Daratumumab Infusion Acceleration
Phase: PHASE2
Conditions: Plasma Cell Myeloma
Sponsor: Ohio State University Comprehensive Cancer Center

1 
 
IRB Approved at 
the Protocol Level 
Feb 22, 2017 
TITLE:   
Daratumumab Infusion Acceleration  
 
Center: 
 
 
 
 
 
 
The Ohio State University 
 
Principal Investigator: 
Craig C. Hofmeister MD MPH 
 
M200G Starling-Loving Hall 
 
320 West 10th Ave 
 
Columbus, OH  43210 
 
614-293-7807 (voice); 614-366-5513 (fax) 
 
Craig.Hofmeister@osumc.edu  
 
Co-Investigators: 
Yvonne A. Efebera MD MPH 
(patient-care) 
Don M. Benson MD PhD 
 
Ashley E. Rosko, MD 
 
Pharmacy: 
Hallie Barr PharmD BCOP 
 
 
Statistician 
Ying Huong PhD 
 
Regulatory 
Nita Williams BS 
 
Data coordination 
Nidhi Sharma PhD 
 
Commercial Agent: 
Daratumumab 
 
 
  
 
Protocol / Version / Date: 
Original / v1.1 / 26-Aug-2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
SCHEMA 
Title: 
Daratumumab Infusion Acceleration 
 
Objectives: 
 
Determine the safety and tolerability of decreasing the 
infusion time of daratumumab in patients that have already 
received 2+ doses of daratumumab and are continuing on 
Daratumumab 
 
Estimate the time savings vs predicted infusion time 
 
Population: 
Any patient receiving daratumumab 
Phase: 
2 
Number of sites: 
1 
Description of treatment : 
Interventional unblinded Simon two-stage design of a 
faster Daratumumab infusion in patients who have 
received ≥ 2 infusions. 
 
Study duration: 
12-24 months 
Participant duration: 
Maximum 3 months 
 
 
  
 
Starting with dose #3 or later of Daratumumab, we propose to infuse approximately 20% 
over 30 minutes, then 80% over 60 minutes, total duration of 1.5 hours, saving an estimated 
2 hours.   
 
Daratumumab Infusion Rates 
Dose 
Total 
Volume1 
Initial Rate 
Rate 
Increment 
Max Rate 
Time2 
Standard of 
care dose ≥ 3 
550 mL 
100 mL/hr 
50 mL/hr 
every 1 hr 
200 mL/hr 
3.5 hr 
Investigational 
dose ≥ 3 
550 mL 
200 mL/hr 
30 minutes 
450 mL/hr 
1.5 hr 
1Includes estimated overfill; 2Estimated 
 
Stage 1
Infuse 7 patients 
at accelerated rate
If no 
grade 3 
IRRs
Stage 2
Infuse 21 
additional patients

3 
 
TABLE OF CONTENTS 
SCHEMA............................................................................................................................................................... 2 
TABLE OF CONTENTS ..................................................................................................................................... 3 
1. 
LIST OF ABBREVIATIONS ...................................................................................................................... 4 
2. 
STATEMENT OF COMPLIANCE ............................................................................................................ 4 
3. 
KEY ROLES ................................................................................................................................................. 4 
4. 
OBJECTIVES ............................................................................................................................................... 5 
5. 
BACKGROUND ........................................................................................................................................... 5 
5.1 
MULTIPLE MYELOMA ..................................................................................................................................... 5 
5.2 
RATIONALE .................................................................................................................................................... 6 
6. 
PATIENT SELECTION .............................................................................................................................. 8 
6.1 
ELIGIBILITY CRITERIA .................................................................................................................................... 8 
6.2 
EXCLUSION CRITERIA ..................................................................................................................................... 8 
7. 
REGISTRATION PROCEDURES ............................................................................................................. 9 
7.1 
GENERAL GUIDELINES ................................................................................................................................... 9 
8. 
TREATMENT PLAN ................................................................................................................................... 9 
8.1 
AGENT ADMINISTRATION ............................................................................................................................... 9 
8.2 
PREMEDICATION ............................................................................................................................................. 9 
8.3 
MONITORING .................................................................................................................................................. 9 
8.4 
DURATION OF THERAPY ................................................................................................................................ 10 
8.5 
DURATION OF FOLLOW-UP ............................................................................................................................ 10 
8.6 
CRITERIA FOR REMOVAL FROM STUDY ......................................................................................................... 10 
9. 
DOSING DELAYS / DOSE MODIFICATIONS ..................................................................................... 10 
9.1 
GRADE 1-2 INFUSION RELATED REACTIONS .................................................................................................. 10 
9.2 
GRADE 3 INFUSION RELATED REACTION ....................................................................................................... 10 
9.3 
GRADE 4 INFUSION RELATED REACTION ....................................................................................................... 10 
10. 
PHARMACEUTICAL INFORMATION ............................................................................................. 10 
10.1 
DARATUMUMAB ........................................................................................................................................... 11 
10.2 
DEXAMETHASONE ........................................................................................................................................ 11 
11. 
STUDY CALENDARS ........................................................................................................................... 12 
11.1 
SCHEDULE OF EVENTS .......................................................................................................................... 12 
12. 
STATISTICAL CONSIDERATIONS .................................................................................................. 12 
12.1 
GENERAL APPROACH .................................................................................................................................... 12 
12.2 
SAFETY ANALYSIS ........................................................................................................................................ 12 
12.3 
DATA SAFETY MONITORING PLAN ................................................................................................................. 13 
REFERENCES ................................................................................................................................................... 14 
APPENDIX A - VERSIONS .............................................................................................................................. 15 
APPENDIX B – INFUSION RN DATA FORM .............................................................................................. 16 
 
