IIT2023-03-Vescio-ColdCap: Scalp Cooling to Prevent Hair Loss in Patients Undergoing Stem Cell Transplantation for Multiple Myeloma
Phase: NA
Conditions: Multiple Myeloma
Sponsor: Cedars-Sinai Medical Center

 
CONFIDENTIAL  
This material is the property of Cedars-Sinai Medical Center. Do not disclose or use except as authorized in writing by the study 
sponsor. 
 
 
 
IIT2023-03-Vescio-ColdCap  
 
Scalp Cooling to Prevent Hair Loss in Patients 
Undergoing Stem Cell Transplantation for 
Multiple Myeloma 
 
Principal Investigator:  
Robert Vescio, MD 
 
 
 
 
Cedars-Sinai Medical Center 
 
 
 
 
8700 Beverly Blvd, Los Angeles, CA 90048 
 
  
Sub-Investigator(s) (CS Cancer at the Samuel 
Oschin Cancer Center) 
Department/Division 
David Oveisi, MD 
Internal Medicine/Hematology-Oncology 
 
 
 
 
Biostatistician: 
Yujie Cui, MS 
 
FDA Status:  
 
 
Abbreviated IDE 
 
Funding Source:  
CSMC 
 
Device Source:  
Penguin Cold Caps 
 
ClinicalTrials.gov Reg:  
Required 
 
NCT Number:   
 
NCT05961215 
 
ClinicalTrials.gov Reporting: Required 
 
Current Version: 
 
Protocol Version 3 dated 20 NOV 2023 
 
Initial version:  
 
Protocol Version 1 dated 03 MAY 2023 
 
 
 
 
 
 

 
CONFIDENTIAL  
This material is the property of Cedars-Sinai Medical Center. Do not disclose or use except as authorized in writing by the study 
sponsor. 
 
IIT2023-03-Vescio-ColdCap 
Protocol Version 3: Dated 20 NOV 2023 
 
Signature Page 
 
 
The signature below constitutes the approval of this protocol and the attachments, and provides the 
necessary assurances that this trial will be conducted according to all stipulations of the protocol, including 
all statements regarding confidentiality, and according to local legal and regulatory requirements and 
applicable U.S. federal regulations and ICH guidelines. 
 
 
 
 
______________________________________________ 
 
 
_________________ 
Principal Investigator (PI) Signature    
 
 
 
 
Date 
 
 

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TABLE OF CONTENTS  
 
LIST OF ABBREVIATIONS............................................................................................................. 1 
STUDY SCHEMA ............................................................................................................................ 2 
STUDY SUMMARY ......................................................................................................................... 3 
1.0 
BACKGROUND AND RATIONALE ................................................................................... 4 
2.0 
STUDY OBJECTIVES ........................................................................................................ 5 
3.0 
STUDY DESIGN ................................................................................................................. 5 
4.0 
PATIENT ELIGIBILITY ....................................................................................................... 6 
5.0 
TREATMENT PLAN ........................................................................................................... 7 
6.0 
STUDY PROCEDURES.................................................................................................... 10 
7.0 
ADVERSE EVENTS (AE), UNANTICIPATED ADVERSE DEVICE EFFECT (UADE), SERIOUS 
ADVERSE EVENTS (SAE), AND UNANTICIPATED PROBLEMS INVOLVING RISK TO SUBJECTS OR 
OTHERS (UPIRSO) ....................................................................................................................... 13 
8.0 
STATISTICAL CONSIDERATIONS ................................................................................. 17 
9.0 
STUDY MANAGEMENT ................................................................................................... 18 
10.0 
REFERENCES .................................................................................................................. 23 
11.0 
APPENDICES ................................................................................................................... 24 
 
 
 

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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
ALC 
Absolute Lymphocyte Count 
AST 
Aspartate Aminotransferase 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CMP 
Comprehensive Metabolic Panel 
CR 
Complete Response 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DSMC 
Data and Safety Monitoring Committee 
DSMP 
Data and Safety Monitoring Plan 
ECOG 
Eastern Cooperative Oncology Group 
H&P 
History & Physical Exam 
HRPP 
Human Research Protections Program 
IV (or iv) 
Intravenously 
MTD 
Maximum Tolerated Dose 
NCI 
National Cancer Institute 
ORR 
Overall Response Rate 
OS 
Overall Survival 
PBMCs 
Peripheral Blood Mononuclear Cells 
PD 
Progressive Disease 
PFS 
Progression Free Survival 
p.o. 
per os/by mouth/orally 
PR 
Partial Response 
SAE 
Serious Adverse Event 
SD 
Stable Disease 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SOC 
Standard of Care 
SPGT 
Serum Glutamic Pyruvic Transaminase 
WBC 
White Blood Cells 
 
 
 
 
 
 
 

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STUDY SCHEMA  
 
 
 
 
 
 
 
 
≥ 18 years with Multiple 
Myeloma
Screening and Enrollment (n=30)
Day -2: Cold cap therapy + SOC 
chemotherapy w/ melphalan
Day -1: Cold cap therapy + SOC 
chemotherapy w/ melphalan
Day 0: SOC Autologous peripheral 
blood stem cell transplant
Post-transplant Follow-Up visits: 
Days 7, 14, 30, 60, and 90
Primary endpoint: Reduced development of hair loss will be defined as < 50% hair loss 
in 75% of patients treated 

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STUDY SUMMARY 
 
Title 
Scalp Cooling to Prevent Hair Loss in Patients Undergoing Stem Cell 
Transplantation for Multiple Myeloma 
Protocol Number 
IIT2023-03-Vescio-ColdCap 
Phase 
Pilot 
Methodology 
Single arm, open label 
Study Duration 
22 months (18 months accrual, 4 months study duration) 
Study Center(s) 
Cedars-Sinai Medical Center:  CS Cancer at the SOCC 
Objectives 
Primary objective: 
• 
To assess the effectiveness of a scalp cooling intervention to reduce 
hair loss in patients with multiple myeloma undergoing an 
autologous peripheral blood stem cell transplant after high-dose 
melphalan 
 
