Study ................................................................................. 60 
13. LEGAL ASPECTS ........................................................................................................................ 61 
13.1 Publication Policies and Disclosure of Data ........................................................................... 61 
 
 
 
 
 

 
 
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Abbreviations 
 
AE: Adverse effects 
 
AlloSCT: Allogeneic stem cell transplant 
 
ALT: Alanine Aminotransferase  
 
ARO: Antibiotic resistant organisms 
 
AST: Aspartate Aminotransferase  
 
ASTCT: American Society for Transplantation and Cellular Therapy 
 
BA: Bile acids 
 
BiPAP: Bilevel positive airway pressure 
 
BMI: Body mass index 
 
BSA: Body surface area 
 
CAR-T: Chimeric antigen receptor T-cell 
 
CBE: Carbapenemase-resistant Enterococci 
 
CMV: Cytomegalovirus 
 
CNS: Central nervous system 
 
CPAP: Continuous positive airway pressure 
 
CPO: Carbapenemase-producing Organisms 
 
CRS: Cytokine release syndrome 
 
CTCAE: Common Terminology Criteria for Adverse Events  
 
DLT: Dose-limiting toxicity 
 
EBV: Epstein barr virus 
 
ESBL: Extended-spectrum beta-lactamases 
 
FMT: Fecal microbiota transplantation 

 
 
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GI: Gastrointestinal 
 
GU: Genitourinary 
 
GVHD: Graft-versus-host-disease 
 
HCW: Health care workers 
 
HHV-6: Human herpes virus-6 
 
HIV: Human immunodeficiency virus 
 
HOMA-IR: Homeostatic Model Assessment for Insulin Resistance 
 
HSV: Herpes simplex virus 
 
HTLV: Human T-lymphotrophic virus 
 
ICANS: Immune effector cell-associated neurotoxicity syndrome 
 
ICMJE: Committee of Medical Journal Editors  
 
IV: Intravenous 
 
MRSA: Methicillin resistant Staphylococcus aureus 
 
MTOP: Microbiota Therapeutics Outcomes Program 
 
NPO: Nil per os; Nothing by mouth 
 
NOS: Not otherwise specified 
 
ORR: Overall response rate 
 
OS: Overall survival 
 
PCR: Polymerase chain reaction 
 
PFS: Progression-free survival 
 
PTLD: Post-transplant lymphoproliferative disorder 
 
RIC: Reduced-intensity conditioning 
 
SCFA: Short-chain fatty acids 

 
 
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SMC: Safety monitoring committee 
 
VISA: Vancomycin-intermediate Staphylococcus aureus 
 
VRE: Vancomycin-resistant Enterococci 
 
VRSA: Vancomycin-resistant Staphylococcus aureus 
 
VZV: Varicella zoster virus 
 
WOCBP: Women of Childbearing Potential  
 

 
 
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1. BACKGROUND & RATIONALE 
 
1.1 
Background 
In patients with relapsed or refractory B-cell lymphoma, a standard of care therapeutic option to 
achieve long term remission is CD19 chimeric antigen receptor T-cell (CAR-T) therapy. This is 
a unique concept involving engineering patients’ autologous T-cells to target the CD19 antigen 
on lymphoma cells; however a minority of patients achieve long term remission.1-6 At the same 
time, patients undergo risks with this treatment, including cytokine storm (cytokine release 
syndrome, CRS) and neurologic toxicity (immune effector cell-associated neurotoxicity 
syndrome, ICANS).7 Though the outcomes of CAR-T are promising, there is room to improve 
upon the efficacy and toxicity of this therapy. 
 
Similarly, in patients with moderate to high-risk acute myeloid leukemia or myelodysplastic 
syndrome, allogeneic stem cell transplant (alloSCT) represents a potential cure for their disease. 
There is long-established efficacy in utilizing donor derived stem cells to create a new 
hematopoietic system, and donor T-cells to cause a graft-versus-tumour effect to eliminate 
microscopic persistence of disease. However, as a by-product, 30% of patients develop 
moderate-to-severe (Grade 2 to 4) graft-versus host-disease (GVHD), with 10% of patients 
having severe disease.8 Additionally, long term survival is less than 50% in all-comers and less 
than 30% in patients who develop severe GVHD.8 Thus, there is also room to improve upon the 
efficacy and safety of alloSCT. 
 
An emerging area of therapeutic interest is the intestinal microbiome, which has been shown to 
be associated with responses to cancer therapeutics including chemotherapy,9 immune 
checkpoint blockade,10-14 and cellular therapies,15-18 potentially by impacting host anti-tumour 
immune response.  
 
Microbiome studies in patients undergoing CAR-T therapy have found impaired alpha diversity 
compared to healthy controls.16 Broad antibiotic exposure within 3 weeks prior to CAR-T has 
been associated with significantly decreased progression-free survival (PFS) which was 
confirmed in an independent cohort, with the highest hazard ratio associated with broad spectrum 
antibiotics.18 However, even when excluding such patients, species, pathway, and gene variance 
still contributed significantly to treatment response and disease progression. Higher abundance of 
taxa such as Ruminococcus, Bacteroides, Faecalibacterium, Akkermansia, and Bifidobacterium 
have correlated with higher rates of complete response and improved progression-free survival 
(PFS),16-18 while peptidoglycan biosynthesis or D- galactose biosynthesis pathways have 
associated with early disease progression and worse survival at 6 months.18 Certain microbes 
have also been associated with higher rates of neurotoxicity. 
 
The contribution of the microbiome has also been well established in patients undergoing 
alloSCT, where a higher diversity of microbiota were associated with a lower risk of death in 
international independent cohorts, including death attributable to GVHD.15 Patients have 
impaired microbiome diversity compared to healthy controls at baseline, while during the 
transplant, a characteristic pattern of domination by single taxa occurs, supporting the use of pre-
transplant and post-transplant normalization of intestinal microbiota.15  

 
 
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1.2 
Investigational Product 
 
Background on fecal microbiota transplantation (FMT) 
 
The concept of FMT is the replacement of abnormal gut microbiome in the recipient with the 
microbiome of a healthy donor who has been screened for infectious diseases, health conditions 
that may be associated with dysbiosis, and risk behaviours that could increase the risk of 
acquiring infectious diseases. FMT is an established therapy in the management of recurrent C. 
difficile infection.19 The therapeutic use of FMT has been studied in numerous malignancies 
including hematological cancers.20 
 
 
Background on route of administration of FMT 
 
Notably, there is no standard for processing and administering human-to-human FMT.21 The donor 
stool is typically homogenized and filtered and either administered directly or frozen for later 
use.21-23 Gastrointestinal tubes, colonoscopy, enema, and recently even oral capsules are used to 
administer FMT.21  
 
To date, many studies have been published showing the efficacy of FMT to treat C. difficile colitis. 
The mode of administration does not seem to have a major impact on the efficacy.24 (See 
Investigator Brochure). The principal investigator group has previously used enema for treatment 
of C. difficile infection (Clinicaltrials.gov (NCT01226992); CTA File #: 9424-U0288/2-25C, 
Control #: 124081). Enema will be used for FMT administration in the current study.    
 
 
Prior data on safety 
 
FMT is generally considered a safe procedure. There are common minor adverse effects 
including transient diarrhea, abdominal cramps or pain, bloating, flatulence, and constipation. 
Risk of infection transmission has been a concern in the past, with prior reports of extended-
spectrum beta-lactamase (ESBL)-producing E. coli infection and Shiga toxin-producing E. coli 
infection associated with deaths, possibly transmitted via the FMT product.25 This led to more 
stringent testing of stool, with a recent registry study suggesting a 4% risk of infection by 6 
months.26 Other theoretical risks include intestinal perforation from enema or colonoscopic 
administration, and unknown long-term impacts on other aspects of health. 
 
FMT has been performed on immunocompromised individuals including those undergoing 
allogeneic stem cell transplant. A challenge with immunocompromised individuals is 
determining whether bacteremia/sepsis events are related to the FMT product or are related to 
patients’ underlying disease and treatment. The largest study was a Phase II 2:1 randomized 
study of FMT versus placebo in 100 patients with acute myeloid leukemia or undergoing 
alloSCT who received oral FMT a median of 43 days after chemotherapy or 23 days after SCT, 
respectively.27 The primary objective was to reduce the incidence of infections compared to 
placebo. This randomized trial was able to establish the safety of FMT in this population. No 
grade 3 or higher adverse events occurred within 24 hours of product administration. Only one 
grade 3 or higher gastrointestinal adverse event (diarrhea) occurred within 7 days after FMT. A 
blood stream infection with cytomegalovirus viremia (CMV) occurred within 7 days after FMT 
and was the only event that counted toward the stopping rule in the study. The patient was CMV-

 
 
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seropositive and their HCT and FMT donors were both CMV-seronegative, making a 
relationship with FMT unlikely.  
 
Another Phase study II reported on an oral FMT product in patients undergoing alloSCT with 
severe GVHD. The publication included 24 patients in the trial and 52 patients in an extended 
access program.28 In the trial population, five infectious complications, including 3 episodes of 
sepsis, could not be excluded from being related to the study intervention, though none of the 
strains involved in the sepsis episodes were found in the donor product. In the extended access 
program, 18 pharmacovigilance cases were reported among 52 treated patients, including 11 
cases of bacteremia/sepsis. Overall, the product was concluded to be safe in this report.  
 
Multiple other prospective studies comprising between 7 and 80 patients of patients receiving 
FMT who were undergoing alloSCT and/or had acute GVHD illustrated the safety of this 
product in this population, with mainly minor or transient AEs such as abdominal distention, 
cramps, or nausea, resolving within hours.27,29-34 One study reported two episodes of bacteremia 
which were from organisms either found in the host at baseline, or not found in the product;34 
another pilot study reported one case of bacteremia, it was not stated whether this was related to 
the FMT product;30 a final study noted pseudomonas bacteremia in a patient with a persistent 
pseudomonas skin infection.29 
 
Overall, the breadth of the data including a large randomized study suggest that FMT appears 
safe in an immunocompromised population of patients with hematologic malignancies.  
 
 
Prior data on efficacy 
 
The study by Rashidi et al described showed that FMT ameliorated intestinal dysbiosis and was 
safe, but it did not achieve its primary objective of reducing infections.27 Other case reports and 
small prospective studies prior to alloSCT have also shown that FMT can restore gut dysbiosis 
and decolonize antibiotic resistant organisms (AROs) in patients with multi-drug resistant 
bacteria.35-37 Furthermore, prospective studies and case reports have shown that FMT can be a 
salvage treatment for severe gut GVHD.28,31-34,38-41 
 
There is also an ongoing study of FMT in the proposed study population. NCT04935684 is a 
Phase II randomized study evaluating FMT by enema route in 150 patients undergoing alloSCT 
within 4 weeks of engraftment, with a primary outcome of occurrence of GVHD and 
engraftment.42  
 
 
Rationale 
 
Despite the novel clinical findings described, no published study has shown a potential 
therapeutic role for pre-emptively restoring normal intestinal microbiota prior to the cellular 
therapy infusion in unselected patients undergoing these procedures. Specifically, all published 
studies in alloSCT have used FMT after engraftment, or as a salvage treatment for gut GVHD. 
Additionally, no therapeutic study of FMT has been conducted on patients undergoing CAR-T 
therapy. 
 

 
 
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Our hypothesis is that we will be able to establish the feasibility and safety of FMT transfer in 
these populations, and explore endpoints of improved treatment toxicity, efficacy, and 
immunological, metabolomic, and ecological outcomes.  
 
 
Study design 
 
This is a single centre open-label, single arm pilot clinical trial of 20 patients, including 10 
patients undergoing CAR-T therapy for relapsed/refractory B-cell lymphoma, and 10 patients 
undergoing alloSCT for AML or MDS. This trial will be conducted in compliance with the 
protocol, GCP and Health Canada regulations. 
 
