Conditions: Refractory Multiple Myeloma Relapse Multiple Myeloma
Keywords: CAR-T Chimeric antigen receptor T-cell therapy CAR Therapy
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 1
Healthy volunteers: no

Brief summary:
This is a multicenter phase II, open-label study evaluating the efficacy and safety of belantamab mafodotin maintenance in participants with relapsed and/or refractory multiple myeloma (RRMM) who have received commercially available anti-BCMA CAR-T-cell therapy. Subjects will be enrolled 60-130 days after chimeric antigen receptor T-cell therapy (CAR-T) and receive belantamab mafodotin as maintenance therapy. Each maintenance cycle will have a duration of 56 days (+/- three days) and belantamab mafodotin will be administered at a dose of 2.5 mg/kg IV on day 1 of each cycle.

Detailed description:
INTERVENTION DESCRIPTION:

Subjects will receive belantamab mafodotin as maintenance therapy. Belantamab mafodotin will be administered IV over approximately 30 minutes at the recommended dose of 2.5 mg/kg IV over 30 minutes on day 1 of every eight-week (+/- three days) cycle for a maximum of 12 cycles. Maintenance therapy with belantamab mafodotin will continue until progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or end of study (maximum of 12 cycles), whichever occurs first. Dose interruptions or reductions may be required to address potential drug-associated toxicities. The dose to be administered will be based on actual body weight calculated at baseline. However, if the change in body weight is greater than 10%, the dose will be recalculated based on the actual body weight at the time of dosing. The dose may be reduced to address toxicity.

Arms:
arm 1: Belantamab mafodotin is an intravenous drug.

Interventions: intervention 1: Belantamab mafodotin
Intervention descriptions: intervention 1: Belantamab mafodotin will be administered IV over approximately 30 minutes at the recommended dose of 2.5 mg/kg IV over 30 minutes on day 1 of every eight-week (+/- three days) cycle for a maximum of 12 cycles. Maintenance therapy with belantamab mafodotin will continue until progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or end of study (maximum of 12 cycles), whichever occurs first.

Protocol document:
Prot_SAP_000.pdf: 
CLINICAL PROTOCOL 
A Multicenter Phase II Study of Maintenance Belantamab Mafodotin (Blenrep®) After 
BCMA-Directed Chimeric Antigen Receptor T-cell Therapy in Patients With Relapsed 
and/or Refractory Multiple Myeloma   
NCT05117008 
December 29, 2022 


Short Title: MCW EMBRACE TRIAL 
1 
Version No.: 3 
 
 
Version Date: 12/29/2022 
 
 
 
 
A Multicenter Phase II Study of Maintenance Belantamab Mafodotin 
(Blenrep®) after BCMA-Directed Chimeric Antigen Receptor T-Cell Therapy 
in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM) 
 
 
Short Title: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Meera Mohan, MD (Study PI) 
 
Saurabh Chhabra, MD, MS (Study Chair) 
 
Current Version Number and Date 
v1.0 12/22/2021 
v2.0 8/1/2021 (noted error in year 2022) 
v3.0 12/29/2022 
 
 
 
 
Proprietary and Confidential The information in this document is considered privileged and 
confidential and may not be disclosed to others except to the extent necessary to obtain Institutional 
Review Board approval and informed consent, or as required by federal and state laws. Persons to 
whom this information is disclosed should be informed that this information is privileged and 
confidential and that it should not be further disclosed. 
MCW 
EMBRACE 
TRIAL 


Short Title: MCW EMBRACE TRIAL 
2 
Version No.: 3 
 
 
Version Date: 12/29/2022 
TITLE:  A Multicenter Phase II Study of Maintenance Belantamab Mafodotin (Blenrep®) after 
BCMA-Directed Chimeric Antigen Receptor T-Cell Therapy in Patients with Relapsed and/or 
Refractory Multiple Myeloma (RRMM) 
 
MCW Protocol No.: Pending 
Funder Protocol No.:  214649  
IRB Pro No.:  42276 
CT.gov No.:  NCT05117008 
FDA IND No.: 159329 
Principal Investigator (sponsor-
investigator): 
Meera Mohan, MD 
Assistant Professor 
Department of Medicine 
Division of Hematology and Oncology 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
414-805-4600 
Email: memohan@mcw.edu 
 
Sub-investigator: 
Anita D’Souza, MD, MS 
Associate Professor 
Department of Medicine 
Division of Hematology and Oncology 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
414-805-4600 
Email: anitadsouza@mcw.edu 
Sub-investigator:  
Binod Dhakal, MD, MS 
Associate Professor 
Department of Medicine 
Division of Hematology and Oncology 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
414-805-4600 
Email: bdhakal@mcw.edu 
Sub-investigator:  
Marcelo Pasquini, MD, MS 
Professor 
Department of Medicine 
Division of Hematology and Oncology 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
414-805-4600 
Email:  mpasquini@mcw.edu  
Biostatistician: 
Aniko Szabo, PhD 
Professor  
Division of Biostatistics 
Institute for Health & Equity 
Medical College of Wisconsin 
8701 Watertown Plank Road 
Milwaukee, WI 53226 
Email: aszabo@mcw.edu 
 
 
Sub-investigator:  
Bryon Johnson, PhD 
Professor 
Pediatrics (Hematology/Oncology/BMT)  
and Microbiology & Immunology 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
414-805-4600 
Email: bjohnson@mcw.edu 
 
Sub-investigator:  
Tyce J. Kearl, MD, PhD 
Assistant Professor 
Department of Medicine 
Division of Hematology and Oncology 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
414-805-4600 
Email: tkearl@mcw.edu  
 
 
Study Chair (external site 1): 
Saurabh Chhabra, MD, MS 
Mayo Clinic  
Phoenix, AZ  
 
Sub-investigator (external site 2): 
Mayo Clinic 
Rochester, MN 
 


Short Title: MCW EMBRACE TRIAL 
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Version No.: 3 
 
 
Version Date: 12/29/2022 
 
 
MCW Multisite Program Lead:  
Alex Hinman, BA, CCRP 
Medical College of Wisconsin 
9200 W. Wisconsin Ave. 
Milwaukee, WI  53226 
  
MCW Multisite Program Coordinator:  
Sonia Maldonado-Schmidt, RN 
Medical College of Wisconsin 
9200 W. Wisconsin Ave. 
Milwaukee, WI  53226 
  
Shared Multisite Study Email: 
EMBRACEtrial@mcw.edu  
Funder:  
GlaxoSmithKline (GSK) 
 
MCW Information Services Help Desk 
414-955-4357 option 8 
 


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Version Date: 12/29/2022 
TABLE OF CONTENTS 
PROTOCOL SUMMARY ......................................................................................................................... 7 
STUDY SCHEMA .................................................................................................................................... 10 
STUDY CALENDAR (SCHEDULE OF ACTIVITIES) ....................................................................... 11 
LIST OF ABBREVIATIONS .................................................................................................................. 16 
1 BACKGROUND .................................................................................................................................... 20 
1.1 MULTIPLE MYELOMA ..................................................................................................................... 20 
1.2 BCMA-DIRECTED CAR-T CELLS .................................................................................................. 20 
1.3 BELANTAMAB MAFODOTIN ............................................................................................................. 21 
1.4 STUDY RATIONALE .......................................................................................................................... 24 
1.5 SUPPLEMENTAL STUDIES ................................................................................................................ 26 
2 HYPOTHESIS AND OBJECTIVES .................................................................................................... 27 
2.1 PRIMARY OBJECTIVES .................................................................................................................... 27 
2.2 PRIMARY ENDPOINT ........................................................................................................................ 27 
2.3 SECONDARY OBJECTIVES................................................................................................................ 27 
2.4 SECONDARY ENDPOINT ................................................................................................................... 28 
3 STUDY DESIGN .................................................................................................................................... 28 
3.1 GENERAL DESCRIPTION .................................................................................................................. 28 
3.2 STUDY POPULATION ........................................................................................................................ 29 
3.3 ESTIMATED TIME FOR COMPLETION OF STUDY ENROLLMENT .................................................. 29 
3.4 ESTIMATED TIME FOR STUDY COMPLETION ................................................................................. 29 
4 SUBJECT PARTICIPATION, DISCONTINUATION AND WITHDRAWAL .............................. 29 
4.1 SUBJECT STATUS .............................................................................................................................. 29 
4.2 PRESCREENING AND SCREENING LOG ........................................................................................... 30 
4.3 CONSENT .......................................................................................................................................... 30 
4.4 SCREENING PROCEDURES ............................................................................................................... 30 
4.5 CENTRAL ELIGIBILITY CONFIRMATION ........................................................................................ 30 
4.6 ELIGIBILITY CRITERIA .................................................................................................................... 32 
4.7 DISCONTINUATION OF STUDY TREATMENT, WITHDRAWAL, AND COMPLIANCE ....................... 37 
4.8 LOST TO FOLLOW-UP ...................................................................................................................... 38 
4.9 ACCRUAL SUSPENSION AND CLOSURE ........................................................................................... 38 
4.10 END OF STUDY DEFINITION ........................................................................................................... 39 
4.11 STUDY DISCONTINUATION AND CLOSURE ................................................................................... 39 
5 TREATMENT PLAN ............................................................................................................................ 39 
5.1 TREATMENT ..................................................................................................................................... 39 
5.2 DOSE MODIFICATIONS .................................................................................................................... 39 
5.2.1 Adjustments Due to Body Weight ............................................................................................. 39 
5.2.2 Dose Reductions for Toxicity .................................................................................................... 40 
5.2.3 Dose Modification Guidelines for Belantamab Mafodotin Treatment Related Corneal 
Adverse Reactions .............................................................................................................................. 43 
5.2.4 Corneal Supportive Care Guidelines for Belantamab Mafodotin ........................................... 45 
5.3 GSK SAFETY STOPPING CRITERIA ................................................................................................. 47 
5.4 MEASURABLE RESIDUAL DISEASE ASSESSMENT........................................................................... 51 
5.5 GENERAL CONCOMITANT MEDICATION AND SUPPORTIVE CARE GUIDELINES ......................... 51 
5.6 PROHIBITED MEDICATIONS ............................................................................................................ 51 
5.7 MONITORING SUBJECT COMPLIANCE ............................................................................................ 51 
5.8 FOLLOW-UP PERIOD ....................................................................................................................... 52 
6 ADVERSE EVENTS: DEFINITIONS, COLLECTION AND REPORTING REQUIREMENTS 52 
6.1 DEFINITIONS ..................................................................................................................................... 52 
6.1.1 Adverse Event ............................................................................................................................ 52 


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6.1.2 Serious Adverse Event (SAE) ................................................................................................... 52 
6.1.3 Attribution of an Adverse Event ............................................................................................... 53 
6.1.4 Expectedness of an Adverse Event ........................................................................................... 54 
6.2 COLLECTION AND REPORTING REQUIREMENTS FOR ADVERSE EVENTS AND SERIOUS ADVERSE 
EVENTS ....................................................................................................................................... 54 
6.2.1 Collection of Adverse Events .................................................................................................... 54 
6.2.2 Reporting of Adverse Events and Serious Adverse Events ...................................................... 54 
6.3 SERIOUS ADVERSE EVENT (SAE) ................................................................................................... 54 
6.4 SERIOUS ADVERSE EVENT REPORTING ......................................................................................... 55 
6.5 UNANTICIPATED PROBLEM INVOLVING RISK TO SUBJECT OR OTHER (UPIRSO ...................... 56 
6.6 DSMC REPORTING .......................................................................................................................... 56 
6.7 REPORTING PREGNANCY ................................................................................................................ 57 
6.8 PROTOCOL DEVIATIONS AND MEDICATION ERRORS ................................................................... 58 
6.9 STAFF, SUBJECT, AND PRODUCT COMPLAINT REPORTING .......................................................... 58 
6.10 SUBJECT WITHDRAWAL ................................................................................................................ 60 
6.11 REPORTING UPIRSO TO PARTICIPANTS ..................................................................................... 60 
6.12 EXTERNAL OR INTERNAL AUDITING AT PARTICIPATING SITES ................................................ 60 
6.13 KNOWN ADVERSE EVENTS LIST ................................................................................................... 60 
7 PHARMACEUTICAL INFORMATION ............................................................................................ 61 
7.1 BELANTAMAB MAFODOTIN ............................................................................................................. 61 
7.1.1 Description ................................................................................................................................ 61 
7.1.2 Storage ...................................................................................................................................... 61 
7.1.3 Biochemical and Structural Information ............................................................................... 61 
7.1.4 Molecular Weight ..................................................................................................................... 61 
7.1.5 Physical Form ........................................................................................................................... 61 
7.1.6 Handling and Drug Accountability .......................................................................................... 61 
7.1.7 Drug Supply .............................................................................................................................. 63 
8 STATISTICAL CONSIDERATIONS ................................................................................................. 63 
8.1 GENERAL DESCRIPTION .................................................................................................................. 63 
8.2 DETERMINATION OF SAMPLE SIZE AND ACCRUAL RATE ............................................................. 64 
8.2.1 Primary Endpoint ...................................................................................................................... 64 
8.2.2 Primary Hypothesis ................................................................................................................... 64 
8.2.3 Sample Size Justification .......................................................................................................... 64 
8.2.4 Analysis Populations ................................................................................................................. 65 
8.2.5 Statistical Analysis Plan ............................................................................................................ 65 
8.3 ACCRUAL ESTIMATES ..................................................................................................................... 67 
9 
OPERATIONAL 
CONSIDERATIONS, 
MULTISITE 
ADMINISTRATION, 
SOURCE 
DOCUMENTS, AND DATA MANAGEMENT .................................................................................... 67 
9.1 STAFF TRAINING, CHANGES, AND DELEGATION OF AUTHORITY LOG ........................................ 67 
9.2 MONITORING PLAN ......................................................................................................................... 67 
9.3 AUDIT PLAN ..................................................................................................................................... 68 
9.4 AUDIT AND MONITORING REPORT AND CORRECTIVE ACTION PLAN (CAP) ............................. 68 
9.5 DE-IDENTIFIED SOURCE DOCUMENTS, REMOTE ACCESS TO RECORDS, AND SHADOW CHARTS
 .................................................................................................................................................... 68 
9.6 TRANSFERRING SUBJECTS .............................................................................................................. 69 
9.7 RETENTION OF STUDY DOCUMENTS .............................................................................................. 69 
9.8 PUBLICATION AND DATA SHARING POLICY .................................................................................. 69 
9.9 ELECTRONIC DATA CAPTURE AND TIMELY DATA ENTRY ........................................................... 70 
10 REGULATORY COMPLIANCE, ETHICS, AND MANAGEMENT ........................................... 70 
10.1 ACTIVATION LETTER FOR PARTICIPATING INSTITUTIONS ........................................................ 71 
10.2 CAP, CLIA, AND REFERENCE RANGES ....................................................................................... 71 


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10.3 SCIENTIFIC REVIEW COMMITTEE ................................................................................................ 71 
10.4 DATA AND SAFETY MONITORING COMMITTEE ........................................................................... 71 
10.5 SUBJECT CONFIDENTIALITY AND ACCESS TO SOURCE DOCUMENTS/DATA ............................. 72 
10.6 PROTECTION FROM UNNECESSARY HARM .................................................................................. 73 
10.7 CHANGES IN THE PROTOCOL, CONSENT, OR OTHER TRIAL DOCUMENT .................................. 73 
APPENDIX 1. PERFORMANCE STATUS CRITERIA ...................................................................... 74 
APPENDIX 2. SUBJECT LOST TO FOLLOW-UP LETTER ............................................................ 75 
APPENDIX 3. IMWG MULTIPLE MYELOMA RESPONSE CRITERIA....................................... 76 
APPENDIX 4. CONTRACEPTIVES USE ............................................................................................. 77 
APPENDIX 5. CORRELATIVE SAMPLE INSTRUCTIONS AND  REQUISITION FORM ........ 78 
APPENDIX 6: PATIENT REPORTED OUTCOMES (PRO) ............................................................. 80 
REFERENCES .......................................................................................................................................... 88 
 


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PROTOCOL SUMMARY 
 
Title 
A Multicenter Phase II Study of Maintenance Belantamab Mafodotin (Blenrep®) 
after BCMA-Directed Chimeric Antigen Receptor T-cell Therapy in Patients with 
Relapsed and/or Refractory Multiple Myeloma (RRMM) 
IND Sponsor 
Sponsor-investigator 
Principal Investigator  
Meera Mohan, MD 
Anticipated Study Sites 
Three (including MCW) 
Clinical Trial Phase 
Phase II 
Study Disease 
Relapsed and/or refractory multiple myeloma 
Main Inclusion 
Criteria 
1. Diagnosis of multiple myeloma with measurable disease (at the time of 
diagnosis: serum M-protein ≥ 0.5 g/dL or urine M-protein ≥200 mg/24 hours 
or involved serum-free light chain ≥10 mg/dL provided that the ratio of 
involved/uninvolved light chain is abnormal) prior to receiving anti-BCMA 
CAR-T. Patients with no biochemically measurable disease prior to CAR-T 
may be enrolled if bidirectionally measurable plasmacytomas or bone 
marrow plasmacytosis >10% are present prior to CAR-T infusion. 
2. Received at least four prior lines of therapy (including a PI, IMiD, and anti-
CD38 monoclonal antibody – note radiation therapy is considered a line of 
therapy) before BCMA-targeted CAR-T,and has not progressed/relapsed 
after receiving CAR-T therapy.  
3. Achieved at least SD as a response to CAR-T therapy and remained 
progression-free after anti-BCMA CAR-T administration until enrollment 
(this requirement is also necessary prior to administration of first study 
drug). 
Main Exclusion 
Criteria 
1. Prior exposure to belantamab mafodotin before enrollment on the trial, 
including before administration of anti-BCMA CAR-T. 
2. Evidence of progression/relapse after BCMA CAR-T before enrollment 
(this requirement is also necessary prior administration of first study 
drug). 
3. Subject has achieved CR/sCR at the time of enrollment (this 
requirement is also necessary prior to administration of first study drug). 
4. Subject was given BCMA CAR-T under EAP (expanded access protocol) 
for non-conforming product. 
5. Subject progressed on a prior anti-BCMA therapy before receiving 
commercial anti-BCMA CAR-T. 
6. Any previous treatment-related adverse events higher than grade 1 at 
enrollment (except for alopecia and grade 2 neuropathy). 
7. Acute active infection requiring treatment within 14 days of enrollment 
(this requirement is necessary also prior to administration of first study 
drug). 
8. Current or prior involvement of the central nervous system by multiple 
myeloma. 
9. Smoldering multiple myeloma or POEMS. 
Primary Objectives 
To describe 12-month progression-free survival (PFS) of patients receiving 
belantamab mafodotin as maintenance therapy (every eight weeks) after anti-
BCMA CAR-T administration for relapsed/refractory myeloma. 
Primary Endpoints 
12-month conditional PFS, defined as the probability of being alive without 
progression/relapse or death at 12 months from the time of CAR-T administration 
conditional on being alive without progression/relapse at 3 months from the time of 
CAR-T. 


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Secondary Objectives 
1. To describe the toxicity profile of belantamab mafodotin given as 
maintenance after CAR-T. 
2. To describe progression-free survival. 
3. To describe changes in International Myeloma Working Group (IMWG) 
response category for patients not in CR when initiating therapy with 
belantamab mafodotin as post-CAR-T maintenance. 
4. To identify the rate of elimination of minimal residual disease (MRD) (≤10–
5) in patients with myeloma at baseline and after starting belantamab 
mafodotin as post-CAR-T maintenance (at screening/baseline, after two, six, 
and 12 cycles). 
5. Patient-reported quality of life studies (QoL).  
6. To describe the overall survival (OS) for the entire cohort from the time of 
CAR-T administration. 
Secondary Endpoints 
1. Best objective response on the trial (by IMWG criteria). 
2. Progression-free survival. 
3. Negative MRD (≤10-5, by clonoSEQ®), including imaging plus MRD-
negativity (≤10-5 in bone marrow and no area of PET-CT FDG uptake 
greater than mediastinal blood pool or surrounding normal tissue).  
4. Duration of response on maintenance. 
5. Time to progression/relapse after CAR-T. 
6. Overall survival for the entire study population. 
7. Adverse events on the trial. 
8. QoL parameters. 
Exploratory Objectives 
1. Exploratory: BCMA expression by flow cytometry and soluble 
BCMA/BAFF/APRIL levels will be monitored at screening/baseline, and 
after two, six, and 12 cycles. 
Exploratory Endpoints 
1. Baseline and on-treatment sBCMA/BAFF/APRIL and BCMA expression on 
myeloma cells. 
Study Design 
This is a multicenter phase II, open-label study evaluating the efficacy and safety 
of belantamab mafodotin maintenance in participants with RRMM who have 
received commercially available anti-BCMA CAR-T-cell therapy. 
Subjects will be enrolled 60–120 days after CAR-T and receive belantamab 
mafodotin as maintenance therapy. Although screening can occur as early as day 
60 post CAR-T therapy, study treatment cannot be started prior to day 90 post 
CAR-T therapy. Each maintenance cycle will have a duration of 56 days (+/- three 
days) and belantamab mafodotin will be administered at a dose of 1.9 mg/kg IV on 
day 1 of each cycle. The study will enroll up to 45 subjects with an interim analysis 
performed when 23 patients have been treated and followed to the 12th month after 
CAR-T. 
Study Intervention 
Description 
Subjects will receive belantamab mafodotin as maintenance therapy. Belantamab 
mafodotin will be administered IV over approximately 30 minutes at the 
recommended dose of 1.9 mg/kg IV on day 1 of every eight-week (+/- three days) 
cycle. Maintenance therapy with belantamab mafodotin will continue until 
progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or 
end of study, whichever occurs first. Dose interruptions or reductions may be 
required to address potential drug-associated toxicities. The dose to be 
administered will be based on actual body weight calculated at baseline. However, 
if the change in body weight is greater than 10%, the dose will be recalculated 
based on the actual body weight at the time of dosing. The dose may be reduced to 
address toxicity, as described in Section 5.3.  
Number of Subjects 
Total sample size for this phase II study will be 45 patients. The sample size was 
computed to achieve 80% power at a one-sided 5% significance level to detect an 
increase in 12-month conditional PFS to 74% from the historical value of 54%. 
This corresponds to raising the 12-month unconditional PFS from 40% to 55%. 


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Estimated Time to 
Complete Enrollment: 
Approximately three years. 
Estimated Time to 
Study Completion: 
Ten years (~3 years enrollment, ~2 years for completion of treatment for all patients, 
and ~5 years of long-term survival follow-up) 


 
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STUDY SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening (screening may occur at least 60 days post CAR-T, but study treatment cannot be started 
until 90-120 days post CAR-T) 
Central Eligibility Confirmation 
70-day post-last dose safety visit 
 Follow-up 
Belantamab Mafodotin Maintenance Therapy 
1.9 mg/kg IV (day 1 of a 56-day cycle) 
(45 subjects) 


 
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Table 1. STUDY CALENDAR (SCHEDULE OF ACTIVITIES) 
Study 
Assessments 
Screenin
g1 
C1D1 
(56 
days)9 
C2D1 
(56 
days 
)9 
C3D1 
(56 
days 
)9 
C4D1 
(56 
days 
)9 
C5D1 
(56 
days 
)9 
C6D1 
(56 
days 
)9 
C7D1 
(56 
days 
)9 
C8D1 
(56 
days 
)9 
C9D1 
(56 
days 
)9 
C10D
1 (56 
days 
)9 
C11D
1 (56 
days 
)9 
C12D
1 (56 
days 
)9 
70-day 
post-
last 
dose 
Safety 
Visit10 
Pre -
Progre
ssion 
Q3 
mo18 
LTF
U 
(Q6 
mo)1
9 
Visit window 
Day -30 
to 
enrollme
nt 
 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 3 
days 
+/- 30 
days 
+/- 
30 
days 
Informed consent 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H&P 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Ocular exam2 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x  
x 
x2 
ECOG 
Performance 
Status 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Adverse 
events/SAEs 
collection/reporti
ng3 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Concomitant 
medications4 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Vital signs (BP, 
HR, body 
temperature) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Height 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body weight 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
 
Hematology5 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Chemistry6 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
eGFR by MDRD  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
HbsAg, HbcAb, 
and hepatitis C 
antibody. 
hepatitis C RNA7 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test for 
WOCBP8 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
12-lead ECG 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Echocardiogram 
or MUGA for 
LVEF 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24-hour urine 
protein 
electrophoresis11 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
x 
 
Urine 
immunofixation11 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
x 
 
Serum 
immunofixation 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
SPEP 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Quantitative IgG, 
IgM, IgA 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
β2-microglobulin 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum kappa, 
lambda free LC, 
FLC ratio 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Imaging for bone 
(lytic) lesions: 
skeletal survey, 
CT or PET-CT12 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
Imaging (whole-
body PET-CT or 
CT or MRI) if 
history of  
extramedullary 
disease13 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
Whole-body 
PET-CT14 
X14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BM 
aspirate/biopsy 
for disease 
assessment15 and 14 
x14 
 
 
x14 
 
 
 
x14 
 
 
 
 
 
x14 
 
 
BM for FISH 
testing15 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 
NGS for MRD 
(ClonoSEQ®)16 
x^ 
 
 
x^ 
 
 
 
x^ 
 
 
 
 
 
x^ 
 
 
Correlatives: BM 
aspirate sample 
flow cytometry 
and cytotoxicity 
assays 
x 
 
 
x 
 
 
 
x 
 
 
 
 
 
x 
 
 
Correlatives: 
Soluble 
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x 
 
 
 
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BCMA/BAFF/AP
RIL (serum) 
Premedication if 
needed 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
Belantamab 
mafodotin IV 
administration 
 
x 
x 
x 
x 
x 
x 
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x 
x 
x 
x 
x 
 
 
 
Preservative-free 
artificial 
tears 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
PRO 
questionaires17 
 
x 
x 
x 
x 
x 
x 
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x 
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x 
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Spot urine 
(creatinine/albumi
n ratio) or urine 
dipstick for 
protein20 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
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LTFU data 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
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Obtain archived 
Diagnostic  
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1. Screening: May start 60 days post-CAR-T, but must be completed within 30 days prior to enrollment. Consent may occur at any time prior to screening 
period and does not count within the 30-day time window requirement. Subjects will be enrolled in the trial within 30 days of screening procedures 
(consent not included) and start treatment within the 90–120 days window after anti-BCMA CAR-T. 
2. Screening ocular examination to be performed by an ophthalmologist (or an optometrist, if an ophthalmologist is not available) within 30 days prior to 
enrollment. See Sections 5.2.4 and 5.3 for lists of ophthalmic exam procedures. On treatment, ocular exams are to be performed prior to each dosing of 
belantamab mafodotin until the 70-day safety visit. In case of persistent or newly developed ocular symptoms or vision changes, participants will have 
further ophthalmologic exams, at least every three months until resolution (to grade 1 or baseline) or more frequently as clinically indicated by the eye 
care specialist or up to one year (whichever comes first). Ocular exam may be performed up to five days prior to second dose onwards for belantamab 
mafodotin. 
3. Continuously, adverse event (AE) assessments: AEs should be documented and recorded at each visit using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. SAEs and AEs will be collected and reported after first treatment dose, through 70 
days post last dose of belantamab mafodotin..  
4. Concomitant treatments: All concomitant treatments, blood products, as well as nondrug interventions received by subjects will be recorded on the eCRF 
from screening through end of study. 
5. Hematology includes complete blood count (CBC) with differential. 
6. Chemistry: alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), bicarbonate, total bilirubin, blood urea 
nitrogen (BUN), chloride, serum calcium, creatinine, glucose, lactate dehydrogenase, magnesium, sodium, phosphorus or phosphate, and potassium. 
7. For subjects with serologic evidence of resolved HBV infection (i.e., positive anti-HBs or positive anti-HBc) at screening, HBV DNA testing by PCR 
must be performed locally Q12W during treatment, at the end-of-treatment visit, and Q12W for up to six months after the last dose of study treatment. 
HBV DNA is not necessary for patients positive for anti-HBs, but negative for anti-HBc and with a history of hepatitis B vaccination. 
8. Perform only in women of childbearing potential (WOCBP). Two serum pregnancy tests should be performed prior to treatment: at screening prior to 
enrollment and within 72 hours prior to C1D1. Other pregnancy tests may be either serum or urine. For questionable cases, follicle-stimulating hormone 
(FSH) and estradiol (as needed in women of non-childbearing potential only) should be performed at local lab. Final pregnancy test (serum or urine) must 
be performed in WOCBP at least 70 days after the last dose of belantamab mafodotin, preferably at a visit, or via a urine pregnancy test kit mailed to the 
participant’s home with results reported by telephone. Follow-up pregnancy assessment by telephone (for WOCBP only) should be performed four months 
after the last dose of belantamab mafodotin. 
9. Subjects will be enrolled in the trial within 30 days of screening procedures (consent not included) and start treatment within the 90–120 days window 
after anti-BCMA CAR-T. Each cycle is eight weeks +/- three days. If treatment cycle cannot be resumed within 16 weeks of the previous cycle (from day 
1), the patient may permanently discontinue belantamab mafodotin treatment on the trial. 
10. 70-day post-last dose safety visit due to half-life of belantamab mafodotin side effect profile: within 70 days +/- three days of last dose. Treatment may 
continue until discontinuation due to AEs, completion of 12 cycles, progression of myeloma, or beginning of a subsequent anti-myeloma therapy. 
11. UPEP with urine immunofixation: Necessary only when M-spike in urine is main parameter for response assessment (based on screening assessment), 
and will be completed on day 1 of cycles two, four, six, eight, 10, 12, and at end of study. After day 0, if urine M-protein is 200 mg/24 hour, 24-hour urine 
collections can be stopped, except to determine/confirm M-protein is <100 mg/24 hours for VGPR or undetectable for CR. 
12. Imaging of bones for lytic lesions by method aligned with institutional guidance (skeletal survey, CT, or MRI). 
13. For patients with extramedullary disease, imaging is only required by either CT, MRI, or PET/CT per local guidance. Needs to be performed by the same 
method throughout the study as was done at baseline. Selected target lesion needs to be measured and followed over time. Plasmacytoma measurements 
should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT scans. Skin lesions, if present, should be measured with a ruler. 
Measurement of tumor size will be determined by the sum of the products of the maximal perpendicular diameters of measured lesions (SPD).  