Secondary objective: 
• 
To assess the potential impact of hair loss versus the discomfort and 
inconvenience of the scalp cooling procedure 
Number of Subjects 
30 
Diagnosis and Main 
Inclusion Criteria 
Patients with multiple myeloma planning to undergo high-dose 
chemotherapy with melphalan and autologous peripheral blood stem cell 
transplant. 
Study Product(s), Dose, 
Route, Regimen 
Subjects will receive Penguin cold cap for 60 minutes prior to melphalan 
infusion and continue for up to 5 hours (+/- 30 minutes) after melphalan 
infusion start time, for a total of 6 hours (+/- 30 minutes). Penguin cold 
cap and melphalan infusion will occur on Days -2 and -1, prior to SOC 
transplant procedure. Subjects will be followed up for 90 days after 
transplant. Subjects will have images taken to record hair length and 
status prior to intervention on Day -2, and after intervention on days 7, 14, 
30, 60, and 90. Questionnaires will be taken at Day 0 and 90. 
Duration of administration 
Penguin cold cap: 60 minutes prior to melphalan infusion and continue for 
5 hours (+/- 30 minutes) after melphalan infusion start time, for a total of 6 
hours (+/- 30 minutes), on Days -2 and -1. 
Reference therapy 
Reference is no use of a scalp cooling device which leads to > 50% hair 
loss in all patients undergoing this procedure historically. 
Statistical Methodology 
80% power to detect a minimum detectable difference of 17.25% based 
on the exact binomial test at 5% significance level. The actual 
significance level is 3.7% 
 
 
 

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1.0 
BACKGROUND AND RATIONALE 
1.1 
Disease Background 
Multiple myeloma is a malignant plasma cell cancer that is currently incurable but 
treatable. The cancer is treated with medications such as lenalidomide, bortezomib and 
corticosteroids to get initial control of the disease. To improve remission rates and 
survival, high-dose chemotherapy using melphalan followed by an autologous stem cell 
transplantation as a rescue is often done. During the transplant process, patients are 
given high doses of melphalan (140 – 200 mg/m2) divided into two days over 20 minutes. 
Melphalan causes hair loss in essentially all patients, (CTCAE v5 Grade 2), at the doses 
used for this procedure. Hair typically falls out after 10-15 days and doesn’t begin to grow 
back for 10-12 weeks. This outcome is widely expected and leads some patients to avoid 
doing an otherwise life sustaining procedure. In those that do proceed with the transplant, 
the hair loss can be emotionally harmful. 
 
Cryotherapy is commonly used to reduce side effects of the melphalan on the GI tract. 
Melphalan typically will cause diarrhea, nausea, and mouth sores yet a randomized trial 
done in 2006 showed that swallowing ice chips for 6 hours starting 30 minutes before the 
melphalan is given can reduce these unpleasant and potentially dangerous side effects 
by 60% (Lilleby et. al. 2006). We at Cedars-Sinai routinely have patients do oral 
cryotherapy for 3.5 hours starting 30 minutes prior to each dose of melphalan. This has 
reduced patient side effects substantially in our experience and is considered standard of 
care. The briefer period of administration seems adequate to prevent most problems. 
 
Scalp cooling has been used to prevent hair loss in many patients undergoing 
chemotherapy for solid tumors. For some women with breast cancer, this hair loss was 
reported to be more traumatizing than losing a breast to mastectomy (Zhang et. al. 2022). 
Certainly, the sudden development of alopecia can impact a patient’s self- image, and 
quality of life. Chemotherapy drugs, such as melphalan, typically injure bone marrow, 
intestinal lining and other cells with high metabolism and rapid cell division. Hair follicles 
also have these properties and is likely why many chemotherapeutics cause hair loss 
when used. The use of cold caps during the time of chemotherapy exposure has helped 
reduce hair loss, presumably by causing vasoconstriction and reducing distribution of the 
drug to the hair follicle. This intervention has been effective even when drugs which have 
longer durations of circulation have been given. While there is a theoretical risk that scalp 
cooling may impair the killing of malignant cells in the scalp by the chemotherapy, there is 
no evidence of a heightened risk in studies. The penetration of the cold should not reach 
the skull bone where myeloma cells may reside and is generally to a depth of only a few 
millimeters. The toxicity of scalp cooling is minimal. In a study of 27 participants using 
scalp cooling for solid tumors, 96% reported that the procedure was worth the time, effort, 
cost and discomfort and would recommend usage to others undergoing the same 
chemotherapy treatment (Sitarz et al). In a randomized trial comparing scalp cooling to 
placebo in women undergoing chemotherapy for breast cancer, successful hair 
preservation occurred in 48 of 95 women using cooling versus 0 of 47 women in the 
control group. The study was closed at the interim analysis due to efficacy (Nangia et. al. 
2017). Fifty-four adverse events occurred in the group undergoing cooling, all grade 1 or 
2.  
 
Scalp cooling may especially be effective in our patients using high-dose melphalan prior 
to stem cell transplantation. Melphalan has a much shorter half-life than most of the other 
chemotherapy drugs used for breast and other solid cancers. Because of melphalan’s 70-
minute half-life, it is anticipated that in 5 hours the concentration of melphalan will be only 
5% of that immediately after administration.  
 
Melphalan concentration at 5 hours (300 minutes) with a t1/2 of 70 minutes = 4.2 half-lives. 
 
Melphalan concentration predicted at 5 hours = 0.54.2 = 0.054 or 5.4%  

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Melphalan when given orally at doses of 7 mg/m2 daily for non-transplant patients does 
not cause hair loss. A 95% reduction in the typical 100 mg/m2 dose of melphalan would 
be only 5 mg/m2. From a literature review by me and by others, this process has not 
been used for patients with hematologic malignancies. Anecdotally, there are reports of 
positive outcomes, but these have not been published. 
 
The hope is that by using scalp cooling, patients would not lose as much hair after the 
stem cell transplant. Since the hair-loss is so universally attained without cold caps, a 
control arm is not felt to be necessary to demonstrate a difference in outcome. A positive 
outcome may improve the percentage of people willing to undergo this life-sustaining 
procedure and improve the quality of life of those who go through with it. 
 
 
2.0 
STUDY OBJECTIVES 
 
2.1 
Primary Objectives 
2.1.1 
To assess the effectiveness of a scalp cooling intervention to reduce hair loss in 
patients with multiple myeloma undergoing an autologous peripheral blood stem 
cell transplant after high-dose melphalan.   
 
2.2 
Secondary Objectives  
2.2.1 
To assess the potential impact of hair loss versus the discomfort and 
inconvenience of the scalp cooling procedure.  
 
2.3 
Endpoints 
 
2.3.1 
Primary Efficacy Endpoint 
 
Reduced development of hair loss will be defined as < 50% hair loss (CTCAE v5 
Grade 0 or 1) in 75% of patients treated.  
 
