Daratumumab-Based Maintenance in Patients With Relapsed Multiple Myeloma After Salvage Autologous Stem Cell Transplantation
Phase: PHASE2
Conditions: Recurrent Plasma Cell Myeloma
Sponsor: M.D. Anderson Cancer Center

  
  
 
Daratumumab-Based Maintenance in Patients with Relapsed  
Multiple Myeloma after Salvage Autologous  
Stem Cell Transplantation 
 
 
 Institution Study Number:   2016-0681  
 
 Financial Supporter: 
Study Number:    
Janssen Scientific Affairs, LLC (J&J) 
54767414MMY2016 
Principal Investigator:   Muzaffar H. Qazilbash, MD  
The University of Texas MD Anderson Cancer Center   
Stem Cell Transplantation and Cellular Therapy Department  
1515 Holcombe Blvd, Unit 0423 Houston, TX 77030  
Telephone: 713.792.2466  
Fax: 713.794.4902 
mqazilba@mdanderson.org 
Co-Chair:   Krina Patel, MD1  
 
Collaborators:   Behrang Amini, MD, PhD2   
Fleur M. Aung3   
Qaiser Bashir, MD4  
Hans C. Lee, MD1    
Katy Rezvani, MD, PhD4   
Dawen Sui, MS5 
Guilin Tang, MD, PhD6 
   
 
 
 
 
 
 
1 The University of Texas MD Anderson Cancer Center, Lymphoma/Myeloma Department  
2 The University of Texas MD Anderson Cancer Center, Musculoskeletal Imaging Department  
3 The University of Texas MD Anderson Cancer Center, Laboratory Medicine Department  
4 The University of Texas MD Anderson Cancer Center, Stem Cell Transplantation and Cellular Therapy Department 
5 The University of Texas MD Anderson Cancer Center, Biostatistics Department  
6 The University of Texas MD Anderson Cancer Center, Department of Hematopathology  
 

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Table of Contents 
  
  
1.0     
Objectives .................................................................................................................................................. 3 
2.0     
Background ................................................................................................................................................ 3 
3.0          Background Drug Information ..................................................................................................................... 5 
4.0  
Patient Eligibility ...................................................................................................................................... 15 
5.0  
Treatment Plan ......................................................................................................................................... 17 
6.0          Evaluation During Study ........................................................................................................................... 21 
7.0    
Statistical Considerations .......................................................................................................................... 22 
8.0  
Reporting Requirements ........................................................................................................................... 25 
9.0.         Data Management and Confidentiality ..................................................................................................... 33 
10.0         References .............................................................................................................................................. 35 
Appendix A.  Treatment and Event Schedule .......................................................................................................... 37 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol Body  
 
1.0     Objectives  
1.1  
Primary Objective  
 
To estimate the complete remission rate (CRR) by the International Myeloma 
Working Group (IMWG) criteria within 9 months post salvage auto-transplant 
with subcutaneous daratumumab and hyaluronidase-fihj plus pomalidomide 
maintenance therapy starting approximately 3 months post salvage auto-
transplant in patients with relapsed myeloma.  
1.2  
Secondary Objective  
  
To evaluate progression-free survival (PFS).  
  
1.3  
Exploratory Objective  
  
To discover the impact of daratumumab and hyaluronidase-fihj plus 
pomalidomide on graft function and immune reconstitution.  
2.0     Background  
2.1      Overview of Disease/Maintenance Therapy post salvage ASCT  
Treatment for multiple myeloma has changed significantly over the past 
decade. Induction therapy followed by upfront autologous stem cell transplant 
(ASCT) with melphalan 200 mg/m2 has shown significantly improved 
progression free survival and quality of life for patients with newly diagnosed 
multiple myeloma (MM).  
  
Maintenance Therapy:  
  
Furthermore, multiple randomized phase III trials have demonstrated 
significantly improved PFS and OS with the use of continued 
lenalidomide maintenance therapy post initial ASCT. However, despite 
these substantial improvements in therapy, the majority of patients will 
relapse 3-4 years later (1-7).  
  
Salvage ASCT:  
  
Due to earlier diagnoses and improved therapies, MM patients are living 
significantly longer and many are eligible for second ASCT that can yield a 
meaningful duration of remission. On the other hand, other patients may not 

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undergo ASCT in first remission, either due to aggressive disease which may 
relapse during 1st line induction therapy (including an IMID) or due to 
preference. Multiple studies have been conducted evaluating salvage ASCT 
and all demonstrated chemosensitivity and duration of remission after first 
ASCT were the most important prognostic factors for subsequent long-term 
disease control (8-17). For patients undergoing salvage ASCT, either as a 
second transplant or as a first transplant with previous relapse to induction 
therapy, no standard maintenance therapy has been established post 
transplant. In a recent study evaluating the addition of lenalidomide to 
melphalan conditioning for salvage transplant, complete remission rates in both 
groups (first ASCT after relapsed disease or second ASCT) is similar at 28%, 
with time for best response of 16-732 days (18).  
  
Maintenance with Daratumumab and Pomalidomide post salvage ASCT:  
  
IMIDs and proteasome inhibitors have been used post salvage ASCT as 
maintenance treatment, however cytopenias, toxicities, and resistance due to 
previous exposure to these drugs, decrease their applicability. The newly FDA 
approved monoclonal antibody daratumumab has established efficacy as a 
single agent in relapsed and refractory disease, however is not FDA approved 
as a maintenance option post autologous stem cell transplant. It is an IgG1 
kappa human monoclonal antibody directed against CD38. It induces apoptosis 
directly through Fc mediated cross linking and immune mediated tumor lysis 
through complement dependent cytotoxicity, antibody dependent cell mediated 
cytotoxicity and antibody dependent cellular phagocytosis. Thus its potential 
role as maintenance therapy post salvage transplant is promising and worthy of 
investigation.  
 
Daratumumab was approved by the FDA in November 2015 for IV infusion. 
More recently, in May 2020, FDA approved its subcutaneous formulation, 
daratumumab/hyaluronidase-fihj. Its advantages include a fixed-dose 
formulation, short administration time of 3-5 minutes, which is significantly 
shorter than the currently used IV formulation that is given over hours, and a 
significant reduction in infusion-related reactions. In the Phase 3 COLUMBA 
study (19) supporting the approval, daratumumab and hyaluronidase-fihj 
demonstrated a consistent overall response rate (ORR) and pharmacokinetics 
and a similar safety profile compared with intravenous daratumumab in patients 
with relapsed or refractory multiple myeloma. In addition, there was a nearly 
two-thirds reduction in systemic infusion-related reactions with daratumumab 
and hyaluronidase-fihj compared to intravenous daratumumab (13 percent vs. 
34 percent, respectively). 
 
Pomalidomide is the third-generation immunomodulatory drug (IMiD) that has 
been approved by the FDA in June 2017 for use in relapsed/refractory multiple 
myeloma in combination with daratumumab IV based on the results of 

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EQUULUS trial (20).  As most of the myeloma patients eligible for salvage 
ASCT have been exposed to daratumumab, and are refractory to the 2nd 
generation IMiD, lenalidomide, we hypothesize that a combination of 
daratumumab and hyaluronidase-fihj plus pomalidomide will improve the patient 
accrual, and the disease control. 
 