As this is a pilot study with primary endpoints of feasibility and safety, we will exclude patients 
with a history of infection or colonization with AROs within the last 2 years prior to enrollment. 
Given that all patients at Princess Margaret Cancer Centre undergoing alloSCT for malignant 
conditions receive cyclophosphamide for GVHD prophylaxis which increases the risk of 
bloodstream infections,43 we will only include patients receiving reduced-intensity conditioning 
(rather than myeloablative conditioning) to mitigate this risk.43 

 
 
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2. OBJECTIVES AND ENDPOINTS 
 
 
2.1 
Primary Objective 
 
Objective 
Endpoints 
To evaluate the feasibility and safety of FMT 
in patients undergoing CAR-T or allogeneic 
stem cell transplantation 
Feasibility: Ability to recruit the target 
population, retention, and successful 
administration of the intervention 
Safety: In each cohort, occurrence of serious 
adverse events or adverse events of special 
interest (AESIs) Grade >3 that are judged by 
the investigator as possibly, probably, or 
definitely related to the FMT intervention 
 
 
2.2 
Secondary Objectives 
 
Objective 
Endpoints 
In patients undergoing CAR-T: To evaluate 
the incidence of all grade and Grade >3 CRS, 
and all grade and Grade >3 ICANS 
Incidence of all grade CRS, grade >3 CRS, all 
grade ICANS, grade >3 ICANS 
In patients undergoing alloSCT: To evaluate 
the incidence of all grade and Grade >3 acute 
GVHD including gut GVHD 
Incidence of all grade and grade >3 acute 
GVHD after allogeneic stem cell transplant 
To assess one and three month overall 
response rates after infusion of CAR-T cells or 
stem cells (alloSCT) 
ORR determined by investigator assessment: 
-For patients with lymphoma, those with 
confirmed complete response or partial 
response by Lugano criteria on PET scan 
-For patients with MDS, achieving complete 
remission, partial remission, or hematologic 
independence based on peripheral blood and 
bone marrow assessment 
-For patients with AML, achieving complete 
remission, partial remission, or a morphologic 
leukemia free state based on peripheral blood 
and bone marrow assessment 

 
 
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To assess progression-free survival at 6 
months 
PFS determined by investigator assessment 
defined as the time from the date of infusion of 
cellular therapy to (first) disease recurrence 
documented via radiologic, laboratory, and/or 
clinical assessment, or death, or last follow up 
when alive without disease 
recurrence/progression  
To assess overall survival at 6 months 
OS, defined as the time from the date of 
infusion of cellular therapy to the date of death 
from any cause 
 
 
2.3 
Exploratory Objectives 
 
Objective 
Endpoints 
To evaluate baseline and day +30, +90, +180 
T-cell phenotypic and functional subsets 
Phenotypic and functional T-cell subsets, 
including but not limited to, CD3, CD4, CD8 
T-cell subsets, T-cell phenotypic and 
functional markers by flow cytometry, T-cell 
functional assays such as interferon gamma 
release assay 
To evaluate baseline and day +30, +90 
intestinal microbiome diversity 
Alpha diversity (Shannon diversity, species 
richness, Berger-Parker dominance); MET-2 
species relative abundance by shotgun 
metagenomic sequencing; Pseudamonadota, 
Enterobacteriaceae, Staphylococcus, 
Enterococcus, Pseudomonas, and Candida 
species relative abundance; Obligate anaerobe 
richness and cumulative relative abundance; 
Butyrogenic anaerobe richness and cumulative 
relative abundance; Compositional 
dissimilarity (Bray-Curtis dissimilarity) 
between groups and within groups and 
individuals/between timepoints; Absolute 
bacterial abundance (by 16S gene qPCR); 
Log-fold changes in relative abundance 
between baseline and post-treatment samples 
will be determined and ‘engraftment’ for any 
species defined as >1-log increase.    
To evaluate engraftment (Donor and recipient 
intestinal microbiome similarity)  
Compositional dissimilarity/similarity (beta-
diversity) will be assessed between groups and 
sample pairs (i.e. pre/post intervention or 
donor/recipient) using Bray-Curtis 
compositional dissimilarity; whole blood flow 
cytometry for anti-FMT bacterial antibodies as 
a correlate of engraftment and immunogenicity 

 
 
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To evaluate baseline and day +30, +90 plasma 
and urine bacterial metabolomics 
Plasma, and urine SCFA and 1oBA/2oBA 
concentrations 
To evaluate baseline and day +30, +90  
incidence of antimicrobial-resistant organisms 
(MRSA, VRE, ESBL, CBE) intestinal 
colonization by rectal swab 
Incidence of MRSA, VRE, ESBL, and CBE 
colonization by rectal swab 
To evaluate incidence of bacteremia, urinary 
tract infections and/or C. difficile infection by 
day +30 
Incidence of bacteremia, urinary tract 
infections, and C. difficile infection by Day 
+30 
To understand patient perspectives on FMT 
gathered by survey at baseline and on day +90 
Patient perspectives on FMT gathered by 
survey, comparing quantitative responses at 
baseline and day +90, and describing 
qualitative responses 
 

 
 
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3. PATIENT SELECTION 
3.1 
Eligibility criteria 
Each patient must meet all of the inclusion criteria and none of the exclusion criteria for this 
study. Waivers will not be granted for this study.  
 
 
Inclusion criteria 
 
For inclusion in the study patients must fulfill all of the following criteria:  
 
1. Men and women ≥ 18 years of age  
2. Diagnosis of the following:  
a. Indolent or aggressive B-cell lymphoma eligible for standard or care CAR-T 
therapy (Cohort A), or 
b. Patients with AML or high risk MDS with indication to undergo reduced-intensity 
conditioning alloSCT, with an available matched related, unrelated, or 
haploidentical donor (Cohort B) 
3. ECOG 0-1 
4. Adequate marrow function defined by: 
a. Hemoglobin >80 g/L without transfusion dependence within the last 7 days 
b. Platelet count >20 x 109/L without transfusion dependence within the last 7 days 
c. Neutrophil count >1.0 x 109/L without growth factor support within the last 7 
days 
5. Adequate liver function as indicated by aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) ≤ 2.5 x the institutional upper limits of normal (ULNs) value; 
serum total bilirubin < 1.5 x ULN (unless documented Gilbert’s syndrome) 
6. Adequate renal function as defined as creatinine clearance ≥ 30 mL/min directly 
measured with a 24-hour urine collection or calculated according to the modified formula 
of Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration 
(CKD-EPI) calculation 
7. Life expectancy >6 months 
8. Women of childbearing potential (WOCBP) who are sexually active must use highly 
effective methods of contraception during treatment and up to 6 months after the last dose 
of protocol therapy. Men who are sexually active must use highly effective methods of 
contraception during treatment and up to 6 months after the last dose of protocol therapy. 
Men require an agreement to remain abstinent (ie, refrain from heterosexual intercourse) 
or use a condom, and an agreement to refrain from donating sperm. Periodic abstinence 
and withdrawal are not acceptable methods of contraception. Fertility preservation 
options should be discussed. Examples of highly effective contraceptive methods include 
an agreement to remain abstinent (ie, refrain from heterosexual intercourse), bilateral 
tubal ligation, male sterilization, established proper use of hormonal contraceptives that 
inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine 
devices.   
9. Willing and able to participate in all required evaluations and procedures in this study.  
10. Ability to understand and the willingness to sign a written informed consent.  
 

 
 
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21 
 
 
Exclusion criteria 
 
Subjects will be ineligible for this study if they meet any of the following criteria:  
1. For patients undergoing alloSCT (Cohort B): plan to undergo myeloablative conditioning 
2. Use of investigational agents within the last 4 weeks before enrollment. 
3. Active or uncontrolled infection 
4. Autoimmune disorder currently being treated with disease-modifying therapy or with 
>10mg/day prednisone 
5. Inflammatory bowel disease 
6. History of intestinal perforation 
7. Gastrointestinal surgical procedure within the past 4 weeks before enrollment 
8. Pregnant or breast-feeding patients 
9. HIV infection with detectable viral load or CD4 count <200 
10. Serologic status reflecting active hepatitis B or C infection as follows:  
a. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody 
(HBcAb) with detectable hepatitis B virus (HBV) DNA. (Note, patients with 
undetectable HBV DNA are permitted to enroll if they are on Hepatitis B 
suppressive therapy) 
b. Patients with presence of hepatitis C virus (HCV) antibody and HCV RNA 
detectable  
11. History of infection or known colonization with antibiotic resistant organism in the last 
two years before enrollment (including ESBL, MRSA, VISA, VRSA, VRE, CPE) 
12. Any serious medical condition or abnormality in clinical laboratory tests that, in the 
investigator’s judgment, precludes the patient’s safe participation in the study  
 
Enrollment Procedures 
 
Diagnostic or laboratory studies performed exclusively to determine eligibility will be done only 
after obtaining written informed consent. Studies or procedures that are performed for clinical 
indications (not exclusively to determine study eligibility) may be used for baseline values 
and/or to determine pre-eligibility, even if the studies were done before informed consent was 
obtained as long as they are within protocol defined windows. The informed consent process is 
to be fully documented and the prospective participant must receive a copy of the signed 
informed consent document. Screening procedures are listed in Section 4.  
 
All patients will be screened by the principal investigator or sub-investigators prior to entry into 
this study. An explanation of the study and discussion of the expected side effects and full 
disclosure of the “informed consent document will take place. Eligible and consented patients 
will be registered into the study.  
 
After the subject has signed and dated the Informed Consent Form (ICF), all screening 
procedures have been completed, and eligibility has been confirmed, the subject can be enrolled 
into the study. 
 

 
 
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22 
Registration will be done through Ozmosis Research Inc. Sites will assign each patient with a 
patient ID number which should be used on all documentation and correspondence.  
 
Prior to registering a patient, each institution must have submitted all necessary regulatory 
documentation to Ozmosis Research Inc. Access to the eCRFs will only be granted once this has 
been received.  
 
No patient can receive protocol treatment until eligibility has been confirmed and the Patient 
Enrollment Form has been submitted to Ozmosis Research Inc. All eligibility criteria must be 
met at the time of enrollment. Waivers will not be accepted. Any questions should be addressed 
with Ozmosis Research Inc. prior to enrollment.  
 
Sites will fax in the signed, completed Patient Enrollment Form to Ozmosis Research Inc. at 
416-634-8333, or e-mail to ozmclinical@ozmosisresearch.ca. The CTS/CTM will then review 
the registration form for completion. There will be NO confirmation of registration sent to the 
site. Patients are considered to be registered once the Patient Enrollment Form has been 
successfully delivered to Ozmosis. Only after this has been done, can the patient receive study 
treatment.  
 
Protocol treatment should begin within 7 working days of patient enrollment.  
 
All eligible patients registered into the study will be entered into a patient registration log at 
Ozmosis Research Inc. 
 
The following information will be required at the time of registration:  
 Patient ID trial code 
 Treatment centre and investigator 
 Patient’s partial date of birth  
 
Note: it is the responsibility of the investigator in charge to satisfy him or herself that the patient 
is indeed eligible before registering.  
 
The Patient Enrollment Form must be completed, and signed by the investigator prior to 
enrollment. There are 2 sections to the Patient Enrollment Form:  
 SCREENING (top section): this section is completed by the site and should be faxed to 
416-634-8333, or e-mailed to ozmclinical@ozmosisresearch.ca at the time of screening.  
 ENROLLMENT (bottom section): this section is completed by the site at the time of 
patient enrollment. The site will fax the signed and completed Patient Enrollment Form to 
Ozmosis Research Inc. at 416-634-8333, or e-mailed to 
ozmclinical@ozmosisresearch.ca.  

 
 
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4. STUDY PROCEDURES 
For a summary of study procedures, see STUDY CALENDAR 
 
The Study Calendar summarizes the trial procedures to be performed at each visit.  It may be 
necessary to perform these procedures at unscheduled time points if deemed clinically necessary 
by the investigator. Furthermore, additional evaluations/testing may be deemed necessary for 
reasons related to subject safety. 
 
4.1 
Description of Procedures  
 
 
Study treatment overview 
 
Eligible patients will be identified during routine standard of care waitlist meetings for patients 
undergoing CAR-T or alloSCT therapy. Patients cleared to undergo CAR-T or alloSCT 
procedures routinely attend in-person follow up visits at the study site. During such standard of 
care visits, patients will be approached by the study coordinator for informed consent. It is 
anticipated that this visit will be the pre-apheresis clearance visit for patients undergoing CAR-T 
therapy, and the pre-alloSCT clearance visit in which a donor has been identified for the patient, 
and patients are medically cleared. 
 
If patients provide informed consent and meet study eligibility guidelines, they will be enrolled 
into the study.  
 
Initial FMT series (see section 5.2 for further details): Patients will receive their initial FMT 
series with two doses separated by 48 hours during their lymphodepleting chemotherapy (for 
patients receiving CAR-T, day -5 and day -3) or conditioning chemotherapy (for patients 
receiving alloSCT, day -5 and day -3). These dates were selected as infusion dates to ensure that 
the FMT administration occurs prior to the onset of chemotherapy-induced neutropenia. Patients 
must have an ANC >1.0 x 109/L documented within 7 days prior to the FMT administration.  
 
For patients receiving CAR-T therapy, the lymphodepleting chemotherapy regimens are aligned 
with standard of care and may vary based on physician preference and institutional practice. 
- 
YESCARTA (axicabtagene ciloleucel): Prior to cell therapy infusion date (Day 0), Day -5 
to Day -3: cyclophosphamide 500 mg/m2 and fludarabine 30 mg/m2 IV daily  
- 
TECARTUS (brexucabtagene autoleucel): Prior to cell therapy infusion date (Day 0), 
Day -5 to Day -3: cyclophosphamide 500 mg/m2 and fludarabine 30 mg/m2 IV daily  
- 
KYMRIAH (tisagenlecleucel): Prior to cell therapy infusion date (Day 0), Day -5 to Day 
-3: cyclophosphamide 250 mg/m2 and fludarabine 25 mg/m2 IV daily  
- 
BREYANZI (lisocabtagene maraleucel): Prior to cell therapy infusion date (Day 0), Day -
5 to Day -3: cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 IV daily  
 
For patients receiving alloSCT, the conditioning chemotherapy regimens are aligned with 
standard of care and the regimen selected may vary based on physician preference and 
institutional practice: 
- 
RUH-FB2: Prior to cell therapy infusion date (Day 0), fludarabine 35mg/m2 IV daily on 

 
 
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Day -5 to Day -2, busulfan 3.2mg/kg IV daily on Day -5 and Day -4 
- 
RUH-FB2T(200): Prior to cell therapy infusion date (Day 0), fludarabine 35mg/m2 IV 
daily on Day -5 to Day -2, busulfan 3.2mg/kg IV daily on Day -5 and Day -4, total body 
irradiation 200 cGy on Day -1 
- 
RU-FluTreo42: Prior to cell therapy infusion date (Day 0), fludarabine 35mg/m2 IV daily 
on Day -5 to Day -2, treosulfan 14g/kg IV daily on Day -5 to Day -3 
- 
RU-FluTreo30: Prior to cell therapy infusion date (Day 0), fludarabine 35mg/m2 IV daily 
on Day -5 to Day -2, treosulfan 10g/kg IV daily on Day -5 to Day -3 
 
Additionally, patients should not have any signs, symptoms, or diagnosis of active infection at 
the time of FMT administration. Prior to administering their initial series, patients will provide a 
fecal swab and bloodwork to bank as a regulatory precaution in case of safety concerns with their 
FMT product.  
 