2.3.2 
Secondary Efficacy Endpoints 
 
Patient determined decision of scalp cooling benefit 
 
 
3.0 
STUDY DESIGN 
We will conduct a pilot study of scalp cooling with Penguin cold caps to examine the feasibility of 
scalp cooling to reduce the development of hair loss in 30 patients with multiple myeloma 
undergoing high-dose chemotherapy with melphalan and autologous peripheral blood stem cell 
transplant at Cedars-Sinai Medical Center.  
For this trial 30 patients will be enrolled to receive scalp cooling with Penguin cold caps prior to 
their stem cell transplant. This device has been used routinely in the Samuel Oschin Cancer 
Center Infusion center at Cedars-Sinai and also on the 4 South ward where stem cell transplants 
are done. The cold cap will be used starting 60 minutes prior to and continued for 5 hours (+/- 30 

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minutes) after melphalan has been started, for a total of 6 hours (+/- 30 minutes). The procedure 
will be done for both days of melphalan infusion, on Days -2 and -1. The remainder of the 
transplant procedure will be performed as is routine and part of standard of care on Day 0. 
The patient will have photographs taken on the day of their first administration of melphalan. 
Photographs of the patient’s hair will occur again at Day 7, Day 14, Day 30, Day 60 and Day 90 
after the stem cell transplant was given. Scalp Cooling questionnaire will be administered on Day 
0 and 90.  
Every effort will be made to coordinate research study appointments/interventions so that they do 
not interfere with the pre-planned, standard of care treatment arrangements. 
See Study Schema and Time & Events Table for reference. 
 
3.1 
Inclusion of Women and Underrepresented Minorities   
 
The total number of subjects involved in the study will be 30. Of those, we estimate that 
approximately 45% will be cisgender women. The estimated racial/ethnic breakdown of 
the study may approximately be that 20% may be Black or African American, 10% may 
be Asian, and 3% may be Native Hawaiian-Pacific Islander. Approximately 30% of the 
subjects may be Hispanic. While this provides only an estimated breakdown of the study 
population, efforts should be made to ensure equitable recruitment of individuals that 
meet the above eligibility requirements.  
 
 
4.0 
PATIENT ELIGIBILITY  
 
4.1 
Inclusion Criteria  
4.1.1 
Age ≥18 years 
4.1.2 
ECOG performance status ≤2 
4.1.3 
Confirmed multiple myeloma diagnosis 
4.1.4 
Planning to undergo SOC high-dose chemotherapy with melphalan (dose to be 
used = 140 – 200 mg/m2 (with rounding per CSMC guidelines)) followed by an 
autologous peripheral blood stem cell transplant. 
4.1.5 
Written informed consent obtained from subject and ability for subject to comply 
with the requirements of the study. 
 
4.2 
Exclusion Criteria 
4.2.1 
Prior or current use of any scalp cooling treatment 
4.2.2 
Medical History and Concurrent Diseases: 
• 
Reynaud’s disease 
• 
Cold sensitivity  
• 
Cold agglutinin disease 
• 
Cryoglobulinemia 

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• 
Cryofibrinogenemia 
4.2.3 
Current spinal or neck injury that may interfere with the subject’s participation for 
the full duration of the study, in the opinion of the treating investigator 
4.2.4 
Skin conditions such as psoriasis, eczema, malignancy, or other condition on the 
scalp that might confound the results of the study, interfere with the subject’s 
participation for the full duration of the study, or is not in the best interest of the 
subject to participate, in the opinion of the treating investigator. 
4.2.5 
Current use of any other investigational agents 
4.2.6 
Contraindication to melphalan 
 
 
5.0 
TREATMENT PLAN 
5.1 
Penguin Cold Cap 
 
The Penguin cold cap is not FDA cleared and is a nonsignificant risk (NSR) medical 
device that is: 
- 
NOT intended as an implant and presents a potential for serious risk to the health, 
safety, or welfare of a subject; 
- 
NOT purported or represented to be for use supporting or sustaining human life and 
presents a potential for serious risk to the health, safety, or welfare of a subject; 
- 
NOT for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health and presents a 
potential for serious risk to the health, safety, or welfare of a subject; or 
- 
Does NOT otherwise present a potential for serious risk to the health, safety, or 
welfare of a subject. 
 
The cold cap or immediate package will be labeled in accordance with all applicable 
federal guidelines. As the Penguin technician will administer the cold cap to subjects and 
packaging will not be provided, the research team will provide a copy of the package 
label in accordance with applicable federal guidelines to the subject. 
 
Manufacturer: Penguin Cold Caps: support@penguincoldcaps.com +44 (0)20 8004 4683 
 
 
5.2 
Treatment Administration 
 
Eligible subjects will receive study intervention Penguin Cold Cap for scalp cooling 
therapy for 60 minutes prior to melphalan infusion and continue for 5 hours (+/- 30 
minutes) after melphalan infusion start time, for a total of 6 hours (+/- 30 minutes). 
Penguin cold cap and melphalan infusion will occur on Days -2 and -1, prior to SOC 
transplant procedure. 
 
The Penguin cold cap will be supplied by the Penguin manufacturer and will be 
administered by Penguin approved technicians only. The technician will provide all 
necessary supplies on the day of scalp cooling procedure.  
 

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5.2.1 
Penguin Cold Cap Procedure 
 
The Penguin Scalp Cooling device has been used by more than 20,000 patients since 
the company was founded in 1992. 
 
Prior to the Cold Cap procedure date, patients will be instructed: Hair should be dry when 
wearing the Cold Cap - The user of the Caps must NOT wet or dampen the hair, or put 
conditioner or oil on your hair or scalp during the Day -2 and Day -1 scalp cooling 
procedure. 
 
1. The patient will be provided with the Penguin cold cap free of charge by the 
study. 
2. Dry ice will be used to cool the gel material within the cap and used per 
product instructions. 
3. A Penguin approved technician will be with the patient and help administer 
the cold cap safely. 
4. The approved technician will stay with the patient for the entire procedure. 
5. Clinic administration and in hospital administration are both expected (Day -2 
in clinic and Day -1 in the hospital on the 4SW). 
6. The approved technician will not be asked to do other patient care outside of 
hair care and will not interfere with the administration of the chemotherapy or 
other medical care for the patient. 
7. The responsibility of the Penguin Cold Cap application will reside solely with 
the approved technician and no clinic/hospital staff will be asked to assist. 
8. The procedure will begin 60 minutes prior to the first administration of 
melphalan (+/- 15 minutes) 
9. The cold cap procedure will end approximately 5 hours (+/- 30 minutes) after 
the start of the melphalan infusion. 
10. The process will be done on Day -2 and Day -1 (for both days of melphalan 
infusion) of the transplant procedure. 
 
Note: Cold Cap start/end times must be documented by the technician and/or research 
staff. 
 