 2.2    Daratumumab  
  
Summary of Relevant Clinical Experience  
  
Several phase I /II and II studies (19-21) in relapsed MM patients (4-5 median 
prior lines of therapy) with daratumumab as monotherapy have been 
completed. The phase 1 part of the GEN501 trial demonstrated the 16 mg/kg 
dose as most efficacious and no dose limiting toxicity was observed at any 
dose level; part 2 revealed an overall response rate of 36% (at least a partial 
response) and PFS of 5.6 months with the dose of 16 mg/kg. The SIRIUS 
phase II study similarly demonstrated ORR of 29% and PFS of 3.7 months. 
Combination therapy with daratumumab, lenalidomide and dexamethasone in 
a phase I/II trial (GEN503) in relapsed refractory patients with a prior median 
of 2 lines of therapy, demonstrated an ORR of 100%, and 18 month PFS of 
72% (22).  
  
  
3.0    Background Drug Information  
  3.1    Daratumumab Preparation – Subcutaneous 
 
Daratumumab and hyaluronidase-fihj will be provided as a fixed-dose (1800 
mg), combination drug product containing rHuPH20 drug substance (2000 
U/mL) and daratumumab drug substance (120 mg/mL) in a single vial.  
3.1.1   Daratumumab Administration – Subcutaneous  
 
[Daratumumab should be given according to product information: 
http://www.janssenlabels.com/package-insert/product-monograph/prescribing-
information/DARZALEX+Faspro-pi.pdf] 
Daratumumab (1800 mg) will be administered by SC injection by manual push 
over approximately 3 – 5 minutes in the abdominal subcutaneous tissues in the 
left/right locations, alternating between individual doses. The volume of the SC 
solution will be 15 mL for the 1800 mg dose.  Reasons for continued observation 
on subsequent daratumumab injection may include but are not limited to the 
following: subjects with a higher risk of respiratory complications (e.g., subjects 
with mild asthma or subjects with COPD who have an FEV1 < 480% at 
screening or developed FEV1 < 80% during the study without any medical 
history), subjects with injection related reaction (IRR) with the first injection of 

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study drug, subject with decreased condition on day of dosing compared to prior 
dosing day. The dose of daratumumab will remain constant throughout the 
study.  
3.1.2   Dara-SC Dosing:  
 
Table 1: Dara-SC dosing schedule (whether in combination or monotherapy)  
Weeks 
Schedule 
Weeks 1 to 8 
Weekly (total of 8 doses) 
Weeks 9 to 24a 
Every two weeks (total of 8 doses) 
Week 25 and onward until PDb 
Every four weeks 
a First dose of the every-2-week dosing schedule is given at Week 9 
b First dose of the every-4-week dosing schedule is given at Week 25 
All daratumumab administrations will be in an outpatient setting. Subjects will 
receive pre-injection medications and post-injection medication as outlined in 
Sections 3.1.3 and 3.1.4 respectively.  
Vital signs should be monitored extensively on Cycle 1 Day 1 before, and after 
the first administration of daratumumab. For all other administrations, vital signs 
should be measured before the start of injection and at the end of the injection. If 
the subject experiences any significant medical event, then the investigator 
should assess whether the subject should stay overnight for observation. If the 
subject has not experienced a significant medical event but is hospitalized 
overnight only for observation, then the hospitalization should not be reported as 
an SAE.  
If an IRR develops, then the injection should be temporarily interrupted or slowed 
downIn the event of a life-threatening injection related reaction (which may 
include pulmonary or cardiac events) or anaphylactic reaction, daratumumab 
and hyaluronidase-fihj   should be discontinued and no additional daratumumab 
and hyaluronidase-fihj should be administered to the participant. See Section 
3.1.5 for instructions on the management of injection related reactions and local 
ISRs.   
3.1.3   Guidelines for Prevention and Management of Injection Reactions:  
 
All participants will receive the following medications 1 to 3 hours prior to each 
study drug administration:  
• An antipyretic: paracetamol (acetaminophen) 650-1000 mg IV or PO 
• An antihistamine: diphenhydramine 25-50 mg IV or PO or equivalent. Avoid IV 
use of promethazine.  
o After Cycle 6, if a participant has not developed an injection-related 
reaction and is intolerant to antihistamines, modifications are acceptable 
as per investigator discretion. 

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 Administer 20 mg dexamethasone (or equivalent) prior to every 
daratumumab injection. When dexamethasone is the background 
regimen specific corticosteroid, the dexamethasone treatment dose 
will instead serve as pre-medication on daratumumab injection days.  
 Dexamethasone is given orally or intravenously prior to the first 
daratumumab injection and oral administration may be considered 
prior to subsequent injection.  
o If the subject does not experience a major systemic administration-related 
reaction after the first 3 doses, consider discontinuing the administration of 
corticosteroids (excluding any background regimen-specific corticosteroid). 
 
Pre-dose administration of a leukotriene inhibitor (montelukast 10 mg PO or 
equivalent) is optional in Cycle 1 Day 1 and can be administered up to 24 hours 
before injection as per investigator discretion.  
If necessary, all PO pre-infusion medications may be administered out of the 
clinic on the day of the injection, provided they are taken within 3 hours before 
the infusion.  
3.1.4   Post-dose Medication: 
 
Administer post-injection medication to reduce the risk of delayed injection 
related reactions as follows:  
 
o Consider administering low-dose methylprednisolone (≤ 20 mg) or equivalent, 
the day after the injection. However, if a background regimen-specific 
corticosteroid (e.g. dexamethasone) is administered the day after the 
injection, additional post-injection steroids are not required, but may be 
considered by the investigator.  
o For participants with a higher risk of respiratory complications (e.g. 
participants with mild asthma or participants with COPD who have an FEV1 < 
80% at screening or developed FEV1 < 80% during the study without any 
medical history) the following post-injection medication should be considered:  
 Antihistamine (diphenhydramine or equivalent)  
 Leukotriene inhibitor (montelukast or equivalent)  
 Short-acting β2 adrenergic receptor agonist such as salbutamol 
aerosol 
 Control medications for lung disease (e.g. inhaled corticosteroids ± 
long-acting β2 adrenergic receptor agonists with asthma; long-acting 
bronchodilators such as tiotropium or salmeterol ± inhaled 
corticosteroids for participants with COPD) 
o In addition, these at-risk participants may be hospitalized for monitoring for 
up to 2 nights after daratumumab administration. If participants are 
hospitalized, then an improvement in FEV1 should be performed and 
documented prior to discharge. If these participants are not hospitalized, then 
a follow-up telephone call should be made to monitor their condition within 48 
hours after all injection. If the participant has not experienced a significant 

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medical event but is hospitalized overnight only for observation, then the 
hospitalization should not be reported as a serious adverse event. 
Investigators may prescribe bronchodilators, H1-antihistamines, and 
corticosteroids that are deemed necessary to provide adequate supportive 
care in the event a bronchospasm occurs after participants are released from 
the hospital/clinic. If an at-risk participant experiences no major injection-
related reactions, then these post-injection medications may be waived after 
4 doses at the investigator’s discretion.  
o Any post-injection medication will be administered after the injection has 
completed.  
 
