Conditions: Multiple Myeloma
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 51
Healthy volunteers: no

Brief summary:
The investigators hypothesize that prophylactic E-selectin inhibition via administration of uproleselan during melphalan conditioning will reduce the gastrointestinal (GI) toxicity in multiple myeloma (MM) patients undergoing auto-transplant, as assessed via diarrhea severity scoring per CTCAE v5.0, while potentially increasing chemosensitivity of malignant MM cells to high-dose melphalan.

Detailed description:

Arms:
arm 1: * On the evening of Day -3, patients will receive dose #1 of uproleselan
* On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of uproleselan
* On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of uproleselan
* On Day -2 following completion of dose #3 of uproleselan, the patient will be administered the conditioning dose of melphalan (200mg/m\^2) as per institutional practice.
* On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of uproleselan
* On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of uproleselan
* On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of uproleselan
* On Day 0, 4 hours (+/- 2 hours) after the final dose of uproleselan, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment arm 2: * On the evening of Day -3, patients will receive dose #1 of placebo
* On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of placebo On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of placebo.
* On Day -2 following completion of dose #3 of placebo, the patient will be administered the conditioning dose of melphalan (200mg/m\^2) as per institutional practice.
* On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of placebo.
* On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of placebo.
* On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of placebo.
* On Day 0, 4 hours (+/- 2 hours) after the final dose of placebo, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment

Interventions: intervention 1: Uproleselan intervention 2: Placebo intervention 3: Melphalan
Intervention descriptions: intervention 1: Provided by study intervention 2: Provided by study intervention 3: -Standard of care

Protocol document:
Prot_SAP_000.pdf: 
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page 1 of 63 
 
 
 
A Phase II Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Uproleselan 
(GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous 
Hematopoietic Cell Transplantation (auto-HCT) for Multiple Myeloma (MM) 
 
Washington University School of Medicine 
Division of Oncology 
660 South Euclid Avenue, Campus Box 8007 
St. Louis, MO  63110 
 
 
Protocol #: 202103086 
Version Date: 22 March 2022 
 
 
Principal Investigator: 
Keith Stockerl-Goldstein, M.D. 
Phone:  (314) 454-8304 
E-mail:  ksgoldstein@wustl.edu  
 
Sub-Investigators 
 
 
Modality 
Zachary D. Crees, M.D. 
 
Bone Marrow Transplant 
Geoffrey Uy, M.D. 
 
 
Bone Marrow Transplant 
Phillip Tarr, M.D. 
 
 
Gastroenterology 
Feng Gao, M.D., Ph.D. 
 
Biostatistics 
 
 
 
 
Study Drug(s): 
 
Uproleselan (GM-1271) 
IND#: 
154990 
IND Sponsor: 
Keith Stockerl-Goldstein, M.D. 
NCT#: 
NCT04682405 
Funded by: 
GlycoMimetics, Inc. (drug only) 
 
Foundation for Barnes-Jewish Hospital 
 
 
 
 
 
CONFIDENTIAL 
The information contained in this document is regarded as confidential and, except to the extent necessary to 
obtain informed consent, may not be disclosed to another party unless law or regulations require such 
disclosure.  Persons to whom the information is disclosed must be informed that the information is 
confidential and may not be further disclosed by them. 
 
 
 


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A Phase II Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Uproleselan 
(GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous 
Hematopoietic Cell Transplantation (auto-HCT) for Multiple Myeloma (MM) 
 
Protocol Revision History 
 
Initial Approval Version 
 
 
 
 
 
 
01 March 2021 
Amendment #1 Version 
 
 
 
 
 
 
01 June 2021 
Amendment #2 Version 
 
 
 
 
 
 
22 March 2022 
 
 
 


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STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 
 
 
 
 
 
 


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Glossary of Abbreviations  
 
AE 
Adverse event 
ALT (SGPT) 
Alanine transaminase (serum glutamate pyruvic transaminase) 
AML 
Acute myeloid leukemia 
ANC 
Absolute neutrophil count 
AST (SGOT) 
Aspartate transaminase (serum glutamic oxaloacetic transaminase) 
B-HCG 
Beta human chorionic gonadotropin  
BMT 
Bone marrow transplant 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CNS 
Central nervous system 
CR 
Complete response 
CRc 
Cytogenetic complete remission 
CRi 
Complete remission incomplete 
CRm 
Morphologic complete remission 
CRF 
Case report form 
CST 
Central standard time 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP 
Cancer Therapy Evaluation Program 
DLT 
Dose limiting toxicity 
DNA 
deoxyribonucleic acid 
DSM 
Data and Safety Monitoring  
DSMC 
Data Safety Monitoring Committee 
ECG (or EKG) 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDTA 
ethylenediaminetetraacetic acid 
FDA 
Food and Drug Administration 
FISH 
fluorescent in situ hybridization 
FWA 
Federal wide assurance 
GCP 
Good Clinical Practice 
HHS 
Department of Health and Human Services 
HIV 
Human Immunodeficiency Virus 
HRPO 
Human Research Protection Office (IRB) 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
MDS 
Myelodysplastic syndrome 
MM 
Multiple myeloma 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
NCCN 
National Cancer Center Network 


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NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
OHRP 
Office of Human Research Protections  
ORR 
Overall response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell 
PD 
Progressive disease 
PI 
Principal investigator 
PR 
Partial response 
QASMC 
Quality Assurance and Safety Monitoring Committee 
RFS 
Relapse free survival 
RR 
Response rate 
SAE 
Serious adverse event 
SCC 
Siteman Cancer Center 
SCT 
Stem cell transplant 
SD 
Stable disease 
TSH 
Thyroid stimulating hormone 
TTP 
Time to progression 
UPN 
Unique patient number 
US 
Ultrasound 
WBC 
White blood cell (count) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table of Contents 
PROTOCOL SUMMARY .............................................................................................................. 8 
SCHEMA ...................................................................................................................................... 11 
SCHEDULE OF ACTIVITIES ..................................................................................................... 12 
1.0 
INTRODUCTION ............................................................................................................. 13 
1.1 
Background .................................................................................................................... 13 
1.2 
Study Design .................................................................................................................. 17 
1.3 
Risk/Benefit Assessment ................................................................................................ 18 
2.0 
OBJECTIVES AND ENDPOINTS ................................................................................... 20 
3.0 
STUDY POPULATION .................................................................................................... 21 
3.1 
Inclusion Criteria ............................................................................................................ 21 
3.2 
Exclusion Criteria ........................................................................................................... 22 
3.3 
Inclusion of Women and Minorities ............................................................................... 24 
4.0 
REGISTRATION PROCEDURES ................................................................................... 24 
4.1 
Confirmation of Patient Eligibility ................................................................................. 24 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database ........................... 24 
4.3 
Assignment of UPN ....................................................................................................... 24 
4.4 
Screen Failures ............................................................................................................... 24 
4.5 
Measures to Minimize Bias:  Randomization and Blinding .......................................... 25 
4.6 
Replacement of Patients ................................................................................................. 26 
5.0 
TREATMENT PLAN ........................................................................................................ 26 
5.1 
Study Intervention Description ...................................................................................... 26 
5.2 
Definitions of Evaluability ............................................................................................. 28 
5.3 
Concomitant Therapy and Supportive Care Guidelines ................................................. 29 
5.4 
Women of Childbearing Potential .................................................................................. 29 
5.5 
Duration of Therapy ....................................................................................................... 30 
5.6 
Duration of Follow-up .................................................................................................... 30 
5.7 
Lost to Follow-Up .......................................................................................................... 31 
6.0 
DOSE DELAYS/DOSE MODIFICATIONS .................................................................... 31 
7.0 
REGULATORY AND REPORTING REQUIREMENTS ............................................... 31 
7.1 
Sponsor-Investigator Reporting Requirements .............................................................. 32 
7.2 
Exceptions to Expedited Reporting ................................................................................ 34 
8.0 
PHARMACEUTICAL INFORMATION .......................................................................... 34 
8.1 
Uproleselan (GMI-1271) ................................................................................................ 34 
8.2 
Placebo ........................................................................................................................... 36 
9.0 
CORRELATIVE STUDIES .............................................................................................. 37 
9.1 
Minimal Residual Disease (MRD) Status Following HCT ............................................ 37 
9.2 
E-selectin Levels ............................................................................................................ 38 
9.3 
GI Epithelial Inflammation and Permeability Biomarkers ............................................ 39 
10.0 DATA SUBMISSION SCHEDULE ................................................................................. 39 
10.1 Adverse Event Collection in the Case Report Forms ..................................................... 40 
11.0 MEASUREMENT OF EFFECT........................................................................................ 40 
11.1 GI Toxicity Adverse Events ........................................................................................... 40 
11.2 Response Criteria ........................................................................................................... 42 
11.3 Progression-Free Survival .............................................................................................. 45 
11.4 Overall Survival ............................................................................................................. 46 


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11.5 Overall Response Rate ................................................................................................... 46 
11.6 Complete Response Rate ................................................................................................ 46 
12.0 DATA AND SAFETY MONITORING ............................................................................ 46 
13.0 STATISTICAL CONSIDERATIONS............................................................................... 47 
13.1 Statistical Hypotheses .................................................................................................... 47 
13.2 Sample Size Determination ............................................................................................ 47 
13.3 Population for Analyses ................................................................................................. 48 
13.4 Statistical Analyses ........................................................................................................ 48 
14.0 REFERENCES .................................................................................................................. 52 
APPENDIX A: ECOG Performance Status Scale ........................................................................ 55 
APPENDIX B: Definitions for Adverse Event Reporting ............................................................ 56 
APPENDIX C: Reporting Timelines ............................................................................................ 58 
APPENDIX D: Bristol Stool Scale ............................................................................................... 61 
SUPPLEMENT 1: GI-Specific NCI CTCAE PRO v1.0 .............................................................. 62 
 
 


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PROTOCOL SUMMARY 
 
Title: 
A Phase II Randomized, Double-Blind, Placebo-Controlled Trial to 
Evaluate Uproleselan (GMI-1271) for GI Toxicity Prophylaxis 
During Melphalan-Conditioned Autologous Hematopoietic Cell 
Transplantation (auto-HCT) for Multiple Myeloma (MM) 
Study Description: 
This is a Phase II, single-center, randomized, double-blind, placebo-
controlled clinical trial. Eligible patients undergoing first auto-HCT 
with melphalan conditioning (200mg/m2) for MM will be 
randomized in a 1:1 allocation to receive either prophylactic 
uproleselan + SOC or placebo + SOC.  Randomization will be 
stratified by age ≥65 years and <65 years, due to increased frequency 
of GI toxicity in elderly populations. 
Objectives: 
Primary Outcome: 
To demonstrate the superiority of prophylactic uproleselan (GMI-
1271) plus standard of care (SOC) compared to placebo plus SOC to 
reduce diarrhea severity in patients receiving high-dose melphalan 
conditioning in preparation for auto-HCT in MM. 
 
Secondary Outcomes: 
• To demonstrate the superiority of prophylactic uproleselan 
(GMI-1271) plus SOC compared to placebo plus SOC to: 
o Reduce oral mucositis severity 
o Reduce alternative GI toxicities (e.g. esophagitis, 
enterocolitis, etc.) 
• To descriptively assess the effects of prophylactic uproleselan 
(GMI-1271) plus SOC compared to placebo plus SOC on: 
o Time to engraftment 
o hospital length of stay (LOS) 
o Use of anti-diarrheal and pain medications 
o Patient nutritional status pre-conditioning and post-HCT 
o Change in Bristol Stool Scale 
o Incidence of post-HCT infection prior to engraftment 
• To descriptively assess the effects of prophylactic uproleselan 
(GMI-1271) plus SOC compared to placebo plus SOC on PRO 
and QoL related to GI toxicity, on D-3, D+8 and date of discharge 
or D+14 (whichever is sooner) 
 
Exploratory Outcomes: 
• To descriptively assess the effects of prophylactic uproleselan 
(GMI-1271) plus SOC compared to placebo plus SOC on: 
o Minimal Residual Disease (MRD) at 100 days post-HCT 
o Soluble E-selectin levels at pre-dose (D-3) and post-
conditioning (D-0) time points 
o Progression Free Survival (PFS)  
o Overall Survival (OS) 


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• To descriptively assess biomarkers of GI permeability and GI 
epithelial injury, in collaboration with the Division of 
Gastroenterology 
Endpoints: 
Primary Endpoint: 
Change in diarrhea severity, assessed per CTCAE v5.0, in patients 
receiving high-dose melphalan conditioning in preparation for auto-
HCT for MM who receive prophylactic uproleselan (GMI-1271) 
plus standard of care (SOC) compared to placebo plus SOC.  
 
Secondary Endpoints: 
• Change in mucositis severity, per CTCAE v5.0 Oral Mucositis 
criteria 
• Change 
in 
alternative 
GI 
toxicities 
(e.g. 
esophagitis, 
enterocolitis, etc; per CTCAE v5.0) 
• Time to neutrophil engraftment defined as ANC ≥0.5 x 109/L for 
3 consecutive days or ≥1.0 x 109/L for 1 day 
• Duration of hospital length of stay (LOS), from date of admission 
for auto-HCT to date of discharge 
• Quantitative use of anti-diarrheal medications (loperamide, 
diphenoxylate, etc.) and pain medications (e.g. opioids converted 
to morphine equivalents) 
• Patient nutritional status before conditioning and at D+14 or date 
of discharge (whichever is sooner), as assessed by total TPN days 
and change in standing weight comparing D-3, D+8 and date of 
discharge or D+14 (whichever is sooner) 
• Change in Bristol Stool Scale, assessed daily 
• Incidence of infection assessed by rates of bacteremia (with 
organism reported when available), time to first antibiotics and 
c. diff infections 
• PRO and QoL, per the CTCAE PRO Form v1.0 with items selected 
for relevance to GI toxicity and patient QoL (see Supplement 1), 
assessed on D-3, D+8 and date of discharge or D+14 (whichever 
is sooner) 
 
Exploratory Endpoints: 
• Post-HCT Minimal Residual Disease (MRD) testing at D+100 
via 
ImmunoSeq 
B-cell 
receptor 
sequencing 
(Adaptive 
Biotechnologies) 
• Soluble E-selectin levels by ELISA assay at pre-dose (D-3) and 
post-conditioning (D-0) time points 
• Progression Free Survival (PFS) with up to 2-year follow up 
assessed by time-to event (Kaplan-Meier analysis) 
• Overall Survival (OS) with up to 2-year follow up assessed by 
time-to event (Kaplan-Meier analysis) 


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• Fecal calprotectin and neutrophil gelatinase-associated lipocalin-
2 (lipocalin-2) biomarkers (Tarr Lab) on D-3, D0, D+8 and date 
of discharge or D+14 (whichever is sooner) 
Study Population: 
Fifty patients with biopsy-proven diagnosis of multiple myeloma 
(MM) aged 18-75 years are eligible for this study. Must have ECOG 
PS 0-1, undergoing first auto-HCT for MM in first PR or better. 
Patients requiring renal replacement therapy, with a history of 
inflammatory bowel disease or alternative chronic diarrheal 
syndrome will be excluded.  
Phase: 
Phase II 
Description 
of 
Study 
Intervention: 
Patients 
enrolled 
on 
study 
will 
receive 
investigational 
product/placebo for 3 consecutive days totaling 6 doses. Follow-up 
for the key secondary endpoints of engraftment will include D+30, 
D+100, 6-month and 12-month assessments. The remaining follow-
up will be conducted via phone-calls every 3-6 months to assess for 
PFS and OS for up to 2 years post-HCT. 
Study Duration: 
12 months (recruitment) + 24 months (intervention and follow-up) + 
12 months (data analysis) = 48 months. 
Participant Duration: 
Approximately 1 week of active study intervention (participants will 
be in-patient during this period); 1 year of in-person follow-up; 1 
year of phone and medical record follow-up.  
 
 
 
 
 
 
 
 
 


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SCHEMA 
 
 
 
 
 
 


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SCHEDULE OF ACTIVITIES 
 
Activity 
Screening1 
Day -3 
Day -2 
Day -1 
Day 0 
Day +1 
Day +8 
DOD or D +1412 
Follow-Up13 
Informed consent 
X 
 
 
 
 
 
 
 
 
Eligibility check 
X 
 
 
 
 
 
 
 
 
Physical exam 
X 
 
 
 
 
 
 
 
X 
Medical history 
X 
 
 
 
 
 
 
 
 
Laboratory evaluation 
X2 
daily labs as per BMT protocol 
X 
Pregnancy test3 
X 
X 
 
 
 
 
 
 
 
Randomization4 
X 
 
 
 
 
 
 
 
 
Bone marrow evaluation 
X5 
 
 
 
 
 
 
 
X5 
Soluble E-selectin levels (peripheral blood) 
 
X 
 
 
X 
 
 
 
 
Fecal calprotectin and lipocalin-2 biomarkers 
 
X 
 
 
X 
 
X 
X 
 
Uproleselan 800 mg (iv) or placebo (iv) q 12 hrs 
 
X 
X6 
X 
X 
 
 
 
 
Melphalan conditioning 200 mg/m2 
 
 
X6 
 
 
 
 
 
 
HSC infusion 
 
 
 
 
X7 
 
 
 
 
Standing weight (unless unable to stand) 
X 
X 
 
 
 
 
X 
X 
 
NCI PRO CTCAE QoL assessment8 
 
X 
 
 
 
 
X 
X 
 
Standard AE assessments9 
X 
X------------------daily------------------X 
X 
Study-specific CTCAE v5.0 AE assessments10 
X 
X------------------daily------------------X 
 
Bristol Stool Scale assessment11 
 
X------------------daily------------------X 
 
1. Screening window to be D-90 through D-3 
2. CBC with differential, CMP, PT/INR, PTT, HIV and acute hepatitis panel. 
3. For women of childbearing potential, pregnancy test must be obtained at screening and on admission to the hospital prior to 
starting treatment on study. 
4. Randomization will occur following consent, screening and confirmation of eligibility. 
5. Screening and D+100 bone marrow assessment to include MRD testing of bone marrow aspirate on all patients. Otherwise, bone 
marrow assessments to be conducted per standard of care and institutional practice for disease response assessments. 
6. 3 doses of uproleselan should be administered prior to administration of the melphalan conditioning regimen and 3 doses of 
uproleselan administered following administration of the melphalan conditioning regimen. 
7. HSC infusion 4 hours (+/- 2 hours) following last dose of uproleselan. 
8. See Supplement 1 for CTI PRO CTCAE assessment form. 
9. Baseline AE assessment is intended to establish patient’s current medical condition. No regulatory reporting of AEs at baseline 
is required unless occurring as a result of a study-related procedure.  AEs are collected through D+30. 
10. Baseline and D-3 through DOD study-specific AE assessments must include the study specific CTCAE v5.0 assessments for the 
primary and secondary endpoints (see Section 11.0). 
11. See Appendix D. 
12. DOD = date of discharge. Assessment on DOD or D+14, whichever is sooner.  
13. Follow-up assessments will take place after transplant, at D+30, D+100, 6 months, and 12 months. Medical record data will be 
collected for up to 2 years post-HCT for survival. 
 