Second FMT series (see section 5.2 for further details): A second FMT series is due at Day +30. 
The second FMT series will only be administered if patients have a neutrophil count of  
ANC>1.0 x 109/L without growth factor support for a 7 day period, documented within 7 days 
prior to the FMT administration. Additionally, patients should not have any signs, symptoms, or 
diagnosis of active infection at the time of FMT administration. If patients remain reliant on 
growth factors and/or they have concerns of active infection, the second FMT series will be 
delayed by a maximum of 30 days, after which time it will be omitted. Prior to the second series, 
in addition to study procedures, patients will provide a fecal swab and bloodwork to bank as a 
regulatory precaution in case of safety concerns with their FMT product.  
 
Follow-up: At Day +90 and +180, patients will be seen during their routine post-cellular therapy 
follow up visit for study visits. Further details of study procedures during these visits are in the 
Study Calendar.  
 
 
Informed Consent 
 
Consent must be documented by the subject’s dated signature or by the subject’s legally 
acceptable representative’s dated signature on a consent form along with the dated signature of 
the person conducting the consent discussion.  
 
A copy of the signed and dated consent form should be given to the subject before participation 
in the trial. Informed consent of study procedures may be obtained prior to the 60-day screening 
window 
 
The initial informed consent form, any subsequent revised written informed consent form and 
any written information provided to the subject must receive the Research Ethics Board (REB)’s 
approval/favorable opinion in advance of use.  The subject or his/her legally acceptable 
representative should be informed in a timely manner if new information becomes available that 
may be relevant to the subject’s willingness to continue participation in the trial. The 
communication of this information will be provided and documented via a revised consent form 

 
 
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25 
or addendum to the original consent form that captures the subject’s dated signature or by the 
subject’s legally acceptable representative’s dated signature. 
 
Specifics about a trial and the trial population will be added to the consent form template at the 
protocol level.   
 
The informed consent will adhere to REB requirements, applicable laws and regulations and 
Sponsor requirements. 
 
 
Inclusion/Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed by the investigator or qualified designee to 
ensure that the subject qualifies for the trial.  
 
 
Medical History 
A medical history will be obtained by the investigator or qualified designee, including history of 
severe and/or anaphylactic food allergies. Medical history will include all active conditions, and 
any condition previously diagnosed that are considered to be clinically significant by the 
Investigator. Details regarding the disease for which the subject has enrolled in this study will be 
recorded separately and not listed as medical history.   
 
 
Prior and Concomitant Medications Review 
4.1.5.1 
Prior Medications 
The investigator or qualified designee will review prior medication use and record prior 
medication taken by the subject within 28 days before starting the trial.  Treatment for the 
disease for which the subject has enrolled in this study will be recorded separately and not listed 
as a prior medication.  
 
4.1.5.2 
Concomitant Medications 
The investigator or qualified designee will record medication, if any, taken by the subject during 
the trial.  All medications related to reportable Serious Adverse Events (SAEs) should be 
recorded as defined in Section 7.6. 
 
4.1.5.3 
Permitted Concomitant Medication  
 
Permitted concomitant medication include:  
 Highly effective contraceptive methods including hormonal contraceptives that 
inhibit ovulation, hormone releasing intrauterine devices, and copper intrauterine 
devices must be used by WOCBP who are sexually active during treatment and 
up to 6 months after the last dose of protocol therapy.  
 Pico-Salax as required in the study   
 
4.1.5.4 
Prohibited Concomitant Medications  
 
Prohibited concomitant medications include: 
 Any investigational agents other than those under investigation in this study.  

 
 
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 Any disease modifying therapy or administration of ≥ 10 mg/day prednisone for 
treatment of autoimmune disorder. 
 
 
Disease Details and Treatments 
4.1.6.1 
Disease Details 
The investigator or qualified designee will obtain prior and current details regarding disease 
status. 
 
4.1.6.2 
Prior Treatment Details 
The investigator or qualified designee will review all prior cancer treatments including systemic 
treatments, radiation and surgeries. 
 
 
Subsequent Anti-Cancer Therapy Status 
The investigator or qualified designee will review all new anti-neoplastic therapy initiated after 
the last dose of trial treatment.   
 
 
Participant questionnaires 
 
Participants will fill out a baseline questionnaire regarding their perceptions of FMT. At Day 
+90, they will fill out a second questionnaire regarding their experience and perceptions of FMT. 
 
4.2 
Safety Monitoring  
Given the immunocompromised nature of patients on this study, only 10 patients will be initially 
accrued and the initial safety will be assessed by a safety monitoring committee (SMC). The 
committee will be composed of clinical specialists with experience in oncology and infectious 
diseases and who have no direct relationship with the study. They will be charged with 
overseeing the monitoring of safety of participants in the clinical trial, and the conduct, progress, 
validity, and the integrity of the data. The committee will review all relevant data to assess 
tolerability to approve further subjects to be enrolled thereafter.  
The SMC will meet at any point deemed necessary during the study on its own initiative or at the 
request of the sponsor and in particular to analyze safety data. Any unexpected safety event 
including SAEs and AESIs Grade >3 that are possibly, probably, or definitely related to the FMT 
will be reported to the SMC, and will require that the study be placed on a hold while the SMC 
review the safety event. 
The meetings will take place between the participating site investigators, the Sponsor and 
Ozmosis Research to review patient safety after 10 patients complete their series of FMT 
administrations and at least 7 days of follow up after the second administration of the last patient 
have passed. During the initial review period or at any time during the study there are two or 
more SAE or AESI considered possibly, probably, or definitely related to the FMT intervention 
in either cohort, enrollment to that cohort will close.  

 
 
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An “Accrual Hold Notice” will be sent out to Sponsor and site personnel by Ozmosis Research 
Inc. once the study has recruited the necessary patients.  
Within 7 working days of each patient completing their second FMT series, the following 
sections of the eCRF and source documentation for laboratory results, must be completed:  
 Study Treatment Data 
 Adverse Events 
 Laboratory Results  
Additional information may also be requested by Ozmosis Research Inc. from the study site. It is 
imperative that the eCRF pages listed above are completed within 7 working days after the last 
patient has completed Day +34, as the information will be used to assess safety.  
If a patient fails to complete the safety observation period (e.g. shows disease progression or 
stops treatment for reasons other than a safety concern), additional patients may be added to 
ensure a minimum of 10 patients. The SMC may recommend enrolling further patients to 
facilitate collection of additional safety data. The decision to enroll additional patients will be 
made in consultation with the SMC.  
The SMC will be responsible for reviewing the following activities: participant accrual, 
summary of all adverse events captured via routine and expedited reporting; a summary of 
deviations; any response information; monitoring reports, and summary comments provided by 
the study team. Other information (e.g. scans, laboratory values) will be provided upon request. 
A review of outcome results (response, toxicity and adverse events) and factors external to the 
study (such as scientific or therapeutic developments) will also be discussed. 

 
 
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5. STUDY INTERVENTION 
If the patient qualifies, based on the Screening evaluations, he/she will be enrolled according to 
the procedures outlined below. 
 
5.1 
FMT Preparation 
 
 
FMT Donors 
 
Stool samples for this study will be obtained via donations through the Microbiota Therapeutics 
Outcomes Program (MTOP) at the University Health Network and Sinai Health in Toronto, 
Ontario. Donors will be evaluated according to MTOP guidelines, Health Canada Regulations 
and standard institutional practices. Individual donations will be used to manufacture FMT.   
 
 
Identification and Screening of FMT Donors  
FMT donors will be supplied from MTOP, using existing criteria and standard procedures for 
identification and screening (see Investigator Brochure). In short, healthy, adult potential donors 
(PDs) are recruited through advertisements in the downtown Toronto region and the MTOP 
website. PDs undergo screening for eligibility through self-screening questionnaire, telephone 
pre-screening, medical assessment, mental health questionnaires and blood testing for diabetes 
risk (homeostatic model assessment for insulin resistance – HOMA-IR). They subsequently 
undergo serologic, urine, rectal swab, upper respiratory tract and/or oral specimen and stool 
testing for infectious diseases and antibiotic-resistant organism colonization. Approved donors 
(who pass all of the aforementioned screening) provide repeat stool donations (goal 3-5 times per 
week).  
Bookend testing of stool for AROs (MRSA, VRE, ESBL and CPO), common enteric pathogens, 
SARS-CoV-2 and mpox occurs at minimum two-month intervals. Rescreening for blood borne 
pathogens and sexually-transmitted infections occurs at least every 6 months. FMT donations 
provided up to 2 weeks preceding re-screening are released only if re-screening is negative for 
AROs and all other screened infectious diseases. In addition, while donating stool to MTOP, 
FMT donors complete self-screening questionnaires with every donation for ongoing assessment 
of their medical health, intake of common allergens, and risk of acquiring infectious diseases. If 
a risk for infection is determined to be present on the questionnaire (e.g. travel to an endemic 
area for infectious disease), the donor is placed in a washout period prior to being rescreened to 
re-enter the program. Diabetes risk (HOMA-IR score), anthropometric measurements and mental 
health questionnaires are repeated at least every 12 months. For patients who have a history of 
severe and/or anaphylactic food allergies, the donor FMT is screened to ensure there has been no 
recent intake of any of the listed allergens. 
FMT donations are processed, concentrated and frozen at -80C, until requested for FMT. Donor 
feces are collected at home and are delivered to MTOP within 24-48 hours. Frozen FMT is 
stored up to 5 years without losing significant viability, as per MTOP internal verification of 
FMT storage conditions.44 MTOP protocols follow Health Canada guidance for FMT donor 

 
 
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screening and selection45 and are approved by the UHN Research Ethics Board (CAPCR ID: 16-
5404). 
 
 
FMT Manufacturing 
 
FMT manufacturing will follow modified methodologies, based on a previous randomized 
controlled trial from the MTOP program.46   
 
Fresh Donor Stools FMT: 
 
a. For the 50g/filtrate dose, fifty (50) grams of screened donor feces will be weighed 
and homogenized with 300 mL of sterile 0.9 N NaCl using a sterile 330 micron 
micro-filter-separated double-compartment polyethylene bag in the Stomacher® 
Lab Blender. . For the 100g/filtrate dose, one hundred (100) grams of screened 
donor feces will be weighed and homogenized with 300 mL of sterile 0.9 N NaCl 
using a sterile 330 micron micro-filter-separated double-compartment 
polyethylene bag in the Stomacher® Lab Blender. 
b. The sample will be homogenized using the Stomacher® Paddle Blender for 30 
seconds at 300rpm until it is a milk-shake consistency. 
c.  The resulting fecal filtrate will be transferred to an enema bag constituting a 
single “FMT dose”. 
d. Part of the final fecal filtrate will be stored in the –80oC freezer in the event that 
further testing is required in the future. 
e. All aliquots of fecal filtrate will be labeled with a unique donor identification 
number. 
f. Any reusable equipment will be autoclaved in order to eliminate C. difficile 
spores.  The Stomacher® will be cleaned as specified by the manufacturers before 
and after each use including the use of a sporicidal agent. 
The preparation area will be cleaned with a sporicidal agent before and after each 
use. 
 
Preparation of Frozen FMT Concentrate: 
 
a. Fifty (50) grams of screened donor feces will be weighed and homogenized with 
45 mL of sterile 0.9 N NaCl + 5 ml glycerol (to make 10% final concentration 
glycerol) using a sterile 330 micron micro-filter- separated double-compartment 
polyethylene bag in the Stomacher® Paddle Blender. 
b. The sample will be homogenized using the Stomacher® Paddle Blender for 30 
seconds at 300rpm until it is a milk-shake consistency. 
c. The resulting fecal filtrate will be transferred to a 50 mL Falcon tube with screw 
top and frozen at -80 oC. 
d. Part of the final fecal filtrate will be stored in the –80oC freezer in the event that 
further testing is required in the future. 
e. All aliquots of fecal filtrate will be labeled with a unique donor identification 
number. 

 
 
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f. Any reusable equipment will be autoclaved in order to eliminate C. difficile 
spores.  The Stomacher® will be cleaned as specified by the manufacturers before 
and after each use including the use of a sporicidal agent. 
g. The preparation area will be cleaned with a sporicidal agent before and after each 
use. 
 
These activities will be carried out within a designated biosafety cabinet in the UHN-SHS 
Clinical Microbiology Laboratory.  
 