3.1.5   Management of injection-related Reactions and Local Injection-    site 
Reactions of Daratumumab-SC injection-related reactions : 
 
Injection-related reactions are systemic reactions related to daratumumab 
administration. Participants should be observed carefully during daratumumab 
administrations. Trained study staff at the clinic should be prepared to intervene 
in case of any injection related reactions, and resources necessary for 
resuscitation (e.g., agents such as epinephrine and aerosolized bronchodilator, 
medical equipment such as oxygen tanks, tracheostomy equipment, and a 
defibrillator) must be available at the bedside. Attention to staffing should be 
considered when multiple participants will be dosed at the same time. If an 
injection related reaction develops during daratumumab and hyaluronidase-fihj 
administration, then the administration should be temporarily interrupted. 
Participants who experience AEs during daratumumab and hyaluronidase-fihj 
administration must be treated for their symptoms. Participants should be treated 
with paracetamol (acetaminophen), antihistamine, or corticosteroids, as needed. 
Intravenous saline may be indicated. For bronchospasm, urticaria, or dyspnea, 
participants may require antihistamines, oxygen, corticosteroids, or 
bronchodilators. For hypotension, participants may require vasopressors. In the 
event of a life-threatening injection related reaction (which may include 
pulmonary or cardiac events) or an anaphylactic reaction, daratumumab and 
hyaluronidase-fihj should be discontinued. 
Injection-related Reactions Grade 1 or Grade 2:  
If the investigator assesses a Grade 1-2 injection related reaction to be related to 
administration of study intervention, then the daratumumab and hyaluronidase-
fihj administration should be interrupted. When the participant's condition is 
stable, daratumumab and hyaluronidase-fihj administration may be restarted at 
the investigator's discretion. Refer to the USPI for further details regarding 
continuation of daratumumab and hyaluronidase-fihj administration.  
If the participant experiences a Grade 2 or higher event of laryngeal edema, or a 
Grade 2 or higher event of bronchospasm that does not respond to systemic 

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therapy and does not resolve within 6 hours from onset, then the participant 
must be permanently discontinued from daratumumab and hyaluronidase-fihj 
treatment. 
Injection-related Reactions Grade 3 or Higher:  
For injection related reaction AEs (other than laryngeal edema or 
bronchospasm) that are Grade 3, the daratumumab and hyaluronidase-fihj 
administration must be stopped, and the participant must be observed carefully 
until resolution of the AE or until the intensity of the event decreases to Grade 1, 
at which point the daratumumab and hyaluronidase-fihj administration may be 
restarted at the investigator’s discretion. Refer to the SIPPM for further details 
regarding continuation of daratumumab and hyaluronidase-fihj administration.  
If the intensity of the AE returns to Grade 3 after restart of the daratumumab and 
hyaluronidase-fihj administration, then the participant must be permanently 
discontinued from daratumumab and hyaluronidase-fihj treatment.  
For injection related reaction AEs that are Grade 4, the daratumumab and 
hyaluronidase-fihj administration must be stopped, and the participant 
permanently discontinued from daratumumab and hyaluronidase-fihj treatment. 
Recurrent Injection-related Reactions:  
If a Grade 3 injection related reaction (or Grade 2 or higher event of laryngeal 
edema, or a Grade 2 or higher event of bronchospasm) recurs during or within 
24 hours after a subsequent daratumumab and hyaluronidase-fihj 
administration, the participant must be permanently discontinued from 
daratumumab and hyaluronidase-fihj treatment. 
Injection Site Reactions (ISR):  
In clinical studies, SC administration of daratumumab was associated with local 
injection site reactions, such as induration and erythema, in some subjects. The 
reactions usually resolved within 60 minutes. Local injection-site reactions 
should be managed per institutional standards. 
 
3.1.6   Blood Typing and Cross-matching Interference  
  
Red cell and platelet transfusions will be required for some patients undergoing 
maintenance therapy post autologous stem cell transplantation. It has previously 
been reported that daratumumab binds to CD38 expressed on the surface of 
red blood cells. Although this additional activity may interfere with blood typing 
and cross-matching, no AEs related to hemolysis have been reported. In 
previous trials, patients had their blood types assessed before their first 
daratumumab infusion. They were also encouraged to carry a card indicating 
their blood type for the duration of the study. In the event of a positive Coombs 

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test, individual blood banks used a variety of mitigation methods to safely 
provide blood products. Blood banks were also made aware that this effect 
could persist for up to 6 months after cessation of daratumumab treatment.  
  
3.1.7 Injection Reactions  
  
Most biologics carry a risk of injection reactions that typically develop during or 
shortly after the injection. They vary from mild to potentially life threatening and 
are commonly associated with various signs and symptoms. The mechanisms 
by which monoclonal antibodies elicit injection reactions remain unclear.  
  
·  Monoclonal antibodies may interact with their molecular targets on circulating 
blood cells, tumor cells, or effector cells recruited to the tumor site (e.g., 
rituximab with CD20), thereby promoting the release of inflammatory 
cytokines.  
·  Injection reactions may have a hypersensitivity component in which the 
molecular structure of the drug or a component of the drug formulation is 
recognized as an antigen by the immune system. IgE mediated events are 
rare but possible.  
·  Non-immune mediated hypersensitivities are frequent following monoclonal 
or polyclonal antibody administration. These reactions resemble immune 
mediated reactions, but an immune mechanism is not detectable. The 
majority of these reactions imitate the clinical features of milder immune 
reactions (erythema, urticaria), but greater severity, even a lethal outcome 
are possible.  
  
There is no difference between the clinical manifestations of the immune-
mediated and non-immune mediated reactions. They both may involve the 
cutaneous, respiratory, gastrointestinal, or cardiovascular systems. The 
management of both types of reactions is the same.  
  
In both monotherapy and combination clinical trials, the incidence of any grade 
infusion reactions was 46% with the first infusion, 2% with the second infusion 
and 4% with subsequent infusions. The incidence of infusion modification due to 
reactions was 41%. Severe grade 3 infusion reactions included bronchospasm, 
dyspnea, laryngeal and or pulmonary edema, hypoxia and hypertension. Less 
serious infusion reactions that occurred in greater than 5% patients were nasal 
congestion, cough, chills, throat irritation and vomiting.  
  
When used as monotherapy in clinical trials with 156 patients with 
relapsed and refractory myeloma, the most frequent serious adverse 
reactions were pneumonia (6%), general physical health deterioration 
(3%), and pyrexia (3%). These resulted in delay of treatment for 15% of 
patients. The below tables are from the United States Product Insert and 

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describe adverse reactions in >10% of patients who (1) received with SC 
Daratumumab, and (2) IV Daratumumab.   
 