 
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14. Whole-body PET-CT must performed at screening. Whole-body PET-CT should be repeated if positive for disease at the time of screening, and 
repeated at the next BM timepoints (e.g., Cycle 3 Day 1, and Cycle 7 Day 1 if not negative at the Cycle 3 Day 1 timepoint). Whole-body PET-CT will 
be performed during/after treatment to confirm MRD-negativity if MRD-positive at screening/prestudy (if FDG-avid extramedullary lesions are seen at 
screening).  
15. This assessment will include morphology, flow cytometry, FISH for myeloma-associated abnormalities and sample to be sent to Adaptive Biotechnologies 
for identification of myeloma-specific sequences. Fluorescence in situ hybridization (FISH) testing to be performed locally at least for t(4;14), t(14;16), 
amp(1q), del(1p) and del(17p13). If participant is known to have tested positive for t(4;14) or t(14;16) on previous tests regardless of timeframe, FISH for 
these translocations does not need to be repeated. FISH results from samples taken within 90 days prior to first dose are acceptable. Samples are also to 
be obtained/sent for correlative studies (refer to Appendix 5). 
16. NGS for MRD assessment (clonoSEQ®) will be performed on bone marrow aspirate sample. Bone marrow aspiration with MRD assay (first pull, in 
subjects found to be MRD-informative based on clone identification sample) and flow cytometry/cytotoxicity assays will be performed within seven days 
before cycle 3 day 1, and cycle 7 day 1 and within seven days before or after cycle 12 day 56. Samples are also to be obtained/sent for correlative studies 
(refer to Appendix 5). 
17. Patient-reported outcomes (refer to Appendix) PRO assessments should be completed before any other study procedures are performed (except for blood 
draws).: 
a. 
EORTC-QLQ-MY20 and EORTC QLQ-C30 
i. Collect at cycle 1 day 1 (prior to treatment), cycle 3 day 1, cycle 7 day 1, cycle 9 day 1, and 70-day safety visit.  
b. OCULAR SURFACE DISEASE INDEX (OSDI) 
i.  Collect at cycle 1 day 1 (prior to treatment), every cycle day 1, and 70-day safety visit.  
18. For patients who discontinue treatment prior to progression, continue standard-of-care follow-up every three months until progression or start of another 
treatment (whichever comes first), then continue to long-term follow-up. 
19. Long-term survival data collected/reported approximately every six months (+/- 30 days). 
20. Urine dipstick for protein may be used to assess for presence of urine protein. Albumin/creatinine ratio needs to be done in any participant with urine 
dipstick result of ≥1+ at screening, or with positive protein if urine dipstick protein quantification is not available. 
 


 
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LIST OF ABBREVIATIONS 
 
ADPR 
adenosine diphosphate-ribose 
AE 
adverse event 
ALL 
acute lymphoblastic leukemia 
ALT 
alanine aminotransferase 
AML 
acute myelogenous leukemia 
ANC 
absolute neutrophil count 
ASCO 
American Society of Clinical Oncology 
ASCT 
autologous stem-cell transplantation 
AST 
aspartate aminotransferase 
BM 
bone marrow 
BMA 
bone marrow aspiration 
BSA 
body surface area 
BUN 
blood urea nitrogen 
CBC 
complete blood cell (count) 
CFR 
Code of Federal Regulations 
CL 
clearance, IV dosing 
CLL 
chronic lymphocytic leukemia 
CR 
complete response 
CRC 
clinical research coordinator 
CRF 
case report form 
CRi 
complete remission with incomplete blood count recovery 
CRM 
continual reassessment method 
CRP 
C-reactive protein 
CSF 
cerebral spinal fluid 
CT 
computerized tomography 
CTCAE  
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DSMC 
Data and Safety Monitoring Committee 
DSMP 
data and safety monitoring plan 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 


 
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EDC 
electronic data capture 
EOS 
end of study (visit) 
EOT 
end of treatment (visit) 
FDA 
United States Food and Drug Administration 
GCP 
good clinical practice 
G-CSF 
granulocyte colony stimulating factor 
GI 
gastrointestinal 
GLP 
good laboratory practices 
GMP 
good manufacturing practice 
Hb 
hemoglobin 
HCT 
hematocrit 
HDT 
high-dose therapy 
HGB 
hemoglobin 
HIV 
human immunodeficiency virus 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IMWG 
International Myeloma Working Group 
IEC 
independent ethics committee 
IP 
investigational product 
IRB 
Institutional Review Board 
IRR 
infusion-related reaction 
ITT 
intent to treat 
IV 
intravenous; intravenously 
kDa 
kilodalton 
KPS 
Karnofsky Performance Status 
LDH 
lactate dehydrogenase 
LFT 
liver function test(s) 
MCWCC 
Medical College of Wisconsin Cancer Center 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIDD 
monoclonal immunoglobulin deposition disease 
MM 
multiple myeloma 
MMBD 
multiple myeloma bone disease  
MRI 
magnetic resonance imaging 
MRD 
minimal residual disease 
MRU 
medical resource utilization 


 
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MTD 
maximum-tolerated dose 
NDMM 
newly diagnosed multiple myeloma 
NCI 
National Cancer Institute 
NHL 
non-Hodgkin lymphoma 
ORR 
overall response rate 
PBMC 
peripheral blood mononuclear cell 
PCR 
polymerase chain reaction 
PD 
disease progression 
PFS 
progression-free survival 
Pgp 
P-glycoprotein 
PK 
pharmacokinetics 
PO 
per os; by mouth (orally) 
PR 
partial response 
PRO 
subject-reported outcome 
PIM 
proto-oncogene serine/threonine-protein kinase 
QTc 
rate-corrected QT interval (millisec) of electrocardiograph 
RBC 
red blood cell (count) 
RI 
renal impairment 
RRMM 
relapsed and/or refractory multiple myeloma 
SAE 
serious adverse event 
SC 
subcutaneous 
sCR 
stringent complete response 
SD 
stable disease 
SD 
standard deviation 
sFLC 
serum-free light chains 
sIRB 
single Institutional Review Board 
SmPC 
summary of product characteristics 
SPEP 
serum M-protein immunoelectrophoresis 
SRC 
Scientific Review Committee 
SQ 
subcutaneous 
t1/2 
terminal disposition half-life 
TEAE 
treatment emergent adverse events 
Tmax 
single-dose time to reach maximum (peak) concentration 
TTP 
time to progression 
ULN 
upper limit of the normal range 
UP 
unanticipated problem 


 
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UPEP 
urine M-protein immune-electrophoresis 
UPIRSO   
unanticipated problems involving risks to subjects or others 
US 
United States 
VGPR 
very good partial response 
WBC 
white blood cell (count) 
WBLD 
whole-body low dose 
WHO 
World Health Organization 
 
 
 


 
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1 BACKGROUND  
 
1.1 Multiple Myeloma  
 
Multiple myeloma (MM) is a malignant plasma cell disease that is characterized by clonal proliferation of 
plasma cells in the bone marrow and the production of excessive amounts of a monoclonal immunoglobulin 
(usually of the IgG or IgA type or free urinary light chain [paraprotein, M-protein or M-component]).(1) It 
is a disease predominantly associated with advancing age with more than 80% of patients aged 60 years or 
older.(2) Patients with MM may experience bone pain, bone fractures, fatigue, anemia, infections, 
hypercalcemia, and kidney problems.(3) The disease course for MM varies with the aggressiveness of the 
disease and related prognostic factors. Median survival is approximately three years; however, some 
patients can live longer than 10 years.(4) Treatment options and survival are based on the patient’s age, 
fitness, and disease status. 
 
Patients under the age of approximately 65, presenting with symptomatic active disease in good physical 
health will generally receive initial therapy with autologous stem cell transplantation (ASCT). To achieve 
cytoreduction of the disease before collecting stem cells, induction chemotherapy is administered. Induction 
treatment regimens include alkylating agents, dexamethasone alone, thalidomide plus dexamethasone, and 
vincristine, Adriamycin® (doxorubicin), and dexamethasone (VAD; or modifications to this regimen); 
however, the latter two regimens are associated with higher toxicity.(3, 4) Newer treatments with Velcade® 
(bortezomib) alone, bortezomib combinations, and Revlimid® (lenalidomide) plus dexamethasone show 
some promise as induction therapy, and these agents demonstrate higher response rates and lower 
toxicity.(3, 4) 
 
The current aim of MM therapy is to control disease as effectively as possible, to maximize quality of life 
and to prolong survival. Treatments for relapsed and/or refractory disease are often referred to as salvage 
therapy. The initial chemotherapy regimen (e.g., melphalan plus prednisone or VAD) can be reinstituted 
for relapsed/refractory disease if the disease relapsed more than six months after the last therapy ended. 
The patients for whom stem cells were cryopreserved early in the disease course, and who are transplant 
candidates, can benefit from ASCT as salvage therapy.(3, 4) Subsequent treatment decisions are based on 
whether the patient experiences an indolent or aggressive relapse. Patients with relapsed disease may 
continue taking one drug or treatment regimen as maintenance therapy until relapse or toxicity. In general, 
MM patients will receive an average of four to eight different regimens during their lifespan utilizing agents 
such as proteasome inhibitors (e.g., bortezomib and carfilzomib) and immune modulatory agents (e.g., 
lenalidomide and pomalidomide). However, once a patient becomes refractory to those agents, survival is 
limited, and newer treatment options are needed to treat patients after they have failed stem cell transplant, 
chemotherapy, proteasome inhibitors, and immunomodulatory imide agents (IMiDs®). Despite the dramatic 
improvement in patient outcomes with newer therapies, MM remains an incurable disease. Thus, the 
treatment of patients who have received at least three different lines of therapy including a proteasome 
inhibitor and an immunomodulatory agent or who are double refractory to a proteasome inhibitor and an 
IMiD® remains an unmet medical need. 
 
1.2 BCMA-directed CAR-T Cells  
 
B-cell maturation antigen (BCMA) is expressed on clonal and polyclonal plasma cells, although the 
intensity of expression can vary with time(5, 6). Highly prevalent expression on plasma cells and exclusivity 
to the B-cell lineage has made BCMA an attractive target for multiple myeloma (MM) therapeutics, 
including chimeric antigen receptor (CAR)-T-cell technology. In a phase 1 study of bb2121, a BCMA-
targeting CAR T-cell construct with 4-1BB costimulatory molecule, 33 of the 36 enrolled patients received 
CAR-T cells after lymphodepleting chemotherapy.(7) ORR was 85%, including a CR rate of 45%. Of the 


 
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16 patients with a response who were evaluated for MRD, 15 were MRD negative at 10-5. Cytokine release 
syndrome occurred in 76% patients and was grade 3 in 6%. Neurotoxicity occurred in 42% patients, with 
grade 3 or 4 in 3%. Based on phase II KarMMa study data, Bristol Myers Squibb and bluebird bio, Inc. 
submitted a biologics license application to the U.S. Food and Drug Administration (FDA) for bb2121 
(idecabtagene vicleucel [ide-cel]) on March 31, 2020 for treatment of myeloma patients who have received 
at least four prior lines of therapy, including immunomodulatory agent (IMiD), proteasome inhibitor (PI) 
and anti-CD38 antibody. 
 
Available data from clinical studies demonstrate that peak expansion of BCMA-directed CAR-T cells 
generally correlates with response, whereas the extent of baseline BCMA expression does not, although 
most MM cells express BCMA.(8-10) BCMA expression on residual MM cells generally decreases after 
CAR T-cell therapy, more so in responders than in non-responders. At the time of progression, an increase 
in BCMA expression has been observed, potentially suggesting that additional BCMA-targeted therapies 
may be a future treatment option. Another postulated mechanism of disease progression is the lack of long-
term persistence of CAR-T cells. Persistence of CAR-T cells has ranged from a few days in most patients 
to a few months in some patients, with some variability across studies. In a phase I study of bb2121, 96%, 
86%, 57%, and 20% patients had detectable CAR-T cells at one, three, six, and 12 months, respectively. 
(7) 
 
In the heavily relapsed/refractory setting, BCMA CAR-T cells, despite their high response rates, do not 
lead to long-term durable remissions in the majority of cases. (7, 9, 11, 12) Relapses are systematically 
observed after BCMA-targeting CAR-T cell therapy, even in patients who achieved minimal residual 
disease negativity, with a median progression-free survival (PFS) of 12.1 months at the target dose of 450 
x 106 CAR-T cells in the KarMMa(12) trial and with a PFS rate of 86% at 9 months in the CARTITUDE-
1 study(13). Although transient downregulation or loss of BCMA expression has been described following 
BCMA CAR-T cell therapy, in most cases BCMA expression is maintained at progression(9, 11), 
suggesting patients may be able to respond to a subsequent BCMA-targeted modality. 
 
 
1.3 Belantamab Mafodotin 
 
Belantamab mafodotin (GSK2857916) is a first-in-class, dual-acting antibody-drug conjugate (ADC), 
comprised of an anti-B-cell maturation antigen (BCMA) afucosylated humanized immunoglobulin G1 
(IgG1) conjugated with the tubulin polymerization disrupting agent monomethyl auristatin F (MMAF).  
 
The normal function of BCMA is to promote cell survival by transduction of signals from two known 
ligands: B-cell activating factor from the tumor necrosis factor (TNF) family (BAFF/BLys) and a 
proliferation inducing ligand (APRIL). BCMA expression is restricted to B cells at later stages of 
differentiation, with expression on germinal center B cells in tonsil, blood plasma blasts, and long-lived 
plasma cells. BCMA is expressed in various B-cell malignancies, including multiple myeloma (MM), 
diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), chronic lymphocytic leukemia 
(CLL), and Waldenstrom’s macroglobulinemia (WM) at varying frequencies.  
 
Belantamab mafodotin binds to BCMA, is internalized, and releases free cys-mcMMAF, which disrupts 
the microtubule network, leading to cell cycle arrest and apoptosis. Belantamab mafodotin also mediates 
antibody-dependent cell-mediated cytotoxicity (ADCC) effector function directed toward BCMA-
expressing cells. The mechanisms of action of belantamab mafodotin are designed to enable anti-tumor 
activity of cells by ADCC activity (non-dividing), as well as ADC activity (dividing cells). Moreover, 
ADC-induced apoptosis by belantamab mafodotin was recently shown to be potentially immunogenic,  as 
measured by cell surface externalization of calreticulin (CRT) and secretion of high mobility group box 1 
(HMGB1) and adenosine triphosphate (ATP). 


 
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In the first-in-human, phase 1 DREAMM-1 study, belantamab mafodotin showed promising anti-myeloma 
activity, inducing responses in heavily pre-treated patients with relapsed or refractory multiple 
myeloma(14). DREAMM-2 built on the results from DREAMM-1, showing that the responses observed 
with single-agent belantamab mafodotin at both the 2.5 mg/kg and 3.4 mg/kg doses (every 3 weeks) 
compare favorably with the responses described with other approved treatments in patients who were 
heavily pretreated and refractory to immunomodulatory drugs and proteasome inhibitors and refractory or 
intolerant to anti-CD38 monoclonal antibodies (either alone or in combination).(15) Results from 
DREAMM-2 also showed that the safety profile of belantamab mafodotin was manageable, with no new 
safety concerns compared to DREAMM-1. Belantamab mafodotin was originally an approved treatment 
option for patients with relapsed or refractory multiple myeloma as a single-agent treatment, who have 
received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor 
(PI), and an immunomodulatory agent (IMiD).  
 
Additional studies of belantamab mafodotin in combination with standard of care or novel agents are 
ongoing. There is, however, currently no safety and efficacy data available from prospective trials of 
belantamab mafodotin in patients who previously received BCMA-directed CAR-T. Most recent trials of 
BCMA-targeted therapies excluded patients previously treated with other BCMA-targeted agents. The 
absence of clinical trial data on patients sequentially exposed to these agents poses a challenge, even though 
at least two BCMA-directed therapies (idecabtagene vicleucel (12) and belantamab mafodotin (15)) are 
commercially available. Conducting a clinical trial using belantamab mafodotin in patients who received 
BMCA-targeting CAR-T therapy will fulfill an unmet clinical need. 
 
The differing mechanisms of action between ADCs and CAR-T cells also support consideration of 
sequential use. CAR T-cell therapy by definition is dependent on patient T-cell function; in fact, 
premanufacturing T-cell phenotype and other parameters of “fitness” may be predictive of in vivo CAR-T 
cell expansion and clinical response.(9, 16) In contrast, ADCs work primarily through T cell-independent 
mechanisms. For belantamab mafodotin, these mechanisms include direct multiple myeloma cell apoptosis 
via internalization and release of the MMAF toxin, antibody-dependent cellular cytotoxicity, via binding to 
Fc receptors on natural killer cells and monocytes, and inhibition of prosurvival and proliferation signals to 
multiple myeloma cells through blockade of the BCMA receptor.(17, 18) While most recently published 
trials excluded patients with prior BCMA-directed therapy exposure, there are case reports of sequential 
use of these agents (19, 20) all demonstrating clinical activity of BCMA-targeted therapies in patients 
previously treated with other BCMA-targeted agents. The long-term response durability of all anti-BCMA 
agents remains unknown currently and the optimal sequencing of these therapies remains unclear.(21)  
 
There is anecdotal data in the published medical literature that demonstrates that patients receiving 
belantamab mafodotin after failing BCMA-targeting CAR-T therapy may experience response, without 
having increased or unanticipated toxicity. Cohen et al. described 2 patients who progressed after 1 BCMA-
targeted therapy and then responded to a subsequent BCMA-targeted therapy, including one patient who 
progressed 1 month after receiving BCMA CAR-T therapy (CD3z/4-1BB domains, lentiviral vector, 
University of Pennsylvania/Novartis study(9)) but responded with minimal response after two doses of 
belantamab mafodotin at 3.4 mg/kg IV every three weeks. Belantamab mafodotin was held for 6 weeks 
because of corneal toxicity, and then restarted at 2.5 mg/kg for two additional doses before she had myeloma 
progression. Gazeau et al. described two clinical cases of patients receiving sequential anti-BCMA 
therapies, illustrating the feasibility of this approach. One patient with RRMM received three sequential 
anti-BCMA therapies: 2 BCMA-targeting CAR T-cell infusions (ide-cel; stringent CR to first CAR-T 
infusion, but no response to second CAR-T infusion) followed by belantamab mafodotin. The patient 
achieved a very good partial response after three doses of belantamab mafodotin and was still in response 
five months later. A second RRMM patient remained in CR after ide-cel infusion, but then progressed with 
plasma cell leukemia. He was subsequently treated with belantamab mafodotin and had a rapid response, 
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Vaxman et al. reported the “real world” efficacy and safety of belantamab in 36 RRMM patients treated at 
Mayo Clinic between Sep 2020 and June 2021. (21) Twenty-seven patients (75%) underwent prior 
autologous transplantation. All patients were refractory to daratumumab, PIs, and IMiDs. Seven patients 
(19%) had received prior CAR-T therapy. This cohort of 36 patients was a heavily pretreated group of 
patients with a median of eight prior lines of therapy and a median time from diagnosis to first belantamab 
dose of seven years. Reasons for treatment discontinuation of belantamab mafodotin were progressive 
disease in 28 patients (77%) and keratopathy in three patients (8%). None of the patients that were treated 
with CAR-T before belantamab responded to therapy (two had stable disease, and five had progressive 
disease). These data emphasize the possibility of using sequential belantamab mafodotin in BCMA+ 
relapses after CAR-T therapy, which remain a functional target even after prior therapeutic pressure on this 
axis and suggest that this population should be included in future trials. 
 
The ALGONQUIN study is a phase I/II trial designed to evaluate the recommended phase II dose (RP2D), 
safety, and preliminary efficacy of belantamab mafodotin in combination with pomalidomide and 
dexamethasone (B-Pd) in patients with RRMM.(22) The initial data from the dose-escalation phase of the 
study identified 2.5 mg/kg in combination with standard dosing of pomalidomide/dexamethasone as the 
maximum tolerated dose (MTD)(23). Pomalidomide was administered at 4 mg days 1-21 Q28 days, 
dexamethasone weekly in conjunction with belantamab mafodotin single (1.92 or 2.5 mg/kg) Q4W, 2.5 
mg/kg loading dose followed by 1.92 mg/kg Q4W from cycle ≥2, 2.5 mg/kg dosed Q8W or Q12W or 
belantamab mafodotin split (2.5 or 3.4 mg/kg) equally on days 1 and 8 Q4W.  
 
As of Oct 2021, 56 patients were enrolled in dose cohorts receiving either 1.92 or 2.5 mg/kg belantamab 
mafodotin with pomalidomide/dexamethasone. Median age was 64 years and median prior lines of 
treatment was 2.5. All patients were PI and lenalidomide-exposed, 75% lenalidomide- and PI-refractory 
and 48% were daratumumab, lenalidomide, and PI-refractory. 54 patients were evaluable for response with 
median follow-up of 11.0 months. Across all dosing cohorts, overall response rate was 89%. The safety 
profile of B-Pd is consistent with that observed for pomalidomide/dexamethasone and belantamab 
mafodotin individually. Both dose cohorts (1.92 and 2.5 mg/kg Q4W) demonstrated deep and durable 
responses; however, the 2.5 mg/kg dose appeared to have better efficacy with PFS of 25.3 months vs. 16.2 
months. The 2.5 mg/kg Q8W dosing schedule has been selected for the part 2 cohort expansion based on 
optimized safety and efficacy: lower rate of Grade ≥3 blurred vision and neutropenia and superior PFS with 
2.5 mg/kg (vs. 1.92 mg/kg).  
 
BelaRd is an open-label, single-center, phase I/II study, aiming to enroll 66 newly diagnosed, transplant-
ineligible MM patients.(24) The study comprises two parts. Part 1 will evaluate three doses of belantamab 
mafodotin (2.5, 1.9, and 1.4 mg/kg) in combination with lenalidomide and dexamethasone (Rd), each given 
in an individual cohort of patients, and will determine the recommended phase 2 dose (RP2D). In this part, 
belantamab mafodotin will be administered Q8W and, depending on toxicity, dosing may be rescheduled 
to Q4W or Q12W. In Part 2, a single cohort of patients will be treated with belantamab mafodotin in the 
RP2D in combination with Rd to further evaluate the safety and clinical activity of this regimen. An initial 
safety analysis of Part 1 was presented at the 63rd ASH Annual Meeting in Dec 2021 and included 18 
patients who received ≥1 belantamab mafodotin dose and were followed up for ≥8 weeks. The median age 
of the patients was 72 years (range, 65–82). By the cut-off date (July 2021), patients had received a median 
of four treatment cycles, with 17 (94%) patients still being on treatment; one (6%) pt died due to pneumonia, 
unrelated to the study treatment. Sixteen (89%) patients experienced ≥1 treatment emergent adverse event 
(TEAE). In total, 11 (61%) patients had ≥1 TEAE grade 3/4, of which one was related to belantamab 
mafodotin; one (6%) patient experienced a serious adverse event (SAE). There were two cases of dose 
reduction and one case of dose delay. Regarding belantamab mafodotin-related ocular AEs, there were two 
cases of superficial punctuate keratopathy (grade 1 and 2 each, both in the 2.5 mg/kg cohort), 10 cases of 
decreased visual acuity (grade 1 [eight patients, 44%]: four in the 1.9 mg/kg cohort and four in the 1.4 
mg/kg cohort.  


 
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With 13-month follow-up in the DREAMM-2 trial, responses (achieved by 32% of patients) with single-
agent belantamab mafodotin 2.5 mg/kg were sustained(15, 25). The median overall survival was 13.7 
months, and the median duration of response in the 2.5 mg/kg group was 11 months. In the overall 
population, the median PFS was 2.8 months. In the belantamab mafodotin 2.5 mg/kg dose group, dose 
delays because of adverse events (AEs) occurred in 51 (54%) of 95 patients. Keratopathy was the most 
frequent reason for dose delays (45 of 95 patients; 47%). However, few (nine of 95 patients; 9%) 
permanently discontinued study treatment because of AEs; one patient discontinued for keratopathy and 2 
additional patients for blurred vision and reduced visual acuity. A post hoc analysis to evaluate the outcomes 
of responding patients in DREAMM2 who had prolonged dose delays (in which ≥3 treatment cycles were 
missed) was performed.(25) Of the patients who had a response in the 2.5 mg/kg group, 16 of 31 patients 
(52%) had ≥1 prolonged dose delay (>63 days, or three treatment cycles). Twelve of 16 patients (75%) 
either had deepening of response (38%) during delay or maintained their response (38%). These data 
provide indirect evidence that Q8W dosing (instead of Q3W dosing as is approved based on DREAMM-2) 
will likely still provide disease control and in addition, will likely reduce the incidence of ocular toxicity.  
 
Based on ongoing prospective ALGONQUIN and BelaRd clinical trials(22, 24), Q8W dosing will be 
selected for maintenance therapy using belantamab mafodotin in this trial. The incidence of ocular toxicity 
is evidently lower with Q8W dosing than more frequent dosing (Q3W-Q4W), based on preliminary clinical 
trials data. DREAMM-2 long-term follow-up data from 16 patients(25) who withheld belantamab 
mafodotin for >3 treatment cycles while waiting for resolution of ocular toxicity demonstrated no 
progression of multiple myeloma in 88% of patients, indicating that less frequent administration of 
belantamab mafodotin, such as Q8W, may be acceptable in maintaining disease control. With regards to 
starting dose of belantamab mafodotin for maintenance, since the objective of the study is to maintain 
response achieved with anti-BCMA CAR-T cell therapy, improve durability of response and prolong 
progression-free survival, a starting dose of 1.9 mg/kg will be selected, based on the limited efficacy data 
from ALGONQUIN and BelaRd trials. Traditionally, maintenance therapies using standard-of-care 
treatment options for multiple myeloma are used at reduced doses, in an effort to lower the incidence of 
toxicity. As these patients are already at lower risk of progression than patients with actively 
relapsed/refractory multiple myeloma, it is critical to use maintenance therapy at a dose and schedule that 
not only maintains response but also does not subject the patients at higher risk of toxicity. Therefore, 
belantamab mafodotin 1.9 mg/kg Q8W will be the starting dose level.   
 
1.4 Study Rationale 
 
While CAR T-cell therapy is dependent on patient T-cell function, (9, 16, 20) belantamab mafodotin works 
primarily through T-cell-independent mechanisms, including direct multiple myeloma cell apoptosis via 
internalization and release of the MMAF toxin, antibody-dependent cellular cytotoxicity, via binding to Fc 
receptors on natural killer cells and monocytes, and inhibition of prosurvival and proliferation signals to 
MM cells through blockade of the BCMA receptor. (26, 27) Belantamab mafodotin has also been postulated 
to induce immunogenic cell death,  (27) potentially priming an endogenous anti-MM immune response.  
 
BCMA expression does not appear to correlate with clinical response with CAR-T. (7, 10)  Baseline soluble 
BCMA (sBCMA) levels have been suggested to be inversely correlated with future response to treatment, 
(5, 28) though this correlation has not been observed in all studies. (29) Changes in sBCMA levels tend to 
correlate with the clinical status of MM patients during treatment. Patients who have responded to therapy 
have reduced sBCMA levels compared with patients with progressive disease. (5, 28) 
 
The loss of CAR-T persistence over time, and the complementary but distinct MOA of belantamab 
mafodotin compared with BCMA CAR-T support the sequential use of CAR-T and belantamab. Indeed, 


 
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early anecdotal reports suggest the benefit of belantamab mafodotin in patients progressing after BCMA 
CAR-T. (20, 30) It is therefore reasonable to consider that the use of belantamab mafodotin as maintenance 
will prolong remission status after BCMA CAR-T.   
 
This trial is investigating belantamab mafodotin maintenance therapy after anti-BCMA CAR-T, and it will 
be started three to four months (day 90–120 days) after CAR-T administration so as to allow recovery of 
blood counts, improvement in performance status, and resolution of non-hematologic toxicity (due to 
lymphodepleting chemotherapy and CAR-T). Statistically, it is prudent to have as narrow a time period as 
possible to start maintenance therapy, as the data used to arrive at the sample size is based on responses to 
the previous treatment (CAR-T therapy in this case) at a fixed time interval, such as day 90. For that reason, 
we have selected a narrow window after CAR-T therapy to start maintenance belantamab mafodotin (30 
days). Extending the time period to initiate maintenance therapy to say 90–180 days will be problematic 
given patients were seen to be progressing in the three to six months post-CAR-T period in pivotal CAR-T 
trial,(7, 12). Therefore, we require a time window to start maintenance belantamab mafodotin 90 to 120 
days after anti-BCMA CAR-T, ensuring adequate patient status and permitting operational flexibility in the 
setting of a research protocol. 
 
Keratopathy was the most common adverse event in DREAMM-2 trial (67 of 95 patients [71%] receiving 
belamaf 2.5 mg/kg).(15) These events were also the most common reason for dose reductions (22 of 95 
patients; 23%) and dose delays (45 of 95 patients; 47%) but rarely led to permanent discontinuation of 
treatment (one of 95 patients; 1%). The median time to the onset of the first keratopathy examination finding 
was 37. days (range, 19–143 days), with 66 of 68 patients who had keratopathy experiencing their first 
finding by treatment cycle 4. Seventy-seven percent patients recovered (resolution or return to baseline) 
from their first keratopathy examination finding of grade ≥2. The median time to recovery of the first 
examination finding was 86.5 days (range, 8-358 days). A post hoc analysis to evaluate the outcomes of 
patients with a response who had prolonged dose delays (in which ≥3 treatment cycles were missed) was 
performed. Of the patients who had a response according to IMWG criteria in the 2.5-mg/kg group, 16 of 
31 patients (52%) had ≥1 prolonged dose delay(25). Fourteen of 16 patients (88%) continued to experience 
a clinical benefit during the first prolonged delay. Taking into account these data on development of 
keratopathy at the approved administration schedule of q3weeks and the fact that myeloma control was 
maintained in patients having dose delays, and the goal of any maintenance therapy to continue treatment 
without dose interruptions and delays, patients will be receiving belantamab mafodotin q56 days. In 
addition, these patients do not have progressive disease and therefore, do not require use of belantamab 
mafodotin at the approved dosing schedule of q3weeks.  
 
Despite improvements in the outcome of myeloma with the use of BCMA-directed CAR-T, the treatment 
is not curative, and most patients will have progression of disease within a year. There is no standard 
approach to treatment after the CAR-T cell therapy. New treatment strategies must be developed for 
maintaining remissions in patients with myeloma following CAR-T and therefore, this trial is important 
because it has the potential to define a new approach to remission extension following BCMA CAR-T 
cell therapy for multiple myeloma. The risks associated with the use of belantamab mafodotin in the study 
are familiar, belantamab mafodotin is approved for the treatment of adult patients with relapsed or 
refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 
monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent..(15, 25) There is 
substantial data available on adverse events associated with belantamab mafodotin. Overall, 93 of 95 
patients (98%) receiving belamaf 2.5 mg/kg experienced at least 1 AE. (31) with treatment-related AEs 
occurring in 84 of 95 patients (88%). Fatal serious AEs occurred in three of 95 patients (3%). One of 
these events (sepsis) was considered treatment related. Grade 3 and 4 AEs were reported in 79 of 95 
patients (83%) and were treatment-related in 54 of 95 patients (57%). The most common any grade and 
grade ≥3 AEs were keratopathy, thrombocytopenia, and anemia.  
 