 
 


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1.0 
INTRODUCTION 
 
1.1 
Background 
 
1.1.1 Multiple Myeloma 
 
Multiple myeloma (MM) is a malignancy of plasma cells resulting in infiltration of 
the bone marrow, pancytopenia and lytic bone lesions.  MM is the second most 
common hematologic malignancy1-3 and accounts for approximately 15% of all 
hematologic malignancies4. The median age of patients at the time of diagnosis is 
approximately 65 years and impacts African Americans at rates 2-3x higher than 
rest of the population5. Common clinical features of MM are bone pain with 
pathologic fractures secondary to lytic lesions, renal failure, fatigue secondary to 
anemia and recurrent infections5. 
 
1.1.2 High-dose Chemotherapy and Stem-cell Rescue Therapy 
 
Historically, with conventional chemotherapy, median overall survival for MM 
patients was 24-30 months. In the 1980s, high-dose chemotherapy and stem-cell 
rescue therapy via autologous hematopoietic cell transplantation (auto-HCT) was 
introduced. In subsequent randomized trials, auto-HCT for the treatment of MM 
has been shown to improve event free survival compared to conventional 
chemotherapy alone in patients with standard-risk MM, while lengthening the time 
patients are without symptoms, treatment and treatment toxicity6-8. Currently, a 
combined approach of auto-HCT with additional novel therapies has increased 
median overall survival to >80 months9-13. 
 
1.1.3 Chemotherapy-Related GI Toxicity 
 
The conditioning regimens used for preparative chemotherapy prior to rescue auto-
HCT are associated with high rates (70-80%) of both hematologic and non-
hematologic AEs14-15. High-dose melphalan, which is one of the most commonly 
used regimens, carries particularly high rates of GI toxicity with diarrhea occurring 
in >90% of patients15-16. These toxicities adversely affect patients and frequently 
increase healthcare utilization by increasing hospital length of stay (LOS), 
increasing palliative medication usage, decreasing nutritional status, worsening 
patient quality of life (QoL) and having a detrimental impact on clinical outcomes17-
20. Meanwhile, current management strategies focus primarily on palliation of the 
GI toxicity once it has occurred, rather than preventing its occurrence21. Improved, 
prophylactic strategies are needed. 
 
1.1.4 Gastrointestinal Inflammation and Permeability 
 
Although the underlying mechanism of chemotherapy-related GI toxicity is not 
completely understood, it is well-documented that cytotoxic chemotherapy 
disproportionately impacts cell populations with high turnover, including 


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malignant cells as well as highly proliferative normal tissues like the GI epithelium, 
likely contributing to high rates of GI toxicity (diarrhea, mucositis, etc.). However, 
a growing body of data suggest that this chemotherapy-initiated epithelial injury 
subsequently leads to inflammatory chemokine and cytokine signaling, as well as 
upregulated selectin and integrin expression on the vascular endothelium at sites of 
inflammation22, 23. For example, upregulated E-selectin expression has been shown 
to be as high as 10x the baseline levels on vascular endothelial cells at sites GI 
epithelial inflammation23. This leads to increased intravascular leukocyte rolling, 
adhesion, trans-endothelial migration and chemotaxis of proinflammatory cells to 
these sites of epithelial injury resulting in additional, pathologic immune-mediated 
inflammatory injury to the GI epithelium22,23.  
 
This concept of pathologic, inflammatory GI epithelial injury by inflammatory 
leukocytes has been well-described in alternative settings of GI injury, such as graft 
versus host disease (GHVD) and inflammatory bowel disease (IBD)24-26. Therefore, 
in addition to evaluating mechanisms of inflammation as a therapeutic target for 
intervention in inflammatory GI disorders, the development of diagnostic 
biomarkers of GI inflammation represents an active area of investigation. Some 
well-described inflammatory markers of intestinal inflammation in GVHD and IBD 
include fecal calprotectin24-26, fecal lipocalin-227, 28 and fecal neopterin29, 30, which 
have been shown to correlate with severity of GI inflammatory epithelial injury and 
have been investigated as measures of treatment response leading to decreased GI 
inflammation.  
 
Therefore, presence of increased biomarkers of GI inflammation would represent 
strong supportive evidence of the proposed mechanism of chemotherapy-initiated 
epithelial injury leading to further inflammatory-mediated GI toxicity.  
 
1.1.5 E-Selectin 
 
E-selectin is a highly conserved adhesion molecule expressed on the surface of 
vascular endothelial cells which is upregulated at sites of inflammation, leading to 
increased intravascular cell rolling, trans-endothelial migration and trafficking of 
proinflammatory cells to these sites of inflammation22. Emerging pre-clinical data 
suggest that chemotherapy-induced mucositis and neutropenia may also be 
associated with E-selectin up-regulation on vascular endothelium at sites of acute 
chemotherapy-related inflammation along the GI epithelium, leading to additional 
cell-mediated inflammatory epithelial injury23. E-selectin is also constitutively 
expressed in vascular niches within the bone marrow, where it has been shown to 
co-localize and bind with malignant acute myeloid leukemia (AML) and multiple 
myeloma (MM) cells leading to cell adhesion-mediated chemotherapy resistance31-
33. 
 
1.1.6 Investigational Intervention – Uproleselan (GMI-1271) 
 
Uproleselan is a synthetic E-selectin antagonist which competitively inhibits E-


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selectin, thereby interrupting E-selectin-mediated interactions and effects34. 
 
1.1.6.1 Pre-Clinical Data  
 
Pre-clinical trials suggest that chemotherapy-induced mucositis and 
neutropenia may be associated with E-selectin up-regulation, while E-
selectin inhibition with uproleselan as an adjunct to chemotherapy protected 
mice from weight loss and chemotherapy induced GI toxicity while also 
enhancing neutrophil recovery23. Importantly, the administration of 
uproleselan effectively blocked secondary migration of inflammatory 
F4/80+ Ly-6C+ macrophages to intestines of mice following chemotherapy 
as one mechanism of reduced GI toxicity (Figure 1)23, 34.  
 
Figure 1: Macrophage Staining of Murine Small Intestines after Administration of Chemotherapy 
Alone and in Combination with Uproleselan (GMI-1271) 
 
A. Chemotherapy-treated with saline control injections, sustained epithelial injury, substantial 
macrophage infiltration, villous loss and epithelial erosions. B. Chemotherapy-treated, 
uproleselan-injected (GMI-1271), prevented macrophage infiltration, villous loss and epithelial 
injury. 
 
E-selectin inhibition with uproleselan in various pre-clinical models has 
also been observed to disrupt adhesion and mobilize malignant cells into 
circulation, increasing sensitivity to cytotoxic chemotherapy31, 
35 
Interestingly, treatment with uproleselan resulted in mobilization of MM 
cells to the peripheral blood beyond drug elimination in mouse xenograft 
models, suggesting a sustained effect following drug administration35. 
Additional in vivo studies using MM mouse models evaluating uproleselan 
plus melphalan demonstrated significantly improved survival and tumor 
growth inhibition when compared to melphalan alone35.   
 
1.1.6.1 Clinical Data  
 
To date, E-selectin inhibition with uproleselan has been evaluated in a total 
of 6 early-phase clinical trials conducted in healthy volunteers 
(NCT02168595, NCT02271113, NCT02703051), AML (NCT02306291) 
- A 
- B 


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and 
MM 
with 
an 
acceptable 
safety, 
pharmacokinetic 
(PK), 
pharmacodynamic (PD) profile34. In a recently completed Phase I/II clinical 
trial (NCT02306291) evaluating uproleselan plus chemotherapy in patients 
with AML demonstrated promising overall response rates of 80% (newly 
Dx AML, 7+3 chemo) and 48% (relapsed/refractory, MEC chemo), leading 
to a Phase III trial (NCT03616470) which our group is currently 
participating in34. Interestingly, only 4/157 (2.5%) of AML patients treated 
with uproleselan plus chemotherapy in the Phase I/II trial experienced grade 
3-4 mucositis, which is remarkably lower than expected based on 
historically observed rates of 10-30% for the chemotherapy agents 
administered (NCT02306291)34. Furthermore, this clinical observation is 
supported by the nonclinical pharmacology data for uproleselan in 
mucositis animal models23. Of note, in a Phase I open-label study evaluating 
uproleselan as a chemo-sensitizing agent added to proteasome-based 
chemotherapy regimens in multiple myeloma patients, E-selectin inhibition 
with uproleselan was found to be relatively safe and well-tolerated 
(NCT02811822)34.  
 
Therefore, considering the frequent prevalence of MM, the pivotal 
therapeutic role of high-dose chemotherapy with rescue auto-HCT and the 
high rates of AEs associated with this treatment approach, these data are 
sufficient to warrant further evaluation of uproleselan as a prophylactic 
supportive-care therapy to reduce conditioning regimen-associated GI 
toxicity and improve patient QoL, while potentially decreasing healthcare 
resource utilization and improving outcomes. 
 
1.1.7 Hypothesis 
 
We hypothesize that prophylactic E-selectin inhibition via administration of 
uproleselan during melphalan conditioning will reduce the GI toxicity in MM 
patients undergoing auto-transplant, as assessed via diarrhea severity scoring per 
CTCAE v5.0, while potentially increasing chemosensitivity of malignant MM cells 
to high-dose melphalan. 
 
1.1.8 Correlative Studies Background 
 
Testing of MRD status on routine bone marrow assessments following auto-HCT) 
has become standard of care. We propose assessment of MRD status at screening 
pre-HCT and D+100 post-transplant in all patients, as post-HCT MRD negativity 
has been correlated with improved survival in multiple studies36-37. We will also 
monitor for PFS and OS to confirm if these are associated with MRD status in this 
cohort. Soluble E-selectin levels will be measured in order to confirm on-target 
effect of the drug, as previously described34. Based on the mechanism of action of 
uproleselan, we are also interested in an interdisciplinary collaboration assessing 
biomarkers of GI epithelial injury including fecal calprotectin, fecal lipocalin-2 and 
potentially additional biomarkers such as neopterin. Calprotectin, a neutrophil-


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derived S100A8-S100A9 dimer is extensively used as a treatment target in IBD24. 
People with GI GVHD have elevated fecal calprotectin concentrations25, 26. 
Lipocalin-2 (Lcn-2) is neutrophil gelatinase-associated lipocalin, a pleotropic 
mediator of intestinal and systemic innate immunity27. The function of lipocalin is 
complex, and includes antibacterial and anti-inflammatory effects in the gut, and 
pro-inflammatory effects on extra-intestinal organs such as the liver. Circulating 
lipocalin concentrations correlate with acute and chronic GVHD, and mortality28. 
Neopterin (from macrophages and T-cells) similarly correlates with disease activity 
in IBD29, 30. Lastly, given the importance of assessing patient reported outcomes in 
clinical trials and in particular supportive care trials, we will assess the effect of 
uproleselan on patient reported quality of life. 
 
1.2 
Study Design 
 
1.2.1 Overall Design 
 
This is a Phase II, single-center, randomized, double-blind, placebo-controlled 
clinical trial. Eligible patients undergoing 1st auto-HCT with melphalan 
conditioning for MM will be randomized in a 1:1 allocation to receive either 
prophylactic uproleselan + SOC or placebo + SOC.  Randomization will be 
stratified by age ≥65 years and <65 years, due to the known increased frequency of 
GI toxicity in elderly populations. 
 
1.2.2 Scientific Rationale for Study Design 
 
Considering the frequent prevalence of MM, the pivotal therapeutic role of high-
dose chemotherapy with rescue auto-HCT and the high rates of AEs associated with 
this treatment approach, further evaluation of uproleselan as a prophylactic therapy 
to reduce conditioning regimen-associated GI toxicity, improve patient QoL, 
decrease healthcare resource utilization and improve outcomes is warranted. Phase 
I data are available to guide safety and dosing. Therefore, this trial is designed as a 
Phase II study to evaluate the RP2D dose for efficacy, safety and tolerability. All 
patients will receive SOC prophylaxis with cryotherapy per institutional protocol. 
Given the lack of additional, highly effective prophylactic strategies, randomization 
to placebo versus investigational treatment is a rational approach. Furthermore, 
given the inherent challenges associated with assessments of diarrhea severity 
along with the potential for multiple confounding variables, randomization, double-
blinding and placebo-control are necessary design elements. 
 
1.2.3 Justification for Dose 
 
Based on the initial Phase I pharmacokinetic and safety data showing clearance of 
uproleselan is not based on body size and in keeping with the dosing approach in 
the Phase II AML study, we propose using a fixed dose of uproleselan (GMI-1271) 
800mg, administered as an initial intravenous (IV) dose in the PM of D-3, followed 


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by 800mg IV every 12 hours through the conditioning chemotherapy period (total 
of 6 doses, last dose AM of D-0, 4 hours prior to HSC infusion). 
 
1.3 
Risk/Benefit Assessment 
 
1.3.1 Known Potential Risks 
 
Uproleselan (GMI-1271) 
Human safety information regarding uproleselan is available from Phase 1 clinical 
trials in healthy volunteers and subjects with MM, and a Phase 1/2 clinical trial in 
subjects with AML. Currently, clinical trials for AML, in which uproleselan is used 
as an adjunct to standard chemotherapy are ongoing, including administration 
alone, with cytarabine-based chemotherapy regimens for AML. To date, no specific 
toxicities, or target organs for toxicity, have been identified thus far in nonclinical 
studies or in clinical trials for uproleselan. Non-specific toxicities considered 
treatment-emergent adverse events (TEAEs) ≥Grade 3 were observed in 34/102 
(33.3%) patients across the aforementioned studies. Hematologic AEs 
(neutropenia, anemia and thrombocytopenia) were most commonly observed, 
accounting for 25/102 of the ≥Grade 3 TEAEs and typically occurring with co-
administration of chemotherapy regimens also associated with myelosuppression. 
Please see IB Table 7-1 for full table listing all observed TEAEs, along with IB 
Section 7.9 for overlap with expected AEs associated with concurrent 
chemotherapy regimens administered34. 
 
High-dose Melphalan and Rescue Auto-HCT 
Melphalan is a commonly used chemotherapy, administered in high-doses as a 
conditioning regimen prior to rescue auto-HCT in the treatment of MM. Commonly 
observed toxicities with melphalan are detailed in Table 1. Auto-HCT in MM is 
associated with a one-year non-relapse related mortality of 2%. All appropriate 
standard of care interventions will be undertaken to manage these associated risks 
and toxicities. 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.3.2 Table 1 Non-Hematologic Adverse Reactions in ≥25% of Patients with 
Multiple Myeloma Who Received Melphalan Conditioning for Auto-
HCT 
 
 
1.3.3 Known Potential Benefits 
 
Uproleselan (GMI-1271) 
The efficacy of uproleselan as prophylaxis for GI-toxicity or as a chemo-sensitizing 
agent has not been established. However, pre-clinical trials suggest that 
chemotherapy-induced mucositis and neutropenia may be associated with E-
selectin up-regulation, while E-selectin inhibition with uproleselan as an adjunct to 
chemotherapy protected mice from weight loss and chemotherapy induced GI 
toxicity while also enhancing neutrophil recovery23. Importantly, the administration 
of uproleselan effectively blocked secondary migration of inflammatory F4/80+ 
Ly-6C+ macrophages to intestines of mice following chemotherapy as one 
mechanism of reduced GI toxicity. To date, uproleselan has been evaluated in 
clinical trials for acute myeloid leukemia (AML) and MM as a potential chemo-
sensitizing 
agent 
with 
an 
acceptable 
safety, 
pharmacokinetic 
(PK), 
pharmacodynamic (PD) profile. Additionally, data from these trials demonstrated 
a low incidence and severity of mucositis in patients administered uproleselan34. 
Therefore, the potential benefits of uproleselan may include reduced trafficking of 
inflammatory cells to the GI epithelium leading to reduced conditioning regimen-
associated GI toxicity and improved patient QoL. Meanwhile, uproleselan may also 
increase MM cell chemosensitivity, leading to improved treatment response to 
high-dose melphalan and improved long-term outcomes. 


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High-dose Melphalan and Rescue Auto-HCT 
In the 1980s, high-dose chemotherapy and stem-cell rescue therapy via autologous 
hematopoietic cell transplantation (auto-HCT) was introduced. High-dose 
melphalan is the standard conditioning regimen prior to rescue auto-HCT in the 
treatment of MM. Randomized trials evaluating melphalan conditioning followed 
by auto-HCT for the treatment of MM have been shown to improve event free 
survival compared to conventional chemotherapy alone in patients with standard-
risk MM, while lengthening the time patients are without symptoms, treatment and 
long-term treatment toxicity6-8.  
 