 
Adverse Reactions (≥10%) in Patients Who Received DARZALEX FASPRO with Bortezomib, 
Melphalan and Prednisone (D-VMP) in PLEIADES (package insert, Rev. 5/2020) 
Adverse Reaction 
DARZALEX FASPRO 
with Bortezomib, Melphalan and Prednisone 
(N=67) 
All Grades 
(%) 
Grades ≥3 
(%) 
Infections 
Upper respiratory tract infectiona 
39 
0 
Bronchitis 
16 
0 
Pneumoniab 
15 
7# 
Gastrointestinal disorders 
Constipation 
37 
0 
Nausea 
36 
0 
Diarrhea 
33 
3# 
Vomiting 
21 
0 
Abdominal painc 
13 
0 
General disorders and administration site conditions 
Fatigued 
36 
3 
Pyrexia 
34 
0 
Edema peripherale 
13 
1# 
Nervous system disorders 
Peripheral sensory neuropathy 
34 
1# 
Dizziness 
10 
0 
Respiratory, thoracic and mediastinal disorders 
Coughf 
24 
0 
Psychiatric disorders 
Insomnia 
22 
3# 
Musculoskeletal and connective tissue disorders 
Back pain 
21 
3# 
Musculoskeletal chest pain 
12 
0 
Metabolism and nutrition disorders 
Decreased appetite 
15 
1# 
Skin and subcutaneous tissue disorders 
Rash 
13 
0 
Pruritus 
12 
0 
Vascular disorders 
Hypertension 
13 
6# 
Hypotension 
10 
3# 
a Upper respiratory tract infection includes nasopharyngitis, respiratory syncytial virus infection, 
respiratory tract infection, rhinitis, tonsillitis, upper respiratory tract infection, and viral pharyngitis. 
b Pneumonia includes lower respiratory tract infection, lung infection, pneumocystis jirovecii 
pneumonia, pneumonia, and pneumonia bacterial. 
c Abdominal pain includes abdominal pain, and abdominal pain upper. 
d Fatigue includes asthenia, and fatigue. 
e Edema peripheral includes edema, edema peripheral, and peripheral swelling. 
f Cough includes cough, and productive cough. 
# Only grade 3 adverse reactions occurred. 

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Select Hematology Laboratory Abnormalities Worsening from Baseline in Patients Who 
Received DARZALEX FASPRO with Bortezomib, Melphalan and Prednisone (D-VMP) in 
PLEIADES 
Laboratory Abnormality 
DARZALEX FASPRO 
with Bortezomib, Melphalan and Prednisone a 
 
All Grades (%) 
 
Grades 3-4 (%) 
Decreased leukocytes 
96 
52 
Decreased lymphocytes 
93 
84 
Decreased platelets 
93 
42 
Decreased neutrophils 
88 
49 
Decreased hemoglobin 
48 
19 
a Denominator is based on the safety population treated with D-VMP (N=67). 
 
3.1.8   Drug Accountability  
  
Accountability for the drug at all study sites is the responsibility of the sponsor-
investigator. The sponsor-investigator will ensure that the drug is used only in 
accordance with this protocol. Drug accountability records indicating the drug’s 
delivery date to the site (if applicable), inventory at the site (if applicable), use by 
each patient, and disposal of the drug will be maintained by the site. 
Accountability records will include drug receipt/destruction dates, quantities, lot 
numbers, expiration dates (if applicable), and corresponding registered patient 
numbers.  
  
All material containing daratumumab will be treated and disposed of as 
hazardous waste in accordance with governing regulations.  
3.1.9   Daratumumab Destruction  
  
Study drug should be destroyed on site according to the institution’s standard 
operating procedure. Be sure to document removal and destruction on drug 
accountability logs.  
 
3.2  
Pomalidomide 
 
Pomalidomide is a thalidomide analogue, which exerts an immunomodulatory, 
antiangiogenic, and antineoplastic effect by the inhibition of the proliferation and 
induction of apoptosis of hematopoietic tumor cells, and enhancement of T cell- 
and natural killer cell-mediated immunity and inhibition of pro-inflammatory 
cytokine production (e.g., TNF-alpha and IL-6) by monocytes. The cytotoxic and 
immunomodulatory effects of pomalidomide are mediated by targeting substrate 
proteins (including Aiolos and Ikaros) for ubiquitination and subsequent 
degradation. Pomalidomide is available as oral capsules in 1, 2, 3 and 4 mg 
doses.  
 

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Pomalidomide will be administered at 2 mg/day PO once daily on Days 1 to 21 
during the 28-day cycle. Pomalidomide dose may be reduced, or the treatment 
schedule may be modified for the management of the study drug-related 
toxicities. Pomalidomide may be taken with water. Subjects should not break, 
chew, or open the capsules. Pomalidomide should be taken without food (at 
least 2 hours before or 2 hours after a meal).  
 
Dose Modification Instructions for 
Pomalidomide for Hematologic Toxicities 
Toxicity 
 
 
Dose Modification 
Neutropenia 
• ANC <500 per mm3 or Febrile neutropenia 
(fever more than or equal to 38.5°C and ANC 
<1,000 per mm3) 
• ANC return to more than or equal to 500 per 
mm3 
 
• Interrupt pomalidomide 
treatment, follow CBC weekly. 
• Resume pomalidomide at 2 
mg daily. 
• For each subsequent drop <500 per mm3 
• Return to more than or equal to 500 per mm3 
• Interrupt pomalidomide 
treatment. 
• Resume pomalidomide at 1 
mg less than the previous 
dose 
Thrombocytopenia 
• Platelets <25,000 per mm3 
• Platelets return to >50,000 per mm3 
• Interrupt pomalidomide 
treatment, follow CBC weekly 
• Resume pomalidomide 
treatment at 2 mg daily 
• For each subsequent drop <25,000 per mm3 
• Return to more than or equal to 50,000 per mm3 
• Interrupt pomalidomide 
treatment 
• Resume pomalidomide at 1 
mg less than previous dose. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Pomalidomide Side Effects 
 
Common (occurring in more than 20% of patients) 
 
 swelling (arm/leg) 
 fatigue 
 nerve damage (possible 
numbness, pain, and/or 
loss of motor function) 
 dizziness 
 fever 
 skin rash 
 abnormal salts, 
minerals, and/or acids in 
the blood (possible 
weakness, swelling, 
fatigue, low blood 
pressure, organ failure, 
heart problems, 
changes in mental 
status, and/or seizure) 
 constipation 
 nausea 
 diarrhea 
 loss of appetite 
 low blood cell counts 
(red, white, platelet) 
 weakness 
 pain 
 muscle spasms 
 difficulty breathing 
 
Pomalidomide may cause low blood cell counts (white blood cells, red blood cells, 
platelets). 
 
 A low white blood cell count increases your risk of infection (such as viral or 
fungal pneumonia and/or severe blood infection). Infections may occur 
anywhere and become life-threatening. Symptoms of infection may include 
fever, pain, redness, and difficulty breathing. 
 A low red blood cell count (anemia) may cause difficulty breathing and/or 
fatigue. You may need a blood transfusion. 
 A low platelet count increases your risk of bleeding (such as nosebleeds, 
bruising, stroke, and/or digestive system bleeding). You may need a platelet 
transfusion. 
 