 
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1.5 Supplemental Studies 
 
Durable responses to antibody-drug conjugates (ADCs) are limited by acquired mechanisms of resistance. 
As part of the proposed clinical study, we aim to prospectively investigate mechanisms of resistance to 
belantamab mafodotin maintenance therapy following anti-BCMA CAR T-cell therapy. Understanding the 
mechanisms of resistance are critically important as we combine emerging immunotherapies. 
 
Preclinical studies of belantamab mafodotin demonstrated mechanisms of action including induction of 
apoptosis through caspase-3/7 pathways, antibody-dependent cell-mediated cytotoxicity (ADCC), and 
antibody-dependent cellular phagocytosis of myeloma cells.(27) As reviewed in Collins et al., resistance 
mechanisms directly affecting mechanisms of action include antibody-antigen interactions and also the 
delivery and response to the cytotoxic drug payload. (32) We anticipate that some patients will relapse 
despite belantamab mafodotin maintenance therapy. We hypothesize that acquired resistance to belantamab 
mafodotin will be found in these patients. 
 
To determine the resistance mechanisms acquired during belantamab mafodotin maintenance therapy 
following anti-BCMA CAR T-cell therapy, we propose to specifically investigate several possible 
mechanisms.  
 
1. To evaluate for antigen downregulation, we will perform flow cytometry on samples from each 
patient to document surface expression of BCMA on myeloma and plasma cells. (33) In addition 
to belantamab mafodotin, persistence of anti-BCMA CAR-T cells will also put selective pressure 
on BCMA expression by myeloma cells. CAR-T cells will be identified by protein L or 
recombinant BCMA staining during flow cytometry. Serum concentrations of soluble BCMA and 
its ligands, BAFF and APRIL, will be determined by ELISA. These studies will be performed on 
bone marrow aspirate samples obtained prior to the start of belantamab mafodotin maintenance 
therapy, and at approximately six-month intervals during the duration of the study. We will 
compare each patient’s samples over time using the screening as a baseline. The samples from each 
timepoint will be analyzed together allowing for mean fluorescent intensity measurements from 
flow cytometric analysis to be directly compared. The percentage of relapse of non-relapsed 
patients with antigen downregulation and the magnitude of the downregulation will be compared. 
 
Biallelic loss of BCMA was recently described as a mechanism of resistance to BCMA-directed 
immunotherapy(34). Samur et al. reported a patient with MM who suffered biallelic loss of BCMA 
and relapse following anti-BCMA CAR T-cell therapy. Sequencing analysis demonstrated a one 
copy deletion of 16p (which includes the BCMA locus on 16p13.13) and a second copy mutation 
which created an early stop codon in the gene. It is unknown how frequent BCMA loss/mutation is 
following BCMA-directed therapy. We propose to investigate this possibility in relapsed patients 
with no detectable membrane-bound or soluble BCMA. For these samples, we will work with the 
MCW Genomic Sciences and Precision Medicine Center to conduct sequencing analysis to detect 
allelic deletions and mutations. To determine when the genetic lesions were acquired, we will 
compare the relapse sample to prior samples from the patient (including diagnostic slides when 
available) and to CD138- cells (germline control). 
 
 
 
2. Acquired resistance to drug-mediated apoptosis and ADCC will be investigated in samples from 
patients who relapse following belantamab mafodotin maintenance. CD138+ cells (largely 
containing the myeloma population) will be isolated from patient bone marrow samples for these 
studies. Two to 4 ml of bone marrow aspirate will provide adequate numbers of CD138+ cells. We 
anticipate using the sample numbers depicted in the table below as these studies are labor intensive 


 
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and it is not feasible to perform them on samples from all the patients in the study. Bone marrow 
samples obtained prior to belantamab mafodotin therapy will serve as a baseline for determining 
resistance in relapsed patients. Samples from non-relapsed patients will serve as controls for 
differences that preceded BCMA-directed therapy. Samples will be selected as they accrue and up 
to the limits proposed in the following table. 
 
 
N= 
BM 
samples 
obtained prior to 
belantamab therapy 
BM samples obtained at 
relapse 
following 
belantamab therapy 
Total samples 
Relapsed 
12 
12 
12 
24 
Non-relapsed 
12 
12 
0 
12 
 
 
 
 
36 
 
a) CD138+ cells will be cultured with belantamab mafodotin in vitro. After two to three days, 
apoptosis will be assessed by flow cytometry for annexin V and propidium iodide staining 
and by bioluminescent detection of caspase-3/7 activity as described by Tai et al. (27) 
b) ADCC against patient CD138+ cells will be assayed using xCELLigence Real-Time Cell 
Analysis system. CD138+ cells (targets) will be tethered by using anti-CD9 antibodies. 
After addition of belantamab mafodotin and autologous CD138- cells or donor NK cells 
(effectors), cytotoxicity will be measured in real time.    
 
These studies will be performed by the MCW Cell Therapy Laboratory under Drs. Johnson and Kearl (refer 
to Appendix for logistical details). 
 
 
2 HYPOTHESIS AND OBJECTIVES  
 
We hypothesize that belantamab mafodotin as maintenance therapy post-CAR-T until progression will be 
safe, and will prolong progression-free survival (PFS) regardless of the degree of best response after CAR-
T. 
 
2.1 Primary Objectives 
 
To describe PFS of patients receiving belantamab mafodotin as maintenance (eight weekly) after anti-
BCMA CAR-T administration for relapsed/refractory myeloma. 
 
 
2.2 Primary Endpoint 
 
1. Twelve-month conditional progression-free survival (PFS), defined as the probability of being alive 
without progression/relapse or death at 12 months from the time of CAR-T administration 
conditional on being alive without progression/relapse at 3 months from the time of CAR-T. 
Follow-up time will be counted from the date of CAR-T cell infusion, left-truncated at the start of 
study treatment, to the date of first documentation of progression or death due to any cause. Patients 
last known to be alive and progression-free are censored at date of last contact.  
 
2.3 
Secondary Objectives 
 
1. To describe the toxicity profile of belantamab mafodotin given as maintenance after CAR-T. 
2. To describe progression-free survival.  
3. To describe changes in IMWG response for patients not in CR when initiating therapy with 


 
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belantamab mafodotin as post-CAR-T maintenance. 
4. To identify the rate of elimination of MRD (<10-5) in patients with myeloma at baseline and after 
starting belantamab mafodotin as post-CART maintenance (at screening/baseline, and after two, 
six, and 12 cycles).  
5. Patient-reported quality of life studies (QoL).  
6. To describe the overall survival for the entire cohort from the time of CAR-T administration. 
 
2.4 
Secondary Endpoints 
 
1. Best objective response on the trial (by IMWG criteria). 
2. Progression-free survival. 
3. Negative MRD (≤10-5, by clonoSEQ®), including imaging plus MRD-negativity (≤10-5 in bone 
marrow and no area of PET-CT FDG uptake greater than mediastinal blood pool or surrounding 
normal tissue.  
4. Duration of response on maintenance. 
5. Time to progression/relapse after CAR-T. 
6. Overall survival for the entire study population. 
7. Adverse events on the trial.  
8. QoL parameters. 
 
2.5 Exploratory Objectives 
 
1. Exploratory: 
myeloma 
cell 
BCMA 
expression 
by 
flow 
cytometry 
and 
soluble 
BCMA/BAFF/APRIL levels will be monitored (at baseline, two, six, and 12 cycles). 
 
2.6 Exploratory Endpoints 
 
1. Baseline and on-treatment sBCMA/BAFF/APRIL and BCMA expression on myeloma cells. 
 
 
3 STUDY DESIGN 
 
3.1 General Description 
 
This is a multicenter phase II, open-label study evaluating the efficacy and safety of belantamab mafodotin 
maintenance in participants with RRMM who have received commercially available anti-BCMA CAR-T 
cell therapy. 
 
Subjects will be screened and enrolled 60–120 days after anti-BCMA CAR-T and receive belantamab 
mafodotin as maintenance therapy. Each maintenance cycle will have a duration of 56 days (+/- three days) 
and belantamab mafodotin will be administered at a dose of 1.9 mg/kg IV on day 1 of each cycle. 
 
The study will include a screening period, central eligibility confirmation, a treatment period, and a follow-
up period. During the 30-day screening period, participants will be evaluated for study eligibility per 
protocol as defined in the inclusion/exclusion criteria. Eligible participants must have a confirmed diagnosis 
of MM, been previously treated with anti-BCMA CAR-T cell therapy and have achieved at least SD, and 
not achieved CR/sCR. Following screening, central eligibility confirmation occurs and participants will be 
started on maintenance therapy within 90–120 days after receiving CAR-T cell therapy. Subjects will be 
enrolled in the trial within 30 days of screening procedures (consent not included) and start treatment within 
the 90–120 days window after anti-BCMA CAR-T.  


 
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During the treatment period, subjects will receive belantamab mafodotin as maintenance therapy. Each 
treatment cycle will have a duration of 56 days (i.e., eight weeks +/- three days). Safety and disease 
assessments will be performed regularly according to the Schedule of Activities.  
 
For all subjects, disease evaluations will continue to be performed at least every 56 days (± seven days) 
until confirmed PD, death, start of a new anti-cancer treatment, withdrawal of consent, or loss to follow-
up, whichever occurs first. Traditional efficacy assessment will be performed every cycle by serum protein 
electrophoresis and immunofixation and serum-free light chains, and after every two cycles by 24-hour 
urine protein electrophoresis and immunofixation. Minimal residual disease (MRD) assessment by next 
generation sequencing (clonoSEQ®), BCMA expression on bone marrow plasma cells and soluble 
BCMA/BAFF/APRIL will occur at screening and after two, six, and 12 cycles of belantamab mafodotin 
maintenance (refer to correlative schedule). In case of PD, subjects will be followed to ascertain subsequent 
anti-cancer therapy, if any, and survival status every six months (± 30 days) until withdrawal of consent, 
lost to follow-up, death, or the end of the study. Patients who discontinue treatment prior to progression 
will continue standard-of-care follow-up every three months until progression or start of another treatment 
(whichever comes first), then they will continue to long-term follow-up. 
 
3.2 Study Population 
 
Adult patients with myeloma who are within 90–120 days after receiving BCMA-directed CAR-T as 
standard of care for relapsed/refractory myeloma and having received at least four prior lines of therapy 
(including a PI, IMiD and anti-CD38 monoclonal antibody) before CAR-T.  
 
3.3 Estimated Time for Completion of Study Enrollment 
 
The study will reach primary enrollment completion in approximately 24 months from the time the study 
opens to accrual. 
 
3.4 Estimated Time for Study Completion 
 
The study will reach study completion in approximately nine years (four years for completion of treatment 
for all patients, and five years of long-term survival follow-up) from the time the study opens to accrual. 
 
 
4 SUBJECT PARTICIPATION, DISCONTINUATION AND 
WITHDRAWAL 
 
The MCW sIRB is the IRB of record for all participating sites. All sites must follow MCW sIRB 
requirements and policies regarding subject participation, found here: 
 
https://www.mcw.edu/HRPP/Policies-Procedures.htm 
 
4.1 Subject Status 
 
Subject statuses throughout the trial are defined as follows:   
 
• 
Prescreening: preconsent (subject considering trial or study staff considering patient for the trial 
per institutional recruitment methods). 
• 
Screening: period after consent, but prior to eligibility confirmation. 


 
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• 
Consented: consented, prior to eligibility confirmation. 
• 
Eligible: the local investigator confirms all eligibly criteria apply. 
• 
On study/enrolled: date eligibility is confirmed. 
• 
On arm: date of enrollment. 
• 
On treatment: first day treatment was given to the last day treatment was given. 
• 
Off treatment: the last day treatment was given. 
• 
Off arm: the last day treatment was given. 
• 
On follow up: from last day of treatment to the end of follow-up period. 
• 
Off study: follow-up period completed, with no additional data gathered. 
• 
Withdrawn: subject fully withdraws consent (i.e., refuses ALL follow-up, even survival) or is taken 
off study by the local PI. 
 
4.2 Prescreening and Screening Log 
 
The MCW study PI regularly reviews screen failure reasons to understand barriers to accrual and consider 
amending eligibility criteria. Screen failures are defined as participants who were considered for the trial to 
participate in the clinical trial with or without consent but are not subsequently assigned to the study 
intervention or enrolled in the study. 
  
Prescreening/screening logs are maintained at each site and provided deidentified to MCW upon request. 
 
4.3 Consent  
 
Investigators or their designees will identify potentially eligible subjects from their clinics, subject self-
referrals, referrals from other clinicians, and/or other sIRB-approved recruitment methods. No study 
conduct, including subject screening, can occur until after sIRB initial study approval and an official 
activation letter. 
 
A written, signed informed consent form (ICF) and a Health Insurance Portability and Accountability Act 
(HIPAA) authorization (as applicable) must be obtained before any study-specific assessments are initiated.  
 
After consent, the following occur: 
• 
The site should email the MCW Multisite Team email as soon as possible.  
• 
An OnCore® new subject entry must occur within 24 hours of consent. 
• 
A case/subject/sequence number is assigned in OnCore® from the site in sequence (i.e., inputted 
from the site staff, not generated by OnCore®). 
• 
Sites enter the case number according to the following template “Site-EMBRACE-001” (unless 
otherwise specified by the MCW Multisite Team), where “site” is an abbreviation of the site name 
(e.g., MCW), EMBRACE indicates the trial, and “001” is the sequential subject who consented to 
the trial at the site (e.g., the first consented subject at MCW would MCW-EMBRACE-001). 
 
4.4 Screening Procedures 
 
Refer to the study calendar of events. 
 
Visit procedures that were performed as standard of care prior to consent (without the specific intent to 
make the subject eligible for the trial), may count toward screening tests and eligibility if they are within 
the screening window. 
 
4.5 Central Eligibility Confirmation 


 
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Central eligibility confirmation occurs in the following manner: 
 
Participating sites prepare eligibility documents.  
• 
The local PI or designated sub-investigator must review and sign/date (or confirm via email) the 
eligibility criteria section.  
• 
It is highly recommended that participating sites include written dates and/or values of procedures 
next to all criteria on the right margin of the page (e.g., ‘ECOG score is 0 on date 01/01/1900).  
• 
Subject initials and study case/sequence number should be written on each page of the eligibility 
pages and supporting source documents — all of which must be deidentified. 
• 
Supporting source documents are required for all item’s eligibility criteria (i.e., pathology report, 
prior therapy history, age, consent, etc.), consent, and documentation of consent process (with key 
information highlighted or circled if possible, to aid in auditing and quick central eligibility 
confirmation). 
 
Central Eligibility Confirmation  
• 
The eligibility documents required above should be uploaded into the shared study folder (site 
folder access shared by the MCW Multisite Team) or emailed, and sites should notify the MCW 
Multisite Team email and MCW PI via email of completion. Participating site staff must inform 
the MCW PI if the MCW Multisite Team email returns an out-of-office email reply. If sites have 
an issue uploading into Box, emailed documents will suffice until the issue is resolved. MCW 
eligibility confirmation may occur via email if a physical signature would significantly delay 
enrollment.  
• 
The MCW PI or MCW sub-investigator, with the assistance from the MCW Multisite Team, will 
review, request additional information, and confirm subject eligibility within approximately one 
business day of receipt of documents via email (Monday through Friday, excluding holidays. Sites 
must email the MCW Multisite Team prior to a Friday enrollment or holiday.)  
• 
Eligibility criteria within a timeframe of “enrollment” means central eligibility confirmation 
from MCW (not the local investigator). Sites must ensure the one business day window for 
central confirmation does not put an eligibility procedure outside of the required time window. If 
this is potentially an issue, sites should notify the MCW Multisite Team email and MCW PI with 
supporting documents prior to intended enrollment date. 
 
*Note (for MCW only): After signoff from the MCW enrolling investigator, MCW staff should provide the 
MCW Multisite Team central eligibility documents for their review and clarification/documentation 
requests. The MCW study PI (or Study Chair) will then sign off (or confirm via email) for central eligibility 
confirmation (if they are unavailable, another MCW designee who is not the local enrolling investigator 
may sign off). If the enrolling investigator is the MCW study PI, MCW staff should provide the MCW 
Multisite Team signed central eligibility documents for their review and clarification/documentation 
requests, then the Study Chair (or vice versa study PI) will sign off (or confirm via email) for central 
eligibility confirmation (if they are unavailable, another MCW investigator may sign off, unless that is not 
possible). 


Subject Initials: _____________ 
 
Subject Study ID: _______________ 
Enrolling physician signature: _________________________  Date: _____________ 
 
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4.6 Eligibility Criteria 
 
Study staff must adhere to MCWCC CTO SOPs regarding eligibility 
review/confirmation. 
 
No waivers of protocol eligibility will be granted. When clinical factors relating 
to an eligibility item are unclear or questionable, the study PI (Meera Mohan, 
memohan@mcw.edu) can only provide guidance or clarification on eligibility. 
 
Inclusion Criteria 
 
Each subject must meet all the following inclusion criteria to be enrolled in the 
study: 
1. 
Diagnosis of multiple myeloma with measurable disease (at the time of diagnosis: 
serum M-protein ≥ 0.5 g/dL or urine M-protein ≥200 mg/24 hour or involved 
serum-free light chain ≥10 mg/dL provided that the ratio of involved/uninvolved 
light chain is abnormal). Patients with no biochemically measurable disease may 
be enrolled if bidirectionally measurable plasmacytomas or bone marrow 
plasmacytomas >10% are present prior to CAR-T infusion (sites must explicitly 
identify these patients to the MCW Multisite Team upon enrollment, as only four 
of these patients will be permitted on study, after which no future patients will be 
permitted to be enrolled). 
2. 
Received at least four prior lines of therapy (including a PI, IMiD, and anti-CD38 
monoclonal antibody – note radiation therapy is considered a line of therapy) 
given before anti-BCMA CAR-T cell therapy, and has not progressed/relapsed 
after receiving CAR-T therapy.  
3. 
Achieved at least SD to CAR-T therapy and remained progression-free after anti-
BCMA CAR-T administration until enrollment (this requirement is also necessary 
prior administration of first study drug). 
4. 
Voluntary consent (per sIRB requirements) must be given before performance of 
any study-related procedure not part of standard medical care, with the 
understanding that consent may be withdrawn by the subject at any time without 
prejudice to future medical care. 
5. 
Age ≥ 18 years. 
6. 
Life expectancy ≥ six months. 
7. 
Eastern Cooperative Oncology Group (ECOG) performance status 0–2.  
8. 
Creatinine clearance (CrCl) ≥ 30 mL/min/1.73 m² (using formula MDRD). 
9. 
Adequate hepatic function evidenced by AST and ALT ≤ 2.5 x ULN, bilirubin ≤ 
1.5 x ULN (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated 
and direct bilirubin <35%). 
10. Adequate bone marrow function evidenced by hemoglobin ≥8 g/dL, platelets 
≥75,000/mm3 (without transfusion of platelets in the prior seven days) and 
absolute neutrophil count ≥1,500/mm3 (growth factors are allowed during 
screening, but not within seven days prior to obtaining this result).  
11. Spot urine (albumin/creatinine ratio) < 500 mg/g (56 mg/mmol) OR urine dipstick 
negative/trace (if ≥ 1+ only eligible if confirmed < 500 mg/g (56 mg/mmol) by 
albumin/creatinine ratio (spot urine from first void). 
12. Female participants: 
Contraceptive use by women should be consistent with local regulations regarding 
the methods of contraception for those participating in clinical studies. 


Subject Initials: _____________ 
 
Subject Study ID: _______________ 
Enrolling physician signature: _________________________  Date: _____________ 
 
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A female participant is eligible to participate if she is not pregnant or 
breastfeeding, and at least one of the following conditions applies: 
 
Is not a woman of childbearing potential (WOCBP). 
OR 
Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of <1% per year), preferably with low user dependency during the 
intervention period and for four months after the last dose of belantamab 
mafodotin and agrees not to donate eggs (ova, oocytes) for the purpose of 
reproduction during this period. The investigator should evaluate the effectiveness 
of the contraceptive method in relationship to the first dose of study intervention. 
• 
WOCBP must have a negative highly sensitive serum pregnancy test within 
72 hours of dosing on C1D1 and agree to use a highly effective method of 
contraception during the study and for four months after the last dose of 
belantamab mafodotin.  
• 
Additional requirements for pregnancy testing during and after study 
intervention are provided in Appendix 4 and the study calendar (schedule of 
activities).  
13. Male participants: 
Contraceptive use by men should be consistent with local regulations regarding 
the methods of contraception for those participating in clinical studies.  
 
Male participants are eligible to participate if they agree to the following from the 
time of first dose of study until six months after the last dose of belantamab 
mafodotin to allow for clearance of any altered sperm:  
 
Refrain from donating sperm. 
 
AND either: 
 
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent. 
 
OR 
 
Must agree to use contraception/barrier as detailed below: 
• 
Agree to use a male condom, even if they have undergone a successful 
vasectomy and female partner to use an additional highly effective 
contraceptive method with a failure rate of <1% per year as described in 
when having sexual intercourse with a WOCBP (including pregnant 
females). 
 
 


Subject Initials: _____________ 
 
Subject Study ID: _______________ 
Enrolling physician signature: _________________________  Date: _____________ 
 
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Version Date: 12/29/2022 
Exclusion Criteria 
Patients meeting any of the following exclusion criteria are not to be enrolled in 
the study: 
1. Prior exposure to belantamab mafodotin before enrollment on the trial, including 
before administration of commercial anti-BCMA CAR-T. 
2. Evidence of progression/relapse after BCMA CAR-T before enrollment (this 
requirement is also necessary prior to administration of first study drug). 
3. Subject has achieved CR/sCR at the time of enrollment (this requirement is also 
necessary prior to administration of first study drug). 
4. 
Patient was given BCMA CAR-T under EAP (expanded access protocol) for non-
conforming product. 
5. 
Subject progressed on a prior anti-BCMA therapy before receiving commercial 
anti-BCMA CAR-T. 
6. 
Any previous treatment-related adverse events higher than grade 1 at enrollment 
(except for alopecia and grade 2 neuropathy). 
7. 
Acute active infection requiring treatment within 14 days of enrollment (this 
requirement is necessary also prior administration of first study drug). 
8. 
Current or prior involvement of central nervous system by multiple myeloma. 
9. 
Smoldering multiple myeloma or POEMS. 
10. Pregnant or lactating females. 
11. Major surgery or prior treatment with a monoclonal antibody within 30 days prior 
to enrollment (this requirement is necessary also prior administration of first study 
drug). 
12. Evidence of cardiovascular risk including any of the following: 
a. Evidence of current clinically significant untreated arrhythmias, including 
clinically significant ECG abnormalities including second-degree (Mobitz 
Type II) or third-degree atrioventricular (AV) block. 
b. History of myocardial infarction, acute coronary syndromes (including 
unstable angina), coronary angioplasty, or stenting or bypass grafting within 
three months of enrollment. 
c. Class III or IV heart failure as defined by the New York Heart Association 
functional classification system (NYHA, 1994)  
d. Uncontrolled hypertension. 
13. Nonhematologic malignancy within the past three years with the exception of a) 
adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid 
cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason 
score 6 or less with stable prostate-specific antigen levels; or d) cancer considered 
cured by surgical resection or unlikely to impact survival during the duration of 
the study, such as localized transitional cell carcinoma of the bladder or benign 
tumors of the adrenal or pancreas. 
14. Participant must not have current corneal epithelial disease except mild changes in 
corneal epithelium. 
15. Participant must not have current unstable liver or biliary disease defined by the 
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal 
or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic 
chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) 
or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry 
criteria. 
16. Participant must not have presence of active renal condition (infection, 
requirement for dialysis or any other condition that could affect participant’s 


Subject Initials: _____________ 
 
Subject Study ID: _______________ 
Enrolling physician signature: _________________________  Date: _____________ 
 
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safety). Participants with isolated proteinuria resulting from MM are eligible, 
provided they fulfil inclusion criteria. 
17. Participant must not use contact lenses while participating in this study, unless 
directed by an ophthalmologist. 
18. Participant must not have used an investigational drug or approved systemic anti-
myeloma therapy (including systemic steroids) within 14 days or five half-lives, 
whichever is shorter, preceding enrollment (this requirement is also necessary 
prior administration of first study drug). Participant must not have received 
radiation therapy within 14 days of enrollment. 
19. Participant must not have had plasmapheresis within seven days prior to 
enrollment (this requirement is also necessary prior administration of first study 
drug). 
20. Participant must not have had major surgery ≤ four weeks prior to enrollment (this 
requirement is also necessary prior administration of first study drug). 
21. Participant must not have any evidence of active mucosal or internal bleeding. 
22. Participant must not have known immediate or delayed hypersensitivity reaction 
or idiosyncratic reactions to belantamab mafodotin or drugs chemically related to 
belantamab mafodotin, or any of the components of the study treatment. 
23. Participant must not have known HIV infection (screening test not required), 
unless the participant can meet all of the following criteria: 
a. Established anti-retroviral therapy (ART) for at least 4 weeks and HIV 
viral load <400 copies/mL 
b. CD4+ T-cell (CD4+) counts ≥350 cells/uL 
c. No history of AIDS-defining opportunistic infections within the last 12 
months  
 
24. Participant must not have presence of hepatitis B surface antigen (HBsAg), or 
hepatitis B core antibody (HBcAb) at screening or within three months prior to 
first dose of study treatment. Note:  presence of hepatitis B surface antibody 
(HBsAb) indicating previous vaccination will not exclude a participant. 
25. Participant must not have positive hepatitis C antibody test result or positive 
hepatitis C RNA test result at screening or within three months prior to first dose 
of study treatment.   
Note: Participants with positive hepatitis C antibody due to prior resolved disease 
can be enrolled, only if a confirmatory negative hepatitis C RNA test is obtained. 
Note: Hepatitis RNA testing is optional and participants with negative hepatitis C 
antibody test are not required to also undergo hepatitis C RNA testing. 
26. Prior allogenic stem cell transplant within one year before enrollment, or current 
evidence of GvHD, or on systemic immunosuppressive therapy for GvHD at least 
six weeks before enrollment. NOTE – Participants who have undergone syngeneic 
transplant will be allowed, only if no history of GvHD 
27. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, 
organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin 
changes) or active plasma cell leukemia at the time of screening. 
28. Any serious and/or unstable pre-existing medical, psychiatric disorder or other 
conditions (including lab abnormalities) that could interfere with participant’s 
safety, obtaining informed consent or compliance to the study procedures. 
29. Administration of live or live-attenuated vaccines are contraindicated 30 days 


Subject Initials: _____________ 
 
Subject Study ID: _______________ 
Enrolling physician signature: _________________________  Date: _____________ 
 
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Version Date: 12/29/2022 
prior to the first dose of study treatment. Killed or inactivated vaccines may be 
administered; however, the response to such vaccines cannot be predicted. 
 
 
“I have reviewed all inclusion/exclusion criteria and confirm the subject is eligible.” 
 
 
Enrolling Investigator Name (print) 
 
 
 
Enrolling Investigator Signature 
Date 
 
 
 
“This subject is eligible for the study and considered on study/enrolled.” 
 
 
MCW Study PI or Study Chair (print) 
*or designee name  
 
 
 
MCW Study PI or Study Chair Signature (or 
email confirmation)  
*or designee 
Date 
 
 


 
 
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4.7 Discontinuation of Study Treatment, Withdrawal, and Compliance 
 
Discontinuation from the study treatment does not mean discontinuation from the study. Subject will be 
considered in follow-up, study procedures should still be completed as indicated by the study protocol, and 
AEs/SAEs will continue to be reported according to this protocol. 
 
It is preferred that in cases of intended discontinuation from study intervention that are not due to adverse 
events or of immediate subject safety concern participating sites email the MCW Multisite Team prior to 
the discontinuation to determine if any efforts/actions might be safely taken to continue subject 
participation. 
 
The MCW Multisite Team should be notified via the MCW Multisite Team email within 24 hours of 
discontinuation of study intervention, describing the nature of the discontinuation. OnCore® subject status 
(treatment and follow-up tabs) and discontinuation eCRF should be completed within 24 hours of 
discontinuation.  
 
In the absence of treatment delays due to adverse events (refer to dose modification section and holds in 
Section 5), study treatment/intervention may continue until:  
• 
Disease progression.  
• 
General or specific changes in the subject’s condition renders the subject unacceptable for further 
treatment in the investigator’s judgment.  
• 
Inter-current illness that prevents further treatment administration.  
• 
Subject decides to withdraw from the study.  
• 
The subject has significant noncompliance with the protocol (see below).   
• 
Unacceptable adverse event(s).  
• 
Study discontinuation or closure.  
 
Subjects who sign the informed consent form and are enrolled but do not receive the study intervention 
may be replaced. Subjects who sign the informed consent form, enroll and receive the study intervention, 
but subsequently withdraw, or are withdrawn or discontinued from the study will not be replaced.  
 
Consent Withdrawal 
 
A subject may decide to withdraw from the study at any time. Sites must follow the sIRB SOPs regarding 
consent withdrawal.  
 
If a subject intends on withdrawing consent, sites should confirm which of the following options the subject 
chooses, document the discussion, upload the documentation to shared site study folder and update 
OnCore®, and email the MCW team email: 
 
a. Full consent withdrawal, with no study follow-up. 
b. Selective consent withdrawal from interventional portion of the study, but agrees to continued 
follow-up of associated clinical outcome information. 
 
Investigator-initiated Withdrawal 
 
The investigator will withdraw a subject whenever continued participation is no longer in the subject’s best 
interests. Reasons for withdrawing a subject include, but are not limited to, disease progression, the 
occurrence of an adverse event or a concurrent illness, a subject’s request to end participation, a subject’s 
noncompliance (see below) or simply significant uncertainty on the part of the investigator that continued 


 
 
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participation is prudent. Sites should notify the MCW Multisite Team (via the MCW Multisite Team email) 
within 24 hours in such cases. The reason for study withdrawal and the date the subject was removed from 
the study must be documented in OnCore®. 
 
Subject Compliance 
 
The study team should re-educate the subject on the importance of compliance as necessary and document 
noncompliance. If this is an ongoing issue, then, the MCW PI should be contacted to determine whether 
the subject should continue on trial. 
 
4.8 Lost to Follow-up 
 
The following actions should be taken if a participant fails to return to the clinic for a required study visit 
and/or is unable to be reached for follow-up: 
 
• 
The investigator or designee should make every effort to regain contact and/or reschedule a missed 
visit with the participant. 
• 
A participant is deemed lost to follow-up if his/her status cannot be obtained after all of the 
following occurs at two consecutive scheduled protocol calendar time points: 
o Three telephone calls (at least one day apart) from the study team are unanswered.  
AND  
o A letter to the participant’s last known mailing address goes unanswered (refer to Appendix 2). 
Sites may use their own letter but must follow sIRB policies regarding approval. 
AND 
o These contact attempts should be documented in the participant’s medical record or study file.  
 