 
Thawing, Dilution and Packaging of frozen FMT: 
 
Frozen FMT will be thawed at room temperature over 2.5 hours in order to best maintain the 
integrity of microorganisms. 
 
For enema administration, of the 50g/filtrate dose of FMT, one (1) Falcon tube of thawed FMT 
concentrate will be diluted to a final volume of 300 ml and transferred to an enema bag. 
 
For enema administration of 100g/filtrate dose of FMT, two (2) Falcon tube of thawed FMT 
concentrate will be diluted to a final volume of 300 ml and transferred to an enema bag. 
 
 
Transportation of FMT product 
 
Enema bags and screw top containers containing prepared fecal filtrate will be transported at 
room temperature to the FMT procedure room in a biosafety specimen transportation bag 
following Transportation of Dangerous Goods procedures. 
 
5.2 
FMT Administration 
FMT will be administered by enema. Two hours prior to the procedure, patients will be advised 
to refrain from consuming any food or drink, a practice known as being ‘nil per os’ alternatively 
nothing by mouth (NPO). Medications may be taken using sips of water. Patients may eat a 
regular diet but will be advised to use a bowel preparation instructions using Pico-Salax the night 
before the FMT procedure will be given. If the bowel preparation is incomplete, missed, or the 
patient refuses bowel prep, they may still proceed with the FMT procedure. 
 
Rectal infusion of FMT will be administered every 48 hours for 2 doses, on 2 separate occasions, 
detailed in the study calendar. For each series of FMT administrations, the first dose will be 100g 
and the second will be 50g. Each FMT will be delivered using a single dose (300 ml of prepared 
fecal filtrate containing 100g or 50g of stool from a donor) delivered using an enema bag and 
rectal catheter. The procedure, including preparation steps, will take less than 20 - 30 minutes. 
Patients will be asked to lie down retaining the enema product for 20 minutes, changing position 
(left lateral decubitus, supine, right lateral decubitus, supine) every 5 minutes. Patients will be 
observed for 30 minutes post-FMT administration for immediate adverse events. Patients will 
have a mandatory rectal swab and serum collection prior to the first FMT of each treatment 
series which will be banked and recalled in the event that there is a concern for transmission of 
infectious agents from FMT. These are performed for quality of care purposes.  
 

 
 
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FMT by enema will be administered by a physician or nurse practitioner with training in enema 
administration of FMT. For patients undergoing CAR-T therapy, the first FMT series will 
typically occur in the Autologous Day Hospital when they attend their standard of care visits for 
leukapheresis chemotherapy. For patients undergoing alloSCT as an outpatient, the first FMT 
series will typically occur in the Allogeneic Day Hospital (outpatient alloSCT), or in the 
inpatient unit (inpatient alloSCT), during their standard of care conditioning chemotherapy. 
Patients must have an ANC >1.0 x 109/L documented within 7 days prior to the FMT 
administration. These dates were selected as infusion dates to ensure that the FMT administration 
occurs prior to the onset of chemotherapy-induced neutropenia. Additionally, patients should not 
have any signs, symptoms, or diagnosis of active infection at the time of FMT administration. 
 
The second FMT administration will occur in either the inpatient or outpatient setting depending 
on whether the patient has been discharged from hospital by the time their second FMT series is 
due at Day +30. The second FMT series will only occur if patients have a neutrophil count of 
ANC>1.0 x 109/L without growth factor support for the last 7 days, documented within 7 days 
prior to the FMT administration. Additionally, patients should not have any signs, symptoms, or 
diagnosis of active infection at the time of FMT administration. If patients remain reliant on 
growth factors or there are concerns of infection, the second FMT series will be delayed by a 
maximum of 30 days, after which time it will be omitted. 
 
5.3 
General Guidelines for Concomitant Medications and Supportive Care  
 
Concomitant Medications 
Concomitant medications to control side effects of therapy will be given at the discretion of the 
investigator.  Medications that are considered necessary for the subject’s welfare, and which are 
not expected to interfere with the evaluation of the study procedure, may be given at the 
discretion of the Investigator.  
 
5.4 
Duration of Therapy 
Safety/efficacy assessments will be made from enrollment onto trial through 180 days after 
cellular therapy which is considered the active treatment phase of the protocol.   
 
Subjects will continue on this phase and defined observation/tests will be repeated until one of 
the following criteria applies: 
 
1. Disease progression. 
2. Clinical progression. 
3. Termination of the protocol by a regulatory agency or Sponsor, or study medication can no 
longer be provided. 
4. Significant non-compliance with the protocol schedule in the opinion of the investigator. 
5. Intercurrent illness that prevents further study participation. 
6. Serious safety event that is judged to be possibly, probably or definitely related to the study 
intervention by the investigator 
7. The Subject decides to withdraw from the study. 
8. General or specific changes in the subject’s condition render the subject unacceptable for 
further treatment in the judgment of the investigator. 

 
 
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5.5 
Duration of Follow-Up 
Patients will be followed on protocol until 180 days after cellular therapy to collect information 
on safety assessment and disease response.  
 
5.6 
Subject Withdrawal/Discontinuation Criteria 
Patients are free to withdraw from the study at any time. If a patient withdraws consent, they will 
be asked if they are withdrawing consent to: 
 
 All further participation in the study including any further follow up 
 Withdrawal of the use of any samples 
 
A patient who withdraws consent will be asked about the reason(s) for withdrawal and the 
presence of any AE. The investigator will promptly notify the Sponsor and will make every 
effort to complete the End of Study assessments. All withdrawn subjects with ongoing clinically 
significant clinical or laboratory findings will be followed until the finding is resolved or 
medically stable; reasonable attempts will be made to follow-up with subjects. 
 
A patient may also be discontinued from the study if, in the investigator’s judgment, continued 
participation would pose unacceptable risk to the subject or to the integrity of the study data.  All 
procedures for discontinuation must be completed. Reasons for discontinuation may include: 
 
 
Noncompliance with the study 
 
Unacceptable toxicity 
 
Disease progression 
 
Continuation in the study is not in the best interest of the patient as judged by the 
investigator 
 
Protocol deviation or violation 
 
Study terminated by sponsor 
 
5.7 
Drug Dispensing and Accountability  
The UHN-SHS Clinical Microbiology Laboratory will be responsible for the receipt, storage, 
dispensing and tracking of the investigational drug. The lab personal will prepare the correct 
dosage of study agent to be administered to the study participant. The responsibility for drug 
accountability, including monitoring of drug dispensed to each study participant, drug supply 
reconciliation, record maintenance and documentation of drug destruction due to expiry or 
remaining supply at the end of the clinical trial, will be the responsibility of the participating 
clinical site. The local Pharmacist or delegate will maintain an accurate record of the receipt of 
investigational drug supply and the dispensing of investigational drug to each study participant 
including the quantity, batch or lot number, date of dispensing and any unused drug. 
 
At study close-out, expired investigational drug should be destroyed at high temperature 
incineration or by the standard institutional practice. Documentation of destruction is required to 
be completed by each clinical site. 

 
 
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33 
6. DOSING DELAYS/DOSE MODIFICATIONS 
There are no dose modifications applicable to this protocol as the study treatments include 
standard dose FMT. As stated, patients must have an ANC >1.0 x 109/L documented within 7 
days prior to the first FMT administration, and they must have an ANC >1.0 x 109/L without 
growth factor support within the last 7 days, documented within 7 days prior to the second FMT 
administration. Additionally, patients should not have any signs, symptoms, or diagnosis of 
active infection at the time of FMT administration. If these criteria are not met at time of first 
FMT, patients would not meet study eligibility criteria. If these criteria are not met at the time of 
the second FMT series, it can be delayed for up to 30 days after which time it will be omitted. 
 
If an adverse event occurs after enrollment that prevents a particular subject from receiving the 
study treatment but then resolves, the subject can be rescreened for study treatment if considered 
appropriate by the study investigator.  The subject must, however, continue to meet eligibility for 
treatment. In cases where the FMT product does not meet manufacture specification criteria for 
administration, the subject will be withdrawn from the study. 
 
 

 
 
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34 
7. ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS  
7.1 
List of Adverse Events and Reporting Requirements 
This study will utilize the CTCAE version 5.0 for toxicity and Adverse Event reporting, for 
adverse events other than those related to infection, CRS, ICANS, and GVHD. For adverse 
events related to infection, the Bone Marrow Transplant Clinical Trials Network Guidance 
will be used.47 For adverse events related to CRS and ICANS, the American Society for 
Transplantation and Cellular Therapy (ASTCT) 2019 guidance will be used.48 For adverse 
events related to GVHD, the Mount Sinai Acute GvHD International Consortium (MAGIC) 
criteria will be used.49 
Please refer to sections 7.3, 7.4 and 7.5 for detailed information on adverse events grading as 
above. 
 
 
Expected Adverse Events and Protocol-Specific Expedited Adverse Event 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The 
following list of AEs and the characteristics of an observed AE will determine whether the event 
requires expedited reporting as an SAE in addition to routine reporting.  In addition, 
hospitalizations for routine procedures, protocol treatment, blood sampling, investigations and 
tissue biopsies are NOT considered SAE in this protocol. 
 
7.1.1.1 
Expected Adverse Events for FMT 
 
Expected adverse events include minor adverse effects such as transient diarrhea, abdominal 
cramps or pain, bloating, flatulence, and constipation. Adverse events of special interest (AESI) 
include Grade >3 bowel perforation, bacteremia and/or sepsis, or ICU admission events 
occurring within 48 hours of each FMT administration. These events, and any serious adverse 
event will be subjected to expedited reporting. 
 
7.2 
Adverse Event Characteristics  
The International Conference on Harmonization (ICH) Guideline for Good Clinical Practice 
(GCP) E6(R1) defines an AE as: 
 
Any untoward medical occurrence in a subject or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product. 
 
An AE includes but is not limited to any clinically significant worsening of a subject’s 
pre-existing condition. The term disease progression should not be reported as an AE or SAE, 
however, medically significant individual events and/or laboratory abnormalities associated with 
disease progression (see definition of disease progression below) that fulfill the AE or SAE 
definition should be reported. An abnormal laboratory finding (including ECG finding) that 
requires medical intervention by the investigator, or a finding judged by the investigator as 
medically significant should be reported as an AE. If clinical sequelae are associated with a 

 
 
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35 
laboratory abnormality, the diagnosis or medical condition should be reported (e.g. renal failure, 
hematuria) not the laboratory abnormality (e.g. elevated creatinine, urine red blood cell 
increased).  
 
AEs may be treatment emergent (i.e. occurring after initial receipt of investigational product) or 
non-treatment emergent. A non-treatment-emergent AE is any new sign or symptom, disease, or 
other untoward medical event that begins after written informed consent has been obtained but 
before the subject has received investigational product. Non-treatment-emergent AEs occurring 
prior to study treatment and not related to study procedures will be captured as baseline 
symptoms. 
 
Effective treatment or surgery or preplanned treatment or surgery (that was scheduled prior to the 
subject being enrolled into the study) for a documented pre-existing condition that did not 
worsen from baseline is not considered an AE (serious or non-serious). An untoward medical 
event occurring during the prescheduled elective procedure or routinely scheduled treatment 
should be recorded as an AE or SAE. 
 
 
CTCAE term (AE description) and Grade:  The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) 
Version 5.0 will be utilized for AE reporting.  All appropriate treatment areas should 
have access to a copy of the CTCAE) Version 5.0.  A copy of the CTCAE Version 5.0 
can be downloaded from the CTEP web site 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
 
 
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. 
 
Associated with the use of the drug:  
There is a reasonable possibility that the experience may have been caused by the drug/biologic. 
 
Life threatening adverse drug experience:  
Any adverse drug/biologic experience that places the subject, in the view of the investigator, at 
immediate risk of death from the reaction as it occurred. 
 
Serious adverse event:  
Any event is an AE occurring at any dose that results in any of the following outcomes: 
 
Death. 
 
A life-threatening AE (The patient was, in the view of the Investigator, at immediate risk of 
death from the event as it occurred.  It does not mean that the event, had it occurred in a 
more severe form, might have caused death). 
 
Hospitalization or prolongation of existing hospitalization (complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization   or   fulfills   any   other   

 
 
Version 1.0, Dec 17, 2025 
36 
serious   criteria, the   event   is   serious. Hospitalization for elective treatment of a pre-
existing condition that did not worsen from baseline is not considered to be an AE). 
 
A persistent or significant disability/incapacity (A substantial disruption of a subject’s ability 
to conduct normal life functions.  This definition is not  intended  to  include  experiences  of 
relatively  minor  medical  significance  such  as  uncomplicated  headache,  nausea, 
vomiting,  diarrhea,  influenza,  accidental  trauma  (i.e.,  sprained  ankle)  that  may interfere  
or  prevent  everyday  life  functions  but  do  not  constitute  a  substantial disruption). 
 
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  and  may  require  medical  or  surgical 
intervention to prevent one of the outcomes listed in this definition  (Examples include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in hospitalization or the development of 
drug dependency or drug abuse). 
 
Events not considered to be serious adverse events are:  
 
hospitalizations for the routine treatment or monitoring of the studied indication, not 
associated with any deterioration in condition,  
 
treatment, which was elective or pre-planned, for a pre-existing condition that is unrelated to 
the indication under study and did not worsen,  
 
admission to a hospital or other institution for general care, not associated with any 
deterioration in condition, or  
 
treatment on an emergency, outpatient basis for an event not fulfilling any of the definitions 
of serious given above and not resulting in hospital admission.  
 