 
2.0 
OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary 
To 
demonstrate 
the 
superiority 
of 
prophylactic uproleselan (GMI-1271) plus 
standard of care (SOC) compared to 
placebo plus SOC to reduce diarrhea 
severity in patients receiving high-dose 
melphalan conditioning in preparation for 
auto-HCT in MM. 
Change in diarrhea severity, assessed per CTCAE 
v5.0, in patients receiving high-dose melphalan 
conditioning in preparation for auto-HCT for MM 
who receive prophylactic uproleselan (GMI-1271) 
plus standard of care (SOC) compared to placebo 
plus SOC.  
Secondary 
• To demonstrate the superiority of 
prophylactic uproleselan (GMI-1271) 
plus SOC compared to placebo plus 
SOC to: 
o Reduce mucositis severity 
o Reduce alternative GI toxicities 
(e.g. esophagitis, enterocolitis, 
etc.) 
• To descriptively assess the effects of 
prophylactic uproleselan (GMI-1271) 
plus SOC compared to placebo plus 
SOC on: 
o Time to engraftment 
o hospital length of stay (LOS) 
o Use of anti-diarrheal and pain 
medications 
o Patient nutritional status pre-
conditioning and post-HCT 
o Change in Bristol Stool Scale 
o Incidence 
of 
post-HCT 
infection prior to engraftment 
• Change in mucositis severity, per CTCAE v5.0 
Oral Mucositis criteria 
• Change in alternative GI toxicities (e.g. 
esophagitis, enterocolitis, etc; per CTCAE v5.0) 
• Time to neutrophil engraftment defined as ANC 
≥0.5 x 109/L for 3 consecutive days or ≥1.0 x 
109/L for 1 day 
• Duration of hospital length of stay (LOS), from 
date of admission for auto-HCT to date of 
discharge 
• Quantitative use of anti-diarrheal medications 
(loperamide, diphenoxylate, etc.) and pain 
medications (e.g. opioids converted to morphine 
equivalents) 
• Patient nutritional status before conditioning and 
at D+14 or date of discharge (whichever is 
sooner), as assessed by total TPN days and 
change in standing weight comparing D-3, D+8 
and date of discharge or D+14 (whichever is 
sooner) 
• Change in Bristol Stool Scale, assessed daily 
(see Appendix D) 


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• To descriptively assess the effects of 
prophylactic uproleselan (GMI-1271) 
plus SOC compared to placebo plus 
SOC on PRO and QoL related to GI 
toxicity, on D-3, D+8 and date of 
discharge or D+14 (whichever is 
sooner) 
 
• Incidence of infection assessed by rates of 
bacteremia (with organism reported when 
available), time to first antibiotics and c. diff 
infections 
• PRO and QoL, per the CTCAE PRO Form v1.0 
with items selected for relevance to GI toxicity 
and patient QoL (see Supplement 1), assessed on 
D-3, D+8 and date of discharge or D+14 
(whichever is sooner) 
Exploratory 
• To descriptively assess the effects of 
prophylactic uproleselan (GMI-1271) 
plus SOC compared to placebo plus 
SOC on: 
o Minimal 
Residual 
Disease 
(MRD) at 100 days post-HCT 
o Soluble E-selectin levels at pre-
dose 
(D-3) 
and 
post-
conditioning (D-0) time points 
o Progression 
Free 
Survival 
(PFS)  
o Overall Survival (OS) 
• To descriptively assess biomarkers of 
GI inflammation and GI epithelial 
injury, in collaboration with the 
Division of Gastroenterology 
• Post-HCT Minimal Residual Disease (MRD) 
testing at D+100 via ImmunoSeq B-cell receptor 
sequencing (Adaptive Biotechnologies) 
• Soluble E-selectin levels by ELISA assay at pre-
dose (D-3) and post-conditioning (D-0) time 
points 
• Progression Free Survival (PFS) with up to 2-
year follow up assessed by time-to event 
(Kaplan-Meier analysis) 
• Overall Survival (OS) with up to 2-year follow 
up assessed by time-to event (Kaplan-Meier 
analysis) 
• Fecal calprotectin and neutrophil gelatinase-
associated lipocalin-2 (lipocalin-2) biomarkers 
(Tarr Lab) on D-3, D0, D+8 and date of 
discharge or D+14 (whichever is sooner) 
 
 
3.0 
STUDY POPULATION 
 
3.1 
Inclusion Criteria 
 
1. Biopsy-confirmed multiple myeloma (MM) (per IMWG criteria). 
 
2. Undergoing first auto-HCT for MM in first partial response (PR) or better (see 
Section 11.0).  
 
3. Conditioning regimen to be single agent melphalan (200 mg/m2) 
 
4. Adults 18 to 75 years of age, inclusive 
 
5. ECOG performance status ≤ 2 (see Appendix A)  
 
6. Mobilized ≥ 5.0 x 106 CD34+ cells/kg (i.e. sufficient CD34+ HSCs for one auto-
HCT, with at least one back-up graft in reserve) 
 


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7. Adequate bone marrow and organ function prior to stem cell mobilization, as defined 
below: 
a. Leukocytes, absolute neutrophil count, and platelets all within institutional standard 
limits for high-dose melphalan autologous stem cell transplant 
b. Total bilirubin ≤ 1.5 x ULN (unless the patient has a history of Gilbert’s Syndrome, 
in which case, total bilirubin must be ≤ 2.5 times the ULN) 
c. AST(SGOT)/ALT(SGPT) ≤ 3.0 x ULN 
d. Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault 
e. Baseline pulmonary function test (PFT) with carbon monoxide diffusion capacity 
in the lung (DLCO) ≥ 50% and  forced expiratory volume in 1 second (FEV1) both 
within institutional standard limits for high-dose melphalan autologous stem cell 
transplant 
 
8. The effects of uproleselan (GMI-1271) on the developing human fetus are unknown.  
For this reason, women of childbearing potential and men must agree to use adequate 
contraception (hormonal or barrier method of birth control, prior sterilization 
procedure, abstinence, etc.) prior to study entry, for the duration of study participation 
and for 12 weeks after the completion of the study.  Should a woman become 
pregnant or suspect she is pregnant while participating in this study, she must inform 
her treating physician immediately.  Should a man who is participating in the study 
become aware that he has impregnated a partner, he must inform his treating 
physician immediately. 
 
9. Ability to understand and willingness to sign an IRB approved written informed 
consent document (or that of legally authorized representative, if applicable). 
 
3.2 
Exclusion Criteria 
 
1. A history of other malignancy with the exception of malignancies for which all 
treatment was completed at least 2 years before registration and the patient has no 
evidence of disease. 
 
2. Active signs or symptoms of CNS involvement by malignancy (lumbar puncture not 
required). Prior history of CNS involvement is acceptable, if patient has completed 
treatment for CNS involvement with documented treatment response.  
 
3. Prior exposure to uproleselan (GMI-1271)  
 
4. Currently receiving any other investigational agents 
 
5. A history of allergic reactions attributed to compounds of similar chemical or biologic 
composition to uproleselan or melphalan 
 
6. Known active infection with hepatitis A, B (e.g., HBsAg positive), or C (e.g., anti-HCV 
positive), or human immunodeficiency virus 
 


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7. Uncontrolled acute life-threatening bacterial, viral, or fungal infection 
 
8. Myocardial infarction within 6 months of uproleselan/placebo dosing, or subject has 
current significant cardiovascular disease, such as uncontrolled or symptomatic 
arrhythmias, congestive heart failure, hemodynamic instability, or any Class 3 or 
4 cardiac disease as defined by the New York Heart Association Functional 
Classification 
 
9. Any medical, psychiatric, or other condition which, in the opinion of the investigator, 
unfavorably alters the risk-benefit of subject participation, is likely to interfere with 
trial completion, assessments, or interpretation of trial results, or otherwise would make 
the subject an inappropriate subject for this trial.  
 
10. Pregnant and/or breastfeeding.   
 
11. Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using highly effective contraception during the trial 
and for 12 weeks following the last dose of uproleselan/placebo. Women who are 
postmenopausal with amenorrhea for at least 1 year prior to trial entry and follicle 
stimulating hormone (FSH) serum levels consistent with postmenopausal status 
(>28U/L) will be considered NOT of childbearing potential. Highly effective 
contraception includes: 
a. Total abstinence with a male partner. 
b. Female sterilization (has had surgical bilateral oophorectomy with or without 
hysterectomy) or tubal ligation at least 6 weeks before uproleselan/placebo. In case 
of oophorectomy alone, the subject would be eligible only when the reproductive 
status of the woman has been confirmed by follow up hormone level assessment. 
c. Male sterilization (at least 6 months prior to Screening). For female subjects on the 
trial, the vasectomized male partner should be the sole partner for that subject. 
d. BOTH of the following forms of contraception consistently used together: 
i. Injected, transdermal, or implanted hormonal methods of contraception or 
other forms of hormonal contraception that have comparable efficacy 
(failure rate <1%) with the exception of intrauterine devices, which are 
excluded due to the risk of infection and bleeding. 
ii. Barrier methods of contraception: condom or occlusive cap (diaphragm or 
cervical/vault 
caps) 
with 
or 
without 
spermicidal 
foam/gel/film/cream/vaginal suppository. 
iii. Men who are sexually active and not willing to use condoms during the trial 
and for 12 weeks following the last dose of uproleselan/placebo, unless they 
have undergone vasectomy for sterilization (at least 6 months prior to 
Screening), are excluded from trial participation. 
 
12. Men who are sexually active and not willing to use condoms during the trial and for 
12 weeks following the last dose of uproleselan/placebo, unless they have undergone 
vasectomy for sterilization (at least 6 months prior to Screening), are excluded from 
trial participation. 


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3.3 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this trial.   
 
 
4.0 
REGISTRATION PROCEDURES 
 
Patients must not start any protocol intervention prior to registration through the Siteman 
Cancer Center. 
 
The following steps must be taken before registering patients to this study: 
 
1. Confirmation of patient eligibility  
2. Registration of patient in the Siteman Cancer Center database 
3. Assignment of unique patient number (UPN) 
 
4.1 
Confirmation of Patient Eligibility 
 
Confirm patient eligibility by collecting the information listed  
1. The registering MD’s name 
2. Patient’s race, sex, and DOB 
3. Three letters (or two letters and a dash) for the patient’s initials 
4. Copy of signed consent form  
5. Completed eligibility checklist, signed and dated by a member of the study team 
6. Copy of appropriate source documentation confirming patient eligibility 
 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database 
 
All patients must be registered through the Siteman Cancer Center OnCore database. 
 
4.3 
Assignment of UPN 
 
Each patient will be identified with a unique patient number (UPN) for this study.  All data 
will be recorded with this identification number on the appropriate CRFs. 
 
4.4 
Screen Failures 
 
Screen failures are defined as participants who consent to participate in the clinical trial 
but are not subsequently randomized to the study intervention or entered in the study.  A 
minimal set of screen failure information is required to ensure transparent reporting of 
screen failure participants, to meet the Consolidated Standards of Reporting Trials 
(CONSORT) publishing requirements and to respond to queries from regulatory 
authorities.  Minimal information includes demography, screen failure details, eligibility 
criteria, and any serious adverse event (if applicable).   
 


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4.5 
Measures to Minimize Bias:  Randomization and Blinding 
 
4.5.1 Randomization 
 
Fifty patients with MM will be randomized in a 1:1 allocation to receive either 
uproleselan plus SOC or placebo plus SOC as GI-toxicity prophylaxis during 
melphalan conditioning prior to auto-HCT.  Randomization will be stratified by age 
≥65 years and <65 years, due to increased frequency of GI toxicity in elderly 
populations.  The randomization table will be generated using the SAS program 
PROC PLAN. To better ensure the balance of patient characteristics across two 
arms, treatment assignment will be implemented in small blocks of 4 or 6 patients. 
Enrollment will continue until 50 evaluable patients are enrolled. Randomization 
will occur following registration and implemented with the OnCore system. 
 
After the Screening evaluations have been performed and a patient is confirmed to 
be eligible for study, they will be to a treatment group. 
 
The Interactive Web Response System (IWRS) will provide the designated 
unblinded investigational pharmacist the subject’s treatment assignment. Dose 
preparation procedures will be performed by the pharmacist utilizing uproleselan 
or placebo provided by GlycoMimetics. 
 
Treatment assignment received at randomization will be maintained throughout the 
conditioning period.  
 
4.5.2 Blinding 
 
This trial will be double-blinded and placebo-controlled. All healthcare providers, 
ancillary support staff, research support staff and patients participating in the trial 
will remain blinded to treatment, including personnel at GlycoMimetics. The 
investigational pharmacists participating in the study will be unblinded to treatment 
assignments. Investigational drug or placebo will be IV saline solution, provided 
by the investigational pharmacy in a blinded manner to the non-pharmacy study 
personnel for administration to trial patients, based on the patients’ treatment 
assignment at randomization. 
 
The blind will be maintained for treatment assignment for randomized subjects until 
30 days after the last patient has completed HCT and has been fully assessed for 
the primary endpoint of the study.  
 
The blind will be maintained in the following manner: 
• The investigational pharmacist (or authorized designee) will be unblinded 
and will prepare uproleselan and placebo in a blinded manner in order to 
maintain the blind for all other trial personnel. 


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• Unblinding may only be performed in emergencies where knowledge of the 
subject’s treatment assignment is essential for immediate management of 
the subject’s medical care. It is anticipated that such situations will be 
extremely rare. If the treatment of the AE/safety issue is the same regardless 
of the treatment assignment, the blind should not be broken. Unblinding a 
subject’s treatment assignment by the investigator under any other 
circumstances will be considered a protocol violation. 
• Subjects whose treatment assignment is unblinded will continue all trial 
treatment and assessments per protocol. 
• Any intentional or unintentional unblinding events must be reported to the 
Principal Investigator (PI) immediately and also documented in the medical 
record, including: date, time, and reason for breaking the blind. 
• Treatment randomization information, and any analytical results will be 
kept confidential and will not be released to the investigator or blinded 
personnel until the conclusion of the trial. 
 
4.6 
Replacement of Patients 
 
Patients who are screened, found to be eligible, and randomized to a treatment arm but who 
subsequently do not undergo auto-HCT or are removed from the study prior to receiving 
study-related treatments are not evaluable for the primary endpoint and therefore will be 
replaced in order to achieve the target enrollment of 50 evaluable patients. 
 
 
5.0 
TREATMENT PLAN 
 
5.1 
Study Intervention Description 
 
Following consent, patients will undergo all screening procedures, and those meeting 
eligibility requirements will be randomized as described in Section 4.5.1 to either 
uproleselan + SOC or placebo + SOC. All patients will be admitted to the hospital 3 days 
(Day -3) prior to the scheduled date of HSC infusion (Day 0).  
 
• On the evening of Day -3, patients will receive dose #1 of uproleselan or placebo 
(suggested dosing time is 8:00pm).  
• On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will 
receive dose #2 of uproleselan or placebo.  
• On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive 
dose #3 of uproleselan or placebo.  
• On Day -2 following completion of dose #3 of uproleselan or placebo, the patient 
will be administered the conditioning dose of melphalan (200mg/m2) as per 
institutional practice.  
• On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will 
receive dose #4 of uproleselan or placebo.  
• On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive 
dose #5 of uproleselan or placebo.  


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• On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will 
receive dose #6 (final dose) of uproleselan or placebo.  
• On Day 0, 4 hours (+/- 2 hours) after the final dose of uproleselan or placebo, the 
patient will be infused with the HSC product. The patient will remain inpatient until 
engraftment and will follow-up for study assessments per the full schedule of 
assessments. 
 
5.1.1 Uproleselan (GMI-1271) and Placebo Preparation and Dosing 
 
Uproleselan injection, 50 mg/mL is supplied in single-dose vials at a concentration 
of 50 mg/mL.  Uproleselan injection 50 mg/mL is stored per the specified 
conditions on the label, frozen (10 °C to -25 °C) prior to administration.  The frozen 
product can appear as a homogenous solid, a striated solid, or as a super-cooled 
liquid.  When using frozen supply, vials should be brought to room temperature 
before dose preparation.  Upon thawing, the product should be gently inverted 4 to 
5 times to ensure homogeneity of the solution.  The thawed solution is clear, 
colorless to slightly yellow, and free from visible particulates.   
 
Uproleselan should be administered IV into a peripheral line, a central catheter, or 
a peripherally inserted central line catheter (PICC). Infusion should take place at a 
steady rate over a period of 20 minutes (+/-2 minutes) using a syringe pump or IV 
pump. Microbore tubing is preferred. In-line filtration is highly recommended. 
Dilution of uproleselan may be performed with normal saline (0.9% Sodium 
Chloride).  
 
Compatibility with other therapeutic agents has not been determined; therefore, 
uproleselan injection should be administered via a separate IV line and should not 
be administered concurrently with anything other than saline.  If a flush is used, 
saline flush is preferred. 
 
When prepared in syringes or intravenous (IV) bags without an administration set 
attached, uproleselan may be stored refrigerated up to 72 hours prior to 
administration or up to 24 hours at controlled room temperature prior to 
administration.  Administration sets manufactured from materials of construction 
other than polyvinyl chloride (PVC) with di(2-ethylhexyl)phthalate (DEHP) can be 
primed up to 72 hours before dosing if stored refrigerated or up to 24 hours before 
dosing if stored at controlled room temperature.  Intravenous lines consisting of 
PVC with DEHP should be avoided when possible.  If PVC with DEHP 
administration sets must be used they should be primed with uproleselan solution 
no more than 2 hours before dosing.  It is highly recommended that uproleselan 
prepared prior to administration be refrigerated until 1 hour prior to dosing. 
 
Uproleselan (GMI-1271) will be given as a single dose at 800 mg, administered as 
an initial intravenous (IV) dose in the evening of Day -3, followed by 800 mg IV 
every 12 hours through the conditioning chemotherapy period (total of 6 doses, last 
dose AM of Day 0 prior to HSC infusion). Three doses of uproleselan should be 


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administered prior to administration of the melphalan conditioning regimen, with 3 
doses administered following administration of the melphalan conditioning 
regimen. 
 
As placebo, commercially available saline (0.9% Sodium Chloride Injection) will 
be prepared by the site’s pharmacist in IV administration components (syringe, bag, 
tubing, etc.) matching those used for active treatment to maintain the blind. The 
dosing schedule and procedure for placebo will be identical to that for uproleselan. 
It is recommended that placebo prepared prior to administration be refrigerated 
until one hour prior to dosing, to match pharmacy procedures for uproleselan. 
Preparation of placebo in advance of administration should be in accordance with 
institutional pharmacy standards and commercial label for the placebo control. 
 
5.1.2 Melphalan Dosing 
 
Melphalan will be administered as a single, IV dose at 200 mg/m2 infused over 20 
minutes on HCT Day -2, with the following guidance: 
o Dosing instructions: 
 If actual Body Weight (BW) is less than ideal BW, use actual BW 
 If actual BW is greater than ideal BW, but less than 120% of ideal BW, 
use ideal BW 
 If actual BW is greater than or equal to 120% of ideal BW, use corrected 
BW 
• Corrected BW = ([actual BW – ideal BW] x 0.2) + ideal BW 
o Dose rounding: 
 Dosing will be rounded to the nearest 50mg provided that the dose is 
within 5% of the calculated dose, as above 
o Dose administration: 
 Melphalan will be administered as per instructional practice and 
guidelines, which is typically at 9PM. 
 
5.2 
Definitions of Evaluability 
 
All patients who receive any study treatment are evaluable for toxicity.  Patients are 
evaluated from first receiving study treatment until a 30-day follow up after the conclusion 
of treatment or death. 
 
All patients who receive at least one dose of uproleselan or placebo and undergo auto-HCT 
are evaluable for disease response unless they are removed from the study prior to 
undergoing any study-related disease response assessment.   Patients who do not undergo 
auto-HCT or are removed from the study prior to receive study-related treatments will be 
replaced. 
 
 
 
 


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5.3 
Concomitant Therapy and Supportive Care Guidelines 
 
At Trial Start: Prior G-CSF, granulocyte macrophage-colony stimulating factor (GM-
CSF) or plerixafor is prohibited within 3 days prior to uproleselan/placebo dosing. 
 
GI Toxicity Prophylaxis: SOC cryotherapy will be provided to all patients for GI-toxicity 
prophylaxis, per institutional practice. 
 
Post-auto-HCT: G-CSF may not be initiated until 72 hours after the last dose of 
uproleselan/placebo in each cycle. The use of erythropoiesis-stimulating agents such as 
epoetin and darbepoetin is not allowed. 
 
Supportive Care: All additional and medically indicated supportive cares, including pain 
medications, anti-diarrheal medications, antimicrobials and any other indicated palliative 
therapy will be available and provided to the patients, per institutional practice and best 
standards of care. 
 
5.4 
Women of Childbearing Potential 
 
Women of childbearing potential (defined as women with regular menses, women with 
amenorrhea, women with irregular cycles, women using a contraceptive method that 
precludes withdrawal bleeding, and women who have had a tubal ligation) are required to 
have a negative serum/urine pregnancy test at screening and again on Day -3 prior to the 
first dose of uproleselan/placebo.  Women who are postmenopausal with amenorrhea for 
at least 1 year prior to trial entry and follicle stimulating hormone (FSH) serum levels 
consistent with postmenopausal status (>28U/L) will be considered NOT of childbearing 
potential.  
 