• 
Update OnCore® (follow-up tab and eCRF) when a participant is officially considered lost to 
follow-up. 
• 
If a subject is considered lost to follow-up, but subsequently contacts the participating site study 
team, the subject should be considered in follow-up again, with subject approval, and the study 
team must notify the MCW Multisite Team via the MCW Multisite Team email. 
 
4.9 Accrual Suspension and Closure 
 
The MCW Multisite Team facilitates the suspension and closing of accrual in the following manner: 
 
• 
The MCW Multisite Team sends accrual reports periodically and notifies sites when nearing 
suspension requirements. 
• 
Sites must inform the MCW Multisite Team (via the MCW Multisite Team email) of any new or 
potential consents by the end of the business day. 
• 
The MCW Multisite Team will inform participating sites when the actual or potential number of 
consents equals the number of available enrollment slots, at which time new consenting is 
suspended. 
• 
If one of the consented subjects (in screening) is ineligible, accrual reopens until a subject is 
consented to fill that accrual spot. 
• 
If all the consented subjects end up being eligible, the MCW Multisite Team emails an accrual 
closure notice.  
 
 
 


 
 
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4.10 End of Study Definition 
 
A participant is considered to have completed the study if he or she completed all phases of the study, 
including the last visit or the last scheduled procedure shown in the calendar of events or has been 
discontinued. 
 
4.11 Study Discontinuation and Closure 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause 
(as determined by the MCW Multisite Team, DSMC, drug manufacturers, FDA, and/or sIRB). Written 
notification documenting the reason for study suspension or termination will be provided by the suspending 
or terminating party to study participants, investigator, funding agency, the investigational new drug (IND) 
sponsor and regulatory authorities. If the study is prematurely terminated or suspended, the MCW Principal 
Investigator (PI) and MCW Multisite Team will promptly inform study sites, the MCW Institutional Review 
Board (sIRB), and sponsor, and will provide the reason(s) for the termination or suspension. Study 
participants will be contacted, as applicable, and be informed of changes. Participating sites will adhere to 
the sIRB policies. 
 
 
5 TREATMENT PLAN 
 
5.1 Treatment 
 
Subjects will receive belantamab mafodotin as maintenance therapy. Belantamab mafodotin will be 
administered IV over approximately 30 minutes at the recommended dose of 1.9 mg/kg IV day 1 of every 
56-day cycle (+/- 3 days).  
 
Maintenance therapy with belantamab mafodotin will continue until progressive disease (PD), death, 
unacceptable toxicity, withdrawal of consent or end of study, whichever occurs first. Dose interruptions or 
reductions may be required to address potential drug-associated toxicities.  
 
The dose to be administered will be based on actual body weight calculated at baseline (cycle 1 day 1). 
However, if the change in body weight is greater than 10%, the dose will be recalculated based on the actual 
body weight at the time of dosing. The dose may be reduced to address toxicity as described in Section 5.2. 
 
Arm 
Belantamab mafodotin 
(Day 1 of every 56-day cycle) 
A 
1.9 mg/kg IV over at least 30 minutes 
 
5.2 Dose Modifications 
 
5.2.1 Adjustments Due to Body Weight 
 
The actual body weight in kg at baseline (on cycle 1 day 1) will be used for dose calculation of belantamab 
mafodotin in all subjects during the treatment period. As noted above, if the change of body weight is 
greater than 10%, the dose should be recalculated based on the actual body weight at the time of dosing. 
 


 
 
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5.2.2 Dose Reductions for Toxicity 
 
Permitted dose reductions for belantamab mafodotin are shown in Table 2. Belantamab mafodotin-related 
AEs are summarized in Table 3. General dose modification and management guidelines for drug-related 
AEs not otherwise specified are summarized in Table 3. Dose modification guidelines for cornea-related 
AEs associated with belantamab mafodotin are summarized in Table 4.  
 
 
 
 
 
Table 2. Permitted dose reduction for belantamab mafodotin 
 
Starting dose 
First reduction 
Additional reduction 
1.9 mg/kg 
1.4 mg/kg 
If dose delays/modifications detailed below do not satisfy the 
conditions needed to avoid another dose reduction, the subject must 
be discontinued. Recommend emailing study PI (cc: MCW Multisite 
Team) prior to this occurring whenever possible. 
 
Only one dose reduction (to 1.4 mg/kg) is permitted from the starting dose of 1.9 mg/kg. If the participant 
cannot tolerate the drug after the allowed dose reduction of belantamab mafodotin, the participant will 
permanently discontinue treatment for lack of tolerability. Any dose level below 1.4 mg/kg is not planned. 
In case of full resolution of symptoms which lead to dose reduction, further treatment at the previous dose 
level may be considered by the investigator, after consultation with the sponsor-investigator (cc: MCW 
Multisite Team email). 
 
Dosing delays are permitted in the case of toxicity, medical/surgical events, or for logistical reasons not 
related to study therapy (e.g., elective surgery, unrelated medical events, subject’s vacation/holidays, but 
not for subject’s decision to delay treatment). The reason for any dose delay should be documented in the 
subject's eCRF and clinic record.  
 
Table 3a. Dose modifications 
 
*Note these toxicities are known to be associated with use of belantamab mafodotin. The following actions 
should be taken whether or not the toxicity may be attributed to other possible causes. 
 
 
 
Toxicity 
Grade/description of 
toxicity 
Action 
Elevated serum creatinine, 
which cannot be explained by 
concomitant sepsis, TLS, 
other severe condition with 
fever, or dehydrationa 
If absolute serum creatinine 
increases from baseline by >0.5 
mg/dL 
 
• 
Repeat serum creatinine or eGFR within 48 hours. 
• 
If confirmed: withhold therapy, institute treatment 
and monitoring as clinically indicated, and follow 
for resolution. 
• 
Discuss any further dosing with study PI (cc:  
MCW Multisite Team email). 
Serum creatinine ≥Grade 3 
(compared to baseline) 
>3.0 mg/dL from baseline Or 
3.0–6.0 X ULN 
• Provide appropriate medical treatment. 
• Hold treatment with belantamab mafodotin. 
• Discuss with study PI to determine 
appropriateness of further dosing (cc: MCW 
Multisite Team email). 
Spot urine 
(creatinine/albumin ratio)  
>2,000 mg/g  
(or 224 mg/mmol) 
• Retest (at least seven days apart). 
• If not confirmed, continue belantamab mafodotin at 
current dose. 
• If confirmed on retest and no clear evidence of 
disease progression. 


 
 
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Version Date: 12/29/2022 
Toxicity 
Grade/description of 
toxicity 
Action 
o Interrupt treatment with belantamab mafodotin. 
o Repeat testing within four weeks. 
-If spot urine ≤2,000 mg/g (224 mg/mmol), may restart 
belantamab mafodotin with one dose-level reduction. 
- If spot urine remains >2,000 mg/g (224 mg/mmol) after 
four weeks, permanently discontinue belantamab 
mafodotin and withdraw participant from study; 
provide treatment as clinically indicated and follow 
for resolution. 
Urine dipstick 
2+ 
• May continue belantamab mafodotin dosing. 
• Confirm by quantitative assessment using 
albumin/creatinine (spot urine from first void).  
If albumin/creatinine ≥2000 mg/g, at the next cycle 
follow guidance above for spot urine. 
 
>3+ 
Interrupt treatment and follow-up for recovery. 
Implement quantification of albumin/creatinine ratio. 
Thrombocytopenia (on days 
of dosing)  
 
Grade 3 (Platelet count 25,000 to 
less than 50,000/mcL) 
• No bleeding: continue treatment with one dose-level 
reduction.  
• Consider reverting to previous dose once 
thrombocytopenia recovered to grade 2, or less. 
• With bleeding: withhold the dose, continue treatment 
after recovery with one dose-level reduction. 
• Consider additional supportive treatment (e.g., 
transfusion), as clinically indicated and per local 
practice. 
Grade 4 (Platelet count less than 
25,000/mcL) 
• Withhold the belantamab mafodotin dose. Consider 
restarting with one dose-level reduction if recovered 
to ≤ grade 3, only if there is no active bleeding at 
time of treatment restart. 
• If thrombocytopenia is considered disease related, is 
not accompanied by bleeding, and recovers with 
transfusion to >25 x109/L, continuing treatment with 
dose reduction may be considered after discussion 
with the sponsor-investigator (cc: MCW Multisite 
Team email). 
Febrile neutropenia 
 
Grades 3–4 
Defined as: single temperature of 
38.3°C, or sustained 38°C for >1 
hour AND ANC <1.0×109/L 
• Withhold belantamab mafodotin and immediately 
hospitalize participant with appropriate management, 
per local institutional guidance. 
• Consider additional supportive treatment per local 
practice (e.g., growth factors). 
• Upon recovery, consider a 25% dose reduction of 
belantamab mafodotin, if neutropenia was drug 
related. 
Afebrile neutropenia 
 
Grades 3–4 (Defined as ANC 
<1.0x109/L) 
• If noted on day 1 of any cycle, withhold belantamab 
mafodotin dose.  
• Resume belantamab mafodotin at preheld dose once 
neutropenia recovers to grade ≤2 (ANC ≥1.0x109/L) 
on day 1 of a subsequent cycle. 
• Prophylactic antibiotics, per physician discretion and 
local institutional guidance. Consider growth factors. 
• Local guidance must be followed for hematological 
monitoring if more conservative than the protocol 
SoA specifications. 
• In cases of frequent recurrent neutropenia 
(ANC<1.0x109/L), consider dose reduction of 
belantamab mafodotin. 
Infusion reactionb 
Grade 2 
Stop the infusion, provide medical treatment and 
continue at slower rate after resolution to grade 0–1. 


 
 
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Version Date: 12/29/2022 
Toxicity 
Grade/description of 
toxicity 
Action 
Grade 3 
Further treatment with belantamab mafodotin needs to 
be discussed with sponsor-investigator. Continuation 
only allowed after recovery to ≤grade 1 and with 
premedication, and extension of infusion time to 2–4 
hours. Any future infusion needs to be premedicated. 
Grade 4 
Permanently discontinue. 
Pneumonitis 
Grade 1 
Continue treatment at the full dose when toxicity 
resolves to grade < 1. 
Grade 2 
• Withhold treatment with belantamab mafodotin. 
• Upon recovery, restart treatment with one dose-level 
reduction. 
• If patient is already at the lowest dose level (1.4 
mg/kg), then rechallenge with the same dose; this 
must be discussed with the study PI. 
Grades 3–4 
Permanently discontinue treatment with belantamab 
mafodotin. 
Urine dipstick 
2+ 
• May continue belantamab mafodotin dosing. 
• Confirm by quantitative assessment using 
albumin/creatinine (spot urine from first void).  
• If albumin/creatinine ≥2,000 mg/g, at the next cycle 
follow guidance above for spot urine. 
≥3+ 
Interrupt treatment and follow up for recovery. 
Implement quantification of albumin/creatinine ratio. 
 
a These criteria do not apply to participants on dialysis. 
b If symptoms resolve within one hour of stopping infusion, the infusion may be restarted at 50% of the original 
infusion rate (e.g., from 100 mL/hr to 50 mL/hr). Otherwise, dosing will be held until symptoms resolve and the 
participant should be premedicated for the next scheduled dose. 
 
Table 3b. Dose modifications (other) 
 
*The following actions should be taken only if toxicity may be possibly attributed to belantamab mafodotin. 
 
Events Not Otherwise 
Specified  
Severity 
Management 
Follow-up 
Grade 1 
• Administer 
symptomatic 
treatment as 
appropriate. 
• Continue study 
drug(s). 
Provide close follow-up to evaluate for increased 
severity, no dose modification necessary 
Grade 2 
• Administer 
symptomatic 
treatment. 
• Investigate etiology. 
• Consider consulting 
subspecialist, and/or 
diagnostic 
procedure. 
Symptoms resolved in ≤7 days: 
• Continue after resolution at the current dose 
 
Symptoms ongoing >7 days or worsening: 
• Consult study PI (cc: MCW Multisite Team email) 
• Delay study drug, or consider one dose level 
reduction. If recovery takes >3 weeks, consult 
with study PI (cc: MCW Multisite Team email) 
• If symptoms continue or worsen to grade 3–4, see 
below. 
Grade 3 
• Provide 
appropriate 
medical treatment. 
• Consider 
consulting 
subspecialist. 
• Consult study PI (cc: MCW Multisite Team 
email). 
• Delay treatment till recovery to grade ≤ 1.   
• Consider dose reduction.  
 
Exceptions: Participants who develop grade 3 


 
 
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toxicities which respond to standard treatment and 
resolve to grade ≤ 1 within 48 hours may continue 
treatment at scheduled or reduced dose.  
Grade 4 
• 
Provide 
appropriate 
medical 
treatment.  
• 
Consider 
consulting 
subspecialist. 
• Interrupt treatment.   
• Further treatment with belantamab mafodotin only 
allowed on individual basis if it is agreed between 
the site investigator and overall study PI (via 
email, cc:  MCW Multisite Team email) that 
benefits outweigh the risks for a given participant 
 
5.2.3 Dose Modification Related Corneal Adverse Reactions 
 
All belantamab mafodotin dose modifications and stopping criteria are to be based on the Keratopathy 
Visual Acuity (KVA) Scale for Treatment-related Corneal Toxicities. Corneal events will be graded 
according to this scale. Refer to reporting section for additional requirements. 
 
Table 4. Corneal adverse reactions and recommendations for belamantab mafodotin dosing.  
 
Grade per KVA 
scale 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
*Recommended 
Dosage 
Modifications 
Continue 
treatment at 
current 
dose. 
Withhold 
belantamab 
mafodotin until 
improvement in 
both corneal 
examination 
findings and 
changes in 
BCVA to grade 
1 or better and 
resume at current 
dose. 
Withhold 
belantamab 
mafodotin until 
improvement in 
both corneal 
examination 
findings and 
changes in BCVA 
to grade 1 or 
better and resume 
at reduced dose. 
 
If already on 
lowest dose, 
participant 
continues 
treatment at same 
dose. 
Consider permanent 
discontinuation of 
belantamab mafodotin. 
 
If based on benefit risk 
assessment and treatment 
of belantamab mafodotin 
is being considered, 
withhold treatment until 
improvement in both 
corneal examination 
findings and change in 
BCVA to grade 1 or 
better and resume at 
reduced dose. 
 
If already on lowest dose, 
participant continues 
treatment at same dose. 
 
 
 


 
 
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Table 5: Keratopathy Visual Acuity (KVA) Scale for treatment-related corneal toxicities 
 
Grade per KVA scale 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Corneal 
Toxicities 
Corneal 
examination 
finding(s) 
Mild superficial 
keratopathya 
Moderate 
superficial 
keratopathyb 
Severe superficial 
keratopathyc 
Corneal 
epithelial defectd 
Change in 
BCVAe 
Decline from 
baseline of one 
line on Snellen 
Visual Acuity 
Decline from 
baseline of two or 
three lines (and 
Snellen Visual 
Acuity not worse 
than 20/200) 
Decline from 
baseline by more 
than three lines 
(and Snellen Visual 
Acuity not worse 
than 20/200) 
Snellen Visual 
Acuity worse 
than 20/200 
Abbreviations: BCVA=Best-Corrected Visual Acuity; KVA=Keratopathy Visual Acuity. 
 
Dose reductions of belantamab mafodotin will be triggered by grade 2 or worse events of ocular exam findings, or 
decrease in BCVA on day of dosing.  
 
a) Mild superficial keratopathy is mild superficial punctate keratopathy (documented worsening from 
baseline), with or without symptoms. 
b) Moderate superficial keratopathy is any/or a combination of moderate superficial punctate keratopathy, 
patchy microcyst like deposits, subepithelial haze (peripheral), or a new peripheral stromal opacity. 
c) Severe superficial keratopathy is any/or a combination of severe superficial punctate keratopathy, diffuse 
microcyst like deposits involving the central cornea, subepithelial haze (central), or a new central stromal 
opacity. 
d) Corneal epithelial defect such as corneal ulcers: corneal ulcer by definition means an epithelial defect with 
underlying stromal infiltration. 
e) Changes in visual acuity due to treatment-related corneal findings: 
• For participants who have BCVA worse than 20/20 in either eye at baseline, dose modification for that 
eye will be determined by the worsening of vision from baseline only (not by absolute BCVA at the 
visits).  
• If a participant has a baseline BCVA of 20/200 or worse in an eye, then belantamab mafodotin-related 
changes in vision in the other eye will drive the dose modification. If a participant has baseline BCVA 
of 20/200 or worse in both the eyes, then the decision to delay or reduce belantamab mafodotin dose 
will be based on site principal investigator’s assessment of benefit vs. risk based on corneal 
examination findings following a discussion with the qualified eye care specialist.  
 
Note: Dose modification should be based on the most severe finding. If eyes differ in severity, dose modification 
guideline should be applied based on the more severe eye. 
 


 
 
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5.2.4 Corneal Supportive Care Guidelines for Belantamab Mafodotin 
 
Corneal events, which commonly manifest as superficial keratopathy, have been observed with antibody 
drug conjugates, including those conjugated to MMAF. As there is no single term which adequately 
captures these events, the term “corneal events” includes preferred terms describing corneal events 
reported with belantamab mafodotin, such as superficial punctate keratopathy, microcyst-like changes, 
subepithelial haze, corneal erosions and corneal ulcers. 
 
Sites are required to establish a close collaboration with a qualified eye care specialist who will be 
responsible for assessing participants and managing those who develop corneal examination findings in 
close communication with the MCW PI (cc: MCW Multisite Team email). 
 
Participants will be assessed by a qualified eye care specialist at screening/baseline and then prior to every 
dosing of belantamab mafodotin, and 70-day safety visit (assessment window of up to five days prior to 
dosing, but all effort should be made to schedule as close to belantamab mafodotin dosing as possible).   
 
• 
If a participant subsequently develops vision changes or other ocular symptoms, the participant 
should be evaluated by a qualified eye care specialist.  


 
 
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• 
In case of persistent ophthalmologic exam findings, newly developed ocular symptoms or vision 
changes, the participants will have further ophthalmologic exams, at least every cycle until 
resolution (to grade 1 or baseline) or more frequently as clinically indicated by a qualified eye care 
specialist.  
• 
Participants who have corneal signs per the Keratopathy Visual Acuity (KVA) scale for treatment-
related corneal toxicities present at the end-of-study treatment will continue to be followed every 
three months for up to 12 months, or until full resolution of findings, which is defined as a return 
to participant’s baseline, or until deemed clinically stable by a qualified eye care specialist, 
whichever comes first.  
 
Ocular Examination and Procedures 
 
Patients will be assessed by ophthalmologist (or an optometrist if an ophthalmologist is not available). A 
full screening/baseline ophthalmic examination for all participants must include for both eyes (OU), but is 
not limited to: 
 
1. Best corrected visual acuity.  
2. Documentation of manifest refraction and the method used to obtain best corrected visual acuity. 
3. Current glasses prescription (if applicable). 
4. Selected anterior segment (slit lamp) examination with focus on the cornea and lens, including 
fluorescein staining of the cornea. 
5. Intraocular pressure measurement. 
6. Dilated funduscopic exam. 
 
The on-treatment and follow-up ophthalmic exam should be performed for both eyes (OU), as described 
below and in the schedule of assessments: 
 
1. Best corrected visual acuity.  
2. Documentation of manifest refraction and the method used to obtain best corrected visual acuity.  
3. Slit anterior segment (slit lamp) examination with focus on the cornea and lens, including 
fluorescein staining of the cornea. 
4. Intraocular pressure measurement (if clinically indicated). 
5. Dilated funduscopic exam (if clinically indicated). 
 
All ocular exam procedures/tests (e.g., BCVA, slit lamp, etc.) performed at screening/baseline exam should 
also be obtained at the next ocular exam obtained following treatment discontinuation (e.g., 70-day safety 
visit). Participants with corneal signs or symptoms at the 70-day safety visit will be followed at least every 
three months until resolution (to grade 1 or baseline) or more frequently as clinically indicated by the eye 
care specialist or up to one year (whichever comes first). Clinically stable is defined as changes less than 
or equal to grade 1 for both Ophthalmic Exam Findings and Visual Acuity according to the Keratopathy 
Visual Acuity (KVA) Scale criteria for eye disorders. Additional examinations should be performed at the 
discretion of the treating eye specialist. 
 
Ocular Prophylaxis 
 
Ocular prophylaxis should be instituted for all participants. Ocular prophylaxis includes: 
 
• 
Prophylactic preservative-free artificial tears must be administered in each eye at least four to eight 
times daily, beginning on cycle 1 day 1 until the end of belantamab mafodotin treatment. 
 


 
 
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Participants must not use contact lenses during the study, unless directed by an ophthalmologist (refer to 
Section 5.6). 
 
Ocular Monitoring — Changes in Corneal Epithelium: Severity Grading and Mitigation Strategy  
 
In order to minimize the changes in corneal epithelium associated with belantamab mafodotin, patients 
must receive prophylactic preservative-free artificial tears. The recommended administration is to use one 
drop in each eye at least four to eight times daily, beginning on cycle 1 day 1 until the subject discontinues 
treatment. In the event of ocular symptoms (e.g., dry eyes), the use of artificial tears may be increased up 
to every two hours as needed. 
 
Corticosteroid eye drops are not required but can be used if clinically indicated per discretion of an eye care 
specialist. Allow at least five to 10 minutes between administration of artificial tears and steroid eye drops 
(if administered). 
 
An ophthalmology or optometry (if ophthalmology is not available) consult is required for all patients who 
develop signs or symptoms of changes in corneal epithelium or require steroid eye drops for more than 
seven days. 
 
Changes in corneal epithelium must be graded according to the KVA scale (Table 5).  
 
5.3 Safety Stopping Criteria 
 
Liver Chemistry Stopping Criteria 
 
Liver chemistry stopping and increased monitoring criteria have been designed to ensure participant safety 
and evaluate liver event etiology. Discontinuation of study treatment for abnormal liver tests is required 
when the participant satisfies any of the stopping rules as shown in the figure below.  
 
 


 
 
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Liver chemistry stopping and increased monitoring algorithm for subjects WITH entry criteria ALT 
≤2.5xULN 
 
 
*NOTE – in diagram above, “Appendix” is listed below in this section. 
 
Phase I/II liver chemistry stopping and increased monitoring criteria  
 
Liver chemistry stopping criteria (for patient treatment)  
ALT - absolute 
ALT ≥ 5xULN 
ALT Increase 
ALT ≥ 3xULN persists for ≥ four weeks 
Bilirubin1, 2 
ALT ≥ 3xULN and total bilirubin ≥ 2xULN (>35% direct bilirubin)  
INR2  
ALT ≥ 3xULN and INR>1.5 
Cannot Monitor 
ALT ≥ 3xULN and cannot be monitored weekly for four weeks 
Symptomatic3 
ALT ≥ 3xULN associated with symptoms (new or worsening) believed to be 
related to liver injury or hypersensitivity 
Required Actions, Monitoring, and Follow-up Assessments 
Actions 
Follow-upp Assessments 
• Immediately discontinue study intervention.  
• Report the event to study PI within 24 hours 
(refer to reporting section). 
• Complete the requirement in reporting section 
and complete SAE if the event also meets the 
criteria for an SAE.2 
• Perform liver event follow-up assessments as 
described in the follow-up assessment column. 
• Viral hepatitis serology.4 
• Obtain INR and recheck with each liver 
chemistry assessment until the 
aminotransferases values show downward 
trend. 
• Serum creatine phosphokinase (CPK) and 
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Liver chemistry stopping criteria (for patient treatment)  
• Monitor the participant until liver chemistries 
resolve, stabilize, or return to within baseline (see 
MONITORING). 
 
MONITORING: 
 
If ALT≥3xULN AND total bilirubin ≥ 2xULN or 
INR >1.5:  
 
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin, and INR) 
and perform liver event follow-up assessments 
within 24 hours. 
• Monitor participants twice weekly until liver 
chemistries resolve, stabilize or return to within 
baseline. 
• A specialist or hepatology consultation is 
recommended. 
 
For all other criteria (bilirubin <2xULN and 
INR ≤1.5):  
 
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin, and INR) 
and perform liver event follow-up assessments 
within 24 to 72 hours. 
• Monitor participants weekly until liver 
chemistries resolve, stabilize or return to within 
baseline. 
 
transferase [GGT], glutamate dehydrogenase 
[GLDH], and serum albumin. 
• Fractionate bilirubin, if total bilirubin 
≥2xULN. 
• Obtain complete blood count with differential 
to assess eosinophilia. 
• Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, 
on the liver event form. 
• Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, recreational 
drugs and other over the counter medications. 
• Record alcohol use.  
 
If ALT ≥3xULN AND total bilirubin ≥2xULN 
or INR >1.5 obtain the following in addition to 
the assessments listed above: 
 
• Anti-nuclear antibody, anti-smooth muscle 
antibody, type 1 anti-liver kidney microsomal 
antibodies, and quantitative total 
immunoglobulin G (IgG or gamma globulins). 
• Serum acetaminophen adduct assay should be 
conducted (where available) to assess potential 
acetaminophen contribution to liver injury 
unless acetaminophen use is very unlikely in 
the preceding week (e.g., where the participant 
has been resident in the clinical unit 
throughout).  
• Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) to 
evaluate liver disease. 
• Liver biopsy may be considered and discussed 
with local specialist if available, in the 
following instances: 
o In participants when serology raises the 
possibility of autoimmune hepatitis (AIH). 
o In patients when suspected DILI progresses or 
fails to resolve on withdrawal of study 
intervention. 
o In participants with acute or chronic atypical 
presentation:  
• If liver biopsy conducted collect all applicable 
data and report information to study PI (and 
MCW Multisite Team). 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation 
is not immediately available, discontinue study intervention for that participant if ALT ≥ 3xULN and 


 
 
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total bilirubin ≥ 2xULN. Additionally, if serum bilirubin fractionation testing is unavailable, record 
presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations and 
suggesting liver injury.  
2. All events of ALT ≥ 3xULN and total bilirubin ≥ 2xULN (>35% direct bilirubin) or ALT ≥ 3xULN 
and INR>1.5, which may indicate severe liver injury (possible “Hy’s Law”), must be reported as an 
AESI (excluding studies of hepatic impairment or cirrhosis); the INR threshold value stated will 
not apply to participants receiving anticoagulants. 
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such 
as fever, rash, or eosinophilia). 
4. Hepatitis A IgM antibody; hepatitis B surface antigen and hepatitis B core antibody (IgM); hepatitis C 
RNA; cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if 
unavailable, obtain heterophile antibody or monospot testing); hepatitis E IgM antibody. In those with 
underlying chronic hepatitis B at study entry (identified by positive hepatitis B surface antigen) 
quantitative hepatitis B DNA and hepatitis delta antibody. If hepatitis delta antibody assay cannot be 
performed, it can be replaced with a PCR of hepatitis D RNA virus (where needed) [Le Gal, 2005]. 
 
Phase 1-2 Liver chemistry increased monitoring criteria with continued therapy  
 
Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study 
Intervention Liver Monitoring Event 
Criteria 
Actions 
ALT ≥3 x ULN but <5 x ULN and 
total bilirubin <2 x ULN or INR 
≤1.5, without symptoms believed 
to be related to liver injury or 
hypersensitivity and who can be 
monitored weekly for four weeks. 
 
• Notify the study PI (cc: MCW Multisite Team email) 
within 24 hours (refer to reporting section) of learning 
of the abnormality to discuss participant safety.  
• Participant can continue study treatment. 
• Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, bilirubin 
and INR) until they resolve, stabilize, or return to within 
baseline. 
• If at any time participant meets the liver chemistry 
stopping criteria, proceed as described above. 
• If, after four weeks of monitoring, ALT <3 x ULN, 
bilirubin <2 x ULN and INR 1.5, monitor participants 
twice monthly until liver chemistries normalize or return 
to within baseline. 
 
Infusion-Related Reactions Stopping Criteria 
 
Premedication is not required prior to infusion unless deemed medically appropriate by the investigator 
following evaluation of infusion-related reactions (IRRs). Premedication should be considered for any 
participant who experienced an IRR at first or any subsequent infusion with belantamab mafodotin. For 
infusion reactions of any grade/severity, immediately interrupt the belantamab mafodotin infusion and 
manage symptoms. Once reaction symptoms resolve, resume the infusion at a reduced rate. Premedication 
may be required with subsequent infusions. 
 
A participant who experiences a grade 4 IRR associated with belantamab mafodotin should be permanently 
withdrawn from the study treatment and enter follow-up. 
 
 


 
 
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5.4 Measurable Residual Disease Assessment 
  
MRD assessment by clonoSEQ® requires an initial marrow sample containing myeloma cells for 
identification of myeloma-specific sequences in IGH-VDJ, IDH-DJ, and/or IGK. During screening, a fresh 
bone marrow sample or archive, non-stained bone marrow aspirate slide (“ID sample”) will be sent to 
Adaptive Biotechnologies to be assessed for the presence of myeloma-specific sequences.  
 
For all samples with MRD assessment, MRD will be reported quantitatively as proportion of multiple 
myeloma-associated sequences. For treatment assignment and clinical trial outcome reporting, we will 
consider MRD-negative if the burden of MM-associated molecules is ≤10-5.  
 
Subjects who achieve confirmed MRD(-) status with ≤10-5 MM-associated molecules during maintenance  
will undergo FDG PET/CT scan. FDG PET/CT will be interpreted by the enrolling site and reported on 
data forms. 
 
5.5 General Concomitant Medication and Supportive Care Guidelines  
 
Concomitant treatments and/or procedures that are required to manage a subject's medical condition 
during the study will also be recorded in the eCRF. 
 
5.6 Prohibited Medications 
 
The following medications are prohibited: 
 
• 
Any concomitant anticancer therapy to treat the disease under study. 
• 
Any investigational study drug, for any indication.  
• 
Concomitant administration of strong P-glycoprotein (P-gp) inhibitors and strong inhibitors of 
OATP (see link below) with belantamab mafodotin should be avoided unless considered medically 
necessary. 
o Refer 
to 
list 
here: 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-
development-and-drug-interactions-table-substrates-inhibitors-and-inducers   
• 
Unless directed by an opthalmologist, contact lenses are not allowed for participants while they are 
receiving belantamab mafodotin treatment.  
o Contact lens use may be restarted after discontinuation of belantamab mafodotin treatment, 
provided the eye care specialist confirms there are no other contraindications. 
• 
Administration of live or live-attenuated vaccines are contraindicated 30 days prior to the first dose 
of study treatment. Use of live or live-attenuated vaccines is further contraindicated for at least 70 
days following the last dose of belantamab mafodotin. Killed or inactivated vaccines may be 
administered; however, the response to such vaccines cannot be predicted. 
 