Any SAE occurring after the patient has provided informed consent for the main research study 
and until 90 days after date of cellular therapy must be reported.  
 
Unexpected adverse drug experience: Any adverse drug experience, the nature, frequency, or 
severity of which is not consistent with the investigator brochure, or not consistent with the risk 
information described above as a protocol-specific expected adverse event (see “Expected 
Adverse Events and Protocol-Specific Expedited Adverse Event Reporting Exclusions,” above). 
 
7.3 
Adverse events grading: Events not related to infection, CRS, ICANS, or GVHD: 
For adverse events not related to infection, CRS, ICANS, or GVHD, definitions found in the 
CTCAE version 5.0 will be used for grading the severity (intensity) of AEs. The CTCAE 
displays Grades 1 through 5 with unique clinical descriptions of severity for each referenced AE.  
Should a subject experience any AE not listed in the CTCAE, the following grading system 
should be used to assess severity: 
● Grade 1 (Mild AE) – experiences which are usually transient, requiring no special 
treatment, and not interfering with the subject’s daily activities 
● Grade 2 (Moderate AE) – experiences which introduce some level of inconvenience 
or concern to the subject, and which may interfere with daily activities, but are 
usually ameliorated by simple therapeutic measures 

 
 
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37 
● Grade 3 (Severe AE) – experiences which are unacceptable or intolerable, 
significantly interrupt the subject’s usual daily activity, and require systemic drug 
therapy or other treatment 
● Grade 4 (Life-threatening or disabling AE) – experiences which cause the subject to 
be in imminent danger of death 
● Grade 5 (Death related to AE) – experiences which result in subject death 
 
7.4 
Adverse events grading: Infectious events  
For infectious adverse events, as noted in guidance from the Bone Marrow Transplant 
Clinical Trials Network,47 it is recognized the CTCAE grading system does not adequately 
capture the nuances of infections in the context of transplant and cell therapy trials, where 
patients have multifactorial immunodeficiency and unique susceptibilities to infections.47 
CTCAE's distinction in grading based on parenteral versus oral therapies does not accurately 
reflect disease severity in patients who are electively hospitalized for their cell therapy. 
These patients may also have mucositis or GVHD. In these contexts patients may receive 
medications intravenously for reasons unrelated to the severity of their infection. 
This trial therefore uses the BMT CTN Guidance for grading infectious complications, as a 
more precise measure to capture the morbidity and mortality associated with infections.  
Table 1. Severity Grading Table for Bacterial Infections 
Type of 
infection/severity 
grade 
Grade 1 
Grade 2 
Grade 3 
Bacterial 
infections 
Bacteremia with skin 
flora [eg, coagulase-
negative Staphylococcu
s (CoNS, S. 
epidermidis), Coryneb
acterium, 
or Cutibacterium (Prop
ionibacterium)] 
requiring antibiotics 
for ≤14 days of therapy 
for treatment 
Bacteremia due to 
other organisms 
(not skin flora) 
Bacteremia with deep 
organ involvement (for 
example, new or 
worsening pulmonary 
infiltrates, endocarditis, 
brain abscess) 
Septic Shock with 
Bacteremia 
Endocarditis 
Brain abscess or 
Meningitis 
Active tuberculosis 
infection 
 
Bacterial focus NOS 
requiring systemic 
antibiotics for ≤14 days 
of therapy for 
treatment (for example, 
urinary tract infection 
Bacterial focus NOS 
requiring only topical, 
ocular, or otic 
treatments 
Bacterial focus 
NOS with 
persistent 
signs/symptoms or 
persistent positive 
cultures requiring 
antibiotics for >14 
days of therapy 
(GI, GU, 
abdominal 
 

 
 
Version 1.0, Dec 17, 2025 
38 
Type of 
infection/severity 
grade 
Grade 1 
Grade 2 
Grade 3 
infections, 
myositis) 
 
Cellulitis responding to 
initial therapy within 
14 days 
Cellulitis requiring 
a change in 
therapy due to 
progression or 
systemic treatment 
for >14 days 
Localized or 
diffuse skin and 
soft tissue 
infections 
requiring incision 
with or without 
drain placement 
but no 
debridement 
Fasciitis or other skin and 
soft tissue infection 
requiring surgical 
debridement 
 
Any bacterial 
pneumonia not 
requiring supplemental 
oxygen 
Any bacterial 
pneumonia 
requiring low-flow 
oxygen* 
Bacterial pneumonia 
requiring high-flow 
oxygen† or positive-
pressure ventilation‡ 
 
C. difficile toxin- or 
PCR-positive stool 
with diarrhea <1L / day 
(<5 episodes / day) 
without abdominal 
pain (child <20 
mL/kg/day) 
C. difficile toxin- 
or PCR-positive 
stool with diarrhea 
≥1 L / day (≥5 
episodes/day) 
(child ≥20 
mL/kg/day) or 
with abdominal 
pain 
C. difficile toxin or PCR-
positive stool with ileus, 
colon dilation, toxic 
megacolon, or need for 
surgical intervention 
⁎Low flow defined as oxygen by nasal cannula ≤ 6L/minute. 
†High-flow oxygen defined as oxygen by nasal cannula at >6L/minute. 
‡Continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), intubation with 
mechanical ventilation. 
CNS: Central nervous system; GI: gastrointestinal; GU: genitourinary; NOS: not otherwise specified; PCR: 
polymerase chain reaction 
 
 
 

 
 
Version 1.0, Dec 17, 2025 
39 
Table 2. Severity Grading Table for Fungal Infections 
 
Type of 
infection/severity 
grade 
Grade 1 
Grade 2 
Grade 3 
Fungal infections 
Mucocutaneous 
candidiasis 
(excluding 
esophagitis), 
including oral 
thrush and vaginal 
candidiasis 
Dermatophyte 
infections (tinea) 
Candida esophagitis 
diagnosed by endoscopy 
Fungemia including 
candidemia 
 
 
Fungal sinusitis 
confirmed radiologically 
without orbital, brain, or 
bone involvement. 
Fungal sinusitis confirmed 
radiologically with orbital, 
brain, or bone involvement 
 
 
Fungal pneumonia or 
pulmonary nodules 
(unless requiring high-
flow oxygen* or positive 
pressure ventilation†) 
Fungal pneumonia or 
pulmonary nodules 
requiring high-flow oxygen 
or positive-pressure 
ventilation 
 
 
Fungal skin and soft 
tissue infection without 
fungemia, involvement 
of other sites, or need for 
debridement‡ 
Disseminated or deep-
seated fungal infections (for 
example, CNS, visceral, or 
ocular fungal infections) or 
fungal infections requiring 
operative debridement or 
other surgery 
 
 
Pneumocystis 
jirovecii pneumonia 
(unless requiring high-
flow oxygen or positive 
pressure ventilation) 
Pneumocystis 
jirovecii pneumonia 
requiring high-flow oxygen 
or positive-pressure 
ventilation 
⁎High-flow oxygen defined as oxygen by nasal cannula at >6L/minute. 
†Continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), intubation with 
mechanical ventilation. 
‡This category is listed to capture locally invasive fungal infection that require treatment eg, IV related 
mucormycosis or skin and soft tissue involvement with endemic yeast etc. 
CNS: Central nervous system 
 
 
 

 
 
Version 1.0, Dec 17, 2025 
40 
Table 3. Severity Grading Table for Viral Infections 
 
Type of 
infection/severity 
grade 
Grade 1 
Grade 2 
Grade 3 
Viral infections 
Mucosal (oral, 
esophageal, vaginal, 
penile) or cutaneous 
HSV infection 
requiring oral antiviral 
therapy or observation 
Mucosal (oral, 
esophageal, vaginal, 
penile) or cutaneous 
HSV infection requiring 
IV nutrition due to pain 
associated with 
infection or IV antiviral 
therapy 
HSV infection with end-
organ involvement 
(encephalitis, hepatitis, 
pneumonitis) 
 
Dermatomal herpes 
zoster (shingles) 
affecting ≤ 2 
dermatomes 
VZV infection 
involving 3 or more 
dermatomes 
Severe VZV infection 
with end-organ 
involvement 
(encephalitis, hepatitis, 
pneumonitis, retinitis) or 
with organ dysfunction 
or severe sepsis (for 
example, coagulopathy) 
 
Asymptomatic CMV 
viremia not requiring 
treatment 
CMV viremia requiring 
therapy or CMV 
viremia requiring a 
change in therapy due to 
resistant or refractory 
disease or persistent 
viremia beyond 4 wk 
while on treatment 
CMV end-organ 
involvement (eg, lung, 
intestines, eye) 
 
EBV viremia not 
requiring treatment 
EBV viremia requiring 
treatment 
EBV PTLD 
 
Adenoviral infection 
not requiring treatment 
Adenoviral upper 
respiratory infection, 
viremia, or symptomatic 
viruria requiring 
treatment 
Adenovirus with end-
organ involvement, 
including pneumonitis 
but excluding 
conjunctivitis and upper 
respiratory tract 
infections 
 
HHV-6 viremia not 
requiring treatment 
HHV-6 infection with 
attributed symptoms or 
cytopenias requiring 
treatment 
HHV-6 with end-organ 
involvement (such as 
encephalitis, hepatitis, 
pneumonitis) 
 
BK viremia or viruria 
with cystitis not 
requiring intervention 
except anti-spasmodic 
or pain medication 
BK viremia or viruria 
with cystitis with 
clinical consequence 
requiring treatment, for 
example, continuous 
bladder irrigation, 
antiviral therapy, or 
procedural intervention 
BK viremia or viruria 
with end-organ damage 
(for example, kidney 
injury) 

 
 
Version 1.0, Dec 17, 2025 
41 
Type of 
infection/severity 
grade 
Grade 1 
Grade 2 
Grade 3 
 
 
Enterocolitis with 
enteric (GI) viruses 
 
 
Symptomatic upper and 
lower tract respiratory 
virus (excludes 
adenovirus, but 
including SARS-Cov-
2) not requiring 
supplemental oxygen 
Viral pneumonia or 
pneumonitis (excludes 
adenovirus but includes 
SARS-CoV-2; see 
above) requiring low-
flow oxygen 
Lower tract respiratory 
viruses (including SARs-
SoV-2) requiring high-
flow oxygen or positive-
pressure ventilation 
 
Viremia (virus not 
otherwise specified) 
not requiring therapy 
Any viremia (virus not 
otherwise specified) 
requiring therapy 
Any viral encephalitis, 
meningitis, or end-organ 
disease 
CMV: cytomegalovirus; EBV: Epstein barr virus; GI: gastrointestinal HHV-6: human herpes virus-6; HSV: 
herpes simplex virus; PTLD: Post-transplant lymphoproliferative disorder; VZV: Varicella zoster virus 
 
 

 
 
Version 1.0, Dec 17, 2025 
42 
Table 4. Severity Grading Table for Parasitic Infections and Clinically Defined Infections 
Type of 
infection/severity 
grade 
Grade 1 
Grade 2 
Grade 3 
Parasitic 
infections 
Giardiasis or other 
parasitic 
gastrointestinal 
infection with diarrhea 
≤1L / day (<5 episodes 
/ day) (child ≤20 
mL/kg/day) 
Giardiasis or other 
parasitic gastrointestinal 
infection with diarrhea 
≥1 L / day (5 episodes / 
day) (child ≥20 
mL/kg/day) or with 
abdominal pain 
 
 
Chronic 
strongyloidiasis treated 
with oral ivermectin or 
other oral therapies 
 
Strongyloides hyper-
infection or disseminated 
infection 
 
Toxoplasma DNAemia 
without organ 
involvement resolving 
spontaneously (without 
treatment) 
Toxoplasma DNAemia 
without organ 
involvement requiring 
treatment 
CNS or another organ 
toxoplasmosis 
Clinically defined 
infections 
Pneumonia or 
bronchopneumonia not 
requiring supplemental 
oxygen 
Pneumonia or 
bronchopneumonia 
requiring low-flow 
oxygen 
Any acute pneumonia 
requiring high-flow 
oxygen or positive-
pressure ventilation 
 
Fever with negative 
cultures responding to 
treatment within 14 
days 
 
 
 
Clinically documented 
infection not requiring 
inpatient management* 
Sepsis without an 
identified organism 
(excluding patients 
receiving immune 
effector therapy 
diagnosed with cytokine 
release syndrome 
(CRS)) 
Septic shock without an 
identified organism 
(excluding patients 
receiving immune 
effector therapy 
diagnosed with CRS) 
 
 
Typhlitis without severe 
sepsis, ileus, or need for 
surgical intervention 
 
⁎Patients should be reported as having CRS and graded as such, not infection, if they exhibit CRS symptoms 
or signs within the time frame expected for a given product AND the treating team prefers CRS over infection 
as the cause of the symptoms or signs. 
 