Female and male patients (along with their female partners) are required to use highly 
effective contraception during participation in the study and for at least 12 weeks following 
the last dose of uproleselan/placebo.  Highly effective contraception includes: 
a. Total abstinence with a male partner. 
b. Female sterilization (surgical bilateral oophorectomy with or without 
hysterectomy) or tubal ligation at least 6 weeks before uproleselan/placebo 
c. Male sterilization (at least 6 months prior to Screening). For female subjects on the 
trial, the vasectomized male partner should be the sole partner for that subject. 
d. BOTH of the following forms of contraception consistently used together: 
i. 
Injected, transdermal, or implanted hormonal methods of contraception or 
other forms of hormonal contraception that have comparable efficacy 
(failure rate <1%) with the exception of intrauterine devices, which are 
excluded due to the risk of infection and bleeding. 
ii. 
Barrier methods of contraception: condom or occlusive cap (diaphragm 
or 
cervical/vault 
caps) 
with 
or 
without 
spermicidal 
foam/gel/film/cream/vaginal suppository. 
 


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If a patient is suspected to be pregnant, uproleselan/placebo should be immediately 
discontinued. In addition, a positive urine test must be confirmed by a serum pregnancy 
test.  If it is confirmed that the patient is not pregnant, the patient may resume dosing. 
 
If a female patient or female partner of a male patient becomes pregnant during therapy or 
within 12 weeks after the last dose of uproleselan/placebo, the investigator must be notified 
in order to facilitate outcome follow-up. 
 
5.5 
Duration of Therapy 
 
If at any time the constraints of this protocol are considered to be detrimental to the 
patient’s health and/or the patient no longer wishes to continue protocol therapy, the 
protocol therapy should be discontinued and the reason(s) for discontinuation documented 
in the case report forms. 
 
In the absence of treatment delays due to adverse events, treatment may continue for 6 
doses of uproleselan or placebo or until one of the following criteria applies: 
 
• Documented and confirmed disease progression 
• Death 
• Adverse event(s) that, in the judgment of the investigator, may cause severe or 
permanent harm or which rule out continuation of study drug 
• General or specific changes in the patient’s condition render the patient unable to 
receive further treatment in the judgment of the investigator 
• Suspected pregnancy 
• Serious noncompliance with the study protocol 
• Lost to follow-up 
• Patient withdraws consent 
• Investigator removes the patient from study 
• The Siteman Cancer Center decides to close the study 
 
Patients who prematurely discontinue treatment for any reason will still be followed as 
indicated in the study calendar. 
 
5.6 
Duration of Follow-up 
 
Patients will be followed at D+30, D+100, 6 months, and 12 months with SOC assessments 
per institutional practice. Of note, the D+100 bone marrow assessment will include a bone 
marrow sample sent for MRD testing. Following that, patients will be contacted by phone 
every 3-6 months to assess for PFS and OS for an additional year (ending at 2 years post-
HCT).  Patients removed from study for unacceptable adverse events will be followed until 
resolution or stabilization of the adverse event.   
 
 
 
 


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5.7 
Lost to Follow-Up 
 
A participant will be considered lost to follow-up if he or she fails to return for 6 weeks 
following a scheduled visit and is unable to be contacted by the study team. 
 
The following actions must be taken if the participant fails to return to clinic for a required 
study visit: 
o The study team will attempt to contact the participant and reschedule the missed 
visit within 6 weeks and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain if the participant wishes to and/or should 
continue in the study. 
o Before a participant is deemed lost to follow-up, the investigator or designee will 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address).  These contact attempts should be documented in the participant’s medical 
record or study file. 
o Should the participant continue to be unreachable, he or she will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up. 
 
 
6.0 
DOSE DELAYS/DOSE MODIFICATIONS 
 
No dose modifications are recommended for uproleselan/placebo, nor should dose modifications 
be made without direct consultation with the PI. Dose delays should only occur in the event of a 
medical emergency, and the PI should be made aware of any anticipated deviations from the dosing 
protocol given the importance of timely administration of uproleselan concurrent with melphalan 
(3 doses of uproleselan prior to melphalan administration and 3 doses following melphalan), as 
well as the completion of the sixth and final dose of uproleselan/placebo 4 hours (+/- 2 hours) prior 
to the HSC infusion. 
 
 
7.0 
REGULATORY AND REPORTING REQUIREMENTS 
 
The entities providing oversight of safety and compliance with the protocol require reporting as 
outlined below.  Please refer to Appendix B for definitions and Appendix C for a grid of reporting 
timelines. 
 
Adverse events will be tracked from start of treatment through D+30 post auto-HCT.  All adverse 
events must be recorded on the toxicity tracking case report form (CRF) with the exception of: 
• Baseline adverse events, which shall be recorded on the medical history CRF 
• AEs related to the initial induction chemotherapy and mobilization  
 
AEs related to the conditioning regimen (melphalan) and auto-HCT should be recorded in the 
CRF, given the primary outcome being reduction in chemotherapy-related GI toxicities. 
 


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Refer to the data submission schedule in Section 10 for instructions on the collection of AEs in the 
EDC. 
 
Reporting requirements for Washington University study team may be found in Section 7.1.   
 
 
 
7.1 
Sponsor-Investigator Reporting Requirements 
 
7.1.1 Reporting to the Human Research Protection Office (HRPO) at 
Washington University 
 
Reporting will be conducted in accordance with Washington University IRB 
Policies. 
 
Pre-approval of all protocol exceptions must be obtained prior to implementing the 
change. 
 
7.1.2 Reporting to the Quality Assurance and Safety Monitoring Committee 
(QASMC) at Washington University 
 
The Sponsor Investigator (or designee) is required to notify the QASMC of any 
unanticipated problems involving risks to participants or others occurring at WU or 
any BJH or SLCH institution that has been reported to and acknowledged by 
HRPO.  (Unanticipated problems reported to HRPO and withdrawn during the 
review process need not be reported to QASMC.) 
 
QASMC must be notified within 10 days of receipt of IRB acknowledgment via 
email to qasmc@wustl.edu.  Submission to QASMC must include the myIRB form 
and any supporting documentation sent with the form. 
 
7.1.3 Reporting to GlycoMimetics, Inc. 
 
According to the timelines referenced in Appendix C, the Sponsor shall use 
commercially reasonable efforts to forward assessed case information regarding 
SAEs and other safety information that it receives from a patient receiving the 
investigational product or placebo. 
 
7.1.4 Reporting to the FDA 
 
The conduct of the study will comply with all FDA safety reporting requirements.  
PLEASE NOTE THAT REPORTING REQUIREMENTS FOR THE FDA 
DIFFER FROM REPORTING REQUIREMENTS FOR HRPO/QASMC.  It 
is the responsibility of the Sponsor-Investigator to report to the FDA as follows: 
 


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• Report any unexpected fatal or life-threatening suspected adverse reaction 
(refer to Appendix B for definitions) no later than 7 calendar days after 
initial receipt of the information.   
• Report a suspected adverse reaction that is both serious and unexpected 
(SUSAR, refer to Appendix B) no later than 15 calendar days after it is 
determined that the information qualifies for reporting.  Report an adverse 
event (refer to Appendix B) as a suspected adverse reaction only if there is 
evidence to suggest a causal relationship between the drug and the adverse 
event, such as: 
o A single occurrence of an event that is uncommon and known to be 
strongly associated with drug exposure 
o One or more occurrences of an event that is not commonly associated 
with drug exposure but is otherwise uncommon in the population 
exposed to the drug 
o An aggregate analysis of specific events observed in a clinical trial that 
indicates those events occur more frequently in the drug treatment 
group than in a concurrent or historical control group 
• Report any findings from epidemiological studies, pooled analysis of 
multiple studies, or clinical studies that suggest a significant risk in humans 
exposed to the drug no later than 15 calendar days after it is determined 
that the information qualifies for reporting. 
• Report any findings from animal or in vitro testing that suggest significant 
risk in humans exposed to the drug no later than 15 calendar days after it 
is determined that the information qualifies for reporting.  
• Report any clinically important increase in the rate of a serious suspected 
adverse reaction of that listed in the protocol or IB within 15 calendar days 
after it is determined that the information qualifies for reporting. 
 
Submit each report as an IND safety report in a narrative format or on FDA Form 
3500A or in an electronic format that FDA can process, review, and archive.  Study 
teams must notify the Siteman Cancer Center Protocol Development team of each 
potentially reportable event within 1 business day after initial receipt of the 
information, and must bring the signed 1571 and FDA Form 3500A to the Siteman 
Cancer Center Protocol Development team no later than 1 business day prior to the 
due date for reporting to the FDA. 
 
Each notification to FDA must bear prominent identification of its contents (“IND 
Safety Report”) and must be transmitted to the review division in the Center for 
Drug Evaluation and Research (CDER) or in the Center for Biologics Evaluation 
and Research (CBER) that has responsibility for review of the IND.  Relevant 
follow-up information to an IND safety report must be submitted as soon as the 
information is available and must be identified as such (“Follow-up IND Safety 
Report”). 
 
 
 


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7.2 
Exceptions to Expedited Reporting 
 
Events that do not require expedited reporting as described in Section 7.1 include: 
• planned hospitalizations 
• hospitalizations < 24 hours 
• respite care 
• events related to disease progression 
 
Events that do not require expedited reporting must still be captured in the EDC. 
 
 
8.0 
PHARMACEUTICAL INFORMATION 
 
8.1 
Uproleselan (GMI-1271) 
 
8.1.1 Uproleselan (GMI-1271) Description 
  
Chemical Name: Sodium (1R, 3R, 4R, 5S)-3-({2-N-acetylamino-2-deoxy-3-O-
[(1S)-1-carboxylato-2-cyclohexylethyl]-β-D-galactopyranosyl}oxy)-4-({6-deoxy-
α-L-galactopyranosyl}oxy)-5-ethyl-cyclohexan-1-yl-(38-oxo-
2,5,8,11,14,17,20,23,26,29, 32,35-dodecaoxa-39-azahentetracontan-41-yl) 
carboxamide  
 
Chemical Formula: C60H108N3NaO27  
 
Molecular Weight: 1326.5  
 
Figure 4-1. Uproleselan Chemical Structure 
 
 
 
 
8.1.2 Clinical Pharmacology 
 


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PK evaluations in healthy volunteers showed a dose-linear relationship in mean PK 
parameters after IV infusion of uproleselan 2 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg 
and 40 mg/kg. Uproleselan is characterized by a half-life of 1.4-2.5 hours and does 
not accumulate after doses up to 20 mg/kg BID. Population PK analysis in healthy 
volunteers and patients with AML demonstrate similar PK profiles, PK parameters, 
and dose-proportionality. Clearance was found to depend on renal function and 
have a similar magnitude in both healthy volunteers and in patients with AML. 
Clearance is not dependent on body size which allows for flat-fixed dosing. The 
PK of uproleselan does not appear to be affected when co-administered with 
chemotherapy.  
 
Absolute CD34+ counts did not increase in peripheral blood after administration of 
uproleselan. 
 
8.1.3 Pharmacokinetics and Drug Metabolism 
 
A population PK analysis was conducted using data from trial GMI-1271-201 to 
understand the PK of uproleselan when administered with cytotoxic chemotherapy 
in patients with AML. This analysis revealed a similar PK profile in these patients 
and healthy volunteers. It was found that clearance of uproleselan varies with renal 
function and does not vary with body size or any other covariate evaluated. Minimal 
accumulation of uproleselan at any dose level was observed, as expected from the 
short half-life.  
 
Following from the population PK finding that clearance does not depend on body 
size, conversion to a flat-fixed dose for subsequent trials is appropriate. Exposure-
response analyses further demonstrated that safety and efficacy responses are not 
dependent on exposure. In the GMI-1271-201 trial, the majority of patients with 
R/R AML were administered a dose of 10 mg/kg at a median body weight of 82.6 
kg. The corresponding flat-fixed dose is 800 mg. Therefore, a flat-fixed dose of 800 
mg will be used in this trial. 
 
8.1.4 Supplier 
 
Uproleselan will be supplied by GlycoMimetics, Inc. 
 
8.1.5 Dosage Form and Preparation 
 
Uproleselan will be supplied in sterile single-dose vials at a concentration of 50 
mg/mL. The drug product should be stored frozen (-10°C to -25°C) or refrigerated 
(2°C to 8°C) per the label directions until time of use. The frozen product can 
appear as a homogenous solid, a striated solid, or as a super-cooled liquid. Frozen 
drug product should be brought to room temperature before dose preparation. Upon 
thawing, the product should be gently inverted 4 to 5 times to ensure homogeneity 
of the solution. The thawed or refrigerated solution is clear, colorless to slightly 
yellow, and free from visible particulates. 


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8.1.6 Storage and Stability 
 
Uproleselan injection 50 mg/mL is stored per the specified conditions on the label, 
either frozen (-10°C to -25°C) or refrigerated (2°C to 8°C), prior to administration. 
The frozen product can appear as a homogenous solid, a striated solid, or as a super-
cooled liquid. Frozen vials should be brought to room temperature before dose 
preparation. Upon thawing, the product should be gently inverted 4 to 5 times to 
ensure homogeneity of the solution. The thawed or refrigerated solution is clear, 
colorless to slightly yellow, and free from visible particulates. Reconstitution and 
dilution are not necessary. Dilution up to 5X may be performed with normal saline.  
 
When prepared in syringes or intravenous (IV) bags without an administration set 
attached, uproleselan may be stored refrigerated up to 72 hours prior to 
administration or up to 24 hours at controlled room temperature prior to 
administration.  Administration sets manufactured from materials of construction 
other than polyvinyl chloride (PVC) with di(2-ethylhexyl)phthalate (DEHP) can be 
primed up to 72 hours before dosing if stored refrigerated or up to 24 hours before 
dosing if stored at controlled room temperature.  Intravenous lines consisting of 
PVC with DEHP should be avoided when possible.  If PVC with DEHP 
administration sets must be used they should be primed with uproleselan solution 
no more than 2 hours before dosing.  It is highly recommended that uproleselan 
prepared prior to administration be refrigerated until 1 hour prior to dosing.  
 
The investigational product is to be in a locked and secured storage facility, 
accessible only to those individuals authorized by the PI. 
 
8.1.7 Administration 
 
Uproleselan injection is a sterile solution for IV administration, supplied in single-
dose vials at a concentration of 50 mg/mL.  
 
Uproleselan injection should be administered IV into a peripheral line, a central 
catheter, or a peripherally inserted central line catheter (PICC). Infusion should take 
place at a steady rate over a period of 20 minutes using a syringe pump or IV pump. 
Microbore tubing is preferred. In-line filtration is highly recommended.  
 
Compatibility with other therapeutic agents has not been determined; therefore, 
uproleselan injection should be administered via a separate IV line, and should not 
be administered concurrently with anything other than saline. If a flush is used, 
saline flush is preferred. 
 
8.2 
Placebo 
 
As placebo, commercially available saline (0.9% Sodium Chloride Injection) will be 
prepared by the site’s pharmacist in IV administration components (syringe, bag, tubing, 
etc.) matching those used for active treatment to maintain the blind. The dosing schedule 


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and procedure for placebo will be identical to that for uproleselan. It is recommended that 
placebo prepared prior to administration be refrigerated until one hour prior to dosing, to 
match pharmacy procedures for uproleselan. Preparation of placebo in advance of 
administration should be in accordance with institutional pharmacy standards and 
commercial label for the placebo control. 
 
 
 
9.0 
CORRELATIVE STUDIES 
 
9.1 
Minimal Residual Disease (MRD) Status Following HCT 
 
Post-HCT MRD testing will be performed on the D+100 bone marrow biopsy sample for 
all patients, with pre-HCT MRD testing during screening as baseline. The MRD testing 
will be performed per SOC and institutional practice as a send-out test via ImmunoSeq B-
cell receptor sequencing (Adaptive Biotechnologies). Standard handling, processing, 
preserving, and shipping will proceed as per the current institutional practices. 
 
9.1.1 Collection of Specimen(s) 
 
Collect 2 mL of bone marrow aspirate (BMA) in an EDTA tube. 
 
9.1.2 Handling of Specimen(s) 
 
• No onsite processing of the specimen is required. 
• The fresh BMA specimen collection and submission kits will include the 
following: 
o One (1) 3 mL EDTA tube for BMA collection 
o One (1) ambient pack 
o One (1) FedEx clinical pack pre-labeled with a FedEx shipping label   
• Store specimen in ambient pack for same day shipment for next day 10 AM 
PT delivery 
• If same day shipment is not an option, store specimen refrigerated until 
shipment for next day 10 AM PT delivery. Fresh specimens should be 
received at Adaptive within 5 days of collection. 
 
9.1.3 Shipping of Specimen(s)  
 
Specimens must be packaged and shipped according to the instructions provided 
with the specimen kit.  
 
Batch shipping is not allowed.  
 
Specimens must be transported on the same day as collected via express courier 
(FedEx is recommended) using standard next day delivery service to arrive on 
Monday through Saturday  


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For Saturday delivery, be sure to check the Saturday delivery box on the express 
courier form. If not checked, the courier will deliver on Monday, and the sample 
will be too old to process. 
 
The specimen will be shipped to Adaptive Biotechnologies: 
Phone: 888-552-8988 
E-mail: clinicalservices@adaptivebiotech.com 
 
9.2 
E-selectin Levels 
 
Soluble E-selectin levels will be assessed on Day -3 prior to administration of uproleselan 
and on D0 following completion of the conditioning regimen and uproleselan dosing, but 
prior to HSC infusion via ELISA assay. 
 
9.2.1 Collection of Specimen(s) 
 
Collect 3 mL of peripheral blood in a Na Citrate (light blue top) tube. 
 
9.2.2 Handling of Specimen(s) 
 
Samples will be taken to the Washington University Tissue Procurement Core and 
processed per standard operating procedure. Blood will be drawn into sodium 
citrate tubes, inverted 3-4 times and stored in an ice bath until centrifugation. 
Samples will be centrifuged at 1,300 g at room temperature for 5 minutes. Ideally, 
samples should be immediately centrifuged following collection. If institutional 
staffing and/or logistics do not allow for this, samples may be stored (via an ice 
bath or at approximately 4°C) for 48-72 hours before centrifugation.   
 
After centrifugation, pipette half of plasma into an appropriately labeled cryovial 
(primary aliquot).  Pipette the remaining plasma into an additional appropriately 
labeled cryovials (back-up aliquot).  Labels should include date and time of 
collection and subject ID/UPN. 
 
The aliquots will be placed into a freezer at -80°C for temporary storage and then 
transferred to storage in liquid nitrogen vapor until shipped for analysis. 
 
9.2.3 Shipping of Specimen(s) 
 
Samples will be batch-shipped at the completion of the study.  The primary and 
back-up aliquots will be shipped on separate days to mitigate loss (Monday - 
Wednesday only), via overnight carrier with the appropriate amount of dry ice. 
QPS, LLC 
ATTN Sample Coordinator 
1 Innovation Way, Suite 200 
Newark, Delaware 19711 


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Contact: Susan ZONDLO 
E-mail: susan.zondlo@qps.com and tlmsmt@qps.com 
Tel.: + 1 302 453 5911 
 
Upon shipment of the samples, an e-mail will be sent containing a sample 
manifest, the name of the courier, the airway bill number, and a confirmation of 
the number of samples in the shipment. 
 