Occasional (occurring in 3-20% of patients) 
 
 headache 
 anxiety 
 confusion 
 chills 
 difficulty sleeping 
 itching/dry skin 
 increased sweating 
 high blood sugar 
(possible diabetes) 
 dehydration 
 weight loss/gain 
 vomiting 
 tremors 
 kidney failure 
 nosebleed 
 cough 
 severe life-threatening 
infection (possible low 
blood pressure, kidney 
failure, and/or heart 
failure) 
 
 
 
 
 
 
 

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Frequency Unknown, but between 1-10% 
 
 heart attack/failure 
 low blood pressure 
(possible 
dizziness/fainting) 
 mental status change 
 depression 
 walking/balance 
problems (possible 
falling) 
 inflammation of the 
intestines 
 mouth blisters/sores 
(possible difficulty 
swallowing) 
 blood in the urine  
 abnormal liver tests 
(possible liver damage, 
yellowing of the skin 
and/or eyes) 
 broken bone(s) 
 collapse of bones in the 
spine 
 bacteria in the blood 
 multiorgan failure 
 
Rare but serious (occurring in fewer than 3% of patients) 
 
 inability to urinate 
 liver failure 
 breakdown products of 
the cancer cells entering 
the blood stream 
(possible weakness, low 
blood pressure, muscle 
cramps, kidney damage, 
and/or other organ 
damage) 
 allergic reaction 
 
Pomalidomide may cause you to develop another type of cancer (such as acute 
myeloid leukemia, a type of blood cancer). 
 
Pomalidomide may also cause blood-clotting events (such as deep vein thrombosis, 
blood clots in the lungs, heart attack, and stroke). 
 
4.0  Patient Eligibility  
 4.1  
Inclusion Criteria  
  
Each patient must meet all the following inclusion criteria to be enrolled in the study:  
  
1. 
Patient must have had relapsed disease prior to transplant, or undergone 
previous ASCT, followed by relapse and at least a partial response to salvage 
therapy.  
2. 
Eligible patients will be enrolled in the protocol no less than 60 days and must be 
initiated no longer than 180 (+/- 14) days post ASCT.  
3. 
Male or female patients 18 years or older.  

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4. 
Patients must have an Eastern Cooperative Oncology Group (ECOG) status of 0 
to 2.  
5. 
Patients’ clinical laboratory values and toxicity must be as specified below within 
14 days before the first dose of the study drug:  
• Platelet count >= 50,000/mm3  
• Absolute neutrophil count >= 1000/ mm3 (no growth factors within 5 days)  
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3 x 
ULN  
• Creatinine <= 2.5 mg/dL  
• Recovered (i.e., <= grade 2 toxicity) from the reversible effects of autologous 
stem cell transplant.  
6. 
Voluntary written informed consent before performance of any study-related 
procedure not part of normal medical care must be obtained, with the 
understanding that consent may be withdrawn by the subject at any time without 
any prejudice to future medical care.  
7. 
Left ventricular ejection fraction >= 40%(at the patient’s last recorded 
echocardiogram (this could refer to pretransplant ECHO. ECHO may be repeated 
if the PI considers a repeat ECHO) No uncontrolled arrhythmias.  
  
 4.2  
Exclusion Criteria  
  
Patients meeting any of the following exclusion criteria are not to be enrolled in the 
study:  
  
1. 
Major surgery within 14 days before the first dose of study drug.  
2. 
Radiotherapy within 14 days before enrollment.  
3. 
Non-secretory disease, plasma cell leukemia, or previous allogeneic transplant.  
4. 
Known active central nervous system involvement.  
5. 
Inability or unwillingness to comply with the drug administration requirements.  
6. 
Female subject is pregnant or lactating.  
7. 
Seropositive for human immunodeficiency virus (HIV).  
8. 
Seropositive for hepatitis B (defined by a positive test for hepatitis B surface 
antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg 
negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or 
antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-
time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) 
DNA levels. Those who are PCR positive will be excluded. EXCEPTION: 
Subjects with serologic findings suggestive of HBV vaccination (anti-HBs 
positivity as the only serologic marker) AND a known history of prior HBV 
vaccination, do not need to be tested for HBV DNA by PCR.  
9. 
Seropositive for hepatitis C (except in the setting of a sustained virologic 
response [SVR], defined as aviremia at least 12 weeks after completion of 
antiviral therapy).  

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10. Patients with a known history of asthma or chronic obstructive pulmonary disease 
with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal.  
11. Patients with moderate or severe persistent asthma within the past 2 years and 
currently uncontrolled asthma of any classification. 
12. Infection requiring IV systemic antibiotic therapy within 7 days before C1D1 of 
therapy.  
13. Known allergy to any of the study medications, their analogues, or excipients in 
the various formulations.  
14. Failure to have fully recovered (i.e., <= grade 2 toxicity) from the effects of prior 
chemotherapy regardless of the interval since last treatment.  
15. Patient is refractory or resistant to daratumumab and pomalidomide.  
16. Co-morbid systemic illnesses or other severe concurrent disease that, in the 
judgment of the investigator, would make the patient inappropriate for entry into 
this study or interfere significantly with the proper assessment of safety and 
toxicity of the prescribed regimens.  
17. If patient was unable to tolerate daratumumab or pomalidomide in the past.  
  
 
5.0  Treatment Plan  
 5.1  
Overall Design and Plan of Study  
  
This will be a single arm, open label phase II, single center study of maintenance 
therapy with daratumumab/hyaluronidase-fihj and pomalidomide post salvage ASCT in 
patients with multiple myeloma.  
  
The total number of patients to be treated in this study is 56 evaluable patients.  
  
Patients should complete 2 cycles of therapy to be evaluable. For patients who receive 
fewer than 2 cycles due to progressive disease will be considered evaluable. Patient 
who received < 2 cycles due to AEs will be inevaluable for efficacy (response). All the 
other analysis will be conducted using intention to treat dataset.  
  
Patients will have standard restaging studies prior to initiation of therapy. Standard 
post transplant therapy per institutional guidelines will be unaltered including 
prophylactic antibiotics, vaccinations and restaging.  
  
Each cycle will be defined as a 28 day cycle. Drug holidays and break in therapy 
including those due to holidays, physician discretion and drug delivery are allowed as 
needed.  
5.2    Daratumumab 1800 mg/hyaluronidase-fihj 30,000 units will be given SC weekly 
for weeks 1-8, followed by every 2 weeks for weeks 9-24, and then every month for 
weeks 25 until progression. On day 1 of each cycle, doses may be held if clinically 
indicated (i.e., active infections) for up to 4 weeks. If longer than 4 weeks, the PI will 

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evaluate and determine if the patient can continue on trial or must be taken off study. 
After day 1 of each cycle, subsequent doses may be held/skipped if clinically indicated 
(i.e., active infections) per PI or treating physician’s discretion.  
 
If daratumumab administration does not commence within the specified window 
(Appendix A), then the dose will be considered a missed dose. Administration may 
resume at the next planned dosing date.  A missed dose will not be made up. Any 
adverse event deemed to be related to daratumumab that requires a dose hold of more 
than 28 days will result in permanent discontinuation of daratumumab. Subjects who 
miss >/= 3 consecutive planned doses of daratumumab for reasons other than toxicity 
will be withdrawn from treatment, unless, upon consultation with the sponsor and 
review of safety and efficacy, continuation is agreed upon.  
        
Subjects will receive pre-injection medications and post-injection medication as 
outlined in Sections 3.1.3 and 3.1.4 respectively. See Section 3.1.5 for instructions on 
the management of IRR and local ISRs. 
 
5.3   Pomalidomide will be given at 2 mg PO daily from day 1-21 in the 28-day cycle. 
On day 1 of each cycle, doses may be held if clinically indicated (i.e., active 
infections) for up to 4 weeks. If longer than 4 weeks, the PI will evaluate and 
determine if the patient can continue on trial or must be taken off study. After 
day 1 of each cycle, subsequent doses may be held/skipped if clinically 
indicated (i.e., active infections) per PI or treating physician’s discretion. 
 