5.3 
Toxicities and Dosing Delays/Dose Modifications  
 
The cold cap may be interrupted and/or removed for side effects of discomfort, skin 
irritation, or at the request of the patient and/or at the investigator’s discretion for any 
reason. This information will be recorded and will not change the follow up procedures 
(photography and questionnaire). 
 
5.3.1 
Expected Toxicities (Penguin Cold Cap) 
The primary toxicity of the treatment is discomfort from the coldness of the device. Skin 
irritation is rare but could occur.  
 
5.4 
Photography of Hair 
A single camera will be used with a SIM card to record hair length and status. The front, 2 
sides, and back views (4 total images) of patient hair will be taken at each time point as 
specified in the study procedures. The images will be captured by the PI and designated 
research staff. The photographs will be stored with labels using the Subject ID as 
identification. The images will be stored in a secure research file in accordance with all 

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applicable federal guidelines and local guidelines. If published, censorship/black out bars 
will be used to disidentify the patient such that only the hair is visible prior to submission. 
 
5.5 
Concomitant Medications/Treatments 
 
All treatments that the investigator considers necessary for a subject’s welfare may be 
administered at the discretion of the investigator in keeping with the community standards 
of medical care. Concomitant medications will NOT be collected and recorded on a case 
report form (CRF).  
 
Excluded Concomitant Medications 
• 
No topical creams/ointments to be applied to the scalp only during the Day -2 and 
Day -1 scalp cooling procedure.  
• 
No conditioner or oil on the hair or scalp during the Day -2 and Day -1 scalp cooling 
procedure 
• 
Oxaliplatin may not be used while on study. 
 
5.6 
Other Modalities or Procedures/ Research vs. Standard of Care Procedures 
SOC: High-dose chemotherapy with melphalan, autologous stem cell transplantation, 
ECOG performance status 
Research: Penguin cold cap, Hair imaging 
 
5.7 
Duration of Study Participation  
The study duration per subject will be up to 4 months, with up to 28 days of screening, 2 
days of treatment and up to 90 (±14) days for follow up. 
 
5.8 
Removal of Patients from Protocol  
Patients will be removed from the study when any of the criteria listed in Section 6.5 
apply. Notify the Principal Investigator and document the reason for study removal and 
the date the patient was removed on the Case Report Form. The patient should be 
followed-up per protocol.  
 
5.9 
Subject Replacement 
Subjects who withdraw from the study treatment prior to starting study intervention (Cold 
Cap use) will be replaced. 
 
5.10 
Evaluable for toxicity  
Any patient who begins use of the Cold Cap is evaluable for toxicity and will be included 
in the safety analysis. 
 
 
 

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6.0 
STUDY PROCEDURES 
 
6.1 
Screening/Baseline Procedures 
Assessments performed exclusively to determine eligibility for this study will be done only 
after obtaining informed consent. Assessments performed for clinical indications (not 
exclusively to determine study eligibility) may be used for baseline values even if the 
studies were done before informed consent was obtained. 
 
All screening procedures must be performed within 28 days prior to enrollment unless 
otherwise stated. The screening procedures include: 
6.1.1 Informed Consent 
6.1.2 Medical history and record review 
Relevant medical history, including history of current disease, and information 
regarding underlying diseases will be recorded at Screening. 
6.1.3 Demographics 
• 
Age 
• 
Sex 
• 
Race 
• 
Ethnicity 
 
 Patients may be offered the Inclusive Demographics Questionnaire, which is a 
standard, non-study-specific document, available on the IRB Intranet. Study team 
to record responses in the subject’s OnCore record. Completion is voluntary; 
patients may decline to complete the Inclusive Demographics Questionnaire. 
6.1.4 Review subject eligibility criteria 
6.1.5 ECOG Performance Status 
6.1.6 Hair loss assessment 
Hair loss (alopecia) will be assessed using CTCAE v5. 
6.1.7 Baseline Adverse Event (AE) assessment 
Baseline adverse events, including duration (start and stop dates and times), 
severity/grade, outcome, treatment, and relation to device will be assessed. See 
section 7.0 for AE monitoring and reporting.  
 
6.2 
Procedures During Treatment 
6.2.1 
Day -2, Cold Cap 
• Prior to Cold Cap and chemotherapy: 
o 
ECOG Performance Status 
o 
Hair loss assessment 
o 
Hair imaging 
• Penguin cold cap application 
• SOC chemotherapy with melphalan 
• Adverse Events (AE) assessment. Only AEs of interest (per Section 7.2.3) to 
be entered into the EDC. 

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6.2.2 
Day -1, Cold Cap 
• Penguin cold cap application 
• SOC chemotherapy with melphalan 
• Adverse Events (AE) assessment. Only AEs of interest (per Section 7.2.3) to 
be entered into the EDC. 
6.2.3 
Day 0, Stem Cell Transplant 
• Scalp Cooling Questionnaire 
• Adverse Events (AE) assessment. Only AEs of interest (per Section 7.2.3) to 
be entered into the EDC. 
• SOC autologous stem cell transplant 
 
6.3 
Follow-up Procedures 
 
Post-stem cell transplant follow-up visits will occur at:  
• 
Day 7 (± 2 days)  
• 
Day 14 (± 2 days)  
• 
Day 30 (± 7 days)  
• 
Day 60 (± 7 days)  
• 
Day 90 (± 14 days)  
 
The following procedures will be performed during each visit: 
 
6.3.1 
Hair loss assessment 
6.3.2 
Hair imaging  
The scalp will be imaged at the above days with photography done of each side 
of the head (four images total). 
6.3.3 
Adverse Events (AE) assessment  
Only AEs of interest (per Section 7.2.3) to be entered into the EDC. 
6.3.4 
Scalp Cooling Questionnaire (Day 90 only)  
 
 
 

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6.4 
Time and Events Table  
 
 
 
Screening 
(within 28 
days) 
Day 
-2 
Day 
-1 
Day 
0 
Follow-up visits: 
Days 7 (± 2), 14 (± 2), 30 (± 
7), 60 (± 7), & 90 (± 14) 
Informed Consent 
X 
 
 
 
 
Medical history and 
record review 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Review subject eligibility 
criteria 
X 
 
 
 
 
Registration 
X 
 
 
 
 
ECOG Performance 
Status 
X 
X1 
 
 
 
Hair loss assessment 
X 
X1 
 
 
X 
Hair imaging 
 
X1 
 
 
X 
Penguin cold cap 
 
X 
X 
 
 
SOC chemotherapy w/ 
melphalan 
 
X 
X 
 
 
Scalp Cooling 
Questionnaire 
 
 
 
X 
X 
(Day 90 only) 
SOC autologous stem 
cell transplant 
 
 
 