 
 
9.3 
GI Epithelial Inflammation and Permeability Biomarkers 
 
Based on the mechanism of action of uproleselan, we are also interested in an 
interdisciplinary collaboration assessing biomarkers of GI epithelial injury and GI 
permeability, including fecal calprotectin and fecal lipocalin-2, as well as other potential 
exploratory biomarkers such as neopterin. Fecal samples for banking will be collected on 
Day -3 (or first available stool), Day 0 (or Day 1 if not available Day 0), Day +8 (or Day 9 
if not available Day 0), and Day +14 or date of discharge (+/-1 day, whichever is sooner). 
 
9.3.1 Fecal calprotectin, lipocalin-2 & Stool Biomarker Banking 
 
Collect 15 mL (minimum 5 mL) of feces/stool in a stool container to be banked as 
a fecal specimen for later assessment of calprotectin, lipocalin-2 and other stool 
biomarkers of inflammation via ELISA assay (or other assay as indicated). 
 
Collect a fresh random fecal specimen, no preservative. 
 
Banked fecal specimens will be sent to the Tissue Procurement Core for frozen 
banking. The total specimen will be divided into 5 aliquots of equal volume. The 5 
aliquots will be placed into a freezer at -80°C for temporary storage and then 
transferred to storage in liquid nitrogen vapor until shipped for analysis. 
 
At the time of specimen analysis, the fecal specimens will be sent out (frozen) to 
Mayo Lab, per standard processing. 
 
 
10.0 
DATA SUBMISSION SCHEDULE 
 
Case report forms with appropriate source documentation will be completed according to the 
schedule listed in this section. 
 
Case Report Form 
Submission Schedule 
Original Consent Form 
Prior to registration 
On-Study Form 
Medical History Form 
Prior to starting treatment 
Treatment Form 
Completion of treatment 


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Toxicity Form 
Continuous (start of treatment through Day +30) 
Follow Up Form 
Day 30, Day 60, Day 100, Month 6, Month 12, Month 
15, Month 18, Month 21, Month 24 
MRD Form 
Day 100 
E-selectin Form 
Day -3 
GI Biomarkers Form 
QOL Form 
Day -3, Day 0 (GI Biomarkers Form only), Day 8, Day 
14/DOD 
Progression Form 
Time of disease progression 
Death Form 
Time of death 
MedWatch Form 
See Section 7.0 for reporting requirements 
 
 
 
10.1 
Adverse Event Collection in the Case Report Forms 
 
All adverse events that occur beginning with start of treatment (minus exceptions defined 
in Section 7.0) must be captured in the Toxicity Form.  Baseline AEs should be captured 
on the Medical History Form. 
 
Participant death due to disease progression should be reported on the Toxicity Form as 
grade 5 disease progression.  If death is due to an AE (e.g. cardiac disorders: cardiac arrest), 
report as a grade 5 event under that AE.  Participant death must also be recorded on the 
Death Form. 
 
 
11.0 
MEASUREMENT OF EFFECT 
 
11.1 
GI Toxicity Adverse Events 
 
Primary and Secondary Endpoints related to GI toxicity Adverse Events, as they pertain 
to the Primary and Secondary Endpoints of the study will be measured via the NIH 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE) v5.0, as detailed below. 
 
11.1.1 Diarrhea Severity (Primary Endpoint) 
 
 
 
 


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11.1.2 Oral Mucositis (Secondary Endpoint) 
 
 
 
 
 
11.1.3 Esophagitis (Secondary Endpoint) 
 
 
 
 
11.1.4 Esophageal Pain (Secondary Endpoint) 
 
 
 
 
11.1.5 Gastritis (Secondary Endpoint) 
 
 
 
 
11.1.6 Abdominal Pain (Secondary Endpoint) 
 
 
 
 
11.1.7 Nausea (Secondary Endpoint) 
 
 
 
 


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11.1.8 Vomiting (Secondary Endpoint) 
 
 
 
 
 
11.1.9 Enterocolitis (Secondary Endpoint) 
 
 
 
 
11.1.10  Proctitis (Secondary Endpoint) 
 
 
 
 
11.1.11  Hemorrhoids (Secondary Endpoint) 
 
 
 
 
11.2 
Response Criteria 
 
Response assessment based on IMWG Response Criteria39 to be determined relative to the 
labs at time of diagnosis prior to induction chemotherapy, as enumerated below.  
 
11.2.1 MRD negative Complete Response 
 
MRD negative complete response requires all of the following: 
 
• CR as defined below 
• Normal free light chain ratio 
• Absence of clonal cells in the bone marrow by immunohistochemistry or 
immunofluorescence 


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• Absence of clonal plasma cells by NGS on bone marrow aspirate using 
ImmunoSeq B-cell receptor sequencing (Adaptive Biotechnologies) 
 
11.2.2 Stringent Complete Response  
 
Stringent complete response (sCR) requires all of the following: 
 
• CR as defined below 
• Normal free light chain ratio 
• Absence of clonal cells in the bone marrow by immunohistochemistry or 
immunofluorescence 
 
11.2.3 Complete Response  
 
Complete response (CR) requires all of the following: 
  
• Disappearance monoclonal protein by both protein electrophoresis and 
immunofixation studies* from the blood and urine 
• <5% plasma cells in the bone marrow 
• Disappearance of soft tissue plasmacytomas 
 
* The monoclonal protein at time of diagnosis, prior to induction 
chemotherapy, will be used for determination  
  
11.2.4 Very Good Partial Response 
 
Very good partial response (VGPR) requires all of the following: 
 
• Serum and urine monoclonal protein detectable by immunofixation* but not 
on electrophoresis 
 
 
 
 
 
OR   
> 90% reduction in serum monoclonal protein with urine monoclonal 
protein < 100 mg per 24 hours 
 
* The monoclonal protein at time of diagnosis, prior to induction 
chemotherapy, will be used for determination 
 
• If present, > 50% reduction in the size of soft tissue plasmacytomas (by 
clinical or radiographic examinations) 
 
11.2.5 Partial Response 
 
Partial response (PR) requires all of the following: 
 
• > 50% reduction in the level of the serum monoclonal protein  
• Reduction in urine monoclonal protein by either > 90% or to < 200 mg 


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• If present, > 50% reduction in the size of soft tissue plasmacytomas (by 
clinical or radiographic examinations) 
• If serum and urine monoclonal protein are unmeasurable, a >50% decrease 
in difference between the involved and uninvolved free light chain levels is 
required in place of monoclonal protein criteria (The absolute decrease must 
be > 10 mg/dl) 
• If serum and urine monoclonal protein are unmeasurable and serum free 
light chain is unmeasurable, a > 50% reduction in plasma cells is required 
in place of monoclonal protein provided that baseline bone marrow plasma 
cell percentage was > 30%  
 
11.2.6 Minimal Response  
 
Minimal response (MR) requires all of the following: 
 
• > 25% to < 49% reduction in the level of serum monoclonal protein  
• If present, a 50 to 89% reduction in 24-hour urine monoclonal protein which 
still exceeds 200 mg/24hr  
• 25-49% reduction in the size of plasmacytomas (by clinical or radiographic 
examinations) 
• No increase in size or number of lytic bone lesions (development of 
compression fracture dose not exclude response) 
 
Note: MR includes participants in whom some but not all criteria for PR are 
fulfilled providing the remaining criteria satisfy the requirements for MR. 
 
 
11.2.7 Stable Disease  
 
Stable disease (SD) is defined as not meeting criteria for any other response as 
defined in this section. 
 
11.2.8 Progressive Disease  
 
Progressive disease (PD) with be defined from T0 and requires one or more of the 
following: 
  
• > 25% increase in the level of serum monoclonal protein, which must also 
be an absolute increase of at least 0.5 g/dL  
• > 25% increase in 24-hour urine monoclonal protein, which must also be an 
absolute increase of at least 200 mg/24hr  
• > 25% increase in plasma cells in a bone marrow aspirate or on trephine 
biopsy, which must also be an absolute increase of at least 10% 
• > 25% increase in the difference between involved and uninvolved free light 
chain levels (The absolute increase must be >10 mg/dl)  
• Definite increase in the size of existing lytic bone lesions or soft tissue 


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plasmacytomas. A definite increase is defined as at least 50% (and at least 
1 cm) increase as measured serially as the sum of the products of the cross-
diameters of the lesions. 
• Development of new bone lesions or soft tissue plasmacytomas (not 
including compression fracture) 
• Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 
2.8 mmol/L not attributable to any cause other than progressive multiple 
myeloma) 
 
Note: A response of progressive disease nullifies any other concurrent response. 
For example, at a given time point a participant meets criteria for VGPR but has 
development of new bone lesions the response is PD not VGPR. 
 
 
11.2.9 Clinical Relapse 
 
Clinical relapse (i.e. progressive disease requiring alternate myeloma treatment) 
requires one or more of the following: 
 
• Decrease in hemoglobin > 2 g/dl not attributable to any cause other than 
progressive multiple myeloma 
• Increase in creatinine by > 2 mg/dl not attributable to any cause other than 
progressive multiple myeloma 
• Other worsening laboratory result, or clinical condition that the treating 
physician determines is not attributable to any cause other than progressive 
multiple myeloma 
 
11.2.10  Relapse from Complete Response 
 
Relapse from a complete response requires a prior CR or sCR as described above 
and subsequently developing one or more of the following: 
 
• Reappearance of serum or urinary paraprotein on immunofixation* or 
routine electrophoresis excluding oligoclonal immune reconstitution for at 
least two determinations.  
• > 5% plasma cells in the bone marrow aspirate or biopsy. 
 
* The monoclonal protein at time of CR or better will be used for 
determination.  
 
11.3 
Progression-Free Survival 
 
Progression-free survival (PFS) will be defined as time from D0 of auto-HCT to 
progressive disease (biochemical and/or clinical) or death. Patients who are alive and 
progression-free or were lost to follow-up at the time of data analyses will be censored on 
the last known alive date. 
 


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11.4 
Overall Survival 
  
Overall survival (OS) will be defined as time from D0 of auto-HCT to death due to any 
causes. Patients who are alive or were lost to follow-up at the time of data analyses will be 
censored on the last known alive date.  
 
 
11.5 
Overall Response Rate 
 
Overall response rate (ORR) will be defined as the proportion of patients meeting the 
criteria for PR, VGPR, CR, sCR or MRD-negative CR.   
 
11.6 
Complete Response Rate 
 
Complete response rate (CRR) will be defined as the proportion of patients meeting the 
criteria CR, sCR or MRD-negative CR. 
 
 
12.0 
DATA AND SAFETY MONITORING 
 
In compliance with the Washington University Institutional Data and Safety Monitoring Plan, an 
independent Data and Safety Monitoring Board (DSMB) will be specifically convened for this 
trial to review toxicity data.  A DSMB will consist of no fewer than 3 members, including 2 clinical 
investigators and a biostatistician.  DSMB members must be employed by Washington University, 
Barnes-Jewish Hospital, or St. Louis Children’s Hospital.  Like investigators, DSMB members are 
subject to the Washington University School of Medicine policies regarding standards of conduct. 
Individuals invited to serve on the DSMB will disclose any potential conflicts of interest to the 
trial principal investigator and/or appropriate university officials, in accordance with institution 
policies. Potential conflicts that develop during a trial or a member’s tenure on a DSMB must also 
be disclosed.  
 
The DSM report for the DSMB will be prepared by the study team with assistance from the study 
statistician, will be reviewed by the DSMB, and will be submitted to the QASM Committee.  The 
DSMB must meet at least every six months beginning six months after study activation at 
Washington University, no more than one month prior to the due date of the DSM report to 
QASMC.  This report will include: 
 
• HRPO protocol number, protocol title, Principal Investigator name, data coordinator 
name, regulatory coordinator name, and statistician. 
• Date of initial HRPO approval, date of most recent consent HRPO approval/revision, 
date of HRPO expiration, date of most recent QA audit, study status, and phase of 
study. 
• History of study including summary of substantive amendments; summary of accrual 
suspensions including start/stop dates and reason; and summary of protocol exceptions, 
error, or breach of confidentiality including start/stop dates and reason. 
• Study-wide target accrual and study-wide actual accrual. 


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• Protocol activation date. 
• Average rate of accrual observed in year 1, year 2, and subsequent years. 
• Expected accrual end date, and accrual by group. 
• Objectives of protocol with supporting data and list the number of participants who 
have met each objective. 
• Measures of efficacy. 
• Early stopping rules with supporting data and list the number of participants who have 
met the early stopping rules. 
• Summary of toxicities. 
• Abstract submissions/publications. 
• Summary of any recent literature that may affect the safety or ethics of the study. 
 
Further DSMB responsibilities are described in the DSMB charter. 
 
The study principal investigator and coordinator will monitor for serious toxicities on an ongoing 
basis. Once the principal investigator or coordinator becomes aware of an adverse event, the AE 
will be reported to the HRPO and QASMC according to institutional guidelines (please refer to 
Section 7.0). 
 
Refer to the Washington University Quality Assurance and Data Safety Monitoring Committee 
Policies and Procedures for full details on the responsibilities of the DSMB. This is located on the 
QASMC website at https://siteman.wustl.edu/research/clinical-research-resources/protocol-
office-prmcqasmc/.   
 
 
13.0 
STATISTICAL CONSIDERATIONS 
 
13.1 
Statistical Hypotheses 
 
Prophylactic administration of uproleselan (GMI-1271) throughout melphalan 
conditioning in preparation for auto-HCT will reduce the rate of diarrhea, as assessed by a 
validated chemotherapy-related diarrhea severity scoring system (CTCAE v5.0 Diarrhea). 
 
13.2 
Sample Size Determination 
 
We expect an event rate of diarrhea of any grade of 90% with a distribution of Grade 1: 
20%, Grade 2: 30%, Grade 3: 40%, Grade 4: 0% and Grade 5: 0%. We estimate a sample 
size of 50 patients (25 per arm) evaluable for the primary endpoint would provide 80% 
power (alpha 0.20) to detect an odds ratio (OR) of 0.42 for reduction in the grade of 
diarrhea severity, using a one-sided proportional odds model for ordinal categorical data.  
We anticipate that more power could be achieved in the actual analysis because of richer 
information (daily during hospitalization) available for GI toxicity evaluation. Note that 
one purpose of a randomized phase II trial design is to detect signals of efficacy in an 
experimental regimen for further evaluation rather than to have a definitive conclusion 
regarding the efficacy of an experimental regimen. Therefore, a relatively larger type I 
error (alpha or false positive error) is acceptable in a randomized phase II setting and the 


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level of type I error can be relaxed to alpha=0.2, according to Korn et al40 and Rubinstein 
et al41.   
 
13.3 
Population for Analyses 
 
All randomized patients evaluable for the primary and secondary endpoints will be 
analyzed on an intention-to-treat basis. Additionally, the same patient population will also 
be analyzed on a per-protocol basis for the same endpoints.  
 
13.4 
Statistical Analyses 
 
13.4.1 General Approach 
 
In general, categorical variables will be expressed as percentages of the total 
number of patients meeting that endpoint. Continuous data will typically be 
expressed as a median value.  
 
13.4.2 Analysis of the Primary Endpoint 
 
The primary endpoint will be the change in diarrhea severity (CTCAE v5.0, Figure 
2) in patients receiving high-dose melphalan conditioning in preparation for auto-
HCT for MM who receive prophylactic uproleselan (GMI-1271) plus standard of 
care (SOC) compared to placebo plus SOC. All randomized patients meeting 
eligibility criteria who receive at least one dose of uproleselan or placebo and who 
undergo a melphalan-conditioned auto-HCT will be evaluable for the primary 
endpoint analysis based on an intent-to-treat principle. Patients will also be 
evaluated for the primary endpoint based on a per-protocol analysis. The outcome 
will be reported as a median score with high/low ranges for the duration of the 
hospitalization, comparing the treatment and placebo cohorts.  The primary 
endpoint is anticipated to follow a non-normal distribution and the overall 
difference between arms will be compared using generalized estimation equation 
(GEE) which is less sensitive to parametric distributions. 
 
Figure 2: CTCAE v5.0 Diarrhea Score: 
 
 
 
13.4.3 Analysis of the Secondary Endpoints 
 
All secondary endpoints will be analyzed using the appropriate, descriptive 
statistics on an intent-to-treat and per-protocol basis, comparing the treatment and 


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placebo cohorts. However, the study will not be powered to detect significant 
differences in these outcomes.  
 
• Change in mucositis severity (per CTCAE v5.0 Oral Mucositis criteria) and 
change in alternative GI toxicities (e.g. esophagitis, enterocolitis, etc.; per 
CTCAE v5.0) will be reported as median scores with high/low ranges for 
the duration of the hospitalization. 
 
• Time to neutrophil engraftment defined as ANC ≥0.5 x 109/L for 3 
consecutive days or ≥1.0 x 109/L for 1 day will be reported as a median time 
engraftment. 
 
• Duration of hospital LOS will be reported in median number of days, from 
date of admission for auto-HCT to date of discharge. 
 
• Quantitative use of anti-diarrheal medications will be reported as the 
median number of daily doses administered (loperamide, diphenoxylate, 
etc.) and pain medications will be reported as the median number of daily 
morphine equivalents, minus the baseline level of morphine equivalents the 
patient may have been taking prior to admission as an outpatient 
medication. 
 
• Nutritional status before conditioning and at D+14 or date of discharge 
(whichever is sooner), will be reported as the median number of TPN days 
and in change in standing weight comparing D-3, D+8 and date of discharge 
or D+14 (whichever is sooner). 
• Change in Bristol Stool Scale, assessed daily (see Appendix D), will be 
reported as the median stool type with high/low ranges. 
 
• Incidence of infection will be reported as a percentage of patients who 
develop of bacteremia during the hospitalization for HCT (with organism 
reported when available), median time to first antibiotics and percentage of 
patients who develop a c. diff infection. 
 
• The differences between treatment arms will be described using GEE (for 
longitudinal endpoints such as mucositis severity, Bristol Stool Scale, 
nutritional status, etc.), Kaplan-Meier product limit methods and log-rank 
test (for time-to-event endpoints such as time to neutrophil engraftment, 
length of hospital stay, etc.), and Fisher’s exact test (for incidence of 
infection) as appropriate. 
 
13.4.4 Analysis of the Exploratory Endpoints 
 
Correlative Endpoints: 
• Minimal Residual Disease (MRD) testing via ImmunoSeq B-cell receptor 
sequencing (Adaptive Biotechnologies) at D+100, expressed as percentage 


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of patients being MRD negative, comparing the treatment and placebo 
cohorts. 
 
• Soluble E-selectin levels by ELISA assay at pre-dose (D-3) and post-
conditioning (D-0) time points, comparing the treatment and placebo 
cohorts. 
 