 
 

4 
 
 
1. LIST OF ABBREVIATIONS 
 
AE 
Adverse event 
BP 
Blood pressure 
CRF 
Case Report Form 
DSMB 
Data Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
HIPAA 
Health Insurance Portability and Accountability Act 
HR 
Heart rate 
IB 
Investigator’s Brochure 
IND 
Investigational New Drug Application 
IRB 
Investigational Review Board 
IRR 
Infusion Related Reaction 
IV 
Intravenous 
NIH 
National Institutes of Health 
PI 
Principal Investigator 
PO 
By mouth 
RR 
Respiratory rate 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
US 
United States 
 
2. STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with the ICH E6, the Code of Federal Regulations on the 
Protection of Human Subjects (45 CFR Part 46). The Principal Investigator will assure that no deviation 
from, or changes to the protocol will take place without prior agreement from the sponsor and 
documented approval from the Institutional Review Board (IRB), except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection Training. I agree to ensure that all staff members involved in the 
conduct of this study are informed about their obligations in meeting the above commitments. 
 
Principal investigator:  
 
 
    Craig Hofmeister  
 
 
3. KEY ROLES 
• Hofmeister – wrote the protocol, assisted with study design, assist with writing the 
manuscript; planned senior author 

5 
 
• Barr – conceived the idea, assisted with study design and protocol writing, consent the 
patients, enroll the patients, assist with tracking and entering data, assist with writing the 
manuscript;  planned first author 
• Benson, Efebera, Rosko – assist with writing the manuscript 
• Williams & Sharma – assist with tracking and entering data, regulatory assistance regarding 
the clinical trial, assist with manuscript writing 
4. OBJECTIVES 
Hypothesis 
Objective 
Endpoint 
Infusing daratumumab 
will not be associated 
with any grade 3-4 
infusion related 
reactions 
Determine the safety and 
tolerability of decreasing the 
infusion time of daratumumab 
in patients that have already 
received 2+ doses of 
daratumumab and are 
continuing on Daratumumab 
 
Analysis of AEs possibly, 
probably, or definitely related to 
protocol therapy will summarize 
infusion related grade 3-4 
reactions.   
 
Accelerated 
daratumumab infusion 
will significantly 
decrease the time 
patients spend waiting 
for daratumumab to 
infuse. 
Estimate the time savings vs 
predicted infusion time 
 
The start and stop times of 
daratumumab infusion will be 
tracked during infusion 
acceleration and the number of 
daratumumab infusions will be 
tracked from the time of consent 
until the last daratumumab 
infusion. 
 
5. BACKGROUND 
5.1 
Multiple myeloma 
Multiple myeloma (MM) affects approximately 83,000 US citizens and over 50% of 
patients die within 5 years of diagnosis; more than half of patients older than 70 years 
with low albumin and high β2microglobulin die within a year of diagnosis1, 2. Of the 
30,330 new cases estimated in 2016 in the U.S.3, is twice as common in African 
Americans as Caucasians, and genetic changes accumulate as plasma cells degenerate 
from monoclonal gammopathy of undetermined significance, through smoldering 
myeloma, to MM4. MM is characterized by fractures, anemia, kidney failure, and 
hypercalcemia with a predisposition for bacterial infections from the inherent 
immunoparesis and varicella reactivation often aided by proteasome inhibition5. 
 