X 
 
Adverse Events (AE) 
assessment 
 
X 
X 
X 
X 
 
  
1. Must be completed prior to Cold Cap and chemotherapy. 
 
 
 

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6.5 
Removal of Subjects from Study 
Patients can be taken off the study treatment and/or study at any time at their own 
request, or they may be withdrawn at the discretion of the investigator for safety, 
behavioral or administrative reasons. The reason(s) for discontinuation will be 
documented and may include: 
6.5.1 
Patient voluntarily withdraws (follow-up permitted).  
6.5.2 
Patient withdraws consent (termination of treatment and follow-up). 
6.5.3 
Patient is unable to comply with protocol requirements. 
6.5.4 
Patient experiences toxicity that makes continuation in the protocol unsafe; 
6.5.5 
Treating physician determines continuation on the study would not be in the 
patient’s best interest; 
6.5.6 
Lost to follow-up. If a research subject cannot be located to document survival 
after a period of 2 months, the subject may be considered “lost to follow-up.” All 
attempts to contact the subject during the two months must be documented. This 
will be reviewed during an interim data monitoring visit. 
 
7.0 
ADVERSE EVENTS (AE), UNANTICIPATED ADVERSE DEVICE EFFECT (UADE), SERIOUS 
ADVERSE EVENTS (SAE), AND UNANTICIPATED PROBLEMS INVOLVING RISK TO 
SUBJECTS OR OTHERS (UPIRSO) 
7.1 
Definitions 
7.1.1 Adverse Event (AE) 
An adverse event is any untoward medical occurrence associated with the use of 
a drug/device in humans, whether or not considered drug/device related.  
 
Planned hospital admissions or procedures for an illness or disease that existed 
before the subject was screened in the study and progression of underlying 
disease are not to be considered AEs unless the condition deteriorated in an 
unexpected manner during the study (e.g., surgery was performed earlier than 
planned).  
 
Diagnostic and therapeutic noninvasive and invasive procedures, such as 
surgeries, must not be reported as AEs. However, the medical condition for 
which the procedure was performed must be reported if it meets the definition of 
an AE.  
7.1.1.1 Laboratory test abnormalities 
A laboratory test abnormality considered clinically relevant (e.g., causing the 
subject to withdraw from the study, requiring treatment or causing apparent 
clinical manifestations, result in a delay or dose modification of study treatment, 
or judged relevant by the investigator), is considered an adverse event.   
7.1.2 Serious Adverse Event (SAE) 
An adverse event is considered “serious” if, in the view of either the investigator 
or sponsor, it results in any of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
Inpatient hospitalization or prolongation of existing hospitalization 

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• 
A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• 
A congenital anomaly/birth defect 
• 
Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject 
and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such medical events include 
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. 
7.1.3 Unanticipated adverse device effect (UADE) 
An unanticipated adverse device effect (UADE) is defined as “any serious 
adverse effect on health or safety or any life-threatening problem or death 
caused by, or associated with, a device, if that effect, problem, or death was not 
previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), 
or any other unanticipated serious problem associated with a device that relates 
to the rights, safety or welfare of subjects”. 
7.1.4 Unanticipated Problem Involving Risk to Subjects or Others (UPIRSO) 
UPIRSOs include any incident, experience, or outcome that meets all of the 
following criteria: 
• 
Unexpected (in terms of nature, severity, frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as 
the IRB-approved research protocol and informed consent document; and 
(b) the characteristics of the subject 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); and 
• 
Suggests that the research places subjects or others at a greater risk of 
harm (including physical, psychological, economic, or social harm) than was 
previously known or recognized 
 
7.2 
Principal Investigator Responsibilities for 
Safety Monitoring 
7.2.1 
AE Reporting Period 
The investigator or designee is responsible for ensuring that all AEs (that are at least 
possibly related to the study intervention) and UADEs (both serious and non-serious) 
observed by the clinical team or reported by the subject which occur from start of study, 
and until 90 days following stem cell transplant, are fully recorded in the subject’s medical 
records. 
7.2.2 
AE Documentation 
The investigator, sub-investigator (treating physician if applicable), or study team 
(according to the responsibilities delegated per the DOA) will document the following for 
all AEs (both serious and non-serious): 

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• 
Event term, according to the NCI Common Terminology Criteria for Adverse 
Events (CTCAE) version (current). The CTCAE current version is available at 
http://ctep.cancer.gov/reporting/ctc.html  
• 
Description of the event 
• 
Date of onset and resolution 
• 
Expectedness of the toxicity 
o 
Expected events are those that have been previously identified as resulting 
from administration of the agent. An adverse event is considered 
unexpected, for expedited reporting purposes only, when either the type of 
event or the severity of the event is not listed in: 
▪ the current known adverse events listed in this protocol; 
▪ the drug package insert; and/or 
▪ the current Investigator’s Brochure 
 
• 
Grade of toxicity, as per CTCAE criteria 
• 
Attribution of relatedness to the investigational agent- (this must be assigned by 
an Investigator, sub-investigator, or treating physician) 
o 
Attribution categories are as follows: 
▪ Definite: 
The AE is clearly related to the study treatment. 
▪ Probable: 
The AE is likely related to the study treatment. 
▪ Possible:   
The AE may be related to the study treatment. 
▪ Unlikely: 
The AE is doubtfully related to the study treatment. 
▪ Unrelated: 
The AE is clearly NOT related to the study treatment. 
 
• 
Action taken as a result of the event, including but not limited to; no changes, 
dose interrupted, reduced, discontinued, etc. or action taken with regard to the 
event, i.e. no action, received conmed or other intervention, etc. 
• 
Outcome of event 
 
Source documentation must be available to support all AEs.  
7.2.3 
Protocol-specific Adverse Event Monitoring / EDC Guidelines 
In this protocol, patients receiving the study intervention (Penguin Cold Cap) will also 
receive concomitant standard of care chemotherapy and autologous stem cell transplant.  
 