 

 
 
Version 1.0, Dec 17, 2025 
43 
 
7.5 
Adverse events grading: CRS, ICANS, and GVHD  
American Society for Transplantation and Cellular Therapy (ASTCT) 2019 will be used to 
grade CRS and ICANS AEs.48 
Table 5. ASTCT CRS Grading  
 
CRS 
parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fever 
Temperature 
>38 Celsius 
Temperature 
>38 Celsius 
Temperature 
>38 Celsius 
Temperature 
>38 Celsius 
with 
Hypotension 
None 
Not requiring 
vasopressors 
Requiring a 
vasopressor 
with or without 
vasopressin 
Requiring 
multiple 
vasopressors 
(excluding 
vasopressin) 
and/or1 
Hypoxia 
None 
Requiring low-
flow nasal 
cannula2 or 
blow-by 
Requiring high-
flow nasal 
cannula2 , 
facemask, 
nonrebreather 
mask, or 
Venturi mask 
Requiring 
positive 
pressure (eg, 
CPAP, BiPAP, 
intubation and 
mechanical 
ventilation) 
Organ toxicities associated with CRS may be graded according to CTCAE v5.0 but they do not influence CRS 
grading.  
*Fever is defined as temperature 38°C not attributable to any other cause. In patients who have CRS then 
receive antipyretic or anticytokine therapy such as tocilizumab or steroids, fever is no longer required to grade 
subsequent CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia.  
1CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other 
cause. For example, a patient with temperature of 39.5° C, hypotension requiring 1 vasopressor, and hypoxia 
requiring low-flow nasal cannula is classified as grade 3 CRS.  
2Low-flow nasal cannula is defined as oxygen delivered at <6 L/minute. Low flow also includes blow-by 
oxygen delivery, sometimes used in pediatrics. High-flow nasal cannula is defined as oxygen delivered at >6 
L/minute. 
BiPAP: Bilevel positive airway pressure; CPAP: Continuous positive airway pressure 
 
Table 6. ASTCT ICANS Grading 
Neurotoxicity 
Domain 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ICE score* 
7-9 
3-6 
0-2 
0 (patient is 
unarousable 
and unable to 
perform ICE) 
Depressed level 
of 
consciousness1 
Awakens 
spontaneously 
Awakens to 
voice 
Awakens only 
to tactile 
stimulus 
Patient is 
unarousable or 
requires 
vigorous or 
repetitive tactile 

 
 
Version 1.0, Dec 17, 2025 
44 
stimuli to 
arouse. Stupor 
or coma. 
Seizure 
N/A 
N/A 
Any clinical 
seizure focal or 
generalized that 
resolves rapidly 
or 
nonconvulsive 
seizures on 
EEG that 
resolve with 
intervention 
Life-threatening 
prolonged 
seizure (>5 
min); or 
Repetitive 
clinical or 
electrical 
seizures 
without return 
to baseline in 
between 
Motor findings2 
N/A 
N/A 
N/A 
Deep focal 
motor weakness 
such as 
hemiparesis or 
paraparesis 
Elevated 
intracerebral 
pressure/cerebral 
edema 
N/A 
N/A 
Focal/local 
edema on 
neuroimaging3 
Diffuse cerebral 
edema on 
neuroimaging; 
decerebrate or 
decorticate 
posturing; or 
cranial nerve VI 
palsy; or 
papilledema; or 
Cushing's triad 
ICE: Immune effector cell encephalopathy  
ICE Scoring: Orientation: orientation to year, month, city, hospital: 4 points; Naming: ability to name 3 objects 
(eg, point to clock, pen, button): 3 points; Following commands: ability to follow simple commands (eg, 
“Show me 2 fingers” or “Close your eyes and stick out your tongue”): 1 point; Writing: ability to write a 
standard sentence (eg, “Our national bird is the bald eagle”): 1 point; Attention: ability to count backwards 
from 100 by 10: 1 point 
ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor 
findings, raised ICP/cerebral edema) not attributable to any other cause; for example, a patient with an ICE 
score of 3 who has a generalized seizure is classified as grade 3 ICANS.  
N/A indicates not applicable.  
*A patient with an ICE score of 0 may be classified as grade 3 ICANS if awake with global aphasia, but a 
patient with an ICE score of 0 may be classified as grade 4 ICANS if unarousable.  
1Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication).  
2Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE 
v5.0, but they do not influence ICANS grading.  
3Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is 
excluded from ICANS grading. It may be graded according to CTCAE v5.0. 
 
 
 

 
 
Version 1.0, Dec 17, 2025 
45 
GVHD Grading:  
The EBMT-NIH-CIBMTR Task Force recommendations supporting the use of the Mount 
Sinai Acute GvHD International Consortium (MAGIC) criteria49 will be used to grade 
GVHD events. 
Table 7. GVHD Grading 
 
Stage 
Skin (active 
erythema only) 
Liver 
(bilirubin) 
Upper GI 
Lower GI (stool 
output/day) 
0 
No active 
(erythematous) 
GVHD rash 
< 2 mg/dl 
(34.2 
umol/L) 
No or 
intermittent 
nausea, 
vomiting or 
anorexia 
Adult: < 500 ml/day or 
<3 episodes/day 
Child: < 10 ml/kg/day or 
<4 episodes/day 
1 
Maculopapular 
rash 
<25% BSA 
2–3 mg/dl 
(34.2-52.3 
umol/L) 
Persistent 
nausea, 
vomiting or 
anorexia 
Adult: 500–999 ml/day 
or 3–4 episodes/day 
Child: 10–19.9 
ml/kg/day or 4–6 
episodes/day 
2 
Maculopapular 
rash 
25 – 50% BSA 
3.1–6 mg/dl 
(53.0-102.6 
umol/L) 
- 
Adult: 1000–1500 
ml/day or 5–7 
episodes/day 
Child: 20 – 30 ml/kg/day 
or 7–10 episodes/day 
3 
Maculopapular 
rash 
> 50% BSA 
6.1–15 mg/dl 
(104.3-256.5 
umol/L) 
- 
Adult: >1500 ml/day or 
>7 episodes/day 
Child: > 30 ml/kg/day or 
>10 episodes/day 
4 
Generalized 
erythroderma 
(>50% 
BSA) plus bullous 
formation and 
desquamation > 
5% BSA 
>15 mg/dl 
(>256.5 
umol/L) 
- 
Severe abdominal pain 
with or without ileus, or 
grossly bloody stool 
(regardless of stool 
volume). 
BSA: body surface area 
Overall clinical grade (based upon most severe target organ involvement): 
 
Grade 0: No stage 1–4 of any organ 
 
Grade I: Stage 1–2 skin without liver, upper GI or lower GI involvement 
 
Grade II: Stage 3 rash and/or stage 1 liver and/or stage 1 upper GI and/or stage 1 lower GI 
 
Grade III: Stage 2–3 liver and/or stage 2–3 lower GI, with stage 0–3 skin and/or stage 0–1 upper GI 
 
Grade IV: Stage 4 skin, liver or lower GI involvement, with stage 0–1 upper GI 
 
7.6 
Serious Adverse Event Reporting 
 
Sponsor Notification 
Any serious adverse event, regardless of whether or not it is considered related to investigational 
product or study procedure(s), must be reported to Ozmosis Research Inc. within 24 hours of the 
Investigator, or other site personnel, learning of the event by a completed SAE form.  The 
adverse event must be submitted through a completed SAE form and be completely described in 
the CRF. Whenever possible, SAEs should be reported by diagnosis term, not as a constellation 
of symptoms. All deaths should be reported with the primary cause of death as the AE term, as 

 
 
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46 
death is typically the outcome of the event, not the event itself. If study procedure is discontinued 
because of an SAE, this information must be included in the SAE report. 
 
AESI and SAE Reporting Instructions:  
 
All AESIs and SAEs must be reported as follows:  
 
Within 24 hours: 
Report initial information (on trial specific SAE report form) by 
fax or e-mail to: 
 
Ozmosis Research Inc.  
Phone: 416-634-8300 
Fax:  416-634-8333 
 
E-mail: ozmsafety@ozmosisresearch.ca 
 
The initial information should always contain:  
- 
Name of Reporter/Investigator,  
- 
Subject Identification,  
 
- 
Adverse Event Term,  
- 
Study Drug Dose and Start/Stop Dates 
 
On the next working day: 
Fax or e-mail completed trial-specific Serious Adverse Event form 
 
 
Reporting Serious Adverse Events to Health Canada  
 
Ozmosis Research Inc. will provide expedited reports of on-study SAEs to Health Canada for 
those events which meet regulatory requirements for expedited reporting, i.e. events which are 
BOTH serious AND unexpected, AND which are thought to be related to protocol treatment (or 
for which a causal relationship with protocol treatment cannot be ruled out).  
 
All adverse signs and symptoms which occur during or following the course of drug 
administration/investigational product infusion must be reported in detail on the subject’s CRF.  
This description is to include the nature of the sign or symptom, time of onset in relation to drug 
application, duration, severity, and possible relationship to drug, required therapy, and outcome.  
The subject should be followed until the adverse reaction is resolved, or until in the opinion of 
the Principal Investigator, reversal of the reaction is not likely to occur.  
 
 
SAE Follow-up 
Follow-up SAE report is subject to the same timelines as the initial report and is sent to the same 
parties to whom the original Serious Adverse Event Form was sent. A new SAE form is 
completed for the follow-up, stating that this is a follow-up to the previously reported SAE and 
giving the date of the original report. Each re-occurrence, complication or progression of the 
original event should be reported as a follow-up to that event. The follow-up information should 
describe whether the event has resolved or continues, if and how it was treated, and whether the 
patient continued or discontinued study participation.  

 
 
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47 
 
 
REB Notification of SAEs 
Ozmosis Research Inc. will notify all Investigators of all SAEs that are reportable to regulatory 
authorities in Canada from this trial. This includes all serious events that are unexpected and 
related to protocol treatment. Investigators must notify their Research Ethics Boards (REBs) and 
file the report with their Investigator Site File. Documentation that SAEs have been reported to 
REBs must be kept on file at Ozmosis Research Inc. Documentation can be any of the following:  
 
letter from the REB acknowledging receipt  
 
stamp from the REB, signed and dated by REB chair, acknowledging receipt 
 
letter demonstrating the SAE was sent to the REB 
 
All expedited SAEs occurring within a centre should also be reported to local REBs.   
 
7.7 
Abnormal Laboratory Value Reporting 
For abnormal laboratory values, it is the responsibility of the Principal Investigator or his 
designate to assess the clinical significance of each abnormality. Only abnormal laboratory 
values that can be assessed for Grade using CTCAE Version 5.0 will be documented. The 
Investigator will determine whether abnormal laboratory values are considered clinically 
significant and represent AEs based on their medical judgment.  
 
Data on all adverse experiences/toxicities regardless of seriousness must be collected for 
documentation purposes only.   
 
Clinical Laboratory Abnormalities: 
 
All abnormal laboratory values should be captured on source documentation and assessed for 
clinical significance by the Investigator.  Only abnormal laboratory values deemed clinically 
significant should be listed as AEs in the CRFs.  All clinically significant abnormal laboratory 
results will be followed up until the related AE resolves, returns to ≤ Grade 1 or baseline value in 
the follow-up period.  Clinically significant laboratory abnormalities will be dictated in the clinic 
notes.  Additionally, laboratory abnormalities resulting in an intervention are considered to be 
clinically significant. 
 
7.8 
Documentation of Adverse Events 
All AEs must be captured in the source documents, as well as reported in Medidata.  AEs 
reported using SAE forms must also be reported in Medidata. 
 
All serious and non-serious AEs occurring from the start of FMT administration until 180 days 
after cellular therapy must be recorded as AEs on the CRF. The Investigator should review all 
documentation (e.g., hospital progress notes, laboratory, or diagnostic reports) relative to the 
event being reported.  
 
7.9 
Follow-Up of AEs, AESIs and SAEs 
SAEs and AEs should be followed until 180 days after cellular therapy or until they are resolved 
(return to normal or baseline values), stabilized, improve to < Grade 2, or the subject is lost to 

 
 
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48 
follow-up and cannot be contacted.  Additional investigations (e.g., laboratory tests, diagnostic 
procedures, or consultation with other healthcare professionals) may be required to completely 
investigate the nature and/or causality of an AE or SAE.  If the patient dies during the study or 
within 7 following the last dose of the FMT, any postmortem findings (including histopathology) 
should be reported to Ozmosis Research Inc. CRF data should be updated with any new 
information as appropriate. 
 
7.10 Deaths 
All deaths that occur during the study, including the protocol-defined follow-up period must be 
reported as follows: 
 
Death which is clearly the result of disease progression, or a complication of disease progression 
should be reported at the next visit and documented in the eCRF but should not be reported as an 
SAE. 
 
Where death is not due (or not clearly due) to disease progression, the AE causing the death must 
be reported as an SAE within 24 hours. The report should contain a comment regarding the co-
involvement of disease progression, if appropriate, and should assign main and contributory 
causes of death. 
 
Deaths with an unknown cause should always be reported as an SAE. A post-mortem may be 
helpful in the assessment of the cause of death. 
 
7.11 Pregnancy 
Any pregnancy of a study subject or of a study subject’s partner that occurs during study 
participation should be reported for pregnancies that occur up to 30 days after the last FMT 
administration.  
 
If pregnancy occurs, then the investigator or other site personnel should inform Ozmosis 
Research within 24 hours of when he/she becomes aware of it. 
 