5.7 Monitoring Subject Compliance  
 
Study drug will be administered or dispensed only to eligible patients under the supervision of the 
investigator or identified sub-investigator(s). The appropriate study personnel will maintain records of study 
drug receipt and dispensing. Comprehensive instructions may be provided to the patient in order to ensure 
compliance with dosing procedures.  
 
 


 
 
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5.8 Follow-up Period 
 
For patients who discontinue treatment prior to progression, continue standard-of-care follow-up every 
three months until progression or start of another treatment (whichever comes first), then continue to long 
term follow-up. 
 
All patients will be followed for survival and follow-up data every six months (± 30 days) until withdrawal 
of consent, loss to follow-up, death, or the end of the study, whichever occurs first. 
 
Refer to section above regarding ocular examination and procedures during follow-up. 
 
 
6 ADVERSE EVENTS: DEFINITIONS, COLLECTION, AND REPORTING 
REQUIREMENTS 
 
6.1 Definitions 
 
6.1.1 Adverse Event 
 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have to have a causal relationship with this 
treatment. (International Conference on Harmonisation [ICH], E2A, E6). 
 
This study will utilize the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, 
located on the CTEP web site: 
 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
 
AEs may be spontaneously reported by the patient and/or in response to an open question from study 
personnel or revealed by observation, physical examination or other diagnostic procedures. 
 
6.1.2 Serious Adverse Event (SAE)  
 
Serious adverse event (SAE) means any untoward medical occurrence that results in any of the following 
outcomes: 
 
• 
Death. Results in death. 
• 
Life-threatening. Is life-threatening (refers to an AE in which the patient was at risk of death at 
the time of the event. It does not refer to an event which hypothetically might have caused death if 
it were more severe). 
• 
Hospitalization. Requires inpatient hospitalization or prolongation of an existing hospitalization 
(see clarification in the paragraph below on planned hospitalizations). 
• 
Disability/incapacity. Results in persistent or significant disability or incapacity. (Disability is 
defined as a substantial disruption of a person’s ability to conduct normal life functions). 
• 
A congenital anomaly/birth defect. 
• 
Medically important event. This refers to an AE that may not result in death, be immediately life-
threatening, or require hospitalization, but may be considered serious when, based on appropriate 
medical judgment, may jeopardize the patient, require medical or surgical intervention to prevent 
one of the outcomes listed above, or involves suspected transmission via a medicinal product of an 
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(excluding the disease[s] under study in oncology protocols, e.g., secondary malignancies), allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of drug dependency 
or drug abuse; any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or nonpathogenic, is considered an 
infectious agent. Secondary malignancies should always be considered as serious adverse events. 
• 
Liver toxicity (as follows): 
o ALT - absolute ALT ≥ 5xULN. 
o ALT ≥ 3xULN persists for ≥ four weeks. 
o ALT ≥ 3xULN and total bilirubin ≥ 2xULN (>35% direct bilirubin).  
 
Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick. If fractionation is unavailable 
and ALT ≥ 3 x ULN and total bilirubin ≥ 2 x ULN, then the event is to be reported.  
o ALT ≥ 3xULN and INR>1.5. 
 
INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants. If INR measurement is obtained, the value is 
to be recorded when reporting. 
o ALT ≥ 3xULN and cannot be monitored weekly for four weeks. 
o ALT ≥ 3xULN associated with symptoms (new or worsening) believed to be related to 
liver injury or hypersensitivity. 
 
6.1.3 Attribution of an Adverse Event 
 
For all collected AEs, the site investigator who examines and evaluates the subject will determine the 
adverse event’s causality to all of the study drugs, based on temporal relationship and his/her clinical 
judgment. The degree of certainty about causality will be graded using the categories below: 
 
• 
Definitely Related: There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out.  
• 
Probably Related: There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely.  
• 
Possibly Related: There is some evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the trial medication). However, the influence of 
other factors may have contributed to the event (e.g., the subject’s clinical condition, other 
concomitant events).  
• 
Unlikely: A clinical event, including an abnormal laboratory test result, whose temporal 
relationship to study agent administration makes a causal relationship improbable (e.g., the event 
did not occur within a reasonable time after administration of the trial medication) and in which 
other drugs or chemicals or underlying disease provides plausible explanations (e.g., the subject’s 
clinical condition, other concomitant treatments).  
• 
Unrelated: The AE is completely independent of study agent administration, and/or evidence 
exists that the event is definitely related to another etiology. 
 
While sites report to the MCW sponsor-investigator based on the above categories, the MCW sponsor-
investigator reports to the funder (GSK) based on the categories “related” or “not related” attribution: 
 
• 
Related: There is a reasonable possibility of a causal relationship between the medicinal product 
and AE, i.e., there are facts, evidence, and/or arguments to suggest a causal relationship, rather than 
a relationship cannot be ruled out. Alternative causes, such as underlying disease(s), concomitant 
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administration will be considered and investigated.  
• 
Not Related: A causal relationship between the medicinal product and the AE cannot be established, 
based on consideration of factors described above.   
 
6.1.4 Expectedness of an Adverse Event 
 
Each site investigator will decide whether an adverse event (AE) is expected or unexpected, but the sponsor 
is ultimately responsible for determination of expectedness and may therefore override the site 
investigator’s determination of expectedness. 
 
6.2 Collection and Reporting Requirements for Adverse Events and Serious Adverse Events 
 
6.2.1 Collection of Adverse Events 
 
All adverse events (including SAEs) must be recorded in OnCore® data forms. All AEs required to be 
collected must be graded according to the CTCAE v5. Investigator’s or treating physician’s assessment of 
AE attributions must also be documented.  
 
SAEs and AEs will be collected and reported after first treatment dose, through 70 days post last dose of 
belantamab mafodotin. All conditions prior to treatment will be considered baseline, medical history unless 
changing in grade after treatment. AEs will be tracked and followed until resolution, subject withdraws 
consent, or is lost to follow-up (including subjects who discontinue early).  
 
 
6.2.2 Reporting of Adverse Events, Serious Adverse Events, and AEs of Special Interest (AESI) 
 
Events requiring expedited 
reporting (i.e., requiring immediate 
action) 
All SAEs (including liver toxicity defined in Section 6.1.2)  
Non-hematological grade 4 AEs not meeting SAE definition. 
Unanticipated problems involving risks to participants or 
others (UPIRSO). 
Pregnancy. 
Deviations that are “significant” (affect subject safety, such as 
medication errors) or planned. 
Action letter from sponsor. 
Product complaint. 
Subject trial withdrawal. 
Events requiring routine reporting 
(i.e., entered into OnCore® in a 
timely manner) 
All grade 1–4 AEs (unless in an above category), including all 
lab abnormalities (regardless of clinical significance) and AEs 
of special interest (AESI). 
Non-significant deviations. 
 
6.3 Serious Adverse Event (SAE)  
 
IMPORTANT NOTE — refer to liver toxicity events defined as an SAE in Section 6.1.2. 
 
SAEs are reported in the following manner: 
 


 
 
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• 
All SAEs (occurring after the subject has received first dose of study drug through the 70 days after 
the last dose of belantamab mafodotin) will be reported within 24 hours of study staff awareness, 
using OnCore® (entered in the SAE tab) and GSK SAE form. Supporting de-identified documents 
(e.g., admission and discharge note) will be uploaded to shared site study folder and emailed (see 
below). An email notice with the SAE or pregnancy PDF report from OnCore® as well as the GSK 
SAE form (provided by the multisite team) will be sent to the MCW study PI and MCW Multisite 
Team (via the MCW Multisite Team email) who will report to GSK (MCW will email to 
OAX37649@gsk.com). 
• 
In addition, if the SAE is unexpected and possibly, probably, or definitely related to study drugs, 
sites must create a reportable event notice with the sIRB, and complete a MedWatch 3500A and 
send it in an email to the study PI and MCW Multisite Team email.  
 
US FDA MedWatch 3500A found here: 
http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/default.htm  
• 
All grade 4 and 5 SAEs and any other expedited SAE reports to the IRB must also be reported to 
DSMC within five calendar days of study staff’s awareness by the MCW Multisite Team. 
• 
All SAEs will be followed until satisfactory resolution, or until the site investigator deems the 
event to be chronic. Any significant update/resolution should be updated in OnCore® follow-up 
SAE report (update the sIRB and MedWatch report, if a SUSAR). The SAE OnCore® PDF 
follow-up SAE form should be reported in the same manner as the SAE process above. 
 
6.4 Adverse Events Not Meeting SAE Definition  
 
Adverse Events 
 
Any medical condition that is present at the time that the participant is screened will be considered a baseline 
condition and captured on the baseline OnCore® CRF form and not reported as an AE (though all SAEs 
that occur after starting treatment are reported in an expedited manner; see below). All new or worsening 
AEs that occur after starting study drug until 70 days post last dose of belantamab mafodotin will be tracked 
and followed until resolution, subject withdraws consent, or is lost to follow-up (including subjects who 
discontinue early).  
 
Changes in the grade of an AE will be documented in the AE CRF to allow an assessment of the duration 
of the event at each level of severity. Information to be collected includes event description, time of onset, 
clinician’s assessment of severity, expectedness, relationship to study product (assessed only by those with 
the training and authority to make a diagnosis), and time of resolution/stabilization of the event. 
 
Adverse Event of Special Interest (AESI) 
 
An adverse event of special interest (AESI) is an adverse event (serious or non-serious) of scientific and 
medical concern specific to the sponsor’s product or program, for which ongoing monitoring and rapid 
communication by the investigator to the sponsor may be appropriate. Such events may require further 
investigation in order to characterize and understand them. AESIs may be added or removed during a study 
by protocol amendment.  
 
Current list of AESIs:  
 
• 
Elevated serum creatinine (increases from baseline by >0.5 mg/dL). 
• 
Serum creatinine >3.0 mg/dL from baseline OR 3.0-6.0 X ULN. 
• 
Thrombocytopenia. 
• 
Infusion-related reactions. 


 
 
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• 
Pneumonitis grade 2. 
• 
Corneal events (severity of corneal events will be graded according to the KVA scale).  
 
All AESIs that meet the definition of an SAE will be reported according to the manner above for SAEs. 
All AESIs that do not meet the definition of an SAE (or grade 4, see below) must be reported in a routine 
manner on data forms (which indicate the event is an AESI). 
 
Grade 4 AEs  
 
Any grade 4 AE that meets the definition of an SAE will be reported according to the manner above for 
SAEs. A hematological grade 4 AE that does not meet the definition of an SAE will be routinely reported.  
 
Any non-hematological grade 4 AE that does not meet the definition of an SAE will be reported within 24 
hours of study staff awareness in the following manner: 
 
• 
Enter the AE into OnCore® AE CRF. 
• 
Email the MCW Study PI and MCW Multisite Team (via the Multisite Team email; the Multisite 
Team will notify DSMC coordinator, if required) detailing the following information: 
o Case/sequence number of the subject. 
o Date of event. 
o CTCAE term. 
o CTCAE grade. 
o Relationship to study drug(s). 
o Expectedness. 
o Any clinical action taken or planned. 
 
6.5 Unanticipated Problem Involving Risk to Subject or Other (UPIRSO)  
 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meet all of the 
following criteria: 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (sIRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied. 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research). 
• 
Suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
 
6.6 DSMC Reporting 
 
All internal reports to the DSMC and subsequent DSMC review letters will be available to participating 
sites (e.g., shared site study folder). For those internal events that do not meet the definition of an SAE but 
are required by the protocol to be reported to the DSMC, the participating site will report according to the 
protocol.  
 
 
 


 
 
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6.7 Reporting Pregnancy 
 
Male participants with partners who become pregnant: 
 
• 
Investigator will attempt to collect pregnancy information on any female partner of a male study 
participant who becomes pregnant while participating in this study and for six months following the 
last dose of belantamab mafodotin. This applies only to male participants who receive study 
intervention. 
• 
After obtaining the necessary signed informed consent from the pregnant female partner directly, the 
investigator will record pregnancy information on the appropriate form and submit it to study PI, MCW 
Multisite Team, and GSK within 24 hours of learning of the partner’s pregnancy.  
• 
Participating sites should report the pregnancy in OnCore® as a grade 3 SAE and complete the 
pregnancy report form (provided by sponsor as an additional document), and email both PDF reports 
to the study PI, MCW Multisite Team (via the MCW Multisite Team email), and commercial 
manufacturers within 24 hours of staff awareness.  
• 
The female partner will also be followed to determine the outcome of the pregnancy. Information on 
the status of the mother and child will be forwarded to GSK within 24 hours of study staff awareness. 
• 
Generally, follow-up will be no longer than six to eight weeks following the estimated delivery date. 
Any termination of the pregnancy will be reported regardless of fetal status (presence or absence of 
anomalies) or indication for procedure.  
 
Female participants who become pregnant: 
 
• 
Investigator will collect pregnancy information on any female participant who becomes pregnant while 
participating in this study and for four months following the last dose of belantamab mafodotin.  
• 
Information will be recorded and submitted to study PI, MCW Multisite Team, and GSK within 24 
hours of learning of a participant's pregnancy.  
• 
Participating sites should report the pregnancy in OnCore® as a grade 3 SAE and complete the 
pregnancy report form (provided by sponsor as an additional document), and email both PDF reports 
to the study PI, MCW Multisite Team (via the MCW Multisite Team email), and commercial 
manufacturers within 24 hours of staff awareness. Participant will be followed to determine the 
outcome of the pregnancy. The investigator will collect follow-up information on participant and 
neonate, which will be forwarded to GSK within 24 hours of study staff awareness. Generally, follow-
up will not be required for longer than six to eight weeks beyond the estimated delivery date.   
• 
Any termination of pregnancy will be reported, regardless of fetal status (presence or absence of 
anomalies) or indication for procedure.  
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be reported as an AE or SAE.  
• 
A spontaneous abortion is always considered to be an SAE and will be reported as such.   
• 
Any SAE occurring as a result of a post-study pregnancy which is considered reasonably related to the 
study intervention by the investigator, will be reported to study PI, MCW Multisite Team, and GSK 
within 24 hours of study staff awareness. according to the SAE reporting process above. 
 
 


 
 
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6.8 Protocol Deviations and Medication Errors 
 
Significant deviations are defined, but not limited to, the following: 
 
• 
Enrolling an ineligible subject. 
• 
Non-compliance: violates federal regulations or institutional policies regarding informed consent 
or research conduct which impacts subjects’ rights, welfare and/or safety or affect the scientific 
integrity of the project. 
• 
Deviations that have an impact on primary objectives of the study. 
• 
Prohibited medications which pose a safety risk to the patient or integrity of the data. 
 
Planned deviations are defined as follows: 
• 
Any temporary protocol deviation that is anticipated to occur but hasn’t occurred yet. 
• 
Sites must follow the sIRB policies regarding acknowledgment prior to deviation initiation. 
 
Significant and/or planned deviations and medication errors are reported in the following manner: 
• 
Participating sites enter the deviation into OnCore® and email the PDF report to the MCW Multisite 
Team (via the MCW Multisite Team email) within five calendar days of staff awareness. 
• 
Participating sites report to the sIRB. 
 
Any other deviation that is not significant or planned is to be reported in OnCore® in a timely manner (refer 
to Section 6). 
 
The following actions may occur due to persistent or significant deficiencies: 
 
• 
Telephone call between the MCW Multisite Team and site staff to discuss resolution or possible 
prevention of future deficiencies. 
• 
Schedule additional, or short interval, monitoring visits and/or training sessions with the MCW 
Multisite Team. 
• 
Formal notification to participating site PI of deficit with request for corrective action plan, and/or 
due date for outstanding items to be completed. 
• 
Warning of potential suspension of participating site accrual until corrective action is completed. 
• 
Suspension of accrual at participating site. 
• 
Participating site accrual closure. 
 
6.9 Staff, Subject, and Product Complaint Reporting 
 
If a complaint is received by anyone on the study staff, it will be addressed on a case-by-case basis. The 
site PI will be notified of any complaints. Complaints will be reported to the sIRB and MCW PI if required. 
If the subject has questions about his or her rights as a study subject, wants to report any problems or 
complaints, obtain information about the study, or offer input, the subject can call the research subject 
advocate. This information is provided to the subject in their consent.  
 
A product complaint is a verbal, written, or electronic expression that implies dissatisfaction regarding the 
identity, strength, purity, quality, or stability of the product. The following are examples of product 
complaint types: 
 
• 
Labeling Complaints 
o Damaged or defective label. 
o Batch number/expiry date issues (for example, not able to read or missing). 


 
 
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o Directions for use not easy to understand. 
• 
Packaging Complaints 
o Defective packaging. 
o Dose difficult to dispense. 
• 
Vial Complaints 
o Broken, dirty, or cracked vial. 
• 
Stopper Issues 
o Coring, damaged, or pushed into vial. 
• 
Appearance Complaints 
o Vials cloudy. 
o Dissolution difficulty. 
o Vials contain foreign material. 
o Dusty capsules. 
o Capsule or tablet color. 
o Capsule difficult to swallow. 
o Drug delivery system complaints. 
o Leaking after injection. 
o Dose knob difficult to push. 
o Pen is jammed. 
o Error codes. 
o Difficult to attach/detach needle. 
o Unable to set dose. 
o Electronic malfunction. 
 
Study staff who identify a product complaint situation for any study agent should report the complaint 
within 24 hours of study staff awareness, in the following manner: 
 
• 
Complete the study-specific product complaint form. 
• 
Email GSK (as relevant), and also the MCW Multisite Team (via the MCW Multisite Team email) 
the product complaint form and upload it into shared site study folder. 
• 
File the original completed product complaint form in the shadow chart. 
• 
Return product sample, if requested by drug manufacturer, with a copy of the product complaint 
form. 
• 
Any written, electronic or oral communication that alleges dissatisfaction related to manufactured 
clinical drug product with regards to its manufacturing, testing, packaging, or shipping, must be 
reported by the sponsor institution or qualified designee to study PI, MCW Multisite Team, and 
GSK within one working day of first becoming aware of the possible defect (email of GSK QA at 
gsk-rd.complaints@gsk.com).  The product and packaging components in question, if available, 
must be stored in a secure area under specified storage conditions until it is determined whether 
the product is required to be returned for investigation of the defect. If the product complaint is 
associated with an SAE, the SAE must be reported separately in accordance with the protocol, 
and the SAE report should mention the product quality complaint. 
 
Product complaints in and of themselves are not reportable events. If a product complaint results in an SAE, 
an SAE form should be completed according to the SAE reporting requirements. 
 
Reporting information is collected for:  
 
• 
A product complaint unrelated to an adverse event. 
• 
A product complaint associated with a serious or non-serious adverse event. 


 
 
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Submit a product complaint if there is any alleged deficiency with the drug delivery system: 
 
• 
Complaints can be expressed directly by the subject or by the MCW PI or Study Chair and staff, 
based on evaluation of the issue.  
• 
The MCW PI or Study Chair  should check the box on the product complaint form: “Adverse Event 
associated with complaint,” when he/she suspects the product complaint may have led to the 
adverse event. 
 
6.10 Subject Withdrawal 
 
The MCW Multisite Team (via the MCW Multisite Team email) must be notified via email within 24 hours 
of discontinuation of study drugs or study intervention (preferably prior to discontinuation, in case the study 
PI could recommend an intervention or clarification), describing the nature of the discontinuation. OnCore® 
subject status updates (off-treatment date and follow-up start date) and discontinuation eCRF must be 
completed within 24 hours of discontinuation. 
 
6.11 Reporting UPIRSO to Participants 
 
The MCW Multisite Team, DSMC, drug manufacturers, and/or MCW or sIRBs may make the 
determination that an event requires reporting to subjects, either verbally/written documentation or 
reconsent. 
 
6.12 External or Internal Auditing at Participating Sites 
 
Sites must inform the MCW Multisite Team (via the MCW Multisite Team email) of any other external or 
internal audit/QA review (outside that performed according to this protocol’s monitoring and auditing 
plans) prior to its occurrence, and send the final findings/report, along with any corrective action plan, to 
the MCW Multisite Team and MCW PI. 
 
6.13 Known Adverse Events List 
 
Please see the latest version of the belantamab mafodotin investigator’s brochure. 
 
 


 
 
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7 PHARMACEUTICAL INFORMATION 
 
7.1 Belantamab Mafodotin 
 
7.1.1 Description  
 
Belantamab mafodotin 
Dosage form: 
Lyophilized powder, 100 mg/vial in single-use vial for reconstitution 
Unit dose strengths: 
100 mg/vial (Lyophilized powder) 
Route of administration 
Delivered as IV solution over at least 30 minutes. 
Dosing instructions: 
Reconstitute belantamab mafodotin lyophilized powder 100 mg/vial 
2.0 mL of water for injection (WFI); dilute with saline before use. 
Manufacturer/ source of 
procurement: 
GSK/Baxter 
 
7.1.2 Storage 
 
Belantamab Mafodotin Solution, 20 mg/mL, 1.5 mL drug product is supplied as a frozen liquid in a 2R 
glass vial. Detailed instructions for preparation and administration of doses are provided in the site 
instruction manual. Prepared doses of belantamab mafodotin in the range of 0.2 – 2.0 mg/mL in 0.9% 
NaCl should be used as soon as possible and no later than 8 hours from the time of dose preparation 
including administration because the product does not contain an antimicrobial preservative. 
 
The recommended storage condition of belantamab mafodotin Solution, 20 mg/mL, 1.5 mL drug product 
is -50°C to -15°C, protected from light. The expiry date, where required, is stated on the product label. 
 
7.1.3 Biochemical and Structural Information 
 
GSK2857916 is an afucosylated humanized IgG1 monoclonal antibody conjugated with an 
average of four maleimidocaproyl monomethyl auristatin F (mcMMAF [SGD-1269]) that binds 
to BCMA. 
 
7.1.4 Molecular Weight 
 
Theoretical mass of protein containing carbohydrate conjugated with four drug linker molecules are 152.1 
kDa (intact mass). 
 
7.1.5 Physical Form 
 
Clear to opalescent; colorless to yellow to brown liquid. 
 
 
7.1.6 Handling and Drug Accountability 
 
Belantamab Mafodotin for Injection, 100 mg drug product is supplied as a lyophilized powder for 
solution for infusion. Detailed instructions for preparation and administration of doses are provided in the 
site instruction manual. Prepared doses of belantamab mafodotin in the range of 0.2 – 2.0 mg/mL in 0.9% 
NaCl should be used as soon as possible and no later than 6 hours from the time of dose preparation 
including administration because the product does not contain an antimicrobial preservative. 
 


 
 
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The recommended storage condition is 2-8°C, protected from light. The expiry date, where required, is 
stated on the product label. Before use, remove the drug product vial(s) from the refrigerator and allow to 
stand for approximately 10 minutes to reach room temperature (68°F to 77°F [20°C to 25°C]). 
 
Each vial of the drug product is reconstituted with 2.0 mL of sterile WFI before use. Once reconstituted, 
the drug product solution in vial(s) should be used to prepare the dose as soon as possible. If the 
reconstituted solution is not used immediately, store the vial(s) refrigerated at 36ºF to 46ºF (2ºC to 8ºC) or 
at room temperature (68ºF to 77ºF [20ºC to 25ºC]) for up to 4 hours in the original container. Do not 
freeze. Discard the reconstituted DP vial(s) if not used to prepare diluted dosing solution within 4 hours. 
 
Visually inspect the reconstituted solution for particulate matter and discoloration. The reconstituted drug 
product solution in vial should be clear to opalescent, colourless to yellow to brown liquid. Discard the 
reconstituted vial if extraneous particulate matter other than translucent to white proteinaceous particles is 
observed. 
 
GSK2857916 (belantamab mafodotin) dose rounding instructions:  
Participant’s weight in kilograms (kg) should be entered to one decimal place and the total dose (mg) will 
be calculated to two decimal places. 
Example:  
Total Dose (mg) = 97.2 kg * 1.9 mg/kg  
Total Dose (mg) = 184.68 mg 
The quantity of vials dispensed will depend on the participant’s weight and dose level. 
For dose preparation, withdraw calculated volume of reconstituted DP from the vial(s) for each dose and 
add to 250 mL IV bag containing 0.9% sodium chloride. The diluted dosing solution is stable at 0.2 
mg/mL to 2 mg/mL in 0.9% sodium chloride for injection for a maximum of 6 hours (including infusion 
time) when stored at room temperature (68ºF to 77ºF [20ºC to 25ºC]).  
 
The diluted dosing solution is compatible with the following contact materials: polyvinylchloride and 
polyolefin IV bags/administration sets and polyurethane catheter. Filtration is not mandatory, but if using 
a filter use a 0.2 um polyethersulfone (PES) filter. If a closed system transfer device (CSTD) is used, 
instructions provided by the manufacturer must be followed to ensure intended dose is delivered. If the 
diluted solution is not used immediately, it may be stored in a refrigerator 36ºF to 46ºF (2ºC to 8ºC) for up 
to 24 hours prior to administration. If refrigerated, allow the diluted solution to equilibrate to room 
temperature prior to administration. The diluted solution should be inspected visually for particulate 
matter and discoloration prior to administration, whenever solution and container permit. The diluted 
infusion solution should be clear and colorless. Discard if particulate matter is observed. 
 
Density of reconstituted belantamab mafodotin after addition of 2 mL sterile WFI to lyophilized powder 
(50mg/mL) is 1.0418 g/cm3 at room temperature 68°F to 77°F (20°C to 25°C). 
The site PI is fully responsible for the investigational products at the trial site. Dispensing of investigational 
products will be delegated to site staff. The person responsible for dispensing the investigational products 
will be accountable for maintaining adequate control of the investigational products and for documenting 
all transactions with them. 
 


 
 
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The site PI, or a responsible party designated by the site PI, will maintain a careful record of the inventory 
and disposition of all agents. Each participating site PI, or authorized designee, is responsible for 
maintaining a careful record of inventory and disposition of all investigational agents received at the site. 
Use of the NCI Drug Accountability Record Form is recommended, but sites may use their own 
accountability logs per institutional standards. Sites must ensure accountability records capture the same 
information as the NCI Drug Accountability Record Form and in addition, capture the preparation time. 
Any used or partially used vials may be destroyed on-site per the institutional standard of practice. Expired 
vials remaining at the end of the study may be destroyed onsite per institutional standards. 
 
7.1.7 Drug Supply 
 
Provided by funder, drug manufacturer. 
 
Belantamab mafadotin will be provided by GSK through ALMAC, a vendor managing the labeling and 
shipping of drug. The initial shipment of drug will be initiated by GSK and resupply orders will be the 
responsibility of each participating site. WebEZ is only used to order drug, it does not require any patient 
information.  
 
 
 
 
 
 
8 STATISTICAL CONSIDERATIONS 
 
8.1 General Description 
 


 
 
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This phase II study will be conducted using an optimal two-stage design based on the methods of Huang 
(35). The enrollment target will be 45 subjects, with an interim analysis for futility after 23 patients have 
been enrolled, and followed for 12 months post diagnosis. Enrollment of new subjects will continue during 
that period. 
 
The design is based on a modification of a binomial two-stage design that allows incorporation of data from 
subjects with less than full follow-up at the interim analysis (Huang, 2010). The study will enroll up to 45 
subjects with an interim analysis performed when 23 patients have been treated and followed to the 12th 
month after CAR-T. The futility decision will use the Kaplan-Meier estimate of the 12-month progression-
free conditional survival using the data from the first 23 subjects and any subject who have been enrolled 
during the follow-up period of the 23rd subject. The study will be stopped for futility, if the one-sided z-
test comparing the 12-month progression-free conditional survival to 54% defined by the null hypothesis 
has a p-value of 0.54 or higher. The study has a 70% probability of stopping for futility if the underlying 
12-month conditional PFS equals to the null-hypothesis value of 54%. 
 
If the study is not stopped for futility, study enrollment will continue until 45 subjects are enrolled. The 
final analysis will be performed when all subjects have been followed to 12 months after CAR-T. The 
Kaplan-Meier estimate of the 12-month progression-free conditional survival will be compared to 54% 
using a one-sided z-test at a 5% significance level. 
 
8.2 Determination of Sample Size and Accrual Rate 
 
8.2.1 Primary Endpoint 
 
The primary endpoint of the study is the 12-month progression-free survival (PFS) with time counted from 
the CAR-T infusion conditional on being alive and progression-free at day +90 post CAR-T. An event will 
be defined as documented progression or death for any cause, subjects without an event will be censored at 
the last date known to be alive without progression. Left truncation at the time of the start of study treatment 
will be used to adjust for “immortal time” after day +90 before study enrollment. 
 
8.2.2 Primary Hypothesis 
 
We hypothesize that, with belantamab mafodotin maintenance, the 12-month PFS conditional on being 
progression-free at day +90 will exceed 54%.  
 
The comparison value was selected based on published and preliminary data from the KarMMa2 trial, with 
three-month PFS of 74%, and 12-month PFS of 40%, resulting in a conditional PFS of 0.4/0.74=0.54. A 
5% one-sided type I error rate will be used. 
 
8.2.3 Sample Size Justification 
 
The sample size was computed using 80% power at a one-sided 5% significance level to detect a significant 
effect if the conditional PFS exceeds the historical value by 20%, that is 74%. Assuming a 74% three-month 
PFS, this corresponds to a 12-month PFS of 55%. 
 
The OptInterim R package was used to compute the optimal two-stage design that minimizes the expected 
sample size, assuming exponential PFS and recruitment of one patient/month during year 1, and two 
patients/months afterwards. The optimal design recruits a total of 45 subjects, with an interim analysis after 
23 subjects have been enrolled, and followed for 12 months post-CAR-T. Recruitment will not be paused 
during for the interim analysis, and the information from all treated subjects (even those with incomplete 


 
 
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follow-up) will be used in the interim analysis. This design achieves an 84% power in the hypothesized 
setting, which exceeds the target due to the discreteness of the design space, 
 
We conducted simulation studies to confirm that the actual study design maintains the target type I error 
and power under a range of scenarios, including non-exponential survival, up to 10% censoring, and an 
enrollment window of 1.5 months without additional adjustment of the sample size. 
 
8.2.4 Analysis Populations 
 
The overall study population will consist of all subjects enrolled into the study. This population will be 
used in study flowcharts and patient disposition summaries. 
 
The efficacy population will consist of all enrolled subjects who received at least one dose of the study 
treatment and had at least one response evaluation after the start of the treatment. This population will be 
used for the primary efficacy. 
 
The safety population will consist of all enrolled subjects who received at least one dose of the study 
treatment.  
 