Only AEs of interest, as outlined below, will be recorded in the EDC. 
• 
All AEs that are at least possibly related to the study intervention will be 
collected. 
7.2.4 
Duration of AE monitoring 
All patients experiencing an AE, regardless of its relationship to study intervention, will be 
monitored until:  
• 
the AE resolves or the symptoms or signs that constitute the AE return to 
baseline 
• 
any abnormal laboratory values deemed an AE, has returned to baseline 
• 
there is a satisfactory explanation other than the study device for the changes  
 
observed 
• 
death, or  

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• 
until 90 (±14) days following the stem cell transplant 
 
7.3 
Safety Reporting Requirements 
7.3.1 Reporting to the Principal Investigator 
The Principal Investigator (PI) must be notified by study staff or co-investigators 
within 24 hours of learning of any SAEs and UADEs, regardless of attribution and 
expectedness, occurring during the study or within 90 days following the stem 
cell transplant  
 
Contact for Expedited Reporting: 
Robert Vescio, MD, (310) 423-1825, Robert.Vescio@cshs.org  
 
Alternate Contact for Expedited Reporting: 
David Oveisi, MD, (310) 423-3720, David.Oveisi@cshs.org  
 
7.3.2 Reporting to DSMC [for interventional cancer IITs]:  
Serious Adverse Events deemed to be related to the protocol and on-study 
deaths, including death of a research subject unless the death is expected (e.g. 
due to disease progression) are to be reported to the DSMC within 24 hours of 
awareness. Hardcopies or electronic versions of the MedWatch Form 3500A 
(Mandatory Reporting) or a narrative report, along with any other supporting 
documentation available, should be submitted to the DSMC Coordinator. The 
DSMC Coordinator will forward the information to the DSMC Chair, and/or 
medical monitor. The DSMC Chair will review all documentation upon receipt 
from the DSMC Coordinator and determination of whether the following actions 
are required: 1) takes action immediately, 2) convenes a special DSMC session 
(physical or electronic), or 3) defers the action until a regularly scheduled DSMC 
meeting. Reports are to be emailed to the DSMC team at 
GroupSOCCICCTODSMCAdmin@cshs.org.  
 
 
7.3.3 Reporting to the Institutional Review Board (IRB) 
As per the Cedars-Sinai IRB Reporting Possible Unanticipated Problems 
Involving Risks to Subject or Others (UPIRSO) Policy, the IRB must be notified of 
all UPIRSOs as soon as possible, but no later than 10 business days from when 
the study team learned of any of the following events:   
 
1. Any internal SAE, AE or Research-Related Subject Injury (RRSI), which in the 
opinion of the Principal Investigator was unanticipated or unexpected, and has 
a reasonable possibility of relationship to the research. 
2. Any actionable external SAE, AE, SUSAR, development safety update report 
(DSUR), or FDA MEDWATCH report deemed to be a UPIRSO. An event is 
considered “actionable” if it warrants a change to the conduct of the study.  
3. Any internal or external UADE. 
4. Any accidental, unintentional protocol or consent/HIPAA related deviation that 
may impact subjects’ rights, safety, or welfare. See section 10.8.3. 
5. Any planned protocol exception or eligibility waiver. See sections 10.8.2 and 
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6. Changes to the research or protocol deviations made without prior IRB 
approval in order to eliminate apparent immediate hazard to a research 
subject. (Note: These must be reported to the IRB within 5 business days.) 
7. Problems, events, unanticipated incidental findings, billing problems, or other 
events, outcomes, or new information related to the research (e.g., publication, 
safety monitoring report, interim findings, product labeling changes, findings 
generated from preclinical, animal studies) that may adversely affect the rights, 
safety, or welfare of the subjects or others, put subjects or others at increased 
risk, compromise the research data, or require/recommend changes to the 
study conduct. 
8. Subject complaints or concerns that cannot be resolved by the research staff to 
the subject’s satisfaction. 
9. Breach or potential breach of confidential or sensitive information.  
10. Incarceration of a subject who is enrolled in a study that is not approved by the 
IRB to include prisoners. 
 
7.3.4 For Sponsor-Investigator IDE trials: Reporting to the Food and Drug 
Administration 
The sponsor-investigator of the IDE must submit all reported UADEs to the FDA as soon 
as possible but no later than 10 working days after the investigator first learns of the 
effect. 
Copies of IDE Safety Reports will be kept in the Trial Master File in the SOCCI 
CCTO. 
 
8.0 
STATISTICAL CONSIDERATIONS 
8.1 
Sample Size 
The PI judges that a proportion of 75% or less of patients treated to reduce the 
development of hair loss (defined as <50% hair loss using the CTCAE v5 Grade 0 or 1 at 
30 days after the transplant) is not worthy of further investigation. Therefore, a test of 
hypothesis H0: p < 0.75 vs H1: p > 0.75 with 30 patients will have 80% power to detect a 
minimum detectable difference of 17.25% based on the exact binomial test at 5% 
significance level. The actual significance level is 3.7%.   
8.2 
Data Sets Analyzed 
All eligible patients who are randomized into the study and receive at least one dose of 
the study intervention (the Safety Population) will be included in the safety analysis. 
8.3 
Analysis of Primary Endpoint 
We will test the null hypothesis that the proportion of patients treated to reduce the 
development of hair loss (<50% using the CTCAE v5 Grade 0 or 1 at 30 days after the 
transplant) is no more than 75% using an exact Binomial test at 5% nominal significance 
level with 3.7% as actual significance level. If the number of patients with reduced 
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hypothesis and declare the study as feasible. Otherwise, we will revise and adapt out 
intervention to improve feasibility in subsequent trials. 
8.4 
Analysis of Secondary Endpoint 
The secondary objective is to assess the potential impact of hair loss versus the 
discomfort and inconvenience of the scalp cooling procedure. Scalp cooling 
questionnaire will be administered on Day 0 and 90. Descriptive statistics will be 
presented as counts and percentages for qualitative variables and as means with 
standard deviations, medians with interquartile ranges for quantitative variables. 
 
9.0 
STUDY MANAGEMENT 
9.1 
Conflict of Interest 
Any reportable conflict of interest will be disclosed to the local IRB and will be outlined in 
the Informed Consent Form. 
9.2 
Institutional Review Board (IRB) Approval and Consent  
It is expected that the IRB will have the proper representation and function in accordance 
with federally mandated regulations.  
 
Any documents that the IRB may need to fulfill its responsibilities (such as protocol, 
protocol amendments, Investigator’s Brochure, consent forms, information concerning 
patient recruitment, payment or compensation procedures, or other pertinent information) 
will be submitted to the IRB.  The IRB’s written approval of the study protocol and the 
informed consent form will be in the possession of the Investigator before the study is 
initiated and prior to the shipment of study supplies to participating sites, if applicable.  
This approval must refer to the study by exact protocol title and number and should 
identify the documents reviewed and the date of review. 
 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s), and should adhere to Good Clinical Practice (GCP) 
and to ethical principles that have their origin in the Declaration of Helsinki. 
 
 
Before recruitment and enrollment onto this study, the patient will be given a full 
explanation of the study and will be given the opportunity to review the consent form. 
Each consent form must include all the relevant elements currently required by the FDA 
Regulations and local or state regulations. Once this essential information has been 
provided to the patient and the investigator is assured that the patient understands the 
implications of participating in the study, the patient will be asked to give consent to 
participate in the study by signing an IRB-approved consent form. 
 