If the study subject is the father, then their partner will be provided with a pregnancy consent 
form to be reviewed and completed. To ensure patient safety each pregnancy must also be 
reported to the trials office. If the subject agrees, the pregnancy should be followed to determine 
outcome, including spontaneous or voluntary termination, details of birth, and the presence or 
absence of any birth defects, congenital abnormalities or maternal and newborn complications.   
 
 
 
 
 

 
 
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49 
8. CORRELATIVE STUDIES 
 
While the concepts of pharmacodynamics, pharmacokinetics and pharmacogenomics are 
established in pharmacology and routinely integrated into clinical trials, equivalent concepts 
have not been established for microbiome-targeting therapeutics. We will assess the following 
microbiome-informed biomarkers:  
  
8.1 
Ecological outcomes 
1. Ecological outcomes will be assessed by 16S rRNA gene and shotgun metagenomic 
sequencing to assess:  
a. Alpha diversity (Shannon diversity, species richness, Berger-Parker dominance);  
b. MET-2 species relative abundance by shotgun metagenomic sequencing;  
c. Pseudamonadota, Enterobacteriaceae, Staphylococcus, Enterococcus, 
Pseudomonas, and Candida species relative abundance;  
d. Obligate anaerobe richness and cumulative relative abundance;  
e. Butyrogenic anaerobe richness and cumulative relative abundance;  
f. Compositional dissimilarity (Bray-Curtis dissimilarity) between groups and 
within groups and individuals/between timepoints;  
g. Absolute bacterial abundance (by 16S gene qPCR).  
h. Log-fold changes in relative abundance between baseline and post-treatment 
samples will be determined and ‘engraftment’ for any species defined as >1-log 
increase.    
2. Engraftment: 
a. Compositional dissimilarity/similarity (beta-diversity) will be assessed between 
groups and sample pairs (i.e. pre/post intervention or donor/recipient) using Bray-
Curtis compositional dissimilarity.  
b. Anti-Donor FMT antibodies will be assessed by a flow-cytometric assay to 
determine pre-treatment and post-treatment anti-FMT bacterial antibodies as a 
correlate of engraftment and immunogenicity.  
8.2 
Metabolomic studies 
1. Metabolomic outcomes will be assessed by shotgun metagenomic sequencing and 
targeted gene detection to assess:  
a. Antimicrobial gene richness, abundance and diversity;  
b. Butyrate biosynthesis gene abundance (by qPCR);  
c. Plasma microbial metabolite concentrations - SCFA and 1oBA/2oBA 
concentrations;  
8.3 
Immunologic studies 
Immunological studies of T-cell phenotypic and functional subsets will be assessed by laboratory 
testing at baseline, Day +30, Day +90 and Day +180. 

 
 
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50 
9. STUDY CALENDAR 
The following schedule of assessments applies to all subjects.  More frequent assessments should 
be obtained if clinically indicated. 
 
Interaction number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Timeline (day, in relation to cell infusion) 
Screening 
-5 
-3 
-1 
0 
+1 
+7 
+30 
+32 +34 
+90 
+180 
Time window (days) 
 
-60  
+/-
1 
+/-
1 
+/
-1 
 
 
 
-3/ 
+30 
-3/ 
+30 
-3/ 
+30 
+/- 
14 
+/- 
14 
Informed consent9 
x 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion criteria 
x 
 
 
 
 
 
 
 
 
 
 
 
Diagnosis 
x 
 
 
 
 
 
 
 
 
 
 
 
Demographics (Age, Sex) 
x 
 
 
 
 
 
 
 
 
 
 
 
Medical history baseline 
x 
 
 
 
 
 
 
 
 
 
 
 
Physical exam including vital signs (blood 
pressure, heart rate, respiration rate oxygen 
saturation, temperature), ECOG, height and 
weight 
-Full physical exam at baseline 
-Symptom directed physical exam at D-5, 
D30 and D90 
x 
x 
 
 
 
 
 
x 
 
 
x 
 
Participant questionnaire on perceptions and 
acceptability of FMT 
 
x 
 
 
 
 
 
 
 
 
x 
 
FMT administration 
 
x8 
x 
 
 
 
 
x2 
x2 
 
 
 
 
Cell infusion (CAR-T cells for CAR-T 
cohort; stem cells for alloSCT cohort) 
 
 
 
 
x 
 
 
 
 
 
 
 
Lymphodepleting Chemotherapy (CAR-T 
Therapy Cohort) 
 
x 
x 
 
 
 
 
 
 
 
 
 
Conditioning Chemotherapy (Allogeneic 
Stem Cell Transplant Cohort) 
 
x 
x 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
Continuous 
Adverse Events 
Continuous 
Ascertainment of adverse events of special 
interest 
 
 
 
x 
 
 
 
 
 
x 
 
 
Ascertainment of adverse events related to 
cellular therapy1 
 
 
 
 
 
 
 
x 
 
 
x 
 
Review of standard of care bloodwork 
including for all inclusion criteria including 
Hepatitis B sAg, sAb, cAb, Hepatitis C, HIV 
testing including viral load and CD4 count if 
HIV positive, HBV viral DNA if Hepatitis B 
sAg positive and HCV viral DNA if 
Hepatitis C antibody positive, and pregnancy 
testing if applicable10 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review of standard of care hematology 
bloodwork 
 
x 
 
 
 
 
 
x 
 
 
 
 

 
 
Version 1.0, Dec 17, 2025 
51 
 
1 MDS/AML: Location and maximal grade of acute GVHD will be assessed from Day 0 (alloSCT) until Day +100.   
B-cell lymphoma: CRS and ICANS events will be documented according to maximal grade for the first 30 days 
after cell therapy.  
2 + up to 30 days if no recovery of neutropenia (ANC must be >1.0 x 109/L without reliance on growth factors for a 
7 day period to administer FMT, and ANC must be documented within 7 days prior to administration) If patients 
remain reliant on growth factors, the second FMT series will be delayed by a maximum of 30 days, after which time 
it will be omitted. Additionally, patients must not have any signs, symptoms, or documented clinical infection at the 
time of second FMT series.  
3 Clinical chart review of standard of care documentation of disease response at Day +30, Day +90 and Day +180 
post cell therapy, based on Lugano 2014 classification criteria from PET scan assessment 
4 Baseline disease assessment scan will be the scan done most recently prior to cellular therapy administration. 
5Clinical chart review of standard of care documentation of disease response at day +100 bone marrow and 
peripheral blood assessment, using MDS International Working Group 2023 criteria. 
6 Baseline bone marrow and peripheral blood assessment will be the most recent testing done prior to cellular 
therapy administration. 
7 Clinical chart review of standard of care documentation of disease response at day +100 bone marrow and 
peripheral blood assessment, using European Leukemia Network criteria. 
8 Protocol treatment should begin within 7 working days of patient enrollment. Patients must have an ANC >1.0 x 
109/L without growth factor support, documented within 7 days prior to both the first and second FMT 
administrations.   
9Consent should be done prior to any screening assessments and according to site institutional timelines. Site should 
follow their institutional guidelines for consenting window prior to FMT administration. Informed consent of study 
procedures may be obtained prior to the 60-day screening window. Subject enrollment with Ozmosis@UHN is 
required. Please refer to section 3.1.3 Enrollment Procedures.  
10 Screening laboratory testing to be done within 60 day screening window prior to starting FMT administration or 
registration; hemoglobin, platelet count, neutrophil count, AST/ALT, and creatinine. The most recent labs prior to 
FMT administration will be used for screening. 
11 Participants will be asked to collect stool at home 24 hours prior to starting their bowel prep for the FMT 
procedure. 
12 Rectal swab(s) will be performed by research nurse on day of visit 
 
 
Bloodwork (serum) for regulatory 
requirements to bank for routine safety 
testing post FMT if required 
 
x 
 
 
 
 
 
x 
 
 
 
 
Bloodwork (plasma, PBMC) for exploratory 
studies 
 
x 
 
 
 
 
 
x 
 
 
x 
x 
Urine sample for exploratory studies 
 
x 
 
 
 
 
 
x 
 
 
x 
 
Stool sample  
 
x11 
 
 
 
 
 
x11 
 
 
x 
 
Rectal swab for regulatory requirements, to 
bank for routine safety testing post FMT if 
required12 
 
 
x 
 
 
 
 
 
x 
 
 
 
 
Rectal swab for research purposes12 
 
x 
 
 
 
 
 
x 
 
 
x 
 
Review of standard of care disease 
assessment – B-cell lymphoma3 
x4 
 
 
 
 
 
 
x 
 
 
x 
x 
Review of standard of care disease 
assessment – MDS5 
x6 
 
 
 
 
 
 
x 
 
 
x 
 
Review of standard of care disease 
assessment – AML7 
x6 
 
 
 
 
 
 
x 
 
 
x 
 

 
 
Version 1.0, Dec 17, 2025 
52 
DATA REPORTING / REGULATORY REQUIREMENTS 
 
9.1 
Compliance with Trial Registration and Results Posting Requirements 
Prior to the first subject being registered/enrolled into this study, the Sponsor will be responsible 
for ensuring that the clinical trial is registered appropriately to remain eligible for publication in 
any major peer-reviewed journal, adhering to the guidelines put forth by the International 
Committee of Medical Journal Editors (ICMJE). Information posted will allow subjects to 
identify potentially appropriate trials for their disease conditions and pursue participation by 
calling a central contact number for further information on appropriate trial locations and trial 
site contact information.     
 
9.2 
Patient Protection 
The responsible investigator will ensure that this study is conducted in agreement with either the 
Declaration of Helsinki (Tokyo, Venice, Hong Kong, Somerset West, Edinburgh 
Washington, Tokyo, Seoul and Fortaleza amendments) or the laws and regulations of the 
country, whichever provides the greatest protection of the patient. The protocol has been written, 
and the study will be conducted according to the ICH Harmonized Tripartite Guideline for Good 
Clinical Practice..50 The protocol will be approved by the Research Ethics Board (REB) and 
Health Canada. 
 
9.3 
Data Collection and Reporting 
All data obtained in the clinical trial described in this protocol will be reported on eCRFs in the 
Medidata Electronic Document Capture system (Medidata).  Data reported on eCRFs should be 
consistent with the source documents and verifiable.   
 
Please see the study specific eCRF Completion Guidelines which have been provided to your site 
by Ozmosis Research Inc. The timelines and details for completion of eCRFs are included in 
these guidelines. 
 
All data for the primary and secondary endpoints will source verified prior to publication.  The 
Investigator will review the data and electronically sign the eCRFs to acknowledge agreement 
with the data entered. Data will be entered into Medidata will be used for developing tables and 
listings for the final study report. 
 
9.4 
Subject Confidentiality and Access to Source Data/Documents 
Any research information obtained about the subject in this study will be kept confidential. A 
subject will not be identified by name, only by his/her study ID code. The subject’s name or any 
identifying information will not appear in any reports published as a result of this study. 
 
However, information obtained from individual subject’s participation in the study may be 
disclosed with his/her consent to the health care providers for the purpose of obtaining 
appropriate medical care. In accordance with federal regulations and GCP guidelines, the 
investigator should make available for direct access all trial-related records upon request of the 

 
 
Version 1.0, Dec 17, 2025 
53 
sponsor, Ozmosis Research, auditor, REB or Health Canada. This is for the purpose of verifying 
information obtained for this study. Confidentiality will be maintained throughout the study 
within the limits of the law.   
 
A subject’s name will not be given to anyone except the researchers conducting the study, who 
have pledged an oath of confidentiality. All identifying information will be kept behind locked 
doors, under the supervision of the study Principal Investigator and will not be transferred 
outside of the hospital.  
A subject may take away his/her permission to collect, use and share information about him/her 
at any time. If this situation occurs, the subject will not be able to remain in the study. No new 
information that identifies the subject will be gathered after that date. However, the information 
about the subject that has already been gathered and transferred may still be used and given to 
others as described above in order to preserve the scientific integrity and quality of the study. 
 
9.5 
Study Monitoring/Auditing 
Data generated as a result of this study are to be available for inspection on request by local 
health authority auditors, the Sponsor’s Study Monitors and other personnel (as appropriate) and 
by the REB. The Investigator shall permit sponsor, authorized agents of the sponsor, CRO and 
regulatory agency employees to enter and inspect any site where the drug or records pertaining to 
the drug are held, and to inspect all source documents. The protocol and other study documents 
contain confidential information and should not be shared or distributed without the prior written 
permission of sponsor.   
 
9.6 
Study Monitoring/Auditing 
This is an investigator-initiated study and study monitoring will be performed by Ozmosis 
Research Inc.  Ozmosis Research Inc. will organize site monitoring for this study to be 
conducted as per the monitoring plan. 
 
As this trial is conducted under a CTA with Health Canada, your site may be subject to an 
inspection by the Health Products and Food Branch Inspectorate. Other audits may be conducted 
by the study sponsor or Ozmosis Research Inc.  
 
9.7 
Quality Control and Quality Assurance 
As per the Guidelines of Good Clinical Practice, the sponsor will be responsible for 
implementing and maintaining quality assurance and quality control systems.  
 
 

 
 
Version 1.0, Dec 17, 2025 
54 
 
9.8 
Data Management Guidelines 
 
The Eligibility Checklist will be a paper CRF. 
 
 
 
Case Report Form Completion 
The paper Eligibility Checklist CRF must be completed using black or blue ink. Any errors must 
be crossed out so that the original entry is still visible, the correction clearly indicated and then 
initialed and dated by the individual making the correction. eCRFs will be completed according 
to the Study Calendar.  
 