8.2.5 Statistical Analysis Plan 
 
Primary outcome 
PFS will be estimated by the Kaplan-Meier (KM) estimator, and presented with pointwise 90% confidence 
intervals. An event will be defined as documented progression or death for any cause, subjects without an 
event will be censored at the last date known to be alive without progression. Left truncation at the time of 
the start of study treatment will be used to adjust for “immortal time” before study enrollment. 
 
The primary efficacy hypothesis of 12-month PFS exceeding 54% will be evaluated by comparing the KM-
estimate to the null-hypothesis values using a one-sided z-test.  
 
The primary outcome will also be summarized separately for subjects with ≤PR, and VGPR at the initiation 
of treatment. No between-group comparisons will be performed. 
 
Secondary outcomes 
Time-to-event outcomes, such duration of response, time to progression/relapse, progression-free survival, 
and overall survival will be described using the Kaplan-Meier estimator. Left truncation at the start of study 
treatment will be used. Best objective response on the trial and negative MRD prevalence at specific 
timepoints will be summarized as counts with percentages. Quality of life scores will be summarized at 
each timepoint with descriptive statistics and analyzed using mixed effect models with a random subject 
intercept. 
 
Safety analyses 
Safety analyses will be performed on the entire safety population. The incidence of severe adverse events 
will be reported for all subjects who received at least one dose of the study treatment. The proportion of 
patients experiencing an SAE will be reported overall, as well as classified by grade and organ system. 
 
Formal toxicity monitoring will be performed for the following adverse events: 
• 
SAEs that are possibly, probably or definitely related to treatment, with 30% acceptable rate  
• 
Treatment-related grade 4 or higher non-hematologic toxicity, with 10% acceptable rate 
• 
Grade 4 corneal adverse events, with 5% acceptable rate 


 
 
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• 
Treatment-related death, i.e., grade 5 hematologic or non-hematologic toxicity, with 3% acceptable 
rate  
 
 
The monitoring rules will suggest stopping the study when there is sufficient evidence that the proportion 
of patients with a specific adverse event exceeds the acceptable rate. Specifically, a Bayesian toxicity 
monitoring approach will be used, recommending stopping if the posterior probability of the event rate 
exceeding the acceptable rate is at least 80%. A Beta distributed prior with effective sample size of 1 and 
prior mean equal to the acceptable event rate was used for each event.  
 
The tables assume that monitoring will be conducted after every five patients. Table 6 shows the cutoffs 
for the number of events that would trigger a stopping rule. For example, the third row shows that if 15 
patients have been enrolled and 3 or more treatment-related non-hematologic AEs have occurred, then there 
is evidence to indicate that the proportion of these AEs exceeds the acceptable rate of 10%. 
 
Table 6. Cutoffs for the number of patients with a specific adverse event indicating excessive 
rate of adverse event as a function of number of subjects in the study. 
 
Subjects 
Outcome  
Treatment-
related SAE 
(30%) 
Treatment-
related grade 4+ 
non-hematologic 
AE (10%) 
Grade 4 corneal 
AE (5%) 
Treatment-
related death 
(3%) 
5 
≥ 3 
≥ 2 
≥ 2 
≥ 1 
10 
≥ 5 
≥ 3 
≥ 2 
≥ 2 
15 
≥ 7 
≥ 3 
≥ 2 
≥ 2 
20 
≥ 8 
≥ 4 
≥ 3 
≥ 2 
25 
≥ 10 
≥ 5 
≥ 3 
≥ 2 
30 
≥ 12 
≥ 5 
≥ 3 
≥ 3 
35 
≥ 13 
≥ 6 
≥ 4 
≥ 3 
40 
≥ 15 
≥ 6 
≥ 4 
≥ 3 
45 
≥ 17 
≥ 7 
≥ 4 
≥ 3 
 
Table 7 shows the operating characteristics of the boundaries listed in Table 6 for several values of true 
underlying probability of the adverse event. For example, if the true proportion of treatment-related SAEs 
is 40%, then the monitoring rule will be triggered over 83.6% of the time.  
 
Table 7. Overall probability of crossing the boundaries defined in Table 6 with up to 45 
subjects as a function of the underlying probability of the adverse event (cells with extremely 
low or high probabilities are left empty for clarity). 
 
Underlying 
probability 
of event 
Outcome (acceptable rate of adverse events) 
Treatment-
related SAE 
(30%) 
Treatment-
related grade 4+ 
non-hematologic 
AE (10%) 
Grade 4 corneal 
AE (5%) 
Treatment-
related death 
(3%) 
2% 
- 
0.6% 
4.9% 
16.9% 
3% 
- 
1.7% 
11.3% 
28.9% 
5% 
0.1% 
6.2% 
29.7% 
52.9% 


 
 
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7.5% 
0.4% 
17.4% 
55.0% 
75.7% 
10% 
1.0% 
33.8% 
75.0% 
88.9% 
20% 
9.8% 
90.0% 
99.1% 
99.8% 
30% 
42.4% 
99.6% 
- 
- 
40% 
83.6% 
- 
- 
- 
50% 
98.6% 
- 
- 
- 
 
8.3 Accrual Estimates 
 
MCW is required (per MCW sIRB) to activate prior to other sites, whose activation times will vary due to 
internal activation timelines. Accrual is expected at one subjects/month during year 1, and two 
subjects/month afterwards. Therefore, enrollment is expected to last 29 months; last subject, last dose and 
assessment are expected to take another 11 months. Therefore, total trial duration would be approximately 
40 months. 
 
The study will reach study completion in approximately 10 years (five years for completion of treatment 
for all patients, and five years of long-term survival follow-up) from the time the study opens to accrual. 
 
 
9 OPERATIONAL CONSIDERATIONS, MULTISITE ADMINISTRATION, 
SOURCE DOCUMENTS, AND DATA MANAGEMENT  
 
9.1 Staff Training, Changes, and Delegation of Authority Log 
 
Documentation of training completion for required items of training (i.e., training log, CITI completion 
certification, etc.) and the delegation of authority (DOA) or local context form (as appropriate) must be 
maintained at each site for all study staff members, uploaded into the shared site study folder, and sent to 
the MCW Multisite Team upon request. 
 
All site study staff must be adequately trained to perform the delegated task(s) approved by the participating 
site PI, as recorded in the delegation of authority log, or local context form (as appropriate), and training 
log (or online training log).  
 
Inform the MCW Multisite Team (via the MCW Multisite Team email) immediately if a change in PI is 
planned. 
 
9.2 Monitoring Plan 
 
The MCWCC DSMC is responsible for monitoring data quality and subject safety for all MCWCC 
investigator-initiated clinical trials, according to the approved MCW DSMP. 
 
Unless otherwise specified in the contract/budget, the following monitoring plan will occur under the 
direction of the MCW Multisite Team: 
 
• 
Onsite monitoring or remote monitoring within two to four weeks of the first subject enrollment (if 
applicable, as determined by the MCW Multisite Team). 
• 
Onsite monitoring or remote monitoring (if applicable, as determined by the MCW Multisite Team) 
visits and outstanding data reports approximately every three months until the MCW PI and DSMC 
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• 
Consents, source documents supporting eligibility, primary and secondary objectives, drug 
accountability/temperature/shipping/receiving logs (if applicable), and key data points should be 
provided to the MCW Multisite Team. The monitor may verify certain data points at his/her 
discretion. 
• 
Data lock at time of interim analysis. 
• 
Study updates via a videoconference meeting may occur (depending upon accrual rate and 
complexity of trial, at the discretion of the MCW Multisite Team and MCW PI). 
 
9.3 Audit Plan 
 
Audit plans are determined by the DSMP according to risk category: 
 
• 
Approximately 30% of enrolled subjects per site randomly selected for review (a maximum of 10 
subjects per site at each review).  
• 
Consent, eligibility, and objective-based data are reviewed for all files selected.  
• 
One subject file per site (of the 30% mentioned above) randomly selected for a comprehensive 
review at each time point. 
• 
100% of regulatory documents. 
• 
The auditor reserves the right to select other subject(s) if deemed necessary (i.e., in case of a 
significant or repetitive finding). 
• 
An audit occurs every year until the DSMC determines that future audits may be deferred. 
 
Audits may be performed by either the MCW QA department, a contracted business partner, and/or another 
entity specified in the consent, contract, or budget. Directed audits, outside of those regularly scheduled, 
may be requested at any time by the MCW Multisite Team or applicable regulatory agency. Studies are 
subject to random or for-cause audits from the sIRB. 
 
Participating sites must promptly inform the MCW Multisite Team (via the MCW Multisite Team email) 
of any other external or internal audit/review of this trial prior to its occurrence and send the final 
findings/report with any corrective action plan to the MCW Multisite Team (via the MCW Multisite Team 
email).  
 
9.4 Audit and Monitoring Report and Corrective Action Plan (CAP) 
 
Audit or monitoring reports occur in the following manner: 
• 
Sites follow local SOP/practices and communicate with MCW as appropriate. 
• 
Sent to the participating site PI after the date of the audit or monitoring visit. 
• 
Must be shared with any other required entity, as required per local SOPs and policies (e.g., DSMC, 
sIRB, etc.). 
• 
Include a brief description of findings. 
• 
Address whether a corrective action plan (CAP) is required, and when it is required. 
• 
Indicate if another short-term audit or monitoring visit is necessary, and within what time frame it 
should occur. 
 
9.5 Deidentified Source Documents, Remote Access to Records, and Shadow Charts 
 
Regulatory authorities, the sIRB, and/or sponsor may request access to all source documents, data capture 
records and other study documentation for audit or inspection. Direct access to these documents must be 
guaranteed by the investigators, who must provide support at all times for these activities. 
 


 
 
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The following (but not limited to) source documentation should be provided to the MCW Multisite Team 
(via the online shared study folder and/or email): 
 
• 
Supporting documents for all eligibility criteria (including consent and documentation of consent 
process). 
• 
Supporting documents for important data points (e.g., primary or secondary endpoints). 
• 
Source(s) indicating all expedited reported events.  
• 
SAE and AESI supporting source documents (e.g., admission/discharge notes and other applicable 
procedures) and SAE/AESI email confirmations. 
• 
Pharmacy drug accountability/temperature/shipping/receiving logs (uploaded prior to monitoring 
visits or as requested (or applicable access to these records via institutional practice, e.g., Vestigo). 
• 
Investigator attribution determination (e.g., AE log signoff, etc.) 
 
If a participating site allows monitors and auditors remote or onsite access to their electronic health record 
(EMR), staff will adhere to their local SOPs. Shadow charts (e.g., paper or electronic copies of the EMR) 
are maintained according to local SOPs and policies. 
 
9.6 Transferring Subjects 
 
If a participant decides to transfer from the enrolling site to another new participating site, the following 
occurs:  
• 
The current enrolling site contacts the MCW Multisite Team (via the MCW Multisite Team email) 
and new participating site. 
• 
Both site PIs agree to the transfer and follow institutional SOPs. 
• 
All data and queries must be completed before transfer. 
• 
After official transfer, documents have been finalized. 
o All applicable source documents are transferred. 
o Data capture system access is transferred.  
o The new participating site PI becomes responsible for the participant. 
 
9.7 Retention of Study Documents 
 
Study documents must be retained according to the following requirements: 
• 
Participating sites must maintain all study records according to FDA and applicable regulatory 
requirement(s). 
• 
Records are retained for at least two years after the last marketing application approval or two years 
after formal discontinuation of the clinical development of study drugs or according to applicable 
regulatory requirement(s), whichever is longest. In either case, sites must inform the MCW PI and 
MCW Multisite Team (via the MCW Multisite Team email) of any intention to no longer retain 
study records. 
• 
Record retention may be extended per local institution policy or sponsor request. 
• 
If the participating site PI withdraws from the responsibility of keeping the study records, custody 
must be transferred to a person willing to accept the responsibility. 
• 
The MCW Multisite Team must be notified in an email (via the MCW Multisite Team email) if a 
custodial change might occur, and approval must be obtained prior to the change. 
 
9.8 Publication and Data Sharing Policy 
 


 
 
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Publication and data sharing requirements are detailed in the clinical trial agreement. The MCW study PI 
determines authorship in a multifaceted manner, based on substantial intellectual input, effort, and 
participation: 
 
Authorship guidelines are as follows: 
 
• 
First author requirements: 
o MCW study PI/Co-PI. 
o Writes the primary manuscript. 
• 
Participating site PI authorship: 
o Each participating site investigator with at least one enrollment may be eligible for 
authorship. 
o Order determined by top accruing sites. 
• 
Last author: 
o Most senior position who contributed to the protocol development (unless otherwise 
specified). 
• 
Acknowledgements: 
o The MCW study PI may include other staff or colleagues, as applicable. 
o Sponsorship from the drug manufacturer(s) per the drug manufacturer(s)’s contractual 
requirements. 
• 
Journal or publication author number limitations: 
o Authors will be removed in reverse order of original order, as determined by the MCW 
study PI. 
 
9.9 Electronic Data Capture and Timely Data Entry  
 
Participating sites enter electronic data into OnCore®, under the supervision and responsibility of the site 
investigator. Study-specific case report forms (CRFs) will document outcomes. All study data will be 
entered into OnCore® via standardized CRFs, in accordance with the study calendar, using single data entry 
with a secure access account. Designated study staff will complete the CRFs as soon as possible upon 
completion of the study visit; the investigator will review and approve the completed CRFs. The 
information collected on CRFs shall be identical to that appearing in original source documents.  
 
Timely data entry is defined as follows (unless otherwise specified in the contract/budget): 
 
• 
OnCore® entry must occur within 24 hours of consent, enrollment, and withdrawal (for any reason). 
• 
Protocol visit time point data should be entered within four weeks of visit occurrence, unless 
otherwise requested by the MCW Multisite Team (e.g., prior to DSMC reviews, audit, etc.). 
• 
Deviations should be entered within four weeks of discovery, if not requiring expedited reporting 
(refer to Section 6). 
• 
Refer to Section 6 for timely reporting of events requiring expedited reporting. 
 
 
10 REGULATORY COMPLIANCE, ETHICS, AND MANAGEMENT  
 
This study will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki as stated in 21 CFR §312.120(c)(4). 
 
This study will be conducted in compliance with: 
• 
The protocol. 


 
 
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• 
Federal regulations, as applicable, including: 21 CFR 50 (Protection of Human Subjects/Informed 
Consent); 21 CFR 56 (Institutional Review Boards) and 45 CFR 46 Subparts A (Common Rule), 
B (Pregnant Women, Human Fetuses and Neonates), C (Prisoners), and D (Children), and all 
applicable regulatory requirements. The sIRB must comply with the regulations in 21 CFR §56 and 
applicable regulatory requirements. 
 
 
 
 
10.1 Activation Letter for Participating Institutions 
 
Study conduct must not occur until an official activation letter has been received at the participating site. 
After all required institutional and regulatory approvals have been obtained, the MCW PI and MCW 
Multisite Team issue an activation letter to the participating site. Then, study conduct may begin.  
 
10.2 CAP, CLIA, and Reference Ranges 
 
Participating sites should ensure their laboratory maintains CAP (if applicable) and CLIA certification. The 
MCW Multisite Team may request reference ranges as necessary. 
 
10.3 Scientific Review Committee 
 
The MCW Scientific Review Committee (SRC) has the following responsibilities: 
 
• 
Establishing and maintaining a review committee of sufficient size and breadth of expertise to 
conduct a critical and fair scientific review of institutional cancer-related research involving human 
subjects. 
• 
Conducting a thorough scientific review of all non-peer-reviewed, cancer-related clinical protocols 
using a standard format based on specific, predetermined review criteria.  
• 
Assisting MCWCC investigators in the development of scientifically and clinically sound research 
through well-written protocols. 
• 
Considering protocol feasibility with regard to budget, resources, and competing trials. 
• 
Establishing clear criteria for determining whether ongoing clinical trials are making sufficient 
scientific progress, including the attainment of adequate subject accrual rates.  
• 
Monitoring all cancer-related research protocols based on the criteria established by the SRC and 
terminating protocols that do not meet these expectations.  
• 
Ensures that clinical trials are scientifically sound and that approved trials maintain subject accrual 
goals and scientific progress. 
 
The levels of reviews are full, expedited, or exempt (based on the chair’s discretion). Amendments may 
require SRC review or be exempt from review depending on whether the changes are major or 
administrative. The SRC may approve, approve with modifications, defer, or disapprove a trial. 
Furthermore, the SRC identifies low-accruing studies and either warns the disease-oriented team (DOT) 
chair and MCW PI of low accrual or recommends study closure. 
 
Participating sites will adhere to their local policies regarding scientific review committee approvals. 
 
10.4 Data and Safety Monitoring Committee  
 


 
 
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The MCW PI only reports DSMC letters to all other participating sites if they meet the FDA definition of 
requiring reporting (i.e., unanticipated problem), are required to be reported to other sites by the DSMC, 
and/or result in a significant finding/recommendation/action (e.g., change in study conduct, study closure, 
study hold). However, all DSMC reports can be sent to participating sites upon request. 
 
After DSMC review of a participating site event, the MCW PI reports the DSMC letter to the participating 
site where the pertinent event occurred. The most recently approved MCW Data and Safety Monitoring 
Plan (DSMP) documents must be followed by all participating sites.  
 
The MCW Data and Safety Monitoring Committee (DSMC) has the following responsibilities: 
 
• 
Reviews the clinical trials for data integrity and safety.  
• 
Reviews all unexpected grade 3, and all grade 4, and 5 adverse events, as well as any others 
requiring expedited reporting as defined in this protocol.  
o Non-hematological grade 4 and all grade 5 events must be reported to the DSMC within 
five calendar days of MCW study staff’s knowledge. Hematological grade 4 events can be 
routine reported.  
• 
Reviews all DSM reports.  
• 
Submits a summary of any recommendations related to study conduct.  
• 
Terminates the study if deemed unsafe for subjects. 
• 
Informs the MCW Multisite Team (via the MCW Multisite Team email) of finalized reports/letters 
to be sent to the participating sites. 
 
The DSMC will review reports no less than biannually (unless otherwise specified/approved by the DSMC). 
MCW institutional monitoring of multisite trials will be conducted according to the approved data and 
safety monitoring plan (DSMP), under the responsibility of the associate director for clinical research 
(ADCR).  
 
10.5 Subject Confidentiality and Access to Source Documents/Data 
 
Participant confidentiality and privacy are strictly held in trust by the participating investigators, their staff, 
and the sponsor(s) and their interventions. This confidentiality is extended to cover testing of biological 
samples and genetic tests, in addition to the clinical information relating to participants. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence.  
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (sIRB), regulatory agencies or pharmaceutical company supplying study product may 
inspect all documents and records required to be maintained by the investigator, including but not limited 
to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this study. The 
clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as long 
a period as dictated by the reviewing sIRB, institutional policies, or sponsor requirements. 
 
Study participant research data, which are for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored in OnCore®. This will not include the participant’s contact or identifying 
information from participating sites outside MCW. Rather, individual participants and their research data 
will be identified by a unique study identification number. The study data entry and study management 


 
 
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systems used by clinical sites and by MCW research staff will be secured and password protected. At the 
end of the study, all study databases will be archived at the Medical College of Wisconsin. 
 
10.6 Protection from Unnecessary Harm 
 
Each clinical site is responsible for protecting all subjects involved in human experimentation. This is 
accomplished through the sIRB mechanism and the informed consent process. The sIRB reviews all 
proposed studies involving human experimentation and ensures that the subject’s rights and welfare are 
protected and that the potential benefits and/or the importance of the knowledge to be gained outweigh the 
risks to the individual. The sIRB also reviews the informed consent document associated with each study 
in order to ensure that the consent document accurately and clearly communicates the nature of the research 
to be done and its associated risks and benefits. 
 
10.7 Changes in the Protocol, Consent, or other Trial Document 
 
A participating site may request changes to trial documents in the following manner: 
 
• 
Major site-specific changes to the consent and ancillary documents are highly discouraged, though 
some changes are necessary (e.g., accrual goal updates, local context changes, etc.). 
• 
Any change must be clearly indicated, then submitted to the MCW Multisite Team (via the MCW 
Multisite Team email) for approval by the MCW PI, the drug manufacturer(s) (if required), and 
sIRB, prior to implementation. 
• 
MCW PI and sIRB approval must occur prior to implementation of any change, unless all of the 
following obtains: 
o Approval cannot be obtained in a reasonable time frame for subject safety and must be 
implemented immediately for subject safety. 
o The MCW PI, Multisite Team (via the MCW Multisite Team email), and applicable 
agencies (SRC, DSMC, sIRB as applicable) are informed as soon as possible, if they cannot 
be informed before implementation. 
o The investigator must then notify the sIRB in writing within five working days after 
implementation.  
 
The sIRB may provide, if applicable regulatory authority(ies) permit, expedited review, and 
approval/favorable opinion for minor change(s) in ongoing studies that have the approval /favorable opinion 
of the IRB. The investigator will submit all protocol modifications to the drug manufacturer(s) and the 
regulatory authority(ies) in accordance with the governing regulations. Changes to the protocol may require 
approval from the drug manufacturers. 


 
 
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APPENDIX 1. PERFORMANCE STATUS CRITERIA 
 
 
ECOG Performance Status Scale 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity 
Fully active, able to carry on all pre-
disease 
performance 
without 
restriction 
100 
Normal, no complaints, no evidence of 
disease 
90 
Able to carry on normal activity; minor 
signs or symptoms of disease 
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) 
80 
Normal activity with effort; some signs 
or symptoms of disease 
70 
Cares for self, unable to carry on normal 
activity or to do active work 
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 
60 
Requires occasional assistance, but is 
able to care for most of his/her needs 
50 
Requires considerable assistance and 
frequent medical care 
3 
In bed > 50% of the time 
Capable of only limited self-care, 
confined to bed or chair more than 
50% of waking hours 
40 
Disabled, requires special care and 
assistance 
30 
Severely 
disabled, 
hospitalization 
indicated 
Death not imminent 
4 
100% bedridden 
Completely disabled 
Cannot carry on any self-care 
Totally confined to bed or chair 
20 
Very sick, hospitalization indicated 
Death not imminent 
10 
Moribund, fatal processes progressing 
rapidly 
5 
Dead 
0 
Dead 


 
 
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APPENDIX 2. SUBJECT LOST TO FOLLOW-UP LETTER 
 
 
 
 
 
Date: ___________________________________ 
 
 
 
Dear ___________________________________, 
 
 
 
 
 
The research study team has been unable to contact you regarding the clinical trial (“A Multicenter Phase 
II Study of Maintenance Belantamab Mafodotin (Blenrep®) after BCMA-directed Chimeric Antigen 
Receptor-T Cell Therapy in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)”) you 
participated in. 
 
 
We would like to discuss how you are doing and if we may continue contacting you. 
 
 
Please contact us at  
 
_____________________________________________________________ 
 
 
 
 
 
 
Sincerely, 
 
 
___________________________________ 
 
 
 


 
 
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APPENDIX 3. IMWG MULTIPLE MYELOMA RESPONSE CRITERIA 
 
(Based on Kumar et al., 2016) 
 
Stringent complete 
response (sCR) 
Complete response (defined below) AND normal free light chain (FLC) ratio 
and absence of clonal cells in marrow by IHC. 
Complete response 
(CR) 
Negative immunofixation (serum and urine) AND disappearance of any 
plasmacytomas AND <5% plasma cells in marrow by IHC. 
Very good partial 
response (VGPR) 
Serum and urine M-protein detectable by immunofixation but not by 
electrophoresis; greater than or equal to 90% reduction in serum M-protein 
level AND urine M-protein level less than 100 mg per 24 hr. 
Partial response (PR) 
50% or greater reduction of serum M-protein AND reduction in 24 hr urinary 
M-protein by 90% or greater or to less than 200 mg/24 hr; if serum and urine 
M-protein are unmeasurable, must have a 50% or greater reduction in the 
difference between involved and uninvolved FLC level; if M-proteins and 
FLC assays are non-contributory, a 50% or greater reduction in plasma cells 
is required. 
Minimal response 
Reduction in serum-protein by 25 to 49% AND reduction in urine M-protein 
by 50 to 89%. 
Stable disease (SD) 
Not meeting any of the definitions listed in this table for response or PD. 
Progressive disease 
(PD) 
Increase of 25% from lowest confirmed response value (one or more of the 
following): Serum M-protein (absolute increase must be ³ 0.5 g/dL); Serum 
M-protein increase ³ 1 g/dL, if the lowest M component was ³ 5 g/dL; Urine 
M-protein (absolute increase must be ³ 200 mg/24 hr.); appearance of a new 
lesion.  
 
 
 


 
 
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APPENDIX 4. CONTRACEPTIVES USE 
 
CONTRACEPTIVES ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb that Have Low User Dependency  
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
 
Note: Vasectomized partner is a highly effective contraceptive method provided that the partner is 
the sole sexual partner of the woman of childbearing potential and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
Spermatogenesis cycle is approximately 90 days. 
 
Highly Effective Methodsb that Are User Dependenta 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
• 
Injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable 
• 
Sexual abstinence 
 
Note: Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant. 
a. Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from 
those when used consistently and correctly. 
c. Male condoms must be used in addition to hormonal contraception. If locally required, in accordance 
with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited 
to those which inhibit ovulation as the primary mode of action. 
 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of 
contraception for this study. Male condom and female condom should not be used together (due to risk of 
failure with friction). 
 
 
 


 
 
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APPENDIX 
5. 
CORRELATIVE 
SAMPLE 
INSTRUCTIONS 
AND  
REQUISITION FORM 
Methods for Preparation of Samples 
1.0 Bone Marrow 
A. ~10 ml of bone marrow aspirate from each patient should be collected in heparinized tube at 
each of the timepoints below, stored at room temperature, and shipped overnight at room 
temperature. 
2.0 Serum 
A. 15 ml of whole blood from each patient should be collected in a serum separator tube (SST) at 
each of the time points below.  
B. The serum should be separated as soon as possible (ideally within two hours) and placed into 
a labeled cryotube and stored at -20°C until shipment. 
3.0 Timepoints 
A. Screening (bone marrow aspirate and serum) 
B. Cycle 3, Day 1 
C. Cycle 7, Day 1 
D. 70 days post-last dose safety visit (or at time of progression, whichever is earlier) 
E. Diagnostic BM samples. If available, after enrollment is confirmed and subject has relapsed. 
• 
Diagnostic BM samples  may be difficult to obtain. If available, the study team requests 
5-10 diagnostic BM slides (e.g., ID sample, recuts are allowed/permitted from the 
institution those samples were obtained), if any additional/obtainable samples are 
available to be sent for study correlatives (and only if/when the subject has relapsed).    
Shipping Instructions 
A. All samples should be securely packaged in a container designed for shipping human 
biospecimens. 
B. All sample labels should include the following information: 
• 
Patient study ID number. 
• 
Center identification. 
• 
Collection date. 
• 
Study day and time point. 
• 
Initials of the individual who collected the specimen, 
C. Marrow samples should be shipped express overnight (day of collection) at room temperature. 
D. Serum samples should be shipped on dry ice and can be sent in batches (upon request from the 
MCW Multisite Team, when approximately half of enrollments are completed). 
E. Site study budget includes shipping costs (please use your site account to ship FedEx/UPS/etc.) 
• 
Shipping Address: 
MCW Cell Therapy Laboratory 
Attention: Immune Monitoring Lab 
Froedtert Hospital Pavilion, Room 304 
9200 W. Wisconsin Ave. 
Milwaukee, WI 53226 
Laboratory telephone: 414-805-6143 
F. Email the MCW Cell Therapy Laboratory (celltherapyresearch@mcw.edu ) and call 414-805-
6143 between the hours of 7 a.m. and 6 p.m. central time to let them know a specimen is 
coming.  
G. Ship samples Monday through Thursday only. Specimens will only be received Tuesday 
through Friday (except holidays). 


 
 
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MCW EMBRACE TRIAL – REQUISITION FORM 
 
Participating site name: 
 
Checkbox 
Sample Type 
Patient Study Number # 
 
☐ 
Bone Marrow 
Date of Sample Collection 
 
☐ 
Serum 
Time of sample collection 
(Please use 24-hour time) 
 
 
 
Timepoint 
☐  Diagnostic BM 
 
☐  Screening  
 
☐  Cycle 3, Day 1 
 
☐  Cycle 7, Day 1 
 
☐  70-days post-last dose Safety Visit (or at time of progression, whichever is earlier) 
 
Site Information: 
 
Site staff contact (full name):  _______________________________________________________   
   
Site staff contact phone number:  _____________________________________________________  
 
Site staff contact email:  _____________________________________________________    
   
Person Filling out Requisition (print full name): _____________________________  
 
 
 
 


 
 
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APPENDIX 6: PATIENT-REPORTED OUTCOMES (PRO) 
 
 
   
EORTC-QLQ-MY20 and EORTC QLQ-C30  
OCULAR SURFACE DISEASE INDEX (OSDI) 


 
 
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EORTC QLQ – MY20 
 
Patients sometimes report that they have the following symptoms or problems. Please indicate the 
extent to which you have experienced these symptoms or problems during the past week. Please 
answer by circling the number that best applies to you. 
 
During the past week: 
 
 
Not at 
A 
Quite 
Very  
All 
Little 
a Bit 
Much 
 
31.  Have you had bone aches or pain? 
 
1 
2 
3 
4 
 
32.  Have you had pain in your back? 
 
1 
2 
3 
4 
 
33.  Have you had pain in your hip?  
 
1 
2 
3 
4 
 
34.  Have you had pain in your arm or shoulder? 
1 
2 
3 
4 
 
35.  Have you had pain in your chest? 
 
1 
2 
3 
4 
 
36.  If you had pain did it increase with activity? 
1 
2 
3 
4 
 
37.  Did you feel drowsy? 
 
 
1 
2 
3 
4 
 
38. Did you feel thirsty? 
 
 
1 
2 
3 
4 
 
39.  Have you felt ill? 
 
 
 
1 
2 
3 
4 
 
40.  Have you had a dry mouth? 
 
 
1 
2 
3 
4 
 
41.  Have you lost any hair? 
 
 
1 
2 
3 
4 
 
42.  Answer this question only if you lost any hair:  
 
Were you upset by the loss of your hair?  
1 
2 
3 
4 
 
43.  Did you have tingling hands or feet? 
 
1 
2 
3 
4 
 
44.  Did you feel restless or agitated? 
 
1 
2 
3 
4 
 
45.  Have you had acid indigestion or heartburn? 
1 
2 
3 
4 
 
46.  Have you had burning or sore eyes? 
 
1 
2 
3 
4 
Please turn to next page 


 
 
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During the past week: 
 
 
Not at 
A 
Quite 
Very  
All 
Little 
a Bit 
Much 
 
47.  Have you felt physically less attractive as a result 
of your disease or treatment? 
 
 
1 
2 
3 
4 
 
48.  Have you been thinking about your illness? 
1 
2 
3 
4 
 
49.  Have you been worried about dying? 
 
1 
2 
3 
4 
 
50. Have you worried about your health in the future? 
1 
2 
3 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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/ 
EORTC QLQ-C30 (version 3)  
 
We are interested in some things about you and your health. Please answer all of the questions yourself by circling the number that best applies 
to you. There are no "right" or "wrong" answers. The information that you provide will remain strictly confidential. 
 