• Fecal calprotectin, lipocalin-2 and any additional fecal biomarkers on D-3, 
D0, D+8 and date of discharge or D+14 (whichever is sooner), comparing 
the treatment and placebo cohorts 
 
• Progression Free Survival (PFS) with up to 2-year follow up assessed by 
time-to event (Kaplan-Meier analysis), comparing the treatment and 
placebo cohorts 
 
• Overall Survival (OS) with up to 2-year follow up assessed by time-to event 
(Kaplan-Meier analysis), comparing the treatment and placebo cohorts 
 
• The differences between treatment arms will be described using Wilcoxon-
Mann-Whitney or GEE (soluble E-selectin levels, fecal biomarkers, etc.), 
Kaplan-Meier product limit methods and log-rank test (PFS, OS), and 
Fisher’s exact test (minimal residual disease at Day 100), as appropriate. 
 
13.4.5 Analysis of the PRO/QoL Endpoint 
 
PRO and QoL scores assessed via the CTCAE PRO Form v1.0 with items selected 
for relevance to GI toxicity and patient quality of life (see Supplement 1) will be 
reported as median scores on D-3, D+8 and date of discharge or D+14 (whichever 
is sooner), comparing the treatment and placebo cohorts. 
 
13.4.6 Baseline Descriptive Statistics 
 
Baseline characteristics, including demographics, laboratory measurements, 
induction treatment regimens and disease response status at the time of HCT will 
be reported, using descriptive statistics.  
 
13.4.7 Safety Analyses 
 
An independent data monitor will assess for treatment-related death and/or non-
engraftment, with enrollment suspended for review whenever there is any case of 
treatment-related death or non-engraftment.  
 
Non-engraftment will be defined as failure to achieve neutrophil engraftment (ANC 
≥0.5 x 109/L for 3 consecutive days or ≥1.0 x 109/L for 1 day) by post-HCT D+21. 
Additionally, all patients participating in the study must have mobilized sufficient 
CD34+ HSCs for initial auto-HCT and a mandatory back-up graft (total cells 


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collected: ≥5.0 x 106 CD34+ cells/kg; and cells per HCT: ≥2.5 x 106 CD34+ 
cells/kg). 
 
A Bayesian safety monitoring rule will also be implemented for each arm separately 
once the first 5 evaluable subjects are available in the given arm. The stopping rule 
is defined as Pr(θT > 0.2 |data)>0.7, where θT denotes the incidence of Grade 3 or 
higher non-hematologic, uproleselan-related toxicities, with the exception of 
toxicities reported in >25% of patients receiving high-dose melphalan conditioning, 
as detailed in Section 1.3.2. That is, enrollment will be stopped early whenever, 
given the accumulated observed data, there is a high probability (>70%) that the 
incidence of targeted toxicities is above 20%. The stopping boundaries are obtained 
using the online study design tools from M.D. Anderson Cancer Center 
(https://www.trialdesign.org/one-page-shell.html#BTOX). 
Specifically, 
we 
assume that θT follows a beta distribution, beta (α + x, β + n – x), where x and n-x 
represent the observed numbers of toxicity and non-toxicity cases, while α and β 
are parameters for prior distribution. We set the prior as beta (0.5, 0.5), i.e., with a 
non-informative prior. A treatment arm will be recommended to stop for excessive 
toxicities if we observe 2 events out of the first 5 subjects, 3 events out of 10 
subjects, 4 events out of 15 subjects, 5 events out of 20 subjects, or 6th event 
observed before the last subject enrolled.  A simulation study (with 1000 simulated 
trials) is also performed to assess the operating characteristics of the above 
monitoring rule. With a true toxicity rate of 10%, there will be only 14% chance of 
early termination. Conversely, there will be 88% chance of claiming excessive 
toxicity when the true toxicity rate is 30%. 
 
13.4.8 Interim Analyses for Futility 
 
An interim analysis will be scheduled to protect patients from receiving inferior 
treatment. An interim analysis will be performed after the first 50% patients are 
randomized. The summary statistics for primary endpoint (diarrhea severity during 
hospital stay) will be calculated. An early termination due to futility will be 
recommended if the statistics of the primary endpoint are in favor of the control 
arm42. 
 
 
 
 


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14.0 
REFERENCES 
 
1. Rajkumar SV. Multiple myeloma. Curr Probl Cancer. 2009;33(1):7-64. 
2. Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet 
Lond Engl. 2009;374(9686):324-339. 
3. Ludwig H, Beksac M, Bladé J, et al. Current multiple myeloma treatment strategies with novel 
agents: a European perspective. The Oncologist. 2010;15(1):6-25. 
4. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple 
myeloma. Mayo Clin Proc. 2003;78(1):21-33. 
5. Lin P. Plasma cell myeloma. Hematol Oncol Clin North Am. 2009;23(4):709-727. 
6. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone 
marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 
1996;335(2):91–97. 
7. Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem- 
cell rescue for multiple myeloma. N Engl J Med. 2003;348(19):1875–1883. 
8. Fermand J-P, Katsahian S, Divine M, et al. High-dose therapy and autologous blood stem- cell 
transplantation compared with conventional treatment in myeloma patients aged 55 to 65 
years: long-term results of a randomized control trial from the Group Myelome- Autogreffe. J 
Clin Oncol Off J Am Soc Clin Oncol. 2005;23(36):9227-9233. 
9. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger 
patients with multiple myeloma. Blood. 2008;111(5):2521-2526. 
10. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and 
the impact of novel therapies. Blood. 2008;111(5):2516-2520. 
11. Ludwig H, Durie BGM, Bolejack V, et al. Myeloma in patients younger than age 50 years 
presents with more favorable features and shows better survival: an analysis of 10 549 patients 
from the International Myeloma Working Group. Blood. 2008;111(8):4039-4047. 
12. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046-1060. 
13. Mccarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide Maintenance After Autologous 
Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis. J Clin 
Oncol. 2017;35(29):3279-3289. 
14. Moreau P, Facon T, Attal M, et al. Comparison of 200 mg/m2 melphalan and 8 Gy total body 
irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell 
transplantation in patients with newly diagnosed multiple myeloma: final analysis of the 
Intergroupe Francophone du Mye ́lome 9502 randomized trial. Blood. 2002;99(3):731-735. 
15. Hari P, Aljitawi OS, Arce-Lara C, et al. A Phase IIb, Multicenter, Open-Label, Safety, and 
Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection 
(EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing 
Autologous Transplantation. Biol Blood Marrow Transplant. 2015;21:2100-2105. 
16. Gyurkocza B and Sandmaier BM. Conditioning regimens for hematopoietic cell 
transplantation: one size does not fit all. Blood. 2014;124(3):344-353. 
17. Malek E, Creger R, Kolk M, et al. Reducing Gastrointestinal Toxicity Associated with 
Autologous Transplantation for Multiple Myeloma without Compromising Its Anti-Myeloma 
Effect. Blood. 2017;130(1):680. 
18. Toro JJ, Arango JI, Westbrook SD, et al. Oral Mucositis Measured by the Oral Mucositis 
Assessment Scale (OMAS), but Not by the World Health Organization (WHO) Scoring 


Version 03/22/2022 
 
page 53 of 63 
System, Correlates with Nutritional Changes after Autologous Peripheral Blood Stem Cell 
Transplantation. Blood. 2007;110(11):4944. 
19. Schuster MW, Shore TB, Greenburg J, et al. Phase I Trial of CG53135-05 to Prevent Mucositis 
in Patients Undergoing High-Dose Chemotherapy (HDCT) and Autologous Peripheral Blood 
Stem Cell Transplantation (PBSCT). Blood. 2004;104(11):1161. 
20. Malek E, Gupta V, Creger R, et al. Amifostine reduces gastro-intestinal toxicity after 
autologous transplantation for multiple myeloma. Leukemia & Lymphoma. 2018;59(8):1905-
1912. 
21. Dans M, Kutner JS, Baker JN, et al. NCCN Clinical Practice Guidelines in Oncology: 
Palliative 
Care. 
Version 
2.2019. 
https://www.nccn.org/professionals/physician_gls/pdf/palliative.pdf. 
22. Ley K, Tedder TF. Leukocyte interactions with vascular endothelium. New insights into 
selectin-mediated attachment and rolling. J Immunol. 1995;155(2):525-528. 
23. Winkler IG, Barbier V, Nutt HL, et al. Administration Of E-Selectin Antagonist GMI- 1271 
Improves Survival After High-Dose Chemotherapy By Alleviating Mucositis and Accelerating 
Neutrophil Recovery. Blood. 2013;122(21):2266-2266.  
24. Bertani L, Mumolo MG, Tapete G, et al. Fecal calprotectin: current and future perspectives for 
inflammatory bowel disease treatment. Eur J Gastroenterol Hepatol. 2020;32(9):1091-1098. 
25. Malik MN, Rafae A, Durer C, Durer S, Anwer F. Fecal Calprotectin as a Diagnostic and 
Prognostic Biomarker for Gastrointestinal Graft Versus Host Disease: A Systematic Review 
of Literature. Cureus. 2019;11(2):e4143. 
26. Weber D, Weber M, Hippe K, et al. Non-invasive diagnosis of acute intestinal graft-versus-
host disease by a new scoring system using ultrasound morphology, compound elastography, 
and contrast-enhanced ultrasound. Bone Marrow Transplant. 2019;54(7):1038-1048. 
27. Moschen AR, Adolph TE, Gerner RR, Wieser V, Tilg H. Lipocalin-2: A Master Mediator of 
Intestinal and Metabolic Inflammation. Trends Endocrinol Metab. 2017;28(5):388-397. 
28. Hermann A, Winkler A, Paschen C, et al. Lipocalin-2 levels in acute and chronic graft-versus-
host disease following allogeneic hematopoietic stem cell transplantation. Exp Hematol. 
2019;74:25-32.e1. 
29. Husain N, Tokoro K, Popov JM, Naides SJ, Kwasny MJ, Buchman AL. Neopterin 
concentration as an index of disease activity in Crohn's disease and ulcerative colitis. J Clin 
Gastroenterol. 2013;47(3):246-51. 
30. Nancey S, Boschetti G, Moussata D, et al. Neopterin is a novel reliable fecal marker as accurate 
as calprotectin for predicting endoscopic disease activity in patients with inflammatory bowel 
diseases. Inflamm Bowel Dis. 2013;19(5):1043-52. 
31. Winkler IG, Barbier V, Ward M, et al. Vascular E-Selectin Protects Leukemia Cells from 
Chemotherapy by Directly Activating Pro-Survival NF-Kb Signalling - Therapeutic Blockade 
of E-Selectin Dampens NF-Kb Activation. Blood. 2016;128(22):2823-2823. 
32. Winkler IG, Erbani JM, Barbier V, et al. Vascular E-Selectin Mediates Chemo- Resistance in 
Acute Myeloid Leukemia Initiating Cells Via Canonical Receptors PSGL-1 (CD162) and Hcell 
(CD44) and AKT Signaling. Blood. 2017;130(Suppl 1):793-793.  
33. Winkler IG, Barbier V, Nowlan B, et al. Vascular niche E-selectin regulates hematopoietic 
stem cell dormancy, self- renewal and chemoresistance. Nat Med. 2012;18(11):1651-1657. 
34. GlycoMimetics, Inc. Uproleselan (GMI-1271) Investigator’s Brochure. Edition No. 6, 4/2018. 
35. Muz B, Azab F, Fiala M, et al. Inhibition of E-Selectin (GMI-1271) or E-selectin together with 
CXCR4 (GMI-1359) re-sensitizes multiple myeloma to therapy. Blood Cancer J. 2019;9(9):68. 


Version 03/22/2022 
 
page 54 of 63 
36. Hahn TE, Wallace PK, Fraser R, et al. Minimal residual disease (MRD) assessment before and 
after autologous hematopoietic cell transplantation (AutoHCT) and maintenance for multiple 
myeloma: Results of the Prognostic Immunophenotyping for Myeloma Response (PRIMeR) 
study. 2019 TCT Meetings. Abstract 6. Presented February 22, 2019. 
37. Stadtmauer EA, Pasquini MC, Blackwell B, et al. Autologous transplantation, consolidation, 
and maintenance therapy in multiple myeloma: Results of the BMT CTN 0702 trial. J Clin 
Oncol. 2019;37:589-597. 
38. Natoni A, Smith TAG, Keane N, et al. E-selectin ligands recognized by HECA452 induce drug 
resistance in myeloma, which is overcome by the E-selectin antagonist, GMI-1271. Leukemia. 
2017;31(12):2642-2651. 
39. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus 
criteria for response and minimal residual disease assessment in multiple myeloma. Lancet 
Oncol. 2016;17(8):e328-e346. 
40. Korn EL, Freidlin B. Interim monitoring for non-inferiority trials: minimizing patient exposure 
to inferior therapies. Ann Oncol. 2018;29(3):573-577. 
41. Rubinstein LV, Korn EL, Freidlin B, Hunsberger S, Ivy SP. Design issues of randomized phase 
II trials and a proposal for phase II screening trials. J Clin Oncol 2005;23:7199–7206. 
42. Wieand S, Schroeder G, O'Fallon JR. Stopping when the experimental regimen does not appear 
to help. Stat Med 1994;13:1453-1458. 
 
 
 


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APPENDIX A: ECOG Performance Status Scale 
 
 
Grade 
 
 
Description 
0 
Normal activity.  Fully active, able to carry on all pre-disease 
performance without restriction. 
1 
Symptoms, but ambulatory.  Restricted in physically strenuous 
activity, but ambulatory and able to carry out work of a light or 
sedentary nature (e.g., light housework, office work). 
2 
In bed <50% of the time.  Ambulatory and capable of all self-care, but 
unable to carry out any work activities.  Up and about more than 50% 
of waking hours. 
3 
 
In bed >50% of the time.  Capable of only limited self-care, confined 
to bed or chair more than 50% of waking hours. 
 
4 
100% bedridden.  Completely disabled.  Cannot carry on any self-care.  
Totally confined to bed or chair. 
5 
 
Dead. 
 
 
 
 


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APPENDIX B: Definitions for Adverse Event Reporting 
 
A. Adverse Events (AEs) 
 
As defined in 21 CFR 312.32: 
 
Definition: any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug-related. 
 
Grading: the descriptions and grading scales found in the revised NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.  A 
copy of the CTCAE version 5.0 can be downloaded from the CTEP website. 
 
Attribution (relatedness), Expectedness, and Seriousness: the definitions for the terms 
listed that should be used are those provided by the Department of Health and Human Services’ 
Office for Human Research Protections (OHRP).  A copy of this guidance can be found on 
OHRP’s website: 
http://www.hhs.gov/ohrp/policy/advevntguid.html 
 
B. Suspected Adverse Reaction (SAR) 
 
As defined in 21 CFR 312.32: 
 
Definition: any adverse event for which there is a reasonable possibility that the drug caused 
the adverse event.  “Reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the adverse event.  “Suspected adverse reaction” implies a 
lesser degree of certainty about causality than adverse reaction, which means any adverse event 
caused by a drug. 
 
C. Life-Threatening Adverse Event / Life Threatening Suspected Adverse Reaction  
 
As defined in 21 CFR 312.32: 
 
Definition: any adverse drug event or suspected adverse reaction is considered “life-
threatening” if, in the view of the investigator, its occurrence places the patient at immediate 
risk of death. It does not include an adverse event or suspected adverse reaction that, had it 
occurred in a more severe form, might have caused death. 
 
D.  Serious Adverse Event (SAE) or Serious Suspected Adverse Reaction 
 
As defined in 21 CFR 312.32: 
 
Definition:  an adverse event or suspected adverse reaction is considered “serious” if, in the 
view of the investigator, it results in any of the following outcomes: 
o Death 
o A life-threatening adverse event 


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o Inpatient hospitalization or prolongation of existing hospitalization 
o A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
o A congenital anomaly/birth defect 
o Any other important medical event that does not fit the criteria above but, based upon 
appropriate medical judgment, may jeopardize the subject and may require medical or 
surgical intervention to prevent one of the outcomes listed above 
 
E. Protocol Exceptions 
 
Definition: A planned change in the conduct of the research for one participant. 
 
F. Deviation 
 
Definition: Any alteration or modification to the IRB-approved research without prospective 
IRB approval.  The term “research” encompasses all IRB-approved materials and documents 
including the detailed protocol, IRB application, consent form, recruitment materials, 
questionnaires/data collection forms, and any other information relating to the research study. 
 
A minor or administrative deviation is one that does not have the potential to negatively impact 
the rights, safety, or welfare of participants or others or the scientific validity of the study. 
 
A major deviation is one that does have the potential to negatively impact the rights, safety, or 
welfare of participants or others or the scientific validity of the study. 


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APPENDIX C: Reporting Timelines 
 
Expedited Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Glycomimetics, Inc. 
Serious AND 
unexpected suspected 
adverse reaction 
 
 
Report no later than 15 calendar 
days after it is determined that 
the information qualifies for 
reporting 
Completed Regulatory Form 
(MedWatch / CIOMS I) for 
initial and follow-up in parallel 
with submission to the FDA for 
patients exposed to GMI 
product. 
Unexpected fatal or 
life-threatening 
suspected adverse 
reaction 
 
 
Report no later than 7 calendar 
days after initial receipt of the 
information 
Completed Regulatory Form 
(MedWatch / CIOMS I) for 
initial and follow-up in parallel 
with submission to the FDA for 
patients exposed to GMI 
product. 
Unanticipated 
problem involving risk 
to participants or 
others 
Report within 10 working days.  If the event 
results in the death of a participant enrolled at 
WU/BJH/SLCH, report within 1 working day. 
Report via email 
after IRB 
acknowledgment 
 
In parallel with the submission 
to the HRPO. 
Major deviation 
Report within 10 working days.  If the event 
results in the death of a participant enrolled at 
WU/BJH/SLCH, report within 1 working day. 
 
 
 
A series of minor 
deviations that are 
being reported as a 
continuing 
noncompliance 
Report within 10 working days.   
 
 
 
Protocol exception 
Approval must be obtained prior to 
implementing the change 
 
 
 
Clinically important 
increase in the rate of 
a serious suspected 
adverse reaction of 
that list in the protocol 
or IB 
 
 
Report no later than 15 calendar 
days after it is determined that 
the information qualifies for 
reporting 
In parallel with submission to 
the FDA. 


Version 03/22/2022 
 
page 59 of 63 
Expedited Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Glycomimetics, Inc. 
Complaints 
If the complaint reveals an unanticipated 
problem involving risks to participants or others 
OR noncompliance, report within 10 working 
days.  If the event results in the death of a 
participant enrolled at WU/BJH/SLCH, report 
within 1 working day.  Otherwise, report at the 
time of continuing review. 
 
 
 
Breach of 
confidentiality 
Within 10 working days. 
 
 
 
Incarceration 
If withdrawing the participant poses a safety 
issue, report within 10 working days.   
 
If withdrawing the participant does not 
represent a safety issue and the patient will be 
withdrawn, report at continuing review. 
 