 
Pomalidomide not administered between days 1-21 in the 28 days cycle will be 
considered a missed dose. Administration may resume after active infection is 
resolved per PI or treating physician discretion. See section 3.2 for further 
instructions on toxicity management. 
     
 
   5.4 
Prophylaxis for herpes zoster reactivation  
  
Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week 
of starting daratumumab and continue for 3 months following treatment.  
  
 5.5  
Dose Delay  
  
Before each cycle, the patient will be evaluated for possible toxicities that may 
have occurred after the previous dose(s). Toxicities are to be assessed 
according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), 
version 4.0 (http://ctep.cancer.gov/reporting/ctc.html).  Each AE should be 
attributed to a specific drug, if possible, so that the dose modifications can be 
made accordingly. If multiple toxicities are noted, the dose delays are per PI 
discretion; refer to guidelines that address the most severe toxicity.  
  

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5.6  
Criteria for beginning a subsequent treatment cycle  
  
Treatment with daratumumab will use a cycle length of 28 days. For a new 
cycle of treatment to begin, the patient must meet the following criteria:  
 
 
·  ANC must be >= 1,000/mm3 
 
·  Platelet count must be >= 50,000/mm3 
  
In addition, all other toxicity considered to be related to treatment must have 
resolved to <= grade 1, to the patient’s baseline values, or to a level considered 
acceptable by the physician (e.g., hypokalemia that can be managed by 
replacements) before a new cycle of treatment may begin.  
  
5.7     Criteria for delaying a subsequent treatment cycle  
  
If the patient fails to meet the above-cited criteria for initiation of the next cycle 
of treatment or has any of the below toxicities, dosing should be delayed until 
recovery.  
 
·  Grade 4 hematologic toxicities  
 
·  Grade 3 thrombocytopenia with bleeding  
 
·  Febrile neutropenia of any grade  
 
·  Neutropenia with infection, of any grade  
 
·  Grade 3 or higher nonhematologic toxicities with the following exceptions:  
• 
Grade 3 nausea that responds to antiemetic treatment within 7 days  
• 
Grade 3 vomiting that responds to antiemetic treatment within 7 days  
• 
Grade 3 diarrhea that responds to antidiarrheal treatment within 7 
days  
• 
Grade 3 fatigue that was present at baseline or that lasts for <7 days 
after the last administration of daratumumab  
• 
Grade 3 asthenia that was present at baseline or that lasts for <7 
days after the last administration of daratumumab  
  
The maximum delay before treatment should be discontinued is 6 weeks or at 
the discretion of the Principal Investigator.  
  
5.8     Management of Clinical Event  
  
5.8.1 Nausea and/or Vomiting  
  
Standard anti-emetics, including 5-HT3 antagonists, are recommended for 
emesis occurring upon treatment initiation; prophylactic anti-emetics may also 
be considered. Dexamethasone should not be administered as an anti-emetic. 
Fluid deficits should be corrected before initiation of study drug and during 
treatment.  

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5.8.2 Diarrhea  
  
Diarrhea should be managed according to clinical practice, including 
administration of antidiarrheal therapy once infectious causes are excluded. 
Fluid intake should be maintained to avoid dehydration. Fluid deficits should be 
corrected before initiation of treatment and during treatment.  
  
5.8.3 Thrombocytopenia  
  
Thrombocytopenia has been reported with daratumumab. Blood counts should 
be monitored regularly as outlined in the protocol with additional testing 
obtained according to standard clinical practice. Thrombocytopenia may be 
severe but has been managed with platelet transfusions according to standard 
clinical practice.  
  
5.8.4 Neutropenia  
  
Neutropenia has been reported with daratumumab. Blood counts should be 
monitored regularly as outlined in the protocol with additional testing obtained 
according to standard clinical practice. Neutropenia may be severe but has 
been managed with G-CSF according to standard clinical practice.  
  
5.9   Concomitant Treatment  
  
Permitted Concomitant Medications and Procedures  
  
All necessary supportive care consistent with optimal patient care shall be 
available to patients as necessary. Radiotherapy is permitted to palliate 
symptoms during maintenance therapy. The following are examples of those 
permitted during the study:  
  
·  Growth factors (e.g., granulocyte colony stimulating factor (G-CSF), 
granulocyte macrophage-colony stimulating factor (GM-CSF), recombinant 
erythropoietin).  
 
·  Red cell and platelet transfusions as clinically indicated  
 
·  Prophylactic antibiotics for pneumocystis (i.e., Bactrim) needed post ASCT  
·     Antiviral prophylaxis (i.e.,Valtrex) is recommended for all patients to prevent 
HSV or zoster  
 
·  Bisphosphonate therapy  
 
·  Medications for neuropathy as needed at the discretion of the investigator.  
Prohibited Concurrent Therapy  

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Other anti-myeloma directed systemic therapy  
  
5.10   Management of Hepatitis B Virus Reactivation  
 
Primary antiviral prophylaxis is permitted as per local standard of care. Per 
protocol, HBV DNA testing by PCR is mandatory for subjects at risk for HBV 
reactivation see Appendix A.  
  
For subjects who are diagnosed with HBV reactivation while on treatment, study 
treatment should be interrupted until the infection is adequately controlled. If the 
benefits outweigh the risks, study treatment may be resumed with concomitant 
antiviral prophylaxis as per local standard of care. Consult a liver disease 
specialist as clinically indicated.  
  
5.11   Contraception Requirements  
  
Animal reproduction studies have not been conducted. Monoclonal antibodies 
such as daratumumab, are known to cross the placenta. Based on the 
mechanism of action, daratumumab may cause myeloid or lymphoid cell 
depletion and decreased bone density in the fetus. Therefore, female patients 
participating in this study should avoid becoming pregnant, and male patients 
should avoid impregnating a female partner.  
  
Non-sterilized female patients of reproductive age and male patients should use 
effective methods of contraception.  
  
5.12      Duration of Treatment and Patient Participation  
  
Patients will be informed that they have the right to withdraw from the study at 
any time for any reason, without prejudice to their medical care. Patients will 
continue indefinitely unless the following occur:  
  
 
·  Lack of clinical benefit  
 
·  Patient’s request to withdraw from the study or refusal of further therapy  
 
·  Unacceptable toxicity  
 
·  Pregnancy  
·  Physicians discretion  
·  Disease progression.  
 
 ·    Completion of up to 36 Cycles of study therapy  
6.0   Evaluation During Study  
  
6.1  Treatment and Event Schedule (see Appendix A.)  
  

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6.2  Efficacy measurements  
  
Patients will be staged once every 3 cycles +/- 7 days while on protocol. 
Efficacy evaluations will be based on changes in: myeloma protein 
measurements in serum and 24 hour urine; serum free light chain assay; bone 
marrow biopsy examination with NGF-based MRD testing at 6 months from the 
start of maintenance (+/- 2 weeks);  as clinically indicated skeletal survey or 
other imaging as clinically indicated; and, extramedullary plasmacytoma 
evaluation as clinically indicated.  
 