Please fill in your initials: 
__________ 
Your birthdate (Day, Month, Year): 
__________ 
Today's date (Day, Month, Year):  
31 __________ 
__________________________________________________________________________________________ 
 
 
Not at 
A 
Quite 
Very 
 
 
All 
Little 
a Bit 
Much 
1. 
Do you have any trouble doing strenuous activities,  
 
like carrying a heavy shopping bag or a suitcase? 
1 
2 
3 
4 
 
2. 
Do you have any trouble taking a long walk? 
1 
2 
3 
4 
 
3. 
Do you have any trouble taking a short walk outside of the house? 
1 
2 
3 
4 
 
4. 
Do you need to stay in bed or a chair during the day? 
1 
2 
3 
4  
 
5. 
Do you need help with eating, dressing, washing  
 
yourself or using the toilet? 
1 
2 
3 
4 
 
 
During the past week:  
Not at 
A 
Quite 
Very 
 
 
All 
Little 
a Bit 
Much 
 
6. 
Were you limited in doing either your work or other daily activities? 
1 
2 
3 
4 
 
7. 
Were you limited in pursuing your hobbies or other 
 
leisure time activities? 
1 
2 
3 
4 
 
8. 
Were you short of breath? 
1 
2 
3 
4 


 
 
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9. 
Have you had pain? 
1 
2 
3 
4 
 
10. Did you need to rest? 
1 
2 
3 
4 
 
11. Have you had trouble sleeping? 
1 
2 
3 
4 
 
12. Have you felt weak? 
1 
2 
3 
4 
 
13. Have you lacked appetite? 
1 
2 
3 
4 
 
14. Have you felt nauseated? 
1 
2 
3 
4 
 
15. Have you vomited? 
1 
2 
3 
4 
 
16. Have you been constipated? 
1 
2 
3 
4 
 
 
Please go on to the next page 
 
 
 


 
 
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During the past week:  
Not at 
A 
Quite 
Very 
 
 
All 
Little 
a Bit 
Much 
 
17. Have you had diarrhea? 
1 
2 
3 
4 
 
18. Were you tired? 
1 
2 
3 
4 
 
19. Did pain interfere with your daily activities? 
1 
2 
3 
4 
 
20. Have you had difficulty in concentrating on things, 
 
like reading a newspaper or watching television? 
1 
2 
3 
4 
 
21. Did you feel tense? 
1 
2 
3 
4 
 
22. Did you worry? 
1 
2 
3 
4 
 
23. Did you feel irritable? 
1 
2 
3 
4 
 
24. Did you feel depressed? 
1 
2 
3 
4 
 
25. Have you had difficulty remembering things? 
1 
2 
3 
4 
 
26. Has your physical condition or medical treatment 
 
interfered with your family life? 
1 
2 
3 
4 
 
27. Has your physical condition or medical treatment 
 
interfered with your social activities? 
1 
2 
3 
4 
 
28. Has your physical condition or medical treatment 
 
caused you financial difficulties? 
1 
2 
3 
4 
 
 
 
 


 
 
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For 
the 
following 
questions 
please 
circle 
the 
number 
between 
1 
and 
7 
that  
best applies to you 
 
29. How would you rate your overall health during the past week? 
 
 
 1 
2 
3 
4 
5 
6 
7 
 
 Very poor 
 
 
 
 
 
Excellent 
 
 
30. How would you rate your overall quality of life during the past week? 
 
 
 1 
2 
3 
4 
5 
6 
7 
 
 Very poor 
 
 
 
 
 
Excellent 
 
 
 


 
 
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Version Date: 12/29/2022 
OCULAR SURFACE DISEASE 
INDEX © 
(US English version of the OSDI) 
 
Please answer the following questions by checking the box that best represents your answer. 
Have you experienced any of the following during the last week: 
 
All of the 
time 
Most of 
the time
Half of 
the 
time 
Some of 
the 
time 
None of the 
time 
1 
Eyes that are sensitive to light? 
2 
Eyes that feel gritty? 
3 
Painful or sore eyes? 
4 
Blurred vision? 
5 
Poor vision? 
 
Have problems with your eyes limited you in performing any of the following during the last week: 
 
All of 
the 
time 
Most 
of the 
time 
Half 
of the 
time 
Some 
of the 
time 
None 
of the 
time 
Not 
applicabl
e 
6 
Reading? 
7 
Driving at night? 
8 
Working with a computer or bank machine 
(ATM)? 
9 
Watching TV? 
Have your eyes felt uncomfortable in any of the following situations during the last week: 
 
All of 
the 
time 
Most 
of the 
time 
Half 
of the 
time 
Some 
of the 
time 
None 
of the 
time 
Not 
applicabl
e 
10 Windy conditions? 
11 Places or areas with low humidity (very 
dry)? 
12 Areas that are air conditioned? 
 
Copyright © 1995 Allergan, Inc. 
 
 


 
 
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Version Date: 12/29/2022 
 
REFERENCES 
1. 
Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351(18):1860-73. 
2. 
Rajkumar SV, Kyle RA. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc. 
2005;80(10):1371-82. 
3. 
Terpos E, Rahemtulla A, Dimopoulos MA. Current treatment options for myeloma. 
Expert Opin Pharmacother. 2005;6(7):1127-42. 
4. 
Palumbo A, Rajkumar SV, San Miguel JF, Larocca A, Niesvizky R, Morgan G, et al. 
International Myeloma Working Group consensus statement for the management, treatment, 
and supportive care of patients with myeloma not eligible for standard autologous stem-cell 
transplantation. J Clin Oncol. 2014;32(6):587-600. 
5. 
Bu D-X, Singh R, Choi EE, Ruella M, Nunez-Cruz S, Mansfield KG, et al. Pre-clinical 
validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple 
myeloma. Oncotarget. 2018;9(40). 
6. 
Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, et al. B-cell 
Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma. 
Clinical Cancer Research. 2013;19(8):2048-60. 
7. 
Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti-BCMA CAR T-
Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. New England Journal of 
Medicine. 2019;380(18):1726-37. 
8. 
Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, et al. T Cells Genetically 
Modified to Express an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor Cause 
Remissions of Poor-Prognosis Relapsed Multiple Myeloma. Journal of Clinical Oncology. 
2018;36(22):2267-80. 
9. 
Cohen AD, Garfall AL, Stadtmauer EA, Melenhorst JJ, Lacey SF, Lancaster E, et al. B 
cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma. The 
Journal of Clinical Investigation. 2019;129(6):2210-21. 
10. 
Zhao W-H, Liu J, Wang B-Y, Chen Y-X, Cao X-M, Yang Y, et al. A phase 1, open-label 
study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell 
maturation antigen, in patients with relapsed or refractory multiple myeloma. Journal of 
Hematology & Oncology. 2018;11(1):141. 
11. 
Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, et al. T Cells Genetically 
Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause 
Remissions of Poor-Prognosis Relapsed Multiple Myeloma. J Clin Oncol. 2018;36(22):2267-80. 
12. 
Munshi NC, Anderson LD, Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene 
Vicleucel in Relapsed and Refractory Multiple Myeloma. New England Journal of Medicine. 
2021;384(8):705-16. 
13. 
Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, et al. 
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell 
therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 
open-label study. The Lancet. 2021;398(10297):314-24. 
14. 
Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, et al. Targeting B-cell 
maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple 
myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 
2018;19(12):1641-53. 
15. 
Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Belantamab mafodotin 
for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, 
phase 2 study. Lancet Oncol. 2020;21(2):207-21. 


 
 
Short Title: MCW EMBRACE TRIAL 
89 
Version No.: 3 
 
 
Version Date: 12/29/2022 
16. 
Fraietta JA, Lacey SF, Orlando EJ, Pruteanu-Malinici I, Gohil M, Lundh S, et al. 
Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell 
therapy of chronic lymphocytic leukemia. Nat Med. 2018;24(5):563-71. 
17. 
Cherkassky L, Morello A, Villena-Vargas J, Feng Y, Dimitrov DS, Jones DR, et al. 
Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated 
inhibition. J Clin Invest. 2016;126(8):3130-44. 
18. 
Tai YT, Mayes PA, Acharya C, Zhong MY, Cea M, Cagnetta A, et al. Novel anti-B-cell 
maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple 
myeloma. Blood. 2014;123(20):3128-38. 
19. 
Gazeau N, Beauvais D, Yakoub-Agha I, Mitra S, Campbell TB, Facon T, et al. Effective 
anti-BCMA retreatment in multiple myeloma. Blood Advances. 2021;5(15):3016-20. 
20. 
Cohen AD, Garfall AL, Dogan A, Lacey SF, Martin C, Lendvai N, et al. Serial treatment 
of relapsed/refractory multiple myeloma with different BCMA-targeting therapies. Blood 
Advances. 2019;3(16):2487-90. 
21. 
Vaxman I, Abeykoon J, Dispenzieri A, Kumar SK, Buadi F, Lacy MQ, et al. “Real-life” 
data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma—the 
Mayo Clinic experience. Blood Cancer J. 2021;11(12):196. 
22. 
Trudel S, McCurdy A, Sutherland HJ, Louzada ML, Venner CP, Mian HS, et al. Part 1 
Results of a Dose-Finding Study of Belantamab Mafodotin in Combination with Pomalidomide 
and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM). 
Blood. 2021;138(Supplement 1):1653-. 
23. 
Trudel S MA, Sutherland HJ, et al. Part 1 results of a dose finding study of belantamab 
mafodotin (GSK2857916) in combination with pomalidomide and dexamethasone for the 
treatment of relapsed/refractory multiple myeloma. Blood 2020;(Suppl 1):abstract 725. 
24. 
Terpos E, Gavriatopoulou M, Ntanasis-Stathopoulos I, Malandrakis P, Fotiou D, 
Kanellias N, et al. A Phase 1/2, Dose and Schedule Evaluation Study to Investigate the Safety 
and Clinical Activity of Belantamab Mafodotin Administered in Combination with Lenalidomide 
and Dexamethasone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma. 
Blood. 2021;138(Supplement 1):2736-. 
25. 
Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Longer term outcomes 
with single-agent belantamab mafodotin in patients with relapsed or refractory multiple 
myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Cancer. 2021;127(22):4198-
212. 
26. 
Lee L, Bounds D, Paterson J, Herledan G, Sully K, Seestaller-Wehr LM, et al. Evaluation 
of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in 
multiple myeloma. Br J Haematol. 2016;174(6):911-22. 
27. 
Tai Y-T, Mayes PA, Acharya C, Zhong MY, Cea M, Cagnetta A, et al. Novel anti–B-cell 
maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple 
myeloma. Blood. 2014;123(20):3128-38. 
28. 
Sidana S, Shah N. CAR T-cell therapy: is it prime time in myeloma? Blood Advances. 
2019;3(21):3473-80. 
29. 
Xu J, Chen L-J, Yang S-S, Sun Y, Wu W, Liu Y-F, et al. Exploratory trial of a biepitopic 
CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma. Proceedings 
of the National Academy of Sciences. 2019;116(19):9543-51. 
30. 
A Phase 3 study comparing oral Ixazomib Plus Lenalidomide and Dexamethasone 
Versus Placebo Plus Lenalidomide and Dexamethasone in adult patients with relapsed and/or 
refractory multiple Myeloma. Clinical trialsgov.Available from: 
https://clinicaltrials.gov/ct2/show/NCT01564537?term=tourmaline+mm1&rank=1. 
31. 
Farooq AV, Degli Esposti S, Popat R, Thulasi P, Lonial S, Nooka AK, et al. Corneal 
Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate 


 
 
Short Title: MCW EMBRACE TRIAL 
90 
Version No.: 3 
 
 
Version Date: 12/29/2022 
Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Ophthalmology and 
therapy. 2020;9(4):889-911. 
32. 
Collins D, Bossenmaier B, Kollmorgen G, Niederfellner G. Acquired Resistance to 
Antibody-Drug Conjugates. Cancers. 2019;11(3):394. 
33. 
Salem DA, Maric I, Yuan CM, Liewehr DJ, Venzon DJ, Kochenderfer J, et al. 
Quantification of B-cell maturation antigen, a target for novel chimeric antigen receptor T-cell 
therapy in Myeloma. Leukemia Research. 2018;71:106-11. 
34. 
Samur MK, Fulciniti M, Aktas Samur A, Bazarbachi AH, Tai Y-T, Prabhala R, et al. 
Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with 
multiple myeloma. Nat Commun. 2021;12(1):868. 
35. 
Huang B, Talukder E, Thomas N. Optimal Two-Stage Phase II Designs with Long-Term 
Endpoints. Statistics in Biopharmaceutical Research. 2010;2(1):51-61. 
 
 

ICF_001.pdf: 
INFORMED CONSENT FORM 
A Multicenter Phase II Study of Maintenance Belantamab Mafodotin (Blenrep®) After 
BCMA-Directed Chimeric Antigen Receptor T-cell Therapy in Patients With Relapsed 
and/or Refractory Multiple Myeloma   
NCT05117008 
IRB Approval Period: 12/14/2023 – 9/13/2024 Effective 12/14/2023 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 1 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
 
Medical College of Wisconsin  
INTRODUCTION TO THE INFORMED CONSENT 
 
IIT-CHHABRA-EMBRACE-MM: A Multicenter Phase II Study of Maintenance Belantamab 
Mafodotin (Blenrep®) after BCMA-Directed Chimeric Antigen Receptor T-Cell Therapy in 
Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM) 
 
Meera Mohan, MD 
Department of Medicine 
Medical College of Wisconsin 
9200 West Wisconsin Avenue 
Milwaukee WI 53226 
414-805-6700 
 
 
 
 
Definitions 
 
CAR-T (Chimeric Antigen Receptor T-Cell) Therapy – a special receptor created in the 
laboratory that is designed to bind to certain proteins on the cancer cell 
 
Biomarker – something found in the blood, other fluids, or tissues that can be used to 
measure the progress of disease or how a treatment is working 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 2 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
 
Purpose 
This project is being done to test the safety 
and effectiveness of a potential new treatment 
called Belantamab Mafodotin for subjects who 
have previously received at least three 
treatments, including CAR-T therapy. 
Length 
1. You will be in this research project for 
about up to 12 cycles or until your cancer 
gets worse. 
2. We would also like to follow you in clinic 
visits and then for every 6 months to see 
how you are doing. 
Risks 
This is a brief list of the most commonly seen 
side effects. The full consent form after this 
introduction contains a more complete list of 
potential research risks. 
 
Belantamab Mafodotin risks: 
 
Excess protein in the urine 
 
Eye problems: blurred vision, dry/itchy 
eyes, changes in vision, eye discomfort, 
difficulty seeing at night, inflammation or 
other changes of front part of eye 
 
Low number of blood cells called platelets  
 
Anemia 
 
Feeling sick to your stomach (nausea) 
 
Feeling tired (fatigue) 
 
Increase in liver function tests 
 
Fever 
 
Pneumonia, or other lung infection 
 
Cold or cold-like symptoms (upper 
respiratory tract infection) 
 
Low number of certain types of white blood 
cells called neutrophils (neutropenia) and 
lymphocytes (lymphopenia), which could 
increase the risk of infection. If you have a 
fever, please contact your study doctor 
immediately. 
 
Diarrhea 
 
Reactions from the infusion of Belantamab 
Mafodotin, usually happen within first 24 
hours after the infusion. Symptoms may 
include flushing, chills, fever, difficulty 
breathing, rapid heartbeat, or a drop in 
blood pressure (feeling light-headed). 
 
 
Procedures 
All subjects in this study will receive 
Belantamab Mafodotin. You will receive the 
study drug on Day 1 of every cycle. Each 
cycle is 56 days (8 weeks). 
 
List of visits: 
 
Screening Visit(s)  
- Total Number: about 1-3 
- Total Time: about 4-10 hours each 
 
Treatment Visits 
- Total Number: about 12 
- Total Time: about 3-6 hours each 
 
Safety Follow-up Visit(s) 
- Total Number: 1 
- Total Time: about 4-6 hours 
 
Pre-Progression Follow-up Visits 
- Total Number: every 3 months until 
your cancer gets worse 
- Total Time: about 2-4 hours each 
 
Long Term Follow-up Visits (after 
progression) 
- Total Number: every 6 months  
- Total Time: about 1-4 hours each 
 
 
 
 
 
 
 
 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 3 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
 
My Other Options 
You do not have to join this project. Your other 
options may include: 
1. Joining a different project 
2. Routine care for this condition  
3. Getting no treatment for this condition 
 
Benefits 
We don’t know if this project will help you. Your 
condition may get better but it could stay the 
same or even get worse. 
Procedures that will occur at various 
visits: 
 
Invasive Procedures 
Study drug administration (Belantamab 
Mafodotin), Blood collection, Bone marrow 
biopsy/aspirate, CT/PET/MRI scan 
 
Non-invasive Procedures 
Physical examination and vital signs, 
Electrocardiogram (ECG), Echocardiogram 
(ECHO)/Multiple Gated Acquisition Scan 
(MUGA), Urine collection, Questionnaires, 
Skeletal survey 
If you have more questions about this project at any time, you can call Meera Mohan, MD at 
414-805-6700. 
 
If you have questions about your rights as a participant, want to report any problems or 
complaints, or offer input, you can call the MCW/Froedtert Hospital Research Subject 
Advocate at 414-955-8844. 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 4 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
CONSENT TO PARTICIPATE IN RESEARCH 
A1. INTRODUCTION – WHY ARE WE ASKING YOU TO PARTICIPATE? 
You are being invited to participate in this research because you have relapsed and/or 
refractory multiple myeloma and have previously received CAR-T therapy in addition to three 
other treatment regimens. 
 
A total of about 45 people are expected to participate in this research nationally including about 
10 at the Medical College of Wisconsin/Froedtert Hospital. 
 
The Director of the project is Meera Mohan, MD in the Department of Medicine. A research 
team works with Meera Mohan, MD. You can ask who these people are.  
 
GlaxoSmithKline (GSK), a drug company, is funding the research.  
 
A2. DO I HAVE TO PARTICIPATE? 
You can decide whether to take part in this research or not. You are free to say yes or no. If you 
do not agree to join, or if you leave, you will not be penalized or lose any benefits that you had 
before starting the research project. Even if you join this project, you do not have to stay in it. 
You may stop at any time. Take as much time as you need to make your choice.  
 
A research project is different from routine medical care in three ways: 1) there are extra risks 
that we will tell you about in this form; 2) you may have some extra medical tests and visits; 3) 
the research procedures, tests and visits follow a set plan that must be kept. 
 
A3. WHY IS THIS PROJECT BEING DONE? 
Current treatment regimens for multiple myeloma attempt to improve a patient’s quality of life 
and prolong survival. These include stem cell transplant, chemotherapy, and other treatments 
which help to improve the immune system’s function. However, over time many patients 
develop resistance to these treatments, and new treatment regimens are needed for these 
patients. 
 
The purpose of this study is to test the safety and effectiveness of a potential new treatment 
called Belantamab Mafodotin for subjects who have previously received at least three 
treatments, including CAR-T therapy. Belantamab Mafodotin is investigational, meaning it is 
approved for other uses, but it is not approved by the FDA for use in this study. 
 
Your condition may get better, but it could stay the same or even get worse. We hope the 
information from this study will help us develop a better treatment for multiple myeloma in the 
future. 
 
 
 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 5 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
B1. WHAT WILL HAPPEN IF I PARTICIPATE? 
STUDY DRUGS 
 
Belantamab Mafodotin is administered by intravenous (IV) infusion over a period of 
approximately 30 minutes. If you do not already have a port that has been surgically inserted, 
you will have a small catheter placed in a vein in your arm for the infusion. You will receive the 
infusion on Day 1 of every cycle lasting 56 days (8 weeks). The dosage will be determined 
based on your body weight and may change if you gain or lose weight.  
 
You may receive pre-medication(s) up front, such as antihistamines, steroids, or pain relievers, 
to prevent drug reactions from happening, if you have side effects from similar drugs before or if 
your doctor think that it is needed in your case. 
 
STUDY GROUPS 
 
All subjects in this study will receive Belantamab Mafodotin. 
 
STUDY VISTS 
 
Screening  
If you agree to participate in the study, you will sign this consent form before screening 
assessments are performed to see if you are eligible. Your study doctor or a member of the 
study team will let you know if you are eligible to participate in the study. If you are unable to 
participate in the study, the study doctor will discuss other treatment options with you.  
 
Treatment  
If you are eligible to participate, you will begin study drug treatment as described above. You will 
return to the clinic about once a week. Assessments to track your disease status and to monitor 
you for side effects will occur during the treatment visits. You will continue treatment with the 
study drug up to 12 cycles or until your cancer gets worse.  
 
Follow-up  
After you stop study drug treatment, you will return to the clinic 70 days after your last dose for a 
Safety Follow-up visit to monitor for any side effects of the study drug.  
 
If you stopped study drug treatment before your disease progressed, you will then be return to 
the clinic every 3 months for follow-up assessments to track the status of your disease. At 
progression, your medical record will be reviewed or you will be contacted every 6 months to 
see how you are doing. 
 
If you stopped study drug treatment due to disease progression, your medical record will be 
reviewed or you will be contacted every 6 months to see how you are doing.  
 
 
 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 6 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
STUDY ASSESSMENTS 
 
Screening 
You will need to have all or some of the following exams, tests, or procedures to find out if you 
can be in the study. Some of them are routine and may be done even if you do not join the 
study. If some of the tests were completed recently, they may not have to be repeated. 
 
Informed consent: Prior to any study-related procedures being performed, you will be 
required to voluntarily sign and date this consent form. 
 
Medical history: You will be asked about your health status, including previous 
treatments for your cancer 
 
Physical examination: You will receive a complete physical examination 
 
Eye Exam: You will have an eye exam performed to assess various parts of your vision 
o Visual Acuity: You will be asked to read different sized letters off a chart to test 
your vision (visual acuity). For this test, you will be asked to wear special glasses 
while different lenses are presented to you. We will test your visual acuity while 
you are wearing the lenses that allow you to read the most clearly 
o Eye Exam: A doctor may check your eyes using a low-powdered microscope with 
a bright light and magnifying lenses. As part of the eye exam, we may measure 
your intraocular pressure (the pressure inside your eye). To check your 
intraocular pressure, you will be given a numbing eye drop and then a special 
instrument will touch your eye for a few seconds to take a measurement. The 
doctor may also apply colored stains or dyes to the front of the eye to check for 
abnormalities of the surface layer of the eye (conjunctiva). The colored stain may 
be applied as a drop or using a sterile paper applicator dampened with eye wash 
or a numbing drop. If you have had a recent eye exam, we may be able to use 
information from your medical record instead of completing an eye exam during 
your study visit. We may also put drops in your eyes to dilate (or widen) your 
pupils. 
o Additional examinations may be performed if the eye doctor thinks it is necessary 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Medications: You will be asked about your current medications, including over-the-
counter medications, vitamins, and herbal supplements 
 
Vital signs: Your blood pressure, heart rate, temperature, height, and weight will be 
checked 
 
Blood tests: Blood samples will be collected for 
o Blood cell counts, blood chemistry, clotting ability 
o Organ function 
o Active Hepatitis B and C infection 
As part of the screening procedures, your blood will be tested for diseases that 
can be passed on to other people by transfusion, including Hepatitis B and C. If 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 7 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
certain tests are positive, we will inform you, and inform certain government 
health agencies as required by law. Results of your blood test will be released 
only to authorized persons as governed by Wisconsin law. A list of persons to be 
notified and reasons that will cause release of your blood test is available upon 
request. Results of the blood test will be released to the study team 
o Pregnancy test (if you are a woman of childbearing potential) 
o Indicators of your disease status 
 
Electrocardiogram (ECG) and Echocardiogram (ECHO)/Multiple Gated Acquisition Scan 
(MUGA): ECG and ECHO/MUGA will be performed to check the activity of your heart 
 
24-hour urine and spot urine collections: Urine samples will be collected for indicators of 
your disease 
 
Whole-body PET/CT, CT, skeletal survey, and/or MRI: You will have a whole-body PET/ 
CT, CT, skeletal survey and/or MRI to assess your cancer  
 
Bone Marrow Biopsy and Aspirate: A bone marrow biopsy/aspiration is required and will 
be performed prior to the planned study treatment start date to assess disease status 
 
Treatment 
You will begin study drug treatment if the results of screening assessments show that you are 
eligible. 
 
The following assessments will be performed at all treatment visits, unless noted. 
 
Medical history: You will be asked about your health status, including previous 
treatments for your cancer 
 
Physical examination: You will receive a complete physical examination 
 
Eye Exam: You will have an eye exam performed to assess various parts of your vision 
at all treatment visits except Cycle 1.  
o Visual Acuity: You will be asked to read different sized letters off a chart to test 
your vision (visual acuity). For this test, you will be asked to wear special glasses 
while different lenses are presented to you. We will test your visual acuity while 
you are wearing the lenses that allow you to read the most clearly 
o Eye Exam A doctor may check your eyes using a low-powdered microscope with 
a bright light and magnifying lenses. As part of the eye exam, we may measure 
your intraocular pressure (the pressure inside your eye). To check your 
intraocular pressure, you will be given a numbing eye drop and then a special 
instrument will touch your eye for a few seconds to take a measurement. The 
doctor may also apply colored stains or dyes to the front of the eye to check for 
abnormalities of the surface layer of the eye (conjunctiva). The colored stain may 
be applied as a drop or using a sterile paper applicator dampened with eye wash 
or a numbing drop. If you have had a recent eye exam, we may be able to use 
information from your medical record instead of completing an eye exam during 
your study visit. We may also put drops in your eyes to dilate (or widen) your 
pupils. 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 8 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
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o Additional examinations may be performed if the eye doctor thinks it is necessary 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Medications: You will be asked about your current medications, including over-the-
counter medications, vitamins, and herbal supplements 
 
Vital signs: Your blood pressure, heart rate, temperature, height, and weight will be 
checked 
 
Blood tests: Blood samples will be collected for 
o Blood cell counts, blood chemistry, clotting ability 
o Organ function 
o Pregnancy test (if you are a woman of childbearing potential) 
o Indicators of your disease status 
 
24-hour urine and spot urine collections: Urine samples will be collected for indicators of 
your disease, at Cycle 2 and every other cycle thereafter 
 
Whole-body PET/CT, CT, skeletal survey, and/or MRI: You will have a whole-body PET/ 
CT, CT, skeletal survey and/or MRI to assess your cancer, at Cycle 7 only 
 
Bone Marrow Biopsy and Aspirate: A bone marrow biopsy/aspiration is required and will 
be performed prior to the planned study treatment start date to assess disease status, at 
Cycle 3 and Cycle 7 
 
Questionnaires: You will be asked to complete questionnaires about your ability to 
perform daily activities 
 
Bone marrow collection from diagnosis: We will analyze some of your stored bone 
marrow collected from your diagnosis, at Cycle 1 only 
 
Follow-up 
Safety Follow-up Visit 
The following assessments will be performed 70 days after you stop study drug treatment: 
 
Medical history: You will be asked about your health status, including previous 
treatments for your cancer 
 
Physical examination: You will receive a complete physical examination 
 
Eye Exam: You will have an eye exam performed to assess various parts of your vision  
o Visual Acuity: You will be asked to read different sized letters off a chart to test 
your vision (visual acuity). For this test, you will be asked to wear special glasses 
while different lenses are presented to you. We will test your visual acuity while 
you are wearing the lenses that allow you to read the most clearly 
o Eye Exam: A doctor may check your eyes using a low-powdered microscope with 
a bright light and magnifying lenses. As part of the eye exam, we may measure 
your intraocular pressure (the pressure inside your eye). To check your 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 9 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
intraocular pressure, you will be given a numbing eye drop and then a special 
instrument will touch your eye for a few seconds to take a measurement. The 
doctor may also apply colored stains or dyes to the front of the eye to check for 
abnormalities of the surface layer of the eye (conjunctiva). The colored stain may 
be applied as a drop or using a sterile paper applicator dampened with eye wash 
or a numbing drop. If you have had a recent eye exam, we may be able to use 
information from your medical record instead of completing an eye exam during 
your study visit. We may also put drops in your eyes to dilate (or widen) your 
pupils. 
o Additional examinations may be performed if the eye doctor thinks it is necessary  
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 
 
Medications: You will be asked about your current medications, including over-the-
counter medications, vitamins, and herbal supplements 
 
Vital signs: Your blood pressure, heart rate, temperature, height, and weight will be 
checked 
 
Blood tests: Blood samples will be collected for 
o Blood cell counts, blood chemistry, clotting ability 
o Organ function 
o Pregnancy test (if you are a woman of childbearing potential) 
o Indicators of your disease status 
 
24-hour urine and spot urine collections: Urine samples will be collected for indicators of 
your disease 
 
Whole-body PET/CT, CT, skeletal survey, and/or MRI: You will have a whole-body PET/ 
CT, CT, skeletal survey and/or MRI to assess your cancer 
 
Bone Marrow Biopsy and Aspirate: A bone marrow biopsy/aspiration is required and will 
be performed to assess disease status 
 
Questionnaires: You will be asked to complete questionnaires about your ability to 
perform daily activities 
 
Pre-Progression Follow-up Visits 
You will return to the clinic every 3 months from your Safety Follow-up visit until your cancer 
gets worse to monitor your health. The following assessments will be performed at each Pre-
Progression Follow-up visit: 
 
Medical history: You will be asked about your health status, including previous 
treatments for your cancer 
 
Physical examination: You will receive a complete physical examination 
 
Performance status: An assessment of your overall health and ability to perform daily 
tasks 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 10 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
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MCW IRB 
 
Medications: You will be asked about your current medications, including over-the-
counter medications, vitamins, and herbal supplements 
 
Height and weight: Your height and weight will be checked 
 
Blood tests: Blood samples will be collected for 
o Blood cell counts, blood chemistry, clotting ability 
o Organ function 
o Pregnancy test (if you are a woman of childbearing potential) 
o Indicators of your disease status 
 
24-hour urine and spot urine collections: Urine samples will be collected for indicators of 
your disease 
 
If the study doctor thinks it is necessary, you will continue to have eye exam visits every 3 
months until 1 year from the end of the study treatment. Additional examinations may be 
performed if the eye doctor thinks it is necessary. 
 
Long-Term Follow-up 
After your cancer gets worse, we will contact you every 6 months to see how you are doing. 
 