 
 
 
Routine Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Glycomimetics, Inc. 
Adverse event or SAE 
that does not require 
expedited reporting 
If they do not meet the definition of an 
unanticipated problem involving risks to 
participants or others, report summary 
information at the time of continuing review 
Adverse events will be 
reported in the toxicity 
table in the DSM report 
which is typically due 
every 6 months. 
The most current 
toxicity table from the 
DSM report is provided 
to the FDA with the 
IND’s annual report. 
All SAEs and follow-up 15 
days post-Sponsor awareness 
date for patients exposed to 
GMI product. 
Overdose, pregnancy, 
and lactation cases not 
associated with an 
SAE where a subject 
was exposed to 
GlycoMimetics 
compound 
 
 
 
Completed Regulatory Form 
(MedWatch / CIOMS I) for 
initial and follow-up in parallel 
on a monthly cycle. 
Minor deviation 
Report summary information at the time of 
continuing review. 
 
 
 
Complaints 
If the complaint reveals an unanticipated problem 
involving risks to participants or others OR 
 
 
 


Version 03/22/2022 
 
page 60 of 63 
noncompliance, report within 10 working days.  If 
the event results in the death of a participant 
enrolled at WU/BJH/SLCH, report within 1 
working day.  Otherwise, report at the time of 
continuing review. 
Incarceration 
If withdrawing the participant poses a safety 
issue, report within 10 working days.   
 
If withdrawing the participant does not represent a 
safety issue and the patient will be withdrawn, 
report at continuing review. 
 
 
 


Version 03/22/2022 
 
page 61 of 63 
APPENDIX D: Bristol Stool Scale 
 
 
 
 
 


Version 03/22/2022 
 
page 62 of 63 
SUPPLEMENT 1: GI-Specific NCI CTCAE PRO v1.0 
As individuals go through treatment for their cancer they sometimes experience different 
symptoms and side effects. For each question, please check or mark an 
 in the one box that 
best describes your experiences over the past 7 days...  
 
1. In the last 7 days, what was the SEVERITY of your DIFFICULTY SWALLOWING at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
2. 
In the last 7 days, what was the SEVERITY of your MOUTH OR THROAT SORES at their WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
In the last 7 days, how much did MOUTH OR THROAT SORES INTERFERE with your usual or 
daily activities?  
○ Not at all  
○ A little bit  
○ Somewhat  
○ Quite a bit  
○ Very much  
3. 
In the last 7 days, what was the SEVERITY of your DECREASED APPETITE at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
In the last 7 days, how much did DECREASED APPETITE INTERFERE with your usual or daily 
activities?  
○ Not at all  
○ A little bit  
○ Somewhat  
○ Quite a bit  
○ Very much  
4. 
In the last 7 days, how OFTEN did you have NAUSEA?  
○ Never  
○ Rarely  
○ Occasionally  
○ Frequently  
○ Almost constantly  
In the last 7 days, what was the SEVERITY of your NAUSEA at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
5. 
In the last 7 days, how OFTEN did you have VOMITING?  
○ Never  
○ Rarely  
○ Occasionally  
○ Frequently  
○ Almost constantly  
In the last 7 days, what was the SEVERITY of your VOMITING at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
6. 
In the last 7 days, how OFTEN did you have HEARTBURN?  
○ Never  
○ Rarely  
○ Occasionally  
○ Frequently  
○ Almost constantly  
In the last 7 days, what was the SEVERITY of your HEARTBURN at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
7. In the last 7 days, did you have any INCREASED PASSING OF GAS (FLATULENCE)?  
○ Yes  
○ No  
8. 
In the last 7 days, how OFTEN did you have BLOATING OF THE ABDOMEN (BELLY)?  
○ Never  
○ Rarely  
○ Occasionally  
○ Frequently  
○ Almost constantly  
In the last 7 days, what was the SEVERITY of your BLOATING OF THE ABDOMEN (BELLY) at its 
WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
9. In the last 7 days, how OFTEN did you have LOOSE OR WATERY STOOLS (DIARRHEA)?  
○ Never  
○ Rarely  
○ Occasionally  
○ Frequently  
○ Almost constantly  
10. In the last 7 days, how OFTEN did you have PAIN IN THE ABDOMEN (BELLY AREA)?  
○ Never  
○ Rarely  
○ Occasionally  
○ Frequently  
○ Almost constantly  


Version 03/22/2022 
 
page 63 of 63 
In the last 7 days, what was the SEVERITY of your PAIN IN THE ABDOMEN (BELLY AREA) at its 
WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
In the last 7 days, how much did PAIN IN THE ABDOMEN (BELLY AREA) INTERFERE with your 
usual or daily activities?  
○ Not at all  
○ A little bit  
○ Somewhat  
○ Quite a bit  
○ Very much  
 
11. 
In the last 7 days, how OFTEN did you LOSE CONTROL OF BOWEL MOVEMENTS?  
○ Never  
○ Rarely  
○ Occasionally  
○ Frequently  
○ Almost constantly  
In the last 7 days, how much did LOSS OF CONTROL OF BOWEL MOVEMENTS INTERFERE with 
your usual or daily activities?  
○ Not at all  
○ A little bit  
○ Somewhat  
○ Quite a bit  
○ Very much  
Do you have any other symptoms that you wish to report?  
○ Yes  
○ No  
Please list any other symptoms:  
1.  
In the last 7 days, what was the SEVERITY of this symptom at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
2.  
In the last 7 days, what was the SEVERITY of this symptom at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
3.  
In the last 7 days, what was the SEVERITY of this symptom at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
4.  
In the last 7 days, what was the SEVERITY of this symptom at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
5.  
In the last 7 days, what was the SEVERITY of this symptom at its WORST?  
○ None  
○ Mild  
○ Moderate  
○ Severe  
○ Very severe  
 

ICF_001.pdf: 
 
FOR IRB USE ONLY 
IRB ID #: 202103086 
APPROVAL DATE: 03/02/22 
RELEASED DATE: 03/04/22 
EXPIRATION DATE: 03/01/23 
 
INFORMED CONSENT DOCUMENT 
 
Project Title: 
A Phase II Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate 
Uproleselan (GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous 
Hematopoietic Cell Transplantation (auto-HCT) for Multiple Myeloma (MM) 
 
Principal Investigator: 
Keith Stockerl-Goldstein, M.D. 
 
Research Team Contact: 
Keith Stockerl-Goldstein, M.D. – (314) 454-8304 
 
 
This consent form describes the research study and helps you decide if you want to participate.  It 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights and responsibilities as a research participant. By signing this 
form you are agreeing to participate in this study. 
• You should read and understand the information in this document including the procedures, 
risks and potential benefits.  
• If you have questions about anything in this form, you should ask the research team for more 
information before you agree to participate.   
• You may also wish to talk to your family or friends about your participation in this study. 
• Do not agree to participate in this study unless the research team has answered your 
questions and you decide that you want to be part of this study.  
 
 
WHAT IS THE PURPOSE OF THIS STUDY? 
This is a research study.  We invite you to participate in this research study because you have been 
diagnosed with multiple myeloma and will be receiving a drug called melphalan as part of the 
autologous hematopoietic cell transplant you will be having.  The melphalan and the transplant are part 
of your standard care. 
 
Some of the most common side effects of melphalan include diarrhea, sores in the mouth and digestive 
tract and inflammation of the digestive tract.  There are a number of treatments that are routinely given 
to help people who experience these side effects.  The purpose of this research study is to look at how a 
drug called uproleselan performs in preventing these side effects from occurring in the first place or in 
decreasing their severity.  In this study, participants will be randomly assigned (like the flip of a coin) to 
receive either uproleselan or placebo (something that looks like the study drug being used but does not 
contain any active medication) so that doctors can study the effects of uproleselan.  Everyone will 
receive the other medications that are given routinely as standard of care to treat these side effects. 
 
Uproleselan is considered investigational, which means that it has not been approved by the U.S. Food 
and Drug Administration.   
 
WHAT WILL HAPPEN DURING THIS STUDY? 
All treatment will be given in the inpatient setting at Siteman Cancer Center, and follow-up procedures 
may happen in the inpatient or outpatient setting. We feel it is important to remind you that any 
procedures, regardless of whether they are tests you would have if you did not take part in the research 


 
FOR IRB USE ONLY 
IRB ID #: 202103086 
APPROVAL DATE: 03/02/22 
RELEASED DATE: 03/04/22 
EXPIRATION DATE: 03/01/23 
 
Version 03/18/21 
Page 2 of 15 
or are research-related, will require you to remain at the Siteman Cancer Center up to several hours. 
There may also be a wide variability in the length of clinic visits. It is important that you are able to be 
available to complete the procedures at each visit to ensure that your safety and treatment needs are met. 
 
Before you begin study treatment: 
You will need to have the following screening exams, tests, or procedures to find out if you can continue 
to be in the study. Most of these procedures are part of regular cancer care and may be done even if you 
do not join the study. If you have had some of them recently, they may not need to be repeated. This will 
be up to your study doctor. 
• Physical exam, including taking of vital signs, measuring your height and weight, reviewing your 
medical history, and talking about any symptoms or health problems you’re having 
• Blood tests to check your blood counts and organ function (approximately 2 teaspoons of blood 
will be drawn from a vein in your arm) 
• Blood tests to check how your blood is clotting (approximately ½ teaspoon of blood will be 
drawn from a vein in your arm) 
• Blood tests to check for hepatitis or HIV (approximately 1 teaspoon of blood will be drawn from 
a vein in your arm) 
• Blood will be drawn for a pregnancy test if you are a woman of childbearing potential (about ½ 
teaspoon of blood will be drawn from a vein in your arm) 
• Bone marrow aspiration for research purposes (approximately ½ teaspoon of aspirate will be 
collected) 
 
It is possible that after your medical history, tests, and procedures are reviewed, you will not be able to 
continue in this study. Your study doctor will go over any reasons why you might not be able to 
continue in the study with you. 
 
Procedures throughout the study: 
If you continue in the study, you will be randomly assigned, like the flip of a coin, to receive infusions 
of either uproleselan or placebo.  Neither you nor your care team will know whether you are receiving 
uproleselan or placebo.  This is called being “blinded.” 
 
You will be admitted to the hospital 3 days before your transplant day.  You will receive infusions of 
uproleselan (or placebo) in the evening of the first day you’re admitted (Day -3), then in the morning 
and evening on Days -2 and -1, and finally one last dose in the morning on Day 0, your transplant day.  
You will also receive the pre-transplant infusion of melphalan on Day -2 sometime after your third dose 
of uproleselan (or placebo).  The infusion of melphalan and the transplant are not occurring because you 
are participating in this study; you would have these treatments anyway.  The infusions of uproleselan 
(or placebo) are being given only because you are participating in this study. 
 
In addition to those treatments, you will have the following tests or procedures while you are admitted to 
the hospital: 
• Blood tests to check your blood counts and organ function (as per routine care, typically daily) 
• Blood draw for research purposes on Days -3 and 0 (½ teaspoon of blood will be drawn from a 
vein in your arm) 
• Some stool will be collected for research purposes on Days -3, 0, 8, and 14 (or the day you’re 


 
FOR IRB USE ONLY 
IRB ID #: 202103086 
APPROVAL DATE: 03/02/22 
RELEASED DATE: 03/04/22 
EXPIRATION DATE: 03/01/23 
 
Version 03/18/21 
Page 3 of 15 
discharged, whichever comes first) 
• Questionnaire to assess your quality of life on Days -3, 8, and 14 (or the day you’re discharged, 
whichever comes first). You are free to skip any questions you prefer not to answer.  
 
Follow-up procedures: 
After you are discharged, you will return for follow-up visits on Day 30, Day 100, Month 6, and Month 
12.  After that, you will be contacted by phone or your medical record will be reviewed for another year 
to collect information on your health and wellbeing. 
 
At your follow-up visits, you will undergo a physical exam, have approximately 2 teaspoons of blood 
drawn to check your counts and organ function, will be assessed for side effects, and will have a bone 
marrow aspiration as standard of care (on Day 100 only). 
 
Will you save my research information and biospecimens to use in future research studies? 
We would like to use the blood, bone marrow aspirate, stool, and data we are obtaining in this study for 
studies going on right now as well as studies that are conducted in the future.  These studies may provide 
additional information that will be helpful in understanding multiple myeloma, or other diseases or 
conditions, including research to develop investigational tests, treatments, drugs or devices that are not 
yet approved by the U.S. Food and Drug Administration.  It is unlikely that what we learn from these 
studies will have a direct benefit to you.  There are no plans to provide financial compensation to you 
should this occur.  By allowing us to use your blood, bone marrow aspirate, stool, and data you give up 
any property rights you may have in the blood, bone marrow aspirate, stool, and data. 
 
Future research may involve genetic research. Genes are a unique combination of molecules (called 
DNA) that we inherit from our parents.  There are millions of tiny differences in our genes.  These 
differences may make us more or less likely to develop certain diseases or conditions or to have certain 
characteristics.  Genetic research involves studying the differences in genes and DNA between 
individuals. This type of testing creates information that is as unique to you as your fingerprint. 
 
We will share your blood, bone marrow aspirate, stool, and data with other researchers. They may be 
doing research in areas similar to this research or in other unrelated areas.  These researchers may be at 
Washington University, at other research centers and institutions, or industry sponsors of research.  We 
may also share your research data with large data repositories (a repository is a database of information) 
for broad sharing with the research community.  If your individual research data is placed in one of these 
repositories only qualified researchers, who have received prior approval from individuals that monitor 
the use of the data, will be able to look at your information.   
 
If you change your mind and do not want us to store and use your blood, bone marrow aspirate, stool, 
and data for future research you should contact the research team member identified at the top of this 
document.  The blood, bone marrow aspirate, stool, and data will no longer be used for research 
purposes. However, if some research with your blood, bone marrow aspirate, stool, and data has already 
been completed, the information from that research may still be used. Also, if the blood, bone marrow 
aspirate, stool, and data has been shared with other researchers it might not be possible to withdraw the 
blood, bone marrow aspirate, stool, and data to the extent it has been shared. 
 
 


 
FOR IRB USE ONLY 
IRB ID #: 202103086 
APPROVAL DATE: 03/02/22 
RELEASED DATE: 03/04/22 
EXPIRATION DATE: 03/01/23 
 
Version 03/18/21 
Page 4 of 15 
Please place your initials in the blank next to Yes or No for the question below: 
 
My blood, bone marrow aspirate, stool, and data may be stored and used for future research as 
described above. 
 
_____ Yes 
_____ No 
Initials  
Initials 
 
 
Unless you agree to future use as described above, your private information including blood, bone 
marrow aspirate, stool, and data collected as part of this study will not be used or distributed for future 
research studies, even if identifiers are removed. 
 
 
 
HOW MANY PEOPLE WILL PARTICIPATE? 
Approximately 50 people will take part in this study conducted by investigators at Washington 
University. 
 
HOW LONG WILL I BE IN THIS STUDY? 
If you agree to take part in this study, your involvement will last for up to 2 years.  There will be 3 days 
of treatment, an additional 2 weeks of active monitoring and specimen collection during the autologous 
hematopoietic cell transplant, and the remaining time will be passive follow-up. 
 
WHAT ARE THE RISKS OF THIS STUDY? 
You may experience one or more of the risks indicated below from being in this study. In addition to 
these, there may be other unknown risks, or risks that we did not anticipate, associated with being in this 
study.  
 
Some risks described in this consent document, if severe, may cause death.  
 
Risks of Uproleselan 
Uproleselan is an investigational medication; how it may affect humans is being studied.  It is not known 
if you will have side effects from this medication and if uproleselan will cause additional side effects 
from ones caused by medications you are taking. As with any investigational medication, there is the 
possibility of side effects that are unknown or unforeseen at this time. There is always a chance that you 
can have an unexpected side effect, and possibly a severe side effect, including death, if you take 
part in this study. This can happen to people who take this or any other medication. 
 
There is a chance that any other medications you may be taking could have a negative interaction with 
uproleselan. In a clinical research study like this one, not every risk or side effect can be known. Each 
person’s reaction to a study medication may be different. 
 
To date, a total of 189 study participants (86 healthy volunteers and 103 participants) have received 
uproleselan alone or with different chemotherapy medicines. 
 


 
FOR IRB USE ONLY 
IRB ID #: 202103086 
APPROVAL DATE: 03/02/22 
RELEASED DATE: 03/04/22 
EXPIRATION DATE: 03/01/23 
 
Version 03/18/21 
Page 5 of 15 
The following side effects considered by Study Doctors to be possibly caused by uproleselan treatment 
are shown below. 
 