Patients have been treated with combinations of cereblon-binding drugs (e.g. 
immunomodulatory drugs [IMiD’s] thalidomide, lenalidomide, pomalidomide), 
proteasome inhibitors (e.g. bortezomib, carfilzomib), and dexamethasone. MM cells 
are strongly dependent on the BM microenvironment (e.g. bone marrow stromal cells, 

6 
 
endothelial cells, osteoclasts) via the production of supportive growth factors. 
Moreover MM cells are able to escape immune surveillance by creating an 
immunosuppressive BM microenvironment favorable to their survival. 
 
Two antibodies have received FDA approval in 2015 for relapsed refractory disease: 
elotuzumab (HuLuc63) is a humanized immunoglobulin (Ig)G1-k antibody targeting 
signaling lymphocytic activation molecule F7 (SLAMF7, CS1 [CD2 Subset 1]), and 
daratumumab (HuMax-CD38) is an immunoglobulin G1 kappa (IgG1κ) human 
monoclonal antibody that binds a CD38 epitope.   
 
5.2 
Rationale 
In SIRIUS, after diphenhydramine 25-50 mg, acetaminophen 650-1000 mg, and 
methylprednisolone 100 mg intravenously, infusion-related reactions occurred in 45 
(42%) patients and were predominantly grade 1 or 2 (grade 3 occurred in five [5%] 
patients).  Thirty-seven percent of patients experienced infusion-related reactions 
during the first infusion and only six (6%) patients had more than one infusion-related 
reaction. The most common (≥5%) infusion-related reactions included nasal 
congestion (13 [12%]), throat irritation (seven [7%]), and cough, dyspnea, chills, and 
vomiting (six [6%] each).  In the dose-escalation study6, the frequency of infusion-
related reactions was lower among patients who received 8 mg/kg in 1000 ml for 6 
hours than among those who received 8 mg/kg in 500 mL for 4-6 hour or 16 mg/kg in 
1000 mL for 6 hours, all suggesting that the infusion rate factors into infusion 
reactions. All IRRs can be considered non-life threatening according to CTCAE 
grading system, most being nasal congestion. 
 
For patients receiving commercial daratumumab now, if a patient suffers grade 1-2 
infusion reactions, we interrupt daratumumab.  When symptoms resolve, we start at 
the last tolerated rate for one hour and begin re-escalating the infusion rate as 
tolerated.  For grade 3 infusion reaction, we stop the infusion, treat medically, and 
restart at half the rate when symptoms improve to grade 0-1.  The first dose of 
daratumumab should be diluted in one liter, but if this is well-tolerated, subsequent 
infusions can be diluted in 500 mL. Daratumumab is approved for 8 weekly 
infusions, 8 every other week infusions, and then monthly thereafter until 
progression.  Our current institutional infusion recommendations for commercial 
daratumumab are shown below. 
 
 
 
 
 

7 
 
 
 
Daratumumab Infusions – Institution Standard 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
**Montelukast typically discontinued after dose #3. 
 
This protocol focuses on dose #3 or later, when the risk of grade 3-4 infusion related 
reactions was very small in trials reported to date, as shown in the figure below. 
First
Acetaminophen 650 mg PO 
Diphenhydramine 50 mg PO 
Dexamethasone 20 mg IV 
Famotidine 20 mg IV 
Montelukast 10 mg PO
Daratumumab 16 mg/kg      
1000 mL total volume; Infuse 
at 50 mL/hour for the first 
hour. If no infusion reactions 
occur, may increase the rate 
by 50 mL/hour every hour 
(max rate: 200 mL/hour)
Second
Acetaminophen 650 mg PO 
Diphenhydramine 50 mg PO 
Dexamethasone 20 mg IV 
Famotidine 20 mg IV 
Montelukast 10 mg PO*
Daratumumab 16 mg/kg      
500 mL total volume; Infuse 
at 50 mL/hour for the first 
hour. If no infusion reactions 
occur, may increase the rate 
by 50 mL/hour every hour 
(max rate: 200 mL/hour)
Subsequent
Acetaminophen 650 mg PO 
Diphenhydramine 50 mg PO 
Dexamethasone 12 mg IV 
Famotidine 20 mg IV
Daratumumab 16 mg/kg      
500 mL total volume; Infuse at 
100 mL/hour for the first 
hour. If no infusion reactions 
occur, may increase the rate 
by 50 mL/hour every hour 
(max rate: 200 mL/hour)