7.0    Statistical Considerations  
  
 7.1 
Sample Size Justification 
 
The primary endpoint of this study is progression-free survival (PFS). According 
to clinical trial #NCT01998971 (28), we expect that the median PFS without 
maintenance therapy is 12 months and the median PFS for the daratumumab-
based maintenance therapy is expected to be 20 months. Given an accrual 
period of 36 months and a maximum follow-up time of 60 months, a sample size 
of 56 with the number of events of 42 will achieve the power of 0.91. The result 
is based on a two-sided test, a significance level of 0.05 with exponential 
assumption for survival time (29). 
 
7.2 
Futility and Toxicity Monitoring 
 
The secondary endpoint is the complete remission rate (CRR). Remission will 
be evaluated 6 months after daratumumab and hyaluronidase-fihj plus 
pomalidomide maintenance therapy (approximately 9 months post ASCT). 
Complete remission is defined as achieving a negative immunofixation of serum 
and urine, disappearance of any soft tissue plasmacytomas, and < 5% plasma 
cells in bone marrow. In patients for whom only measurable disease is by serum 
FLC level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required.  
The futility and toxicity will be monitored during the study. 
  
  
We desire that the CRR is at least 10%and the dose-limiting toxicity rate is no 
higher than 33%. Toxicity is defined as treatment-related unmanageable 
toxicities, including grade 3 non-hematologic effects or grade 4 hematologic 
effects, that require delay or termination of the treatment during cycle one. 
Futility and toxicity will be monitored by the Bayesian stopping boundaries 
calculated on the basis of beta-binomial distributions using the method of Thall, 
Simon, and Estey (30). Independence is assumed between CR and toxicity. 
Patients will be monitored in cohorts of size (8).  
 
We will enroll a minimum of 16 patients before stopping. The following stopping 
rules and boundaries were developed using the Multc Lean application (version 

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2.1) from the MDACC Biostatistics department. The stopping rules are as 
follows:  
Pr [θΕ < 0.10 | data] > 0.90  
Pr [TΕ> 0.33|data] > 0.95  
 
Enrollment will be stopped early if there is > 90% probability that the CRR is < 
10% or there is > 95% probability that the toxicity rate is higher than 33%. The 
notation θΕ denotes the marginal remission rate, assuming that θΕ follows a prior 
distribution of beta (0.2,1.8). TE denotes the toxicity rate, assuming that TE has 
a prior distribution of beta (0.66, 1.34). The corresponding stopping boundaries 
for futility monitoring are as follows: enrollment will be stopped early due to 
futility if (# of patients with remission) / (# patients evaluated) </= 0/16-24, 1/32, 
2/40-48, or 3/56. 
  
Stopping boundaries corresponding to this probability criterion for toxicity will 
terminate the trial if (# of patients with toxicity) / (# patients evaluated) >/= 9/16, 
13/24, 16/32, 19/40, 22/48, or 25/56.  
  
We will suspend accrual while waiting to assess patient outcomes.  
The operating characteristics of these rules are shown in the table below.  
  
 
True 
Pr(Response)  
True Pr 
(Tox)  
Pr (Stop 
Early)  
Average # 
treated  
1  
10%  
15%  
0.32  
46.0  
2  
10%  
33%  
0.38  
44.0  
3  
10%  
40%  
0.55  
39.1  
4  
20%  
25%  
0.04  
54.4  
5  
20%  
33%  
0.13  
52.0  
6  
20%  
40%  
0.36  
45.6  
7  
25%  
20%  
0.013  
55.5  
8  
25%  
33%  
0.10  
52.8  
9  
25%  
40%  
0.35  
46.2  
10  
30%  
20%  
0.005  
55.8  
11  
30%  
33%  
0.10  
53.1  
12  
30%  
45%  
0.60  
39.0  
13  
40%  
20%  
0.002  
55.9  
14  
40%  
33%  
0.09  
53.2  
15  
40%  
45%  
0.60  
39.1  
  
  
The dataset for efficacy will be based on evaluable patients while the dataset for 
safety includes all patients who receive the maintenance therapy and will be  

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evaluated as intention to treat (ITT). Based on the toxicity profile of 
daratumumab, we do not expect to have patients who receive fewer than 2 
cycles due to AE’s.  
 
Patient who received < 2 cycles due to AEs will be inevaluable for efficacy 
(response). All the other analysis will be conducted using intention to treat 
dataset.  
  
 
 
 
 7.3  
Analysis Plan  
  
Patients’ demographic, clinical characteristics, and safety data will be 
summarized using descriptive statistics such as mean, standard deviation, 
median, interquartile range, and frequency where appropriate.  
  
Progression-free survival is defined as the interval from the date of initiation of 
maintenance therapy after salvage ASCT to the earlier of the first 
documentation of objective disease progression or death from any cause. 
Disease progression will be assessed using myeloma protein measurements in 
serum and 24 hour urine; serum free light chain assay; bone marrow biopsy 
examination with MGF-based MRD testing at 6 months (+/- 2 weeks) from the 
start of maintenance, and then yearly as indicated; skeletal survey or other 
imaging as clinically indicated; and, extramedullary plasmacytoma evaluation 
as clinically indicated. Progression is defined by the IMWG as a 25% increase 
from the lowest response value in any of the following: a) serum M protein with 
absolute increase >= 0.5 g/dL, b) urine M protein with absolute increase of at 
least 200 mg/24 hour, c) difference between involved and uninvolved FLC 
levels with absolute increase of at least 10 mg/dL (in patients without 
measurable serum or urine M protein), d) bone marrow plasma cell percentage 
with absolute percentage of at least 10% (in patients without measurable 
serum or urine M protein or FLC levels), e) new or definite increase in size of 
existing bone lesions or soft tissue plasmacytoma, f) development of 
hypercalcemia that can be attributed solely to myeloma. Data from surviving, 
non-progressing patients will be censored at the last time of follow-up. 
Progression-free survival will be summarized descriptively using the Kaplan-
Meier method (including the median, 95% confidence interval, and survival 
curve). The proportion of patients alive and without disease progression at 6 
months of daratumumab and hyaluronidase-fihj plus pomalidomide 
maintenance therapy will be summarized. The estimate will be accompanied by 
a two-sided exact 95% binomial confidence interval. In addition, a Cox 
regression analysis may be performed if demographic and clinical factors 
potentially affecting PFS are identified.  
 

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The associations between/among safety data, prognostic factors, and the 
response will be assessed using student t-test/Wilcoxon rank test, 
ANOVA/Kruskal-Wallis test, chi-squared test/Fisher’s exact test, or Logistic 
regression model as appropriate. Complete remission rate will be estimated 
along with a 95% credible interval. 
  
 
 
8.0  Reporting Requirements  
Safety Measurements and Reporting  
  
Before starting each cycle, patients will be evaluated for toxicity. Safety evaluations 
will be based on changes in physical examinations, ECOG Performance Status 
scores, clinical laboratory findings from pretreatment to the End-of-Treatment Visit, 
and on the observation or report of any AEs (including laboratory abnormalities 
reported as AEs) that occur from time of consent until 30 days after the last dose of 
study agent and those SAEs (including laboratory abnormalities reported as AEs) 
occurring after 30 days if considered related to daratumumab. The intensity (severity) 
of AEs will be assessed using the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE), Version 4.0.  
  