Very common (greater than10% of participants). 
• nausea 
• diarrhea 
 
Common (5-9% of participants) 
• headache 
• back pain 
• febrile neutropenia (fever when white blood cell count is low) 
• fatigue (tiredness) 
• decreased appetite 
• thrombocytopenia (low number of platelets in the blood) 
 
Less common (2-4% of participants) 
• stomach pain or upper stomach pain 
• chills 
• vomiting 
• constipation 
• colitis (inflammation of the digestive tract) 
• stomatitis (inflammation of the mouth and lips) 
• infusion site pain 
• pyrexia (fever) 
• dysgeusia (distorted sense of taste) 
• anemia (low numbers of red blood cells) or neutropenia (low levels of neutrophils, a type of 
white blood cell) 
• platelet count decreased 
• increased liver enzyme (aspartate aminotransferase) 
• electrolyte imbalance (low potassium levels in the blood) 
• dizziness 
• arthralgia (pain in a joint) 
• pneumonia (an infection in the lungs) 
• pruritus (itchy skin) or rash 
 
Rare (1% of participants) 
• asthenia (physical weakness or lack of energy) or somnolence (sleepiness or drowsiness) 
• electrolyte imbalances (including low calcium, magnesium or phosphate levels in the blood) 
• musculoskeletal pain or neck pain or pain in extremity 
• myalgia (muscle pain) or muscle spasms or muscular weakness 
• increased liver enzyme (alanine aminotransferase) 
• white blood cell or neutrophil count decreased 
• sepsis (a severe type of infection) 
• bradycardia (slow heart rate) 


 
FOR IRB USE ONLY 
IRB ID #: 202103086 
APPROVAL DATE: 03/02/22 
RELEASED DATE: 03/04/22 
EXPIRATION DATE: 03/01/23 
 
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• dyspepsia (indigestion) 
• chest discomfort 
• edema peripheral (accumulation of fluid causing swelling; usually lower limbs) 
• tumor lysis syndrome (when large amount of tumor cells is killed by treatment and contents enter 
the blood stream) 
• alkaline phosphatase or ALP increase (elevated levels of ALP in the blood are most commonly 
caused by liver disease, bile duct obstruction, gallbladder disease, or bone disorders) 
• increased bilirubin (yellowish substance in your blood) 
• dry skin or generalized pruritus (itchy skin) or rash maculopapular (a specific type of rash) 
• cough or dyspnea (difficult/labored breathing) 
• hypoxia (low level of oxygen in the blood) 
• stomach discomfort or swelling/stretching 
• pulmonary edema (excess fluid in the lungs) 
• sinus tachycardia (fast heart rate) 
• restlessness 
• hypertension/hypotension (high/low blood pressure) 
 
Very rare (less than 1% of participants) 
• enteritis or enterocolitis (inflammation of the digestive tract) 
• stomach tenderness or symptoms 
• ascites (the accumulation of fluid, causing abdominal swelling) 
• digestive tract swelling or thickening or hemorrhage (bleeding) 
• dry mouth or gum pain or blisters in the mouth or blisters on the tongue or oral candidiasis 
(yeast/fungal infection in the mouth) 
• retching (to make the sounds and movement of vomiting without actually vomiting) 
• tachycardia (fast heart rate) 
• proctalgia (pain due to a spasm of the pelvic floor muscles, the muscles of the anal sphincter, or 
the muscles of the rectum) 
• infusion site reactions such as redness or swelling or extravasation (leakage of intravenously 
infused into the tissue around the site of infusion) 
• feeling hot or a burning sensation 
• lack of energy 
• eosinophilia (high levels of eosinophils; Eosinophils are a type of disease-fighting white blood 
cell) 
• lymphadenopathy (disease of the lymph nodes, in which they are abnormal in size or 
consistency) 
• dehydration 
• hypoalbuminemia (level of albumin in the blood is low) or hyponatremia (level in sodium in the 
blood is low) 
• international normalized ratio (INR) decrease (INR is a lab test to check how your blood clots) 
• liver function test increases 
• musculoskeletal stiffness 
• weight changes (increase or decrease) 
• electrocardiogram changes 


 
FOR IRB USE ONLY 
IRB ID #: 202103086 
APPROVAL DATE: 03/02/22 
RELEASED DATE: 03/04/22 
EXPIRATION DATE: 03/01/23 
 
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• cellulitis (painful bacterial skin infection. It may first appear as a red, swollen area that feels hot 
and tender to the touch) 
• clostridium difficile colitis (a bacteria that causes diarrhea and colitis (inflammation of the 
colon)) 
• enterococcal bacteremia or streptococcal bacteremia (types of bacteria that can cause a variety of 
infections) 
• otitis media (inflammatory disease of the middle ear) 
• upper or lower respiratory infections 
• alopecia (hair loss) 
• erythema multiforme (hypersensitivity reaction usually triggered by infections) 
• palmar erythema (rare skin condition where the palms of both hands become reddish) 
• palmar-plantar erythrodysesthesia (hand-foot syndrome causes redness, swelling, and pain on the 
palms of the hands and/or the soles of the feet. Sometimes blisters appear) 
• purpura (purple-colored spots that are mostly seen on the skin) 
• erythemeous or macular rash (specific types of rash) 
• skin exfoliation (peeling skin) 
• acute respiratory distress syndrome (lung injury that allows fluid to leak into the lungs) 
• breathing becomes difficult and oxygen cannot get into the body or tachypnea (faster than 
normal breathing) 
• nasal congestion or discomfort or nosebleed 
• throat pain or swelling 
• dry eye or pink eye or eye swelling or blurred vision or retinal hemorrhage (disorder of the eye in 
which bleeding occurs in the retina) 
• anxiety or confused state 
• painful urination or kidney injury or urinary tract infections 
• transfusion reaction 
 
Risks of Placebo 
You may receive a placebo (an inactive substance) during this study.  This means that you would receive 
no active study treatment while participating but will receive all standard of care treatments and 
supportive care for the gastrointestinal side effects you experience as a result of treatment with 
melphalan. 
 
Risks of Randomization 
Because chance decides whether you will receive uproleselan or placebo, your treatment may not be 
what your own doctor would choose for you if both options were presented to him/her to choose from. 
 
Risks of Blood Draw 
Possible side effects from a blood draw include fainting, feeling dizzy, pain, swelling, bruising, or 
bleeding where the needle is inserted. There is also a slight possibility of infection where the needle is 
inserted. 
 
Risks of Bone Marrow Aspiration 
It is likely that you will experience discomfort or pain, redness, swelling, and bruising at the site of the 
needle insertion. It is less likely that you will experience bleeding from the site of the needle insertion. 


 
FOR IRB USE ONLY 
IRB ID #: 202103086 
APPROVAL DATE: 03/02/22 
RELEASED DATE: 03/04/22 
EXPIRATION DATE: 03/01/23 
 
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Page 8 of 15 
There is a rare chance (approximately less than 1/100) of developing a significant infection or bleeding 
from this procedure. An allergic reaction to the anesthetic may occur. A scar may form at the site of 
needle entry. 
 
Risks of Testing for Reportable Diseases 
If you decide to participate in this study, we will test you for hepatitis and HIV.  The results of these 
tests could indicate that you have one of these conditions.  If that happens, we will refer you to a doctor 
who specializes in treating your condition.  We will make every effort to keep your personal information 
confidential.  However, we are required by law to report certain positive tests to the state of Missouri 
and/or local agencies.  The test results could also be reported to the Centers for Disease Control.  You 
may be contacted by these agencies for more information.  Becoming aware of a new diagnosis could 
have serious health, personal and/or social consequences.  For more information about the risks of this 
testing, please talk to your study doctor. 
 
Risks of Questionnaires 
There is a risk that some of the questions may make you feel uncomfortable.  You don’t have to answer 
any questions you’d prefer not to answer. 
 
Risks for Women Capable of Becoming Pregnant 
If you are a woman capable of becoming pregnant, we will ask you to have a pregnancy test before 
beginning this study.  You must use effective birth control methods and try not to become pregnant 
while participating in this study or for 12 weeks after you discontinue treatment.  If you become 
pregnant, there may be unknown risks to your unborn child, or risks to your unborn child that we did not 
anticipate.  There may be long-term effects of the treatment being studied that could increase the risk of 
harm to an unborn child.  You must tell the doctor if your birth control method fails while you are on the 
study. If you believe or know you have become pregnant while participating in this research study, 
please contact the research team member identified at the top of this document as soon as possible.  
Please discuss with the research team how long you need to wait before becoming pregnant after 
completing the treatment or procedures on this study. 
 
Risks for Sexually Active Males 
If you are a sexually active male it is important that you not impregnate anyone or donate sperm during 
your participation in this study. There may be unknown risks to the unborn child or risks we did not 
anticipate. If pregnancy is a possibility, you must agree to use birth control if you want to take part in this 
study and for 12 weeks after you discontinue treatment. If you believe or know that you have 
impregnated anyone, donated sperm or otherwise fathered a child during your participation in this study, 
please contact the research team member identified at the top of the document as soon as possible. 
 
Risk of Breach of Confidentiality 
One risk of participating in this study is that confidential information about you may be accidentally 
disclosed.  We will use our best efforts to keep the information about you secure.  Please see the section 
in this consent form titled “How will you keep my information confidential?” for more information. 
 


 
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WHAT ARE THE BENEFITS OF THIS STUDY? 
You may or may not benefit from being in this study.   
 
However, we hope that, in the future, other people might benefit from this study because it will help 
researchers learn more about ways to prevent or reduce melphalan-related gastrointestinal side effects. 
 
WHAT OTHER TREATMENT OPTIONS ARE THERE? 
Before you decide whether or not to be in this study, your doctor will discuss the other options that are 
available to you.  Instead of being in this study, you could: 
• receive standard of care treatments for melphalan-related gastrointestinal side effects 
• take part in another research study 
 
WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
As part of this study you will receive tests and procedures that are similar to what you would receive 
during routine clinical care of your condition.  Your health plan/insurance company will be billed for 
some or all of these costs, and you will be responsible for any co-pays and deductibles that are normally 
required by your health plan/insurance.  Not all insurance plans cover the costs associated with being in 
a study. Even if they do, you may be responsible for more out-of-pocket expenses, such as co-pays and 
deductibles, when there are more tests and procedures or more expensive tests and procedures involved 
in the study than if you were to receive routine clinical care outside the study.   
 
If you wish to know whether there are more tests and procedures or more expensive tests and procedures 
in the study, you should ask your study doctor.   
 
If you wish to know whether your insurance will pay, you should contact them directly, or speak with 
the study team about obtaining a financial pre-certification prior to enrolling in the study. 
 
GlycoMimetics, Inc., the manufacturer of uproleselan, is providing it at no cost to you. 
 
WILL I BE PAID FOR PARTICIPATING? 
You will not be paid for being in this research study.   
 
WHO IS FUNDING THIS STUDY? 
The Barnes-Jewish Hospital Foundation is funding this research study.  This means that Washington 
University is receiving payments from the BJH Foundation to support the activities that are required to 
conduct the study.  No one on the research team will receive a direct payment or increase in salary from 
the BJH Foundation for conducting this study. 
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
Washington University investigators and staff will try to reduce, control, and treat any complications 
from this research. If you feel you are injured because of the study, please contact the investigator at 
(314) 454-8304 and/or the Human Research Protection Office at 1-(800)-438-0445.  
 
Decisions about whether payment for medical treatment for injuries relating to your participation in 


 
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research will be made by Washington University. If you need to seek medical care for a research-related 
injury, please notify the investigator as soon as possible.  
 
HOW WILL YOU KEEP MY INFORMATION CONFIDENTIAL? 
Other people such as those indicated below may become aware of your participation in this study and 
may inspect and copy records pertaining to this research.  Some of these records could contain 
information that personally identifies you. We will keep your participation in this research study 
confidential to the extent permitted by law.   
• Government representatives (including the Office for Human Research Protections) to complete 
federal or state responsibilities 
• The U.S. Food and Drug Administration 
• GlycoMimetics, Inc., manufacturer of uproleselan 
• Your primary care physician if a medical condition that needs urgent attention is discovered 
• Public health agencies to complete public health reporting requirements 
• Hospital or University representatives to complete Hospital or University responsibilities 
• Information about your participation in this study may be documented in your health care records 
and will be available to anyone with access to your health care record, including your health 
insurance company.  This information may also be released as part of a release of information 
request. 
• The last four digits of your social security number may be used in hospital or University systems 
to track billing information for research procedures. 
• Washington University’s Institutional Review Board (a committee that oversees the conduct of 
research involving human participants) and the Human Research Protection Office. The 
Institutional Review Board has reviewed and approved this study.  
• The Siteman Cancer Center Clinical Trials Office 
• The independent data and safety monitoring board (DSMB) 
• The Quality Assurance and Safety Monitoring Committee, to monitor the conduct of this study 
• Any report or article that we write will not include information that can directly identify you.  
The journals that publish these reports or articles require that we share your information that was 
collected for this study with others to make sure the results of this study are correct and help 
develop new ideas for research. Your information will be shared in a way that cannot directly 
identify you. 
 
To help protect your confidentiality, we will make sure that your study information is kept secure. We 
will keep study information in a secure database that requires a username and password. To help protect 
your confidentiality, no identifying information such as your name, birth date, or social security number 
will be made available to researchers who receive your health information. Furthermore, the study team 
will keep the master code list that links your unique study number with your name and other identifying 
information in locked storage in a locked office (for paper copies) or on a secured network on a 
password-protected computer (for electronic copies). Access to either paper or electronic copies will be 
limited to the Principal Investigator and members of the study team. 
 
The research team will send study results to GlycoMimetics, Inc.  Information sent to GlycoMimetics 
will be deidentified and may be used to analyze the safety and effectiveness of the study medication.  In 
the future, GlycoMimetics may continue to use your health information that is collected as part of this 


 
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study. For example, GlycoMimetics may combine information from this study with the results of other 
studies to re-analyze the safety and effectiveness of the study medication, to evaluate other products or 
therapies, to develop a better understanding of a disease, or to improve the design of future research 
studies. GlycoMimetics may also share information from the study with regulatory agencies in foreign 
countries. 
 
If you receive Medicare benefits, are injured as part of your participation in this research study and 
medical treatment relating to this injury is paid by anyone other than you or your insurance company, 
that payer will need to collect personal information about you.  This information includes your name, 
date of birth, gender, social security number, Medicare identification number and information related to 
this research study. The payer will report this information to the Centers for Medicare & Medicaid 
Services (CMS), the federal agency that oversees the Medicare program, during your participation in the 
study and for as long as the payer is required by CMS to report this information.  If you do not want to 
release your personal or treatment related information you have the right to refuse reimbursement by the 
payer for any research injury.  The payer will not use this information for any other purpose. 
 
The Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital 
is supported by funding from the National Cancer Institute (NCI). To meet NCI requirements, your 
protected health information relating to your participation in this study (including your social security 
number) will be stored in a secure database at the Siteman Cancer Center.  This database and also your 
health care records may be reviewed by Siteman Cancer Center personnel.  All information will be 
securely and confidentially maintained.  
 
A description of this clinical trial will be available on http://www.clinicaltrials.gov/, as required by U.S. 
law. This website will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time. 
 
Are there additional protections for my health information? 
Protected Health Information (PHI) is health information that identifies you. PHI is protected by federal 
law under HIPAA (the Health Insurance Portability and Accountability Act). To take part in this 
research, you must give the research team permission to use and disclose (share) your PHI for the study 
as explained in this consent form.  The research team will follow state and federal laws and may share 
your health information with the agencies and people listed under the previous section titled, “How will 
you keep my information confidential?” 
 
Once your health information is shared with someone outside of the research team, it may no longer be 
protected by HIPAA.   
 
The research team will only use and share your information as talked about in this form or as permitted 
or required by law.  When possible, the research team will make sure information cannot be linked to 
you (de-identified).  Once information is de-identified, it may be used and shared for other purposes not 
discussed in this consent form. If you have questions or concerns about your privacy and the use of your 
PHI, please contact the University’s Privacy Officer at 866-747-4975.  
 
Although you will not be allowed to see the study information, you may be given access to your health 
care records by contacting your health care provider.  


 
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If you decide not to sign this form, it will not affect 
• your treatment or the care given by your health provider. 
• your insurance payment or enrollment in any health plans.   
• any benefits to which you are entitled. 
However, it will not be possible for you to take part in the study. 
 
If you sign this form: 
• You authorize the use of your PHI for this research 
• This authorization does not expire. 
• You may later change your mind and not let the research team use or share your information 
(you may revoke your authorization).  
• To revoke your authorization, complete the withdrawal letter, found in the Participant section 
of 
the 
Human 
Research 
Protection 
Office 
website 
at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ or you may request that the 
investigator send you a copy of the letter.    
 
 
 
o If you revoke your authorization: 
 The research team may only use and share information already collected for 
the study. 
 Your information may still be used and shared as necessary to maintain the 
integrity of the research, for example, to account for a participant’s 
withdrawal from the research study or for safety reasons. 
 You will not be allowed to continue to participate in the study. 
 
Can we contact you by email and/or text? 
We would like to contact you by email and/or text for the purposes listed below.  Some of these 
messages may contain health information that identifies you. 
• Appointment reminders and scheduling 
• Education 
• Check-ins 
 
Only the research team will have access to your email and/or text communications.  We will only 
communicate in this method to send you the information listed above.  If you have any questions, wish 
us to stop sending these messages or need to contact us for an urgent or emergent situation, please 
contact the research team member identified at the top of this document. 
 
You should be aware that there are risks associated with sending your health information via email 
and/or text.   
• Text messaging is not a secure communication method. 
• There is always a risk that the message could be intercepted or sent to the wrong email 
address and/or phone number.  To avoid this, we will send a test message to ensure we have 
the correct email address and/or telephone number. 
• When using any computer, you should be careful to protect your username and password.  
Make sure you log-out before getting up from the computer.   


 
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• If you share a home computer or cell phone with other family members, and do not want 
them to know you are participating in this study make sure you provide an email address that 
only you can access.  
• Your employer will have access to any messages sent or received on any electronic devices 
used for work or through a work server. 
• If you lose your phone, others may be able to access the messages that we send. 
  
Do you agree to allow us to send your health information via email?   
 
_____ Yes  
_____ No 
Initials  
Initials 
 
Do you agree to allow us to send your health information via text?   
 
_____ Yes  
_____ No 
Initials  
Initials 
 
IS BEING IN THIS STUDY VOLUNTARY? 
Taking part in this research study is completely voluntary.  You may choose not to take part at all.  If 
you decide to be in this study, you may stop participating at any time. Any data that was collected as 
part of your participation in the study will remain as part of the study records and cannot be removed.   
 
If you decide not to be in this study, or if you stop participating at any time, you won’t be penalized or 
lose any benefits for which you otherwise qualify.   
 
What if I decide to withdraw from the study? 
You may withdraw by telling the study team you are no longer interested in participating in the study or 
you may send in a withdrawal letter. A sample withdrawal letter can be found at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ under Withdrawing from a Research 
Study. 
 
If you decide to leave the study early, we will ask you to tell the study doctor if you are thinking about 
stopping so any risks can be evaluated by your doctor. Another reason to tell your doctor that you are 
thinking about stopping is to discuss what follow-up care and testing could be most helpful for you. 
 
Will I receive new information about the study while participating? 
If we obtain any new information during this study that might affect your willingness to continue 
participating in the study, we’ll promptly provide you with that information. 
 
Can someone else end my participation in this study? 
Under certain circumstances, the investigator might decide to end your participation in this research 
study earlier than planned.  This might happen for no reason or because staying in the study would be 
harmful, you need treatment that is not allowed while on the study, you fail to follow instructions, you 
become pregnant, or the study is canceled. 
 


 
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WHAT IF I HAVE QUESTIONS? 
We encourage you to ask questions.  If you have any questions about the research study itself, please 
contact Dr. Keith Stockerl-Goldstein at (314) 454-8304.  If you experience a research-related injury, 
please contact Dr. Stockerl-Goldstein as well; if this is after hours, you will be directed to the exchange 
number, which will be covered by a resident or fellow on call. Please tell this person that you are a 
research participant.  
 
If you have questions, concerns, or complaints about your rights as a research participant, please contact 
the Human Research Protection Office 1-(800)-438-0445, or email hrpo@wustl.edu.   General 
information about being a research participant can be found on the Human Research Protection Office 
web site, http://hrpo.wustl.edu.  To offer input about your experiences as a research participant or to 
speak to someone other than the research staff, call the Human Research Protection Office at the number 
above. 
 
 
This consent form is not a contract. It is a written explanation of what will happen during the study if 
you decide to participate. You are not waiving any legal rights by agreeing to participate in this study. 
As a participant you have rights and responsibilities as described in this document and including: 
• To be given enough time before signing below to weigh the risks and potential benefits and 
decide if you want to participate without any pressure from the research team or others. 
• To understand all of the information included in the document, have your questions answered, 
and receive an explanation of anything you do not understand. 
• To follow the procedures described in this document and the instructions of the research team to 
the best of your ability unless you choose to stop your participation in the research study. 
• To give the research team accurate and complete information. 
• To tell the research team promptly about any problems you have related to your participation, or 
if you are unable to continue and wish to stop participating in the research study. 
 
Your signature indicates that this research study has been explained to you, that your questions have 
been answered, and that you agree to take part in this study.  You will receive a signed and dated copy 
of this form. 
 
 
Do not sign this form if today’s date is after EXPIRATION DATE: 03/01/23. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Participant) 
 
 
 
 
(Date) 
 
 
____________________________________________ 
(Participant's name – printed) 
 
 
 


 
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Statement of Person Who Obtained Consent 
 
The information in this document has been discussed with the participant or, where appropriate, with the 
participant’s legally authorized representative.  The participant has indicated that they understand the 
risks, benefits, and procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date) 
 
 
___________________________________________ 
(Name of Person who Obtained Consent - printed)