8 
 
 
 
6. PATIENT SELECTION 
6.1 
Eligibility criteria 
6.1.1 Patients must have received ≥ 2 daratumumab infusions and be scheduled to 
receive another dose. 
6.1.2 Both men and women of all races and ethnic groups are eligible for this study. 
6.1.3 Age >18 years.  Because no dosing or adverse event data are currently 
available on the use of daratumumab in patients <18 years of age, children are 
excluded from this study. 
6.1.4 Ability to understand and the willingness to sign a written informed consent 
document. 
6.2 
Exclusion Criteria 
6.2.1 Any other medical condition, including mental illness or substance abuse, 
deemed by the principal investigator to likely interfere with a patient’s ability 
to sign informed consent, cooperate and participate in the study, or interfere 
with the interpretation of the results. 
6.2.2 Concurrent use of complementary or alternative medicines that in the opinion 
of the principal investigator would confound the interpretation of toxicities 
and/or antitumor activity of the study drug 
6.2.3 Prisoner 
 
IRRs (%), 87
IRRs (%), 4
IRRs (%), 9
FIRST INFUSION
SECOND INFUSION
SUBSEQUENT INFUSIONS
Percentage
Proportion of infusion reactions at 16 mg/kg

9 
 
7. REGISTRATION PROCEDURES 
7.1 
General Guidelines 
Eligible patients will be entered on study at Ohio State University by Hallie Barr.   
 
8. TREATMENT PLAN 
8.1 
Agent administration 
Treatment will be administered on an outpatient basis.  
 
Starting with dose #3 or later of daratumumab 16 mg/kg IV, we will infuse 
approximately 20% over 30 minutes, then 80% over 60 minutes, total duration of 1.5 
hours, saving an estimated 2 hours.  The initial rate will be 200 mL/hr (30 mins) and 
then 450 mL/hr (60 mins).   
8.2 
Premedication 
The following premedications are recommended approximately 1 hour prior to 
daratumumab infusion per the package insert: 
 
• 
Dexamethasone 12 - 20 mg IV/PO 
• 
Diphenhydramine 25 - 50 mg IV/PO 
• 
Acetaminophen 650 mg PO 
 
The OSU institutional standard for infusion #3 and onward is 
 
• 
Dexamethasone 12-20 mg IV/PO 
• 
Famotidine 20 mg IV/PO 
• 
Montelukast 10 mg PO (typically discontinued after dose #3) 
• 
Consider acetaminophen 325-650 mg PO 
• 
Consider diphenhydramine 12-25 mg IV/PO 
 
If the premedication regimen has been adjusted due to prior tolerability or physician 
preference, the appropriateness of the premedication regimen will be evaluated by the 
study team. 
 
 
8.3 
Monitoring 
Vital signs (HR, BP, temp, RR) will be taken just prior to infusion start, then every 15 
minutes for the first hour of infusion, then lastly at the end of infusion (see Appendix 
B monitoring form).  Patient will remain in the infusion clinic for a 30-minute post 
observation period after the first accelerated infusion only.  If the infusion is well-
tolerated, subsequent vital sign monitoring will occur prior to infusion start, at rate 
increase, and lastly at the end of infusion.  Patients will be educated on the signs of 

10 
 
delayed infusion reaction and instructed to contact physician for any issues after 
discharge from clinic. 
8.4 
Duration of therapy 
All further doses of daratumumab may be administered as described in section 8.1, 
however patient will be considered “off-study” after the pre-defined follow-up period.   
8.5 
Duration of follow-up 
Patients will be followed for 4 weeks from the first accelerated infusion.   
 
Patients removed from study for unacceptable adverse event(s) will be followed until 
resolution or stabilization of the adverse event. 
8.6 
Criteria for removal from study 
If the patient suffers a grade 4 infusion reaction, the patient will be removed from the 
study. 
9. DOSING DELAYS / DOSE MODIFICATIONS 
Infusion reactions will be recorded as described in Appendix B. 
9.1 
Grade 1-2 infusion related reactions 
At the time that this protocol was written, for daratumumab grade 1-2 infusion 
reactions, interrupt daratumumab.  When symptoms resolve, start at the last tolerated 
rate for one hour and begin re-escalating the infusion rate as tolerated.   
9.2 
Grade 3 infusion related reaction 
Follow institutional protocol.  At the time that this protocol was written, for grade 3 
infusion reactions, stop the infusion, treat medically, and restart at half the rate when 
symptoms improve to grade 0-1.  Subsequent rate escalation is to occur at physician 
discretion. 
9.3 
Grade 4 infusion related reaction 
Protocol accrual will be halted and the protocol modified. 
 