Prior to a patient’s participation in the trial, the written informed consent form should be 
signed and personally dated by the patient and by the person who conducted the 
informed consent discussion. 
 
9.3 
Registration/Enrollment Procedures 
 
All patients will be tracked following written informed consent.  Those patients who are 
consented to participate in the clinical trial but do not meet one or more criteria required 
for participation during the screening phase will be listed as screen failures on the master 
list of consented subjects.  Eligible subjects, as determined by screening procedures and 

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verified by a treating investigator, will be registered on study at Cedars Sinai Medical 
Center by the Study Coordinator.   
 
Issues that would cause treatment delays after registration should be discussed with the 
Principal Investigator (PI). If a patient does not receive protocol therapy following 
registration, the patient’s registration on the study may be canceled.  The Study 
Coordinator should be notified of cancellations as soon as possible. 
 
Assignment of Subject ID: The study teams will track all subjects who sign consent using 
OnCore. Subjects found to be ineligible will be recorded as screen failures. Subjects 
found to be eligible will be registered using a three-digit numeric ID that follows the 
standard SOCCI format (001, 002, etc.).   
 
A) 
Eligibility Verification 
 
Prior to registration/enrollment, all subjects must undergo an eligibility verification by the 
study-specific research staff. Minimal risk studies are exempt from SOCCI Quality 
Management Core (QMC) central eligibility checklist review and eligibility verification. 
QMC central eligibility checklist review and eligibility verification for all subjects enrolled is 
performed only if requested by the PI at any time during the life of the study. 
 
For patients requiring a protocol exception request and/or waiver due to eligibility 
concerns, refer to Section 9.7.2, Protocol Exceptions and Eligibility Waivers for 
instructions. 
 
B) 
Registration 
 
After eligibility is verified, each site will assign the subject a study number and site staff 
will then register the patient in OnCore®.   
 
 
Registration is completed as follows: 
 
• 
Assignment of a patient study number 
• 
Assignment to the patient a dose/treatment arm  
• 
Enter the patient in OnCore 
• 
Notify the investigational pharmacy and treating physicians that a subject has 
gone on study and anticipated treatment start date 
 
Oversight by the principal investigator is required throughout the entire registration 
process. 
 
9.4 
Data Management, Quality Assurance, and Quality Control and Reporting 
REDCap is the Cedars-Sinai Cancer institutional choice for the electronic data capture of 
case report forms for SOCCI Investigator Initiated Trials. REDCap, a HIPAA-compliant 
database, will be used for electronic case report forms in accordance with institutional 
requirements, as appropriate for the project. The Study Staff will be responsible for data 
processing, in accordance with procedural documentation. Database lock will occur once 
quality assurance procedures have been completed. See also Section 9.5.2, Monitoring. 
 
All procedures for the handling and analysis of data will be conducted using good 
computing practices meeting FDA guidelines for the handling and analysis of data for 
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9.5 
Data and Safety Monitoring 
 
9.5.1 
Safety Oversight 
Adherence to the protocol, Good Clinical Practices (GCP), and institutional policy will be 
monitored by the PI during the course of the study through routine Disease Research 
Group (DRG) meetings (or equivalent). The PI will maintain continuous safety monitoring 
for the duration of the study by reviewing subject/study data. It is the responsibility of the 
principal investigator to adhere to the Data Safety Monitoring Plan throughout the life of 
the study. 
 
In addition, safety oversight and efficacy data will be reviewed by the SOCC Data and 
Safety Monitoring Committee (DSMC). The DSMC will review this trial commensurate 
with the assigned risk class as categorized by the PRMC. The DSMC membership and 
responsibilities are governed by the committee charter. The DSMC findings and 
recommendations will be reported in writing to the Principal Investigator as a summary 
letter which will be forwarded by the Principal Investigator or designee to the CS-IRB. 
The DSMC outcome letters will be furnished to the FDA, as applicable. Refer to the 
DSMC Charter for details of the DSMC review. 
 
9.5.2 
Monitoring 
The SOCC Cancer Clinical Trials Office (CCTO) Quality Management Core (QMC) will 
conduct internal monitoring visits and audits to ensure that the rights and well-being of 
trial participants are protected, that the reported trial data are accurate, complete, and 
verifiable, and that the conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), and with applicable regulatory requirement(s). 
 
Refer to the DSMP for details pertaining to the type, frequency, and extent of monitoring 
that will be performed 
 
9.6 
Record Retention 
 
Study documentation includes all Case Report Forms, data correction forms or queries, 
source documents, monitoring/auditing logs/letters, records of study drug receipt, 
dispensation, destruction, and regulatory documents (e.g., protocol and amendments, IRB 
correspondence and approval, signed patient consent forms). Source documents include 
all recordings of observations or notations of clinical activities and all reports and records 
necessary for the evaluation and reconstruction of the clinical research study. Government 
agency regulations and directives require that the study investigator must retain all study 
documentation pertaining to the conduct of a clinical trial. Study documents should be kept 
on file in accordance with all applicable federal guidelines and local guidelines. 
 
 
Investigators must make study data accessible to the monitor, other authorized 
representatives of the Sponsor (or designee), IRB, and Regulatory Agency (e.g., FDA) 
inspectors upon request. 
 
9.7 
Adherence to Protocol 
It is the responsibility of the Investigator-sponsor to ensure that patient recruitment and 
enrollment, treatment, follow-up for toxicities and response, and documentation and 
reporting at SOCCI are all performed as specified in the protocol. Except for an 
emergency situation in which proper care for the protection, safety, and well-being of the 

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study patient requires alternative treatment, or a protocol exception request approved by 
the IRB of record, the study shall be conducted exactly as described in the approved 
protocol. 
 
9.7.1 
Emergency Modifications 
Investigators may implement a deviation from, or a change of, the protocol to eliminate 
an immediate hazard(s) to trial subjects without prior IRB approval. For any such 
emergency modification implemented, the IRB must be notified as soon as possible, but 
no more than 72 hours from the investigator’s awareness of the event. 
 