STUDY SAMPLES FOR RESEARCH 
 
We would also like to collect samples during the study to be used for future research. These 
samples are required to participate in the main study. The samples will be used to analyze 
different biomarkers. A biomarker is something found in the blood, other fluids, or tissues that 
can be used to measure the progress of disease or how a treatment is working. 
 
The following samples will be collected at the visits listed below: 
 
Bone marrow aspirate (about 5-10 mL at each time point) 
 
Screening 
 
Cycle 3 Day 1 
 
Cycle 7 Day 1 
 
70 days post-last dose safety visit or progression, whichever is earlier 
 
Bone marrow that was collected from your diagnosis 
 
Blood (about 15 mL of blood at each time point) 
 
Screening 
 
Cycle 3 Day 1 
 
Cycle 7 Day 1 
 
70 days post-last dose safety visit or progression, whichever is earlier 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 11 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
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MCW IRB 
GENETIC TESTING 
In this project, we will do genetic testing on your biospecimens. This will be collected at the time 
points listed in the “STUDY SAMPLES FOR RESEARCH” heading above. Genetic testing will 
be done because researchers would like to better understand the mechanisms of how the study 
drug affects your multiple myeloma. 
This genetic testing is for research only. The purpose is not to discover information that could be 
used to change your medical care, make or change your diagnosis, or advise you on your risk of 
diseases.  
 
The biospecimens collected for this part of the project will be coded, which means they will be 
labeled with numbers and/or letters instead of information that could identify you. Only the 
research team will be able to link the code to you. The samples will also be labeled with date of 
collection, which could potentially be used to identify you. The research team will make every 
effort to protect the information and keep it confidential, but it is possible that an unauthorized 
person might see it. Depending on the kind of information being collected, it might be used in a 
way that could embarrass you.  
 
It is against federal law (Genetic Information Nondiscrimination Act, or GINA) for health 
insurance companies to deny health insurance, or large employers to deny jobs, based on your 
genetic information. But the same law does not protect your ability to get disability, life, or long-
term care insurance. If you have questions, you can talk to the research doctor about whether 
this could apply to you. 
 
You will not be given your genetic test results. 
 
B2. HOW LONG WILL I BE IN THE PROJECT? 
You will continue treatment with the study drug up to 12 cycles or until your cancer gets worse.  
 
After you stop study drug treatment, you will return to the clinic 70 days after your last dose for a 
Safety Follow-up visit to monitor for any side effects of the study drug.  
 
If you stopped study drug treatment before your disease progressed, you will then be return to 
the clinic every 3 months for follow-up assessments to track the status of your disease. At 
progression, your medical record will be reviewed or you will be contacted every 6 months to 
see how you are doing. 
 
If you stopped study drug treatment due to disease progression, your medical record will be 
reviewed or you will be contacted every 6 months to see how you are doing.  
 
B3. CAN I STOP BEING IN THE PROJECT?   
You are free to withdraw from the project at any time. If you leave, your regular medical care will 
not change. If you are thinking about leaving, please tell the research doctor.  
 
The research doctor can tell you about the effects of stopping, and you and the research doctor 
can talk about what follow-up care would help you the most. 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 12 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
You might be asked to come back for one more visit to check your health. 
 
The research doctor may take you out of this project at any time. This would happen if: 
 
They think it is in your best interest. 
 
You do not follow the project rules. 
 
The whole project is stopped. 
 
If this happens, the research doctor will tell you. 
B4. ARE THERE ANY SPECIAL INSTRUCTIONS WHILE I AM IN THE PROJECT?  
You must attend all of the study appointments. If you have to miss an appointment, you must 
reschedule with the study doctor or staff. 
 
You must tell the study doctor about any medicines you are currently taking or may take during 
the course of the study (e.g., prescription, vitamins, over the counter, herbal supplements etc.), 
as some of these may need to be stopped/reduced. 
 
You must not wear contact lenses while participating this study. If you are experiencing 
discomfort in your eyes, please talk to your doctor about the use of preservative-free artificial 
tears or cooling eye masks. 
 
Please discuss with your doctor if you plan to receive any vaccines, including the COVID-19 
vaccine. 
 
You should not breastfeed a baby while you are participating in the study and for 3 months after 
the last dose of study drug. 
 
C1. WHAT HEALTH RISKS OR PROBLEMS CAN I EXPECT FROM THE PROJECT? 
There are risks to taking part in any research project. There is a risk that you may get a drug 
that does not help your condition or may make it worse.  There also may be problems (side 
effects) we do not know about yet, from the drug itself, or how it combines with other drugs you 
are taking. If we learn about new important side effects, we will tell you.  
 
We watch everyone in the project for problems (side effects). You need to tell the research 
doctor or a member of the research team immediately if you experience any problems, 
side effects, or changes in your health. In an emergency, call 911. 
 
C2. RISKS OF STUDY DRUG 
The research drug itself may cause problems (side effects).  Side effects may be mild or very 
serious.  Some can last a long time or never go away.   
 
Many go away soon after you stop taking the drugs. Drugs can affect individuals in different 
ways. Complications of some of the side effects below may lead to life-threatening events, 
possibly resulting in death. 
 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 13 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
The side effects that other people have experienced so far with the study drug are:  
 
Belantamab Mafodotin 
 
Belantamab Mafodotin is an approved drug in the European Union, United Kingdom, 
Switzerland, Singapore, Hong Kong, and Israel with ongoing clinical development; therefore, not 
all of its side effects are known at this time. As of 27 February 2023, over 1,600 people with MM 
have received Belantamab Mafodotin across all ongoing and completed clinical studies. 
 
Some common side effects reported with Belantamab Mafodotin are described below. 
 
Eye Problems 
Some participants who have received Belantamab Mafodotin in clinical studies developed 
problems in the front part of the eye called the cornea. Sometimes the changes can only be 
observed by an eye doctor during eye examination, and they do not result in any symptoms. 
Those changes might be more frequent in patients who had problems with dry eye prior to 
treatment with Belantamab Mafodotin. Some patients, however, develop symptoms related to 
Belantamab Mafodotin. The symptoms could range from a feeling of dryness in the eye to more 
severe symptoms, like blurry vision or changes in your eyesight, that could affect your ability to 
see things clearly and may affect your reading ability or difficulty in driving. A few people have 
developed eye sores. These effects typically go away if the study drug is held and the dose 
reduced upon re-start, but please discuss with your study doctor if you have questions. In 
severe cases, sores can develop on the eye, possibly with infection. If untreated this could 
potentially lead to scarring which may permanently affect your eyesight. If you experience new 
eye symptoms (such as pain or irritation, blurry vision, or feeling like something is in your eye), 
you should urgently seek medical attention by an eye care specialist. Your eyes will be 
examined repeatedly during the study, as it is important to monitor the effects of Belantamab 
Mafodotin on your eyes. If you develop problems with your eyesight or other problems with your 
eyes, do not drive or operate heavy machinery until you have had your eyes examined by an 
eye care specialist. 
 
Abnormal Bruising and Bleeding 
Belantamab Mafodotin can decrease the number of blood cells called platelets, which help to 
clot your blood. Symptoms of low platelets counts (called thrombocytopenia) can include 
abnormal bruising of your skin, bleeding for longer than usual after your blood has been drawn, 
or bleeding from your nose or gums. In some cases, the bleeding can occur from other areas of 
your body. Bleeding may be serious, or life threatening and may require a transfusion. Your 
study doctor will closely monitor your platelets by checking your blood tests before you start 
your treatment and regularly during the study. 
 
Infusion-related reactions 
Some people may have allergic-like reactions when they receive an infusion of Belantamab 
Mafodotin. These usually develop within minutes or hours but can develop up to 24 hours after 
your dose is given. It is a reaction to the drug being a foreign protein, and you may have 
flushing, chills, fever, problems with breathing, feeling like your heart is racing or a drop in blood 
pressure (which may cause you to feel dizzy, light-headed or like you’re going to faint). You will 
usually spend an hour after your dose to check whether you will develop these symptoms but if 
you experience any of these symptoms at any time contact your study doctor immediately. 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 14 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
Inflammation of the lungs 
Some people who have received Belantamab Mafodotin experienced inflammation of the lungs 
which can cause cough, shortness of breath and difficulty breathing, and in some cases, death. 
It is not certain if Belantamab Mafodotin causes the inflammation or not. If you experience new 
or worsening breathing problems like cough or shortness of breath with an unknown cause, 
contact your study doctor immediately. 
 
Excess protein in the urine 
Some people receiving Belantamab Mafodotin have developed excess levels of protein (called 
albumin) in the urine, which can sometimes be a sign of a kidney disorder. Your study doctor 
will closely monitor protein levels in your urine regularly during the study. If your urine looks 
foamy or frothy or if you notice new swelling or more swelling than usual in your feet, legs or 
other parts of your body, contact your study doctor immediately. 
 
Side Effects 
The side effects described below are from 95 patients with RRMM who received at least one 
dose of Belantamab Mafodotin at doses of 2.5 mg/kg. 
 
The most common side effects occurring in more than 20% of people (20 or more out of 100 
people) were: 
 
Eye problems: blurred vision, dry/itchy eyes, changes in vision, eye discomfort, difficulty 
seeing at night, inflammation or other changes of front part of eye. 
 
Low number of blood cells called platelets (thrombocytopenia), which may cause 
bleeding and easy bruising. Bleeding may be serious, or life threatening and may require 
a transfusion. 
 
Having fewer red blood cells than normal (anemia) 
 
Feeling sick to your stomach (nausea) 
 
Feeling tired (fatigue) 
 
Increase in liver function tests 
 
Fever (if you have a fever, please contact your study doctor immediately) 
 
Pneumonia, or other lung infection 
 
Cold or cold-like symptoms (upper respiratory tract infection) 
 
Low number of certain types of white blood cells called neutrophils (neutropenia) and 
lymphocytes (lymphopenia), which could increase the risk of infection. If you have a 
fever, please contact your study doctor immediately. 
 
Diarrhea 
 
Reactions from the infusion of Belantamab Mafodotin, usually happen within first 24 
hours after the infusion. Symptoms may include flushing, chills, fever, difficulty breathing, 
rapid heartbeat, or a drop in blood pressure (feeling light-headed). 
 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 15 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
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MCW IRB 
Other common side effects seen in 1% to 10% of subjects (between 1 to 10 out of 100 people) 
were: 
 
Other eye problems: eye irritation, abnormal sensitivity of the eyes to light, and cores on 
the eyes possibly with infection. 
 
Increased albumin, a type of protein in the urine, (albuminuria) 
 
An increase in an enzyme released into the blood when muscle is damaged (creatine 
phosphokinase) 
 
Vomiting 
 
In another study which is testing Belantamab Mafodotin in combination with two medicines 
already approved for the treatment of RRMM, called Lenalidomide and Dexamethasone, two 
patients who had low neutrophil counts developed serious infections which led to death. 
 
Embryo-fetal toxicity: Belantamab Mafodotin may harm an unborn baby. You must have 
negative pregnancy tests to continue in the study if you are a woman who can have children.  
 
Fertility: Belantamab Mafodotin treatment may affect men and women’s ability to have children.  
 
There may be other side effects that may happen that are not known now. For example, all 
drugs can cause an allergic reaction in some participants. Certain problems can become worse 
if not treated quickly. Call the study doctor right away if:  
 
You feel very tired or faint 
 
You feel pain or sick in your stomach and you do not want to eat 
 
You bruise easily or develop itching 
 
You have yellow eyes or skin, or dark urine 
 
You become confused. 
 
C3. OTHER RISKS OF THIS RESEARCH PROJECT 
Other procedures that are part of the research also involve some risks: 
 
Intravenous (IV) Drug Administration 
It is recommended that the study drug is given into a vein in the arm. There is a risk that the 
study drug could leak outside the vein. If that happens, the drug could leak into the surrounding 
tissue and cause considerable irritation, and even tissue damage. The nurses and doctors will 
take every precaution to prevent leaks from the peripheral line, but there is still a risk that the 
tissue around the injection site could become damaged if it comes into contact with the study 
drug. Immediately tell the study doctor or nurse if you feel a burning sensation or irritation at the 
injection site any time during or after being given the study drug. 
 
Blood Draws: 
Blood draws are necessary to monitor the disease being treated as well as the side effects of 
the treatment. However, by participating in the study you may require a higher frequency of 
blood draws that would be performed if your doctor was treating you with standard, 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 16 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
nonexperimental therapies. Risks associated with blood draws include pain, itching, and, more 
rarely, anemia, fainting and dizziness. 
 
Electrocardiogram (ECG) 
An ECG is a simple and painless test that detects and records the electrical activity of your 
heart. Soft adhesive patches the size of a quarter (called electrodes) will be attached to the skin 
of the chest, arms, and legs. You will be requested to lie still for a few minutes while a machine 
records the electrical signals. Rarely, localized rash or skin irritation may occur where the 
electrode patches are placed. These reactions are typically temporary. 
 
Echocardiogram (ECHO) 
During the echocardiogram, electrodes will be placed onto your chest to allow for an ECG to be 
performed. Then a transducer (a device that looks like a computer mouse) will be applied. You 
may feel slight pressure on your chest from the transducer. In addition, you may be asked to 
breathe in a certain way or to rest on your side during the test. 
 
Multiple Gated Acquisition Scan (MUGA) 
A MUGA scan takes images of the beating heart to see how well your heart is pumping blood. A 
small amount of radioactive material will be injected into your vein and bind to your red blood 
cells (blood cells that carry oxygen throughout your body) in order for the special camera to take 
pictures of how the blood moves through your heart. You will be asked to lie very still during this 
scan, because any movement can cause the images to be blurry. There may be some 
discomfort from having to lie still during the length of the procedure. Allergic reactions to the 
radioactive material are rare but may occur. The injection of the radioactive material may cause 
some slight discomfort.   
 
Bone marrow biopsy or aspirate 
Your study doctor will explain the risks associated with collecting the bone marrow biopsy 
and/or aspiration. Having a biopsy or aspiration performed may cause some pain, bruising, 
redness, inflammation, bleeding, low blood pressure, swelling and/or infection at the site of the 
biopsy or aspiration.  
 
PET Scan 
Positron emission tomography (PET) is a type of imaging test that uses a small amount of 
radioactive material injected into your vein to see how cells or tissues are functioning. It is 
combined with a CT scan (3D x-ray) in one machine so doctors can better see the structures the 
PET agent goes to. 
 
Before the scan, you will have to follow preparation instructions including not eating for 6 hours 
before the test. After the PET agent is injected, you will wait 45-60 minutes before being 
scanned. The scan will take several minutes, and you must lie still during that time.  
 
CT Scan 
CT scans use x-rays to create an image. If frequent CT scans are performed, the cumulative 
amount of radiation involved could be concerning. People who have a small but increased 
radiation exposure may have the risk of cancer development in later life. However, there is 
considerable uncertainty regarding the risk estimates for low levels of radiation exposure from 
the CT scans you will undergo. 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 17 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
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MCW IRB 
Skeletal survey X-ray 
An X-ray exposes your body to radiation. The amount of radiation you get from an X-ray is 
small, and from skeletal survey X-rays it is usually equal to 4–6 months of background radiation. 
 
MRI Scan 
MRI, which uses a large magnet instead of x-rays to take pictures of your body, you may feel 
mild vibrations throughout your body. The machine will produce a loud knocking noise. This is 
normal. You will be given earplugs to protect your ears. Some people, especially those who 
tend to feel uncomfortable in small or closed spaces, may feel “closed in” and become anxious 
while in the scanner. The scanner has an intercom, which will allow you to speak to the staff 
during the procedure. If you feel ill or anxious during scanning, tell the MRI staff and the 
scanning will be stopped if you wish.  
 
The MRI may require a catheter to be inserted into one of your veins in order to inject the MRI 
contrast agent. This may cause skin irritation, bleeding, and/or infection. You may have an 
allergic reaction to the contrast agent.  
 
The magnetic field used in MRI scanning may harm people who have metal in their bodies 
(pacemakers, neurostimulators, certain clips, or staples from surgery). It may cause problems 
with devices, such as pacemakers. If you have metal in your body or a pacemaker, you should 
not have an MRI. Your study doctor will discuss with you whether you should have a MRI scan 
with a contrast agent based on your health status. 
 
Eye Exam Procedures 
Eye Exam 
The lights used by the doctor for the eye exam are bright and may be uncomfortable, but they 
are not expected to harm your eyes. Intraocular pressure testing can rarely cause minor 
scratching to the front of the eye. Since you will be given numbing drops before this test, it is 
important to avoid rubbing your eyes for at least fifteen minutes after receiving the drops, since 
small particles or dust could scratch the front of your eye without you noticing any pain. Colored 
stains used for the exam may cause mild irritation and may cause your eye to look discolored 
temporarily. If you wear contact lenses and put them in while the stain is still present, the stain 
may discolor your contact lens 
 
Pupil Dilation 
Dilating drops may sting temporarily when they are placed in your eyes. While your eyes are 
dilated, you will likely experience blurred vision, difficulty focusing, and sensitivity to light. You 
may also experience a headache or watering of the eyes. The effect of the dilating drops lasts 
several hours. Very rarely (less than 1% of the time), you may have redness, discomfort, or an 
allergic reaction to the drops that are used to dilate the pupil. This is generally not serious and 
can be treated if it occurs. Some types of glaucoma (i.e., angle-closure glaucoma) may be made 
worse by dilating drops in some people, but this can also be treated. 
 
Quality of Life Questionnaires 
The answers that you give are confidential, but there is always a risk that your answers will be 
read by people who should not read your personal information. You may also feel 
uncomfortable completing some of the assessments. 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
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Privacy and Confidentiality 
Another risk may be loss of confidentiality. Every effort will be made to keep your research 
records confidential but we cannot guarantee it. Depending on the kind of information being 
collected, if your research information were accidentally seen, it might be used in a way that 
could embarrass you or affect your ability to get insurance. If you have questions, you can talk 
to the project director about whether this could apply to you. 
  
C4. REPRODUCTIVE RISKS 
Risks to subjects who could become pregnant  
We do not know if the drug causes harm to a baby, so we do not want anyone who might be 
pregnant to enter the project.  
 
You should not become pregnant or nurse a baby while in this project. You must tell the 
research doctor right away if you think you are pregnant. You will be asked to have a pregnancy 
test to be sure you are not pregnant at the start of the project, during the project, and at the end 
of the project. 
 
You may not donate eggs during your participation in the project or for 4 months after stopping 
the drug. 
 
If you become pregnant during the project, the research drug will be stopped for safety reasons. 
If you become pregnant while you are taking this experimental drug or within 4 months after you 
have stopped taking it, we ask that you inform the research doctor immediately. The research 
doctor will ask you for written permission to obtain information from you or your obstetrician on 
your pregnancy and the health of the baby. 
 
Risks to a subject who could father a child and the subject’s partner(s) 
If you and your partner(s) are able to become pregnant, one or both of you must use some form 
of effective birth control, because it is unknown if the drug could affect a baby. You must tell the 
research doctor right away if you think your partner is pregnant. 
 
You may not donate sperm during your participation in the project or for 6 months after stopping 
drug.      
 
If you think you have gotten your partner pregnant while you are taking this experimental drug or 
within 6 months after you have stopped taking it, we ask that you inform the research doctor 
immediately. At that time, the research doctor will ask permission of your partner for the use and 
disclosure of health information regarding the pregnancy. Your partner will be asked to sign a 
separate consent form and can choose to do this or not. Your partner will be asked to sign this 
form to allow your research doctor to contact your partner’s obstetrician to collect information on 
the progress of the pregnancy and its outcome. The research doctor will make this information 
available to the sponsor for safety monitoring. 
 
Birth control methods for all subjects 
Check with the research doctor about the birth control methods needed for this project and how 
long to use them. Some methods might not be good enough for this project. If you are having 
sex that could lead to pregnancy, you should use one form of highly effective birth control while 
you are in this project.   


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 19 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
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MCW IRB 
This may include: 
 
Not having vaginal sex (abstinence) 
 
Taking birth control pills orally 
 
Having birth control shots or patches such as Depo-Provera 
 
Surgical sterilization (hysterectomy/tubal ligation or vasectomy) 
 
Limiting sexual activity to a partner who has undergone surgical sterilization  
 
Use of an intrauterine device (IUD) 
 
Use of diaphragm with contraceptive jelly 
 
Use of condoms with contraceptive foam 
 
Use of diaphragm with condoms (“double barrier”) 
 
Subjects able to become pregnant should use birth control for 4 months after stopping the study 
drug. 
 
Subjects able make their partners pregnant should use birth control for 6 months after stopping 
the study drug. 
 
C5. ARE THERE ANY BENEFITS TO TAKING PART IN THE PROJECT? 
We don’t know if this study will help you. Your condition may get better, but it could stay the 
same or even get worse. We hope the information from this study will help us develop better 
treatments multiple myeloma. 
 
D1. ARE THERE ANY COSTS TO BEING IN THE PROJECT? 
Most of the medical care that you will receive in this project is considered routine care for your 
condition and would be recommended whether or not you join the project.  Costs for routine 
care will be billed to you or your insurance carrier.  For routine clinical care, you will be 
responsible for paying any copayment, coinsurance, or deductible that is required by your 
insurance carrier.  
 
Activities / costs that are part of the project will not be billed to you or your insurance company. 
These are: the study drug, Belantamab Mafodotin; all Eye exams required for this study; the 
ECG at screening; the ECHO/MUGA done at screening; labs not part of your normal care that 
are drawn or collected for research purposes; and the processing and shipping of research 
samples.  
 
Some insurers will not pay for drugs, tests or hospitalization that are part of research, so check 
with your insurer before you join this project. If you have questions regarding costs, please 
contact Dr. Mohan. 
 
If you participate in this research, the costs of any necessary emergency medical treatment in 
the event of a research-related injury will be billed to you or your health insurance. 
 
D2. WILL I BE PAID FOR PARTICIPATING IN THE PROJECT? 
There is no payment for being in this project. 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 20 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
Sponsor, other researchers, or research companies may patent or sell products, discoveries 
and data or information that result from this research. Neither Sponsor nor Dr. Mohan will pay 
you if this happens. You will not receive any payment or commercial rights for products, data, 
discoveries, or materials gained or produced from your biospecimens. 
 
D3. WHAT OTHER HEALTHCARE CHOICES DO I HAVE? 
You do not have to join this project. You are free to say yes or no. If you do not join this project, 
your research doctor can discuss other healthcare choices with you.  
 
Your other choices may include: 
 
Routine care for your type of cancer, including other FDA-approved therapies for 
relapsed/refractory multiple myeloma. Belantamab Mafodotin is also available to you as 
standard of care approved by the FDA if you have progressive myeloma. 
 
Joining a different research project 
 
The research doctor can explain both the possible benefits and the risks of other options that 
are available to you. 
 
D4. WILL I BE GIVEN NEW INFORMATION ABOUT THE PROJECT? 
If we learn any important new information about the drugs that might change your mind about 
being in the project, we will tell you about it right away.  You can then decide if you want to stay 
in the project. 
 
When research biospecimens are collected and analyzed, there is the chance of finding 
something clinically relevant. There may be benefits to learning such results (such as early 
detection and treatment of a medical condition), but there are risks as well (such as feeling 
worried about a finding for which no treatment is required or appropriate). 
 
The results from the biospecimens we collect in this research study are not the same quality as 
what you would receive as part of your health care, so you will not be informed of any clinically 
relevant research findings. The results of your research biospecimens will not be placed in your 
medical record.  
 
D5. WHAT HAPPENS IF I AM INJURED BECAUSE I TOOK PART IN THE PROJECT?  
Emergency medical treatment for injuries directly related to your participation in this research 
project will be provided to you. You or your health insurance will be billed for the costs of this 
emergency treatment.  MCW will decide on a case by case basis if they will reimburse you or 
your insurer for emergency treatment costs.  If your research-related injury requires medical 
care beyond this emergency treatment, you or your insurer will be responsible for the costs of 
this follow-up care.  
 
At this time, there is no plan for any additional financial payments. 
 
If you believe that you have been injured because of your participation in this project, contact 
the research doctors right away.  Contact information: Meera Mohan, MD, 414-805-6700  
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 21 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
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MCW IRB 
Nothing in this consent form affects any legal rights you may have nor does it release the 
investigator, the sponsor, the institution, or its agents from liability for negligence. 
 
D6. WHO CAN ANSWER MY QUESTIONS ABOUT THE PROJECT? 
 
If you have more questions about this project at any time, you can call Meera Mohan, MD 
at 414-805-6700. 
 
If you have questions about your rights as a research participant, want to report any 
problems or complaints, or offer input, you can call the MCW/Froedtert Hospital Research 
Subject Advocate at 414-955-8844. 
 
E. PERMISSION TO COLLECT, USE AND SHARE HEALTH INFORMATION 
E1. What health information will be collected and used for this project? 
To be in this research project, the research team needs your permission to access, collect and 
use some of your health information. If you say no, you cannot be in the project. This 
information may come from questions we ask, forms we ask you to fill out, or your medical 
record, as described below. We will only collect and use information needed for the project. 
 
The protected health information (PHI) originates from services you will or have received at one 
or more of the following locations: the Medical College of Wisconsin (MCW); Versiti, Inc.; 
Children’s Hospital of Wisconsin (CHW); any Froedtert Health Affiliate- Froedtert Hospital (FH), 
Inc.; Froedtert Menomonee Falls Hospital;  Froedtert West Bend Hospital;  Froedtert & The 
Medical College of Wisconsin Community Physicians Clinics, Inc. (FMCWCP); the West Bend 
Surgery Center, LLC; and the Froedtert Surgery Center, LLC.  
 
The health information to be collected and used for this project is:  
 
 
Past and present medical records to document relevant pre-existing conditions 
 
Records about your Study visits and results of tests done during the study 
 
Records about phone calls made as part of this research  
 
Research records  
 
E2. Who will see the health information collected for this project? 
The only MCW/Froedtert Hospital employees allowed to handle your health information are 
those on the research team, those on the Institutional Review Board (IRB) and those who check 
on the research activities to make sure the hospital’s rules are followed. 
 
If the costs of any necessary emergency medical treatment in the event of a research-related 
injury are billed to your health insurance, your health information may need to be disclosed to 
the insurer for billing purposes. 
 
The research team may share your information with people who don’t work at MCW/Froedtert 
Hospital because they planned, pay for, or work with us on this project.  The federal Privacy 
Rule may no longer protect your health information once it leaves MCW/Froedtert Hospital.  For 
this project, we plan to share information with those doctors, researchers or government 
representatives working with us on this project at the institutions or companies listed here: 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 22 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
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MCW IRB 
 
Florence Healthcare, Inc. 
 
The study sponsor and its research partners 
 
Doctors and healthcare professionals at other sites taking part in the study 
 
Companies that fund the study 
 
Government agencies in the U.S., such as the Food and Drug Administration (FDA), 
National Cancer Institute (NCI), and National Institutes of Health (NIH) 
 
Other federal and state agencies, such as the Office of Human Research Protections, 
(OHRP) 
 
Those required by law who monitor research data 
 
Because this project involves the use of drugs and/or devices, the FDA also has the right to 
inspect all project records. 
 
We may record your research information, including results of tests and procedures done for 
research, in your Froedtert Hospital and/or Medical College of Wisconsin medical record.  As a 
result, this research information may be seen by people allowed to see your medical records for 
healthcare operations or treatment, by those you allow to see your medical records by giving 
written permission, and by others when required by law. 
 
We will not use your personal health information for a different project without your permission 
or the permission of a hospital research review board (IRB). Once all personal identification is 
removed from your health information and/or biospecimens, the information and/or 
biospecimens may be used for future research or distributed to another investigator for future 
research without additional informed consent from you or your legally authorized representative. 
The information might also be used or released for other purposes without asking you. Results 
of the project may be presented in public talks or written articles, but no information will be 
presented that identifies you. 
 
E3. What are the risks of sharing this health information? 
One risk of taking part in a research project is that more people will handle your personal health 
information collected for this project. The research team will make every effort to protect the 
information and keep it confidential, but it is possible that an unauthorized person might see it. If 
you have questions, you can talk to the research doctor about whether this could apply to you.  
 
E4. How long will you keep the health information for this project? 
If you sign this form, we plan to keep your information without any end-date in case we need to 
check it again for this project. 
 
E5. Can I cancel my permission to share this health information? 
If you change your mind later and do not want us to collect or share your health information, you 
need to send a letter to Meera Mohan, MD at  
 
Department of Medicine 
Medical College of Wisconsin 
9200 West Wisconsin Avenue 
Milwaukee WI 53226 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 23 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
The letter must say that you have changed your mind and do not want the researcher to collect 
and share your health information. At that time, we will decide that you cannot continue to be 
part of the project. We may still use the information we have already collected. 
 
E6. Access to records 
 
You may not be able to see, or copy, your project-related health information until after the 
project has been completed; otherwise, it could affect the study. 
 
F1. FOR MORE INFORMATION ABOUT THE PROJECT 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
 
You can look up this project by referring to the ClinicalTrials.gov number (NCT05117008) or by 
asking the research team for a printed copy. 
 
 
 


Medical College of Wisconsin  
Informed Consent for Research 
Clinical Interventions template - Version: December 1, 2020 
 
IRB Protocol Number: PRO 42276 
IRB Approval Period: 12/14/2023 – 9/13/2024 
Page 24 of 24 
Protocol Version: V3 v. 12/29/22 
MCW Version: 7/21/23 
EFFECTIVE 
 
12/14/2023 
 
MCW IRB 
CONSENT TO PARTICIPATE 
 
By signing my name below, I confirm the following: 
 
I have read (or had read to me) this entire consent document.  
All of my questions have been answered to my satisfaction. 
 
The project’s purpose, procedures, risks and possible benefits have been explained to me.   
 
I agree to let the research team use and share the health information and other information 
gathered for this project. 
 
I voluntarily agree to participate in this research project. I agree to follow the procedures as 
directed. I have been told that I can stop at any time. 
 
IMPORTANT: You will receive a signed and dated copy of this consent form.  Please keep it 
where you can find it easily.  It will help you remember what we discussed today. 
 
 
 
 
Subject's Name please print  
Subject's Signature 
Date   
 
 
 
Name of Witness, if applicable 
please print 
Signature of Witness 
 
Date 
Rationale for Use of Witness 
 Subject has limited/no literacy 
 Subject has limited English 
proficiency 
 Subject has limited/no vision 
 
 Sponsor requirement 
 Other ____________________ 
 
 
 
 
 
* Name of person discussing/ 
obtaining consent please print  
Signature of person 
discussing/obtaining consent 
Date 
* A member of the research team trained and authorized by the Principal Investigator to act on 
her/his behalf in obtaining informed consent according to the protocol. The Principal Investigator 
is responsible and accountable for the research project.