10. PHARMACEUTICAL INFORMATION 
A list of the adverse events and potential risks associated with daratumumab can be found in 
the FDA approved package inserts. 

11 
 
10.1 
Daratumumab 
Classification: fully human IgG1κ monoclonal antibody 
 
Mode of Action: Daratumumab is an antibody directed against myeloma cell surface 
glycoprotein CD38 and inhibits tumor growth by 1) direct apoptosis through Fc 
mediated cross-linking and 2) immune-mediated cell lysis through complement 
dependent cytotoxicity (CDC), antibody dependent cell mediated cytotoxicity 
(ADCC), and antibody dependent cellular phagocytosis (ADCP). 
 
Administration: Per protocol, see section 8.1 
 
Dosing: For treatment of myeloma, dose of daratumumab is 16 mg/kg IV, see 
prescribing information for dosing schedule.  Dose is calculated based on actual body 
weight. 
 
How supplied: Commercially 
 
Preparation/Handling/Storage:  Daratumumab will be prepared aseptically 
according to local procedures.  See manufacturer package insert or institutional 
protocol for proper handling and storage of the medication. 
10.2 
Dexamethasone 
Classification:  Corticosteroid 
 
Mode of Action:  Dexamethasone is a synthetic adrenocortical steroid with potent 
anti-inflammatory effects in disorders of many organ systems.  It decreases 
inflammation by suppression of neutrophil migration, decreased production or 
inflammatory mediators, and reversal of increased capillary permeability. 
 
Administration:  Administer the 4 mg/mL or 10 mg/mL intravenously as an 
undiluted or diluted solution.  Oral tablets at an equivalent dose may be substituted 
for IV. 
 
 
Dosing: Per treating physician. 
 
How supplied: Commercially 
 
Preparation/Handling/Storage:  Dexamethasone will be prepared according to local 
procedures.  See manufacturer package insert or institutional protocol for proper 
handling and storage of the medication. 
 
 

12 
 
11. STUDY CALENDARS 
Patients will be approached in the infusion suite for consent, generally within 4 weeks of day 1. 
Screening and first infusion can occur on the same day.   
11.1 
 SCHEDULE OF EVENTS  
Assessment 
Screening 
First accelerated 
infusion 
Signed informed consent 
X 
 
Inclusion/Exclusion Criteria 
X 
 
Height and weighta 
X 
 
Vital signs 
X 
X 
Daratumumab administration 
 
X 
Record adverse events 
 
X 
12. STATISTICAL CONSIDERATIONS 
12.1 
General approach 
The primary objective of this study is to assess the safety of administering 
Daratumumab over a shortened period of time following the first two standard doses. 
The primary endpoint is infusion-related reactions (IRR) assessed with the first dose 
using the accelerated dosing regimen. The incidence rate of IRR is defined and 
calculated as the number of patients with grade 3 IRR divided by the total number of 
patients who receive the accelerated dosing regimen. 
12.2 
Safety analysis 
Simon’s two-stage optimal design was used to design the study. Two previous trials 
SIRIUS (n=106) and GEN501 (n=42) reported no grade 3 IRR with the 3rd or 
subsequent infusions. Given this observed proportion of 0/148, the upper bound of a 
95% binomial confidence interval is 0.02, which translates to the alternative 
hypothesis that a desirable safety rate is at least 98%.  
 
Based on previous clinical experience with daratumumab at our institution, 15% or 
higher incidence rate of grade 3 IRR is not acceptable, which leads to a null 
hypothesis that the true safety rate is at most 85%. With a type I error probability of 
0.05 and 80% power, Simon’s two-stage optimal design allows an interim analysis 
after 7 patients are enrolled. If only 6 or fewer patients are grade 3 IRR-free, we will 
conclude the regimen is not safe enough and trial accrual will be halted and the 
protocol modified. If all 7 patients are grade 3 IRR-free, we will continue to accrue to 
a total of 28 patients.  
 