9.9 
REB Composition 
The composition of the REB will be kept on file. The composition and procedures of the REB 
must be compliant with the ICH-GCP Guidelines and be consistent with Canadian regulatory 
requirements. 
 
9.10 Initial Approval 
All study sites are required to obtain full board ethics approval of the protocol and consent form 
by the appropriate ethics board prior to commencement of the clinical trial at each site. 
 
9.11 Annual Re-Approvals 
Annual (or as required by the ethics board) re-approval may be required for as long as patients 
are being followed on protocol. It will be the Principal Investigator’s responsibility to apply for 
and obtain the re-approval. 
 
9.12  Amendments / Revisions 
All protocol amendments will be confirmed in writing and submitted, as appropriate, for review 
by the ethics board and health authorities.  Amendments will be reviewed and approved by 
Health Canada prior to central implementation of the study, and by REB prior to local 
implementation, EXCEPT when the amendment eliminates an immediate hazard to clinical trial 
patients or when the change(s) involve(s) only logistical or administrative aspects of the trial. 
 
9.13 REB Refusals 
If an REB refuses to approve this protocol (or an amendment/revision to this protocol), Ozmosis 
Research Inc. must be notified immediately of the date of refusal and the reason(s) for the 
refusal. 
 
9.14 Serious Adverse Events, Safety Updates, and Investigator Brochure Updates 
During the course of the study SAEs, safety updates or investigator brochure updates may be sent 
to sites for reporting to their ethics board. If/when this occurs documentation of ethics board 
submission must be forwarded to Ozmosis. 
 

 
 
Version 1.0, Dec 17, 2025 
55 
9.15 Informed Consent Document 
The REB must approve the consent form document which will be used prior to its local 
activation; changes to the consent form in the course of the study will also require REB 
notification/approval. 
 
The consent form should include all elements required by ICH-Good Clinical Practice 
Guidelines. 
 
9.16 Consent Process/ Patient Eligibility 
Patients who cannot give informed consent (i.e. mentally incompetent patients, or those 
physically incapacitated such as comatose patients) are not to be recruited into the study. Patients 
competent but physically unable to sign the consent form may have the document signed by their 
nearest relative or legal guardian. Each patient will be provided with a full explanation of the 
study before consent is requested. 
 
9.17 Site and Study Closure 
 
Upon completion of the study, the following activities, when applicable, will be completed: 
 
 
Collection of study materials (i.e., specimen collection kits, drug shippers, etc.) 
 
Data clarifications and/or resolutions 
 
Review of site study records for completeness 
 
If the Sponsor or Investigator or appropriate regulatory officials identify conditions arising 
during the study that indicate that the study should be halted, this action may be taken after 
appropriate consultation with the Investigator. Conditions that may warrant termination of the 
study include, but are not limited to, the following: 
 
 
The discovery of an unexpected, serious, or unacceptable risk to the patients enrolled in 
the study. 
 
A decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of the product. 
 
Failure of the Investigator to enroll patients into the study at an acceptable rate. 
 
Failure of the Investigator to comply with pertinent regulations of appropriate regulatory 
authorities. 
 
Submission of knowingly false information to the Sponsor, or appropriate regulatory 
authority. 
 
Insufficient adherence to protocol requirements. 
 
Refusal of the Investigator to supply source documentation of work performed in this 
clinical trial. 
 
Study termination and follow-up will be performed in compliance with the conditions set forth in 
the International Conference on Harmonization (ICH) sixth efficacy publication (E6) on Good 
Clinical Practice, Section 4.12, ICH E6 4.13, ICH E6 5.20, and ICH E6 5.21. 

 
 
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56 
10. STATISTICAL CONSIDERATIONS 
 
10.1 Study Design/Endpoints 
This is a single centre,  non-randomized, single-arm interventional pilot study in patients 
undergoing CAR-T or allogeneic stem cell transplantation (alloSCT).  
The primary endpoints are feasibility and safety.  
 
We hypothesize that we will be able to successfully recruit at least 50% of approached patients, 
retain at least 80% of patients on the study, and successfully administer at least one FMT series 
to 80% of retained patients. We also hypothesize that FMT will be safe in this population. Each 
cohort will be considered separately in considering the differing risks of CAR-T and alloSCT. 
We hypothesize that in each cohort there will be no greater than 10% incidence (N< 1 of 10 
participants in each cohort), of serious adverse events, or Grade >3 adverse events of special 
interest (sepsis and/or bacteremia, ICU admission, bowel perforation, or death) within 48 hours 
of administration of FMT, which are judged to be possibly, probably or definitely related to 
FMT. 
 
The primary endpoints will be analyzed using descriptive statistical methods in the safety-
evaluable population, which consists of all subjects who receive any amount of FMT treatment. 
Each disease type (B-cell lymphoma and AML/MDS) will also be analyzed separately. 
 
10.2 Sample size/Accrual Rate 
Since no preliminary information on the primary endpoints in previous relevant studies/literature 
are available for sample size justification, for this pilot study, we will enroll a convenient sample 
size of 20 eligible patients.  
 
10.3 Secondary Endpoints 
The secondary endpoints such as the incidence of AEs, response rates will be summarized using 
descriptive statistical methods. The time to event endpoints, eg, progression-free survival (PFS), 
overall survival (OS),  will be analyzed using Kaplan-Meier method. 
 
10.4 Exploratory Endpoints 
An exploratory safety endpoint will include the finding of any newly acquired antibiotic resistant 
organism during the time period of follow up. If a new ARO is found, the FMT product will be 
retrospectively analysed to determine if it might be related to the ARO, as it is possible the 
recipient may also have acquired the ARO from health care contact.  
 
For microbial safety endpoints, DNA will be extracted from stool using the Qiagen PowerSoil 
kits prior to bacterial density quantitation (by 16S rRNA gene qPCR). A two-stage sample 
analysis will be performed with 16S rRNA gene amplicon sequencing for composition, followed 
by sequencing to optimize depth to detect/assess donor species/strain relative abundance based 

 
 
Version 1.0, Dec 17, 2025 
57 
on genus relative abundance determined from 16S rRNA sequencing (i.e. with variable 
sequencing depth for optimal sensitivity based on 16S analysis). Alpha diversity (Shannon 
diversity index, taxonomic richness, Berger-Parker dominance) will be calculated on tables 
rarefied to control for sampling depth. Compositional dissimilarity/similarity (beta-diversity) will 
be assessed between groups and sample pairs (i.e. pre/post intervention or donor/recipient) using 
Bray-Curtis compositional dissimilarity. Functional outcomes will be studied using shotgun 
metagenomic sequencing and targeted gene detection to assess for aspects including but not 
limited to antimicrobial gene richness, abundance and diversity, butyrate biosynthesis gene 
abundance, stool versus urine and plasma short-chain fatty acids and 1o bile acid (BA)/2oBA 
concentrations. Blood will also analyzed for T-cell phenotypic and functional subsets and 
diversity, and via flow for anti-FMT bacterial antibodies as a correlate of engraftment and 
immunogenicity. Methods are established in the Coburn Laboratory.51-53 
 
Patient reported perceptions and experience with FMT will be reported in a descriptive manner. 
 
10.5 Missing Data Handling 
No imputation of values for missing data will be performed except that missing or partial start 
and end dates for AEs and concomitant medication will be imputed according to pre-specified, 
conservative imputation rules.  Subjects lost to follow-up (or drop out) will be included in 
statistical analyses to the point of their last evaluation. Any deviation from the original statistical 
plan will be described in the final report.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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58 
11. DOCUMENTATION, RECORD ACCESS AND MAINTENANCE OF STUDY RECORDS 
 
11.1 Documentation of Patient’s Participation 
 
A statement acknowledging the participation of a patient in this clinical trial must be documented 
in the patient's medical records along with the signed ICF.  
 
11.2 Regulatory Requirements 
 
The following documents are required: 
 For participating Canadian sites only:  
 All Principal Investigators must complete and sign the Health Canada Qualified 
Investigator Undertaking form. The completed forms must be returned to Ozmosis 
prior to any drug shipment. 
 Ozmosis will submit a completed Health Canada Clinical Trial Site Information 
Form to Health Canada after local activation of each participating Canadian site. 
 All applicable regulatory documents as listed in the Site Activation Checklist provided by 
Ozmosis to the sites. 
 A copy of the initial full board approval letter from the ethics board. Continuing approval 
(full board) will be obtained at least yearly until follow-up on patients is completed and no 
further data is being obtained for research purpose. 
 
11.3 Patient Confidentiality and Access to Source Data/Documents 
 
Any research information obtained about the patient in this study will be kept confidential. A 
patient will not be identified by name. The patient’s name or any identifying information will not 
appear in any reports published as a result of this study. 
 
However, information obtained from the patients participation in the study may be disclosed with 
their consent to the health care providers for the purpose of obtaining appropriate medical care. 
The patients medical records/charts, tests will be made available to Ozmosis, the Sponsor’s 
partners, the Canadian regulatory authority Health Canada, the ethics boards and any other 
regulatory authorities. This is for the purpose of verifying information obtained for this study. 
Confidentiality will be maintained throughout the study within the limits of the law.   
 
A patient’s name will not be given to anyone except the researchers conducting the study, who 
have pledged an oath of confidentiality. All identifying information will be kept behind locked 
doors, under the supervision of the study Principal Investigator and will not be transferred outside 
of the hospital.  
 
A patient may take away their permission to collect, use and share information about them at any 
time. If this situation occurs, the patient will not be able to remain in the study. No new information 
that identifies the patient will be gathered after that date. However, the information about the 
patient that has already been gathered and transferred may still be used and given to others as 
described above in order to preserve the scientific integrity and quality of the study. 
 

 
 
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11.4 Confidentiality of the Study 
 
Data generated as a result of this study are to be available for inspection on request by local health 
authority auditors, the Sponsor’s Study Monitors and other personnel (as appropriate) and by the 
ethics board. The Principal Investigator shall permit the Sponsor, authorized agents of the Sponsor, 
CRO and regulatory agency employees to enter and inspect any site where the drug or records 
pertaining to the drug are held, and to inspect all source documents. The protocol and other study 
documents contain confidential information and should not be shared or distributed without the 
prior written permission of the Sponsor.   
 
11.5 Study Data at the End of Registration of Clinical Trial 
 
Prior to the first patient being enrolled into this study, the Sponsor will be responsible for ensuring 
that the clinical trial is registered (e.g. clinicaltrials.gov) appropriately to remain eligible for 
publication in any major peer-reviewed journal, adhering to the guidelines put forth by the 
International Committee of Medical Journal Editors (ICMJE). 
 
11.6 Data Reporting 
 
The data will be collected in eCRFs using a Medidata database. 
 
11.7 Maintenance of Study Records 
 
To enable evaluations and/or audits from regulatory authorities, Ozmosis or the Sponsor, the 
Principal Investigator agrees to keep records, including the identity of all participating patients 
(sufficient information to link records, eCRFs and hospital records), all original signed informed 
consent forms, copies of all source documents, and detailed records of treatment disposition. The 
Principal Investigator should retain these records for 15 years after study close-out as required by 
Canadian regulations or as specified in the Clinical Trial Agreement, whichever is longer 
 
If the Principal Investigator relocates, retires, or for any reason withdraws from the study, then 
the Sponsor should be prospectively notified. The study records must be transferred to an 
acceptable designee, such as another Site Investigator, another institution, or to the Sponsor. The 
Principal Investigator must obtain the Sponsor’s written permission before disposing of any 
records. 
 
 
 
 

 
 
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12. ADMINISTRATIVE PROCEDURES  
12.1 Amendments to the Protocol  
Modifications of the signed protocol are only possible by approved protocol amendments 
authorized by the sponsor. All protocol amendments will be approved by the REB prior to 
implementation. The Investigator must not implement any deviation from, or change to the 
protocol, except where it is necessary to eliminate an immediate hazard to trial subjects or when 
the change(s) involves only logistical administrative aspects of the trial.  
 
12.2 Protocol Deviations and Violations  
All violations or deviations are to be reported to the site’s REB (as per REB guidelines). All 
REB correspondence is to be forwarded to Ozmosis Research. The site must notify Ozmosis 
Research and/or sponsor immediately of any protocol violations.  
 
12.3 Premature Discontinuation of the Study 
The Sponsor reserves the right to discontinue the trial for any reason but intends only to exercise 
this right for valid scientific or administrative reasons.  After such a decision, the Investigators 
must contact all participating patients immediately after notification.  Standard therapy and 
follow-up for subjects will be assured and, where required by the applicable regulatory 
requirement(s), the relevant regulatory authority(ies) will be informed. 
The REB will be informed promptly and provided with a detailed written explanation for the 
termination or suspension. 
As directed by the Sponsor, all study materials must be collected and all eCRFs completed to the 
greatest extent possible. 

 
 
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13. LEGAL ASPECTS 
 
13.1 Publication Policies and Disclosure of Data  
For publications, the first author will be the Principal Investigator of the study. Additional 
authors will be those who have made the most significant contribution to the overall success of 
the study. This contribution will be reviewed at the end of the trial by the Principal Investigator.  
 
 
 
 
 
 
 

 
 
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