9.7.2 
Protocol Exceptions and Eligibility Waivers  
Minimal Risk 
A protocol exception is an anticipated or planned deviation from the IRB-approved 
research protocol, as described in the CSMC IRB Policy, Reporting Possible 
Unanticipated Problems Involving Risks to Subject or Others (UPIRSO) Policy: 
Institutional Review Board/Research Compliance and Quality Improvement.  A protocol 
exception most often involves a single subject and is not a permanent revision to the 
research protocol. Protocol exceptions that extend beyond a single subject should result 
in a protocol amendment to avoid serial violations.  
Planned exceptions to the protocol that are more than logistical in nature and/or impact 
an eligibility criterion, affect timing of study drug administration, or the investigator 
assesses the event may impact subject safety and/or study integrity, may not be 
implemented without prior IRB approval. The PI or her/his designee is responsible for 
submitting a protocol exception request and its supporting documents to the CSMC IRB if 
it meets the CS-IRB UPIRSO policy guidelines of a reportable exception/waiver. Study 
team should also refer to the IRB Reporting Possible Unanticipated Problems Involving 
Risks to Subject or Others (UPIRSO) Policy: Institutional Review Board/Research 
Compliance and Quality Improvement guidelines to determine which deviations and 
exception requests require IRB reporting. Once IRB approved, the deviation or exception 
can be implemented. 
 
Special considerations for Eligibility Waivers (EW) 
In general, subjects who do not meet the eligibility requirements should not be enrolled. 
In the rare event that it is appropriate for subject inclusion, the rationale/justification and 
subject case history should be submitted to the IRB for approval. Such requests for 
minimal risk studies do not require prior review by the CCTO Medical Director.  
 
9.7.3 
Other Protocol Deviations 
Logistical deviations from the protocol (e.g., minor changes to the study schedule for an 
individual subject) do not require prior IRB approval unless the deviation has the potential 
to affect the subject’s safety or study integrity. Such planned deviations that do meet this 
definition and do not affect the subject’s safety or study integrity should be noted in the 
subject’s research record or deviation log as described in the SOCCI CCTO’s Standard 
Operating Procedure 12: Deviation and Noncompliance Reporting. 
 
Unintentional deviations from the protocol that might affect subject safety or study 
integrity should be reported to the IRB within 10 days from when the investigator 
becomes aware that such a deviation has occurred, as outlined in the SOCCI CCTO’s 
Standard Operating Procedure 12: Deviation and Noncompliance Reporting (or local 
policy, for multi-site studies). In this case, a Protocol Deviation report must be submitted 
in CS-IRB, per CSMC IRB policy, Reporting Possible Unanticipated Problems Involving 
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Compliance and Quality Improvement. All submissions should include a description of the 
plan to avoid similar deviations or exceptions in the future.   
 
9.7.4 
Amendments to the Protocol  
Should amendments to the protocol be required, the amendments will be originated and 
documented by the Principal Investigator. It should also be noted that when an 
amendment to the protocol substantially alters the study design or the potential risk to the 
patient, a revised consent form might be required.  
 
The written amendment, and if required the amended consent form, must be sent to the 
IRB for approval prior to implementation. Repeat exceptions or deviations to the protocol 
may suggest a protocol amendment is needed. 
9.8 
Obligations of Investigators 
 
The Principal Investigator is responsible for the conduct of the clinical trial at the site in 
accordance with Title 21 of the Code of Federal Regulations and/or the Declaration of 
Helsinki. The Principal Investigator is responsible for personally overseeing the treatment 
of all study patients. The Principal Investigator must assure that all study site personnel, 
including sub-investigators and other study staff members, adhere to the study protocol 
and all FDA/GCP/NCI regulations and guidelines regarding clinical trials both during and 
after study completion. 
 
 
The Principal Investigator will be responsible for assuring that all the required data will be 
collected and entered onto the Case Report Forms and/or into a HIPAA-compliant study 
database. Periodically, monitoring visits will be conducted and the Principal Investigator 
will provide access to his/her original records to permit verification of proper entry of data. 
At the completion of the study, all case report forms will be reviewed by the Principal 
Investigator and will require his/her final signature to verify the accuracy of the data. 
9.9 
Publications 
The preparation and submittal for publication of manuscripts containing the study results 
shall be in accordance with a process determined by mutual written agreement among 
the sponsor-investigator and participating institutions.  The publication or presentation of 
any study results shall comply with all applicable privacy laws, including, but not limited 
to, the Health Insurance Portability and Accountability Act of 1996.  
 
 
 

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10.0 
REFERENCES 
 
1. Lilleby, K, et. al., A prospective, randomized study of cryotherapy during administration of high-
dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple 
myeloma undergoing autologous peripheral blood stem cell transplantation. Bone Marrow 
Transplant (2006): 37(11), 1031-5 
2. Zhang, Xin-Yu, et. al., Effectiveness, Safety, and Tolerance of Scalp Cooling for Chemotherapy-
Induced Alopecia. Oncology Nursing Forum, (2022): 49(4) 369-384. 
3. Sitarz, Jamie, and Spencer, Cara, Chemotherapy-Induced Alopecia: Examining Patient 
Perceptions and Adherence to Home Haircare Recommendations. Clinical Journal of Oncology 
Nursing (2022); 26 (2), 190-197. 
4. Nangia, Julie et. al, Effect of a Scalp Cooling Device on Alopecia in Women Undergoing 
Chemotherapy for Breast Cancer: The SCALP Randomized Clinical Trial. JAMA (2017) 317(6):596-
605. 
 
 
 
 

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11.0 
APPENDICES 
 
 

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11.1 
APPENDIX A: SUMMARY OF CHANGES  
 
Protocol Amendment 1 (Protocol version 2, dated 31OCT2023) 
• 
Sec. 3.0 clarification of imaging timepoints and removal of stopping rule reference. 
• 
Sec. 4.1.4 removal of hair covering percentage inclusion criterion 
• 
Sec. 4.2.2 removal of duplicative exclusion criterion 
• 
Sec. 4.2.6 removal of exclusion criterion for current use of oxaliplatin 
 
Protocol Amendment 2 (Protocol version 3, dated 20NOV2023) 
• 
Sec. 3.0 addition of cold cap administration window of +/- 30 minutes 
• 
Sec. 5.2 addition of cold cap administration window of +/- 30 minutes 
 
 

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11.2 
APPENDIX B: QUESTIONNAIRE 
 
Days 0 and 90 Scalp Cooling Questionnaire will be attached as a separate file. 
 
 

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11.3 
APPENDIX C: ECOG Performance Status Scale 
 
 
 
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity 
And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982. 
 
 
 
 
 

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11.4 
APPENDIX D: HAIR LOSS ASSESSMENT  
 
 
Grading of Hair Loss (Alopecia) to be assessed by treating investigator or designee. 
 
These will be completed at Screening, Days -2, 7 (± 2), 14 (± 2), 30 (± 7), 60 (± 7), & 90 (± 14). 
 
Alopecia as defined by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 
CTCAE version 5.0 defines alopecia only through Grade 2.