Out of all 28 patients, if the total grade 3 IRR-free patients is ≤26 (i.e. 2 or more 
patient with grade 3 IRR), we will conclude the regimen is too toxic. In addition, if 
any grade 4 IRR is observed, the trial will be suspended temporarily, and the regimen 

13 
 
will be reevaluated and modified to alleviate safety concerns. If the regimen is indeed 
too toxic with true safety rate no higher than 85%, we will have a 68% chance of 
early termination at the interim analysis. 
 
With anticipated accrual rate of around 5-6 patients each month, the accrual period 
will be less than 6 months to achieve our 28 total enrollment goal. 
 
12.3 
Data safety monitoring plan 
The data and safety monitoring plan will involve the evaluation of safety and data 
quality. Investigators will conduct review of data and patient safety at the regular 
myeloma census meetings (at least monthly). The PI of the trial will review reports of 
unexpected toxicities of the trial possibly, probably, or definitely related to 
Daratumumab infusion and determine if the risk/benefit ratio of the trial changes.  
Frequency and severity of related adverse events will be reviewed by the PI and 
compared to what is expected with Daratumumab infusion, including published 
literature and scientific meetings, to determine if the trial should be terminated before 
completion.  
The study conduct will be reviewed by The Ohio State University – Comprehensive 
Cancer Center Data and Safety Monitoring Committee (DSMC). Any portion of the 
trial may be reviewed, but the DSMC will focus on unexpected toxicities possibly, 
probably, or definitely related to study intervention as well as the adequacy of the 
randomization of subjects.   
 
 
 
 

14 
 
REFERENCES 
1. 
Howlander N, Noone A, Krapcho M, Garshell J, Miller D, Altekruse S, et al. SEER Cancer 
Statistics Review, 1975-2011, National Cancer Institute. http://seer.cancer.gov/csr/1975_2011/; 
2014. 
 
2. 
Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued 
improvement in survival in multiple myeloma: changes in early mortality and outcomes in older 
patients. Leukemia 2014 May; 28(5): 1122-1128. 
 
3. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016 Jan; 66(1): 7-30. 
 
4. 
Walker BA, Wardell CP, Melchor L, Brioli A, Johnson DC, Kaiser MF, et al. Intraclonal 
heterogeneity is a critical early event in the development of myeloma and precedes the 
development of clinical symptoms. Leukemia 2014 Feb; 28(2): 384-390. 
 
5. 
Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International 
Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 
2014 Nov; 15(12): e538-548. 
 
6. 
Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 
with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med 2015 Sep 24; 373(13): 
1207-1219. 
 
 
 
 
 
 
 
 

15 
 
APPENDIX A - VERSIONS 
 
Version 
Date 
Significant Revisions  
 
6-Aug -2016 
Original 
1.1 
26-Sep-2016 
Response to CSRC pharmacy stipulations.  Some 
clerical updates 
 
 
 
 
 

16 
 
APPENDIX B – INFUSION RN DATA FORM 
Assessment of hypersensitivity reactions and feasibility of an accelerated infusion Daratumumab protocol 
in patients with multiple myeloma.  The following form will be entered into IHIS as a SmartPhrase. 
Subject #____________  
Date:_______________  
Infusion start time: __________________  
Daratumumab dose: ________________________ 
 
Rate 
BP 
HR 
Temp 
RR 
Comments 
Initial 
 
 
 
 
 
 
15 min 
 
 
 
 
 
 
30 min 
 
 
 
 
 
 
45 min 
 
 
 
 
 
 
60 min 
 
 
 
 
 
 
EOI 
 
 
 
 
 
 
EOI = end of infusion 
Medications 
Administered 
Description of 
Symptoms 
Grade 
Grade 1: Mild transient reaction; infusion 
interruption not indicated; intervention not 
indicated 
 
Grade 2: Therapy or infusion interruption 
indicated but responds promptly to 
symptomatic treatment (e.g., 
antihistamines, NSAIDS, narcotics, IV 
fluids); prophylactic medications indicated 
for <=24 hrs 
 
Grade 3: Prolonged (e.g., not rapidly 
responsive to symptomatic medication 
and/or brief interruption of infusion); 
recurrence of symptoms following initial 
improvement; hospitalization indicated for 
clinical sequelae 
 
Grade 4: Life-threatening consequences; 
urgent intervention indicated 
 
Grade 5: Death 
 
 
Time: 
 
 
Time: 
 
 
Time: 
 
 
Time: 
 
 
Adapted from: Common terminology criteria for adverse events (CTCAE): General disorders and administration site conditions. 
Version 4.03. June 14, 2010. 
 
 
End time: ___________