 8.1  
Overview  
  
As the sponsor of the Study, the University of Texas MD Anderson Cancer 
Center (UTMDACC) and the Principal Investigator shall be solely responsible 
for complying, within the required timelines, any safety reporting obligation to 
competent Health Authorities, IRB/ECs and any participating (co or sub) 
investigators, as defined in applicable laws and regulations. For the purposes 
of this section, safety data includes adverse events, product quality complaints 
(PQCs), and special situations including pregnancies.  
  
UTMDACC and the Principal Investigator will provide safety information to 
J&J on adverse events, special situations including pregnancies and product 
quality complaints as defined within this section.  
  
 8.2  
Management of Safety Data  
  
This Study has been designated as an interventional study. As such, all 
adverse events for J&J Medicinal Products regardless of causality and 
special situations excluding those from subjects not exposed to a Janssen 
Medicinal Product and product quality complaints with or without an 
adverse event as described in this Exhibit will be reported from the time a 

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subject has signed and dated an Informed Consent Form (ICF) until 30 
days after the last documented dose of study drug within the study.  
  
For the purposes of this study, the J&J medicinal product is: 
DARZALEX™ (daratumumab) and 
DARZALEX Faspro™ (daratumumab and hyaluronidase-fihj).  
  
 
 
 
 8.3  
Definitions:  
  
8.3.1  Adverse Event (AE)  
  
An adverse event is any untoward medical occurrence in a clinical 
study subject administered a medicinal (investigational or non-
investigational) product. An adverse event does not necessarily have a 
causal relationship with the treatment. An adverse event can therefore 
be any unfavorable and unintended sign (including an abnormal 
finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational or non- investigational) product, whether or 
not related to that medicinal (investigational or non-investigational) 
product. (Definition per International Conference on Harmonisation 
[ICH]). This includes any occurrence that is new in onset or aggravated 
in severity or frequency from the baseline condition, or abnormal 
results of diagnostic procedures, including laboratory test 
abnormalities.  
  
8.3.2  Adverse Events of Special Interest  
  
Adverse events of special interest are events that J&J is actively 
monitoring as a result of a previously identified signal (even if non- 
serious).   
  
 
·     These adverse events are: Infusion reactions: ≥ grade 3  
 
·  
Infections: ≥ grade 4  
 
·  
Cytopenias: ≥ grade 4  
 
·  
HBV Reactivation  
 
·  
Other malignancies  
  
Any Adverse Event of Special Interest that is to be reported to J&J 
should be recorded on a Serious Adverse Event Report Form and be 
reported to J&J within 24 hours of knowledge of the event.  
  

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8.3.3  Individual Case Safety Report (ICSR)  
  
A valid ICSR must contain the four minimum criteria required to meet 
regulatory reporting requirements.  
  
·  an identifiable subject (but not disclosing personal information such 
as the subject’s name, initials or address)  
 
·  an identifiable reporter (investigational site)  
 
·  a J&J medicinal product  
 
·  an adverse event, outcome, or certain special situations  
The minimum information required is:  
 
·  suspected J&J medicinal product (doses, indication)  
 
·  date of therapy (start and end date, if available)  
 
·  batch or lot number, if available  
 
·  subject details (subject ID and country)  
 
·  gender  
 
·  age at AE onset  
 
·  reporter ID  
·  adverse event detail (AE verbatim in English), onset date, 
relatedness, causality, action taken, outcome, (if available) 
· 
J&J protocol ID 
 
  
8.3.4  Product Quality Complaint (PQC)  
  
A product quality compliant is defined as any suspicion of a product 
defect related to a potential quality issue during manufacturing, 
packaging, release testing, stability monitoring, dose preparation, 
storage or distribution of the product, or delivery system. Not all PQCs 
involve a subject. Lot and batch numbers are of high significance and 
need to be collected whenever available.  
  
Examples of PQC include but not limited to:  
  
·  Functional Problem: e.g., altered delivery rate in a controlled 
release product  
·  Physical Defect: e.g., abnormal odor, broken or crushed 
tablets/capsules  
 
·  Potential Dosing Device Malfunction: e.g., autoinjector button not  
working, needle detaching from syringe  
 
·  Suspected Contamination  
 
·  Suspected Counterfeit  
 

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8.3.5  Serious Adverse Event (SAE)  
  
A serious adverse event based on ICH and EU Guidelines on 
Pharmacovigilance for Medicinal Products for Human Use is any 
untoward medical occurrence that at any dose:  
  
 
·  Results in death  
·  Is life-threatening (The subject was at risk of death at the time of the 
event. It does not refer to an event that hypothetically might have 
caused death if it were more severe.)  
·  Requires inpatient hospitalization or prolongation of existing 
hospitalization  
 
·  Results in persistent or significant disability/incapacity  
 
·  Is a congenital anomaly/birth defect  
·  Is a suspected transmission of any infectious agent via a medicinal 
product  
 
·  Is medically important*  
  
*Medical and scientific judgment should be exercised in deciding 
whether expedited reporting is also appropriate in other situations, 
such as important medical events that may not be immediately life 
threatening or result in death or hospitalization but may jeopardize the 
subject or may require intervention to prevent one of the other 
outcomes listed in the definition above. These should usually be 
considered serious.  
  
NOTE: DEATH FOR ANY REASON SHOULD BE REPORTED AS A 
SERIOUS ADVERSE EVENT.  
  
Hospitalization  
  
For reports of hospitalization, it is the sign, symptom or diagnosis which 
led to the hospitalization that is the serious event for which details must 
be provided.  
  
Any event requiring hospitalization or prolongation of hospitalization that 
occurs during the study must be reported as a serious adverse event, 
except hospitalizations for the following:  
·  Hospitalizations not intended to treat an acute illness or adverse 
event (e.g., social reasons such as pending placement in long-term 
care facility)  
 
·  Surgery or procedure planned before entry into the study. [Note:  
Hospitalizations that were planned before the start of data 
collection and where the underlying condition for which the 

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hospitalization was planned has not worsened will not be 
considered serious adverse events. Any adverse event that 
results in a prolongation of the originally planned hospitalization is to 
be reported as a new serious adverse event.]  
·  [For convenience the investigator may choose to hospitalize the 
subject for the duration of the treatment period.]  
  
 
 
 
Life-Threatening Conditions  
  
Disease progression should not be recorded as an adverse event or 
serious adverse event term; instead, signs and symptoms of clinical 
sequelae resulting from disease progression/lack of efficacy will be 
reported if they fulfill the serious adverse event definition.  
  
 8.4  
Unlisted (Unexpected) Adverse Event/Reference Safety Information  
  
An adverse event is considered unlisted if the nature or severity is not 
consistent with the applicable product reference safety information. For a 
medicinal product(s) with a marketing authorization, the expectedness of an 
adverse event will be determined by whether or not it is listed in the applicable 
product information.  
                 http://www.darzalex.com/shared/product/darzalex/darzalex-prescribing- 
information.pdf  
 
http://www.janssenlabels.com/package-insert/product-monograph/prescribinginformation/ 
DARZALEX+Faspro-pi.pd 
 
 For DARZALEX™ (daratumumab) and DARZALEX Faspro™, the expectedness of an 
adverse event will be determined by whether or not it is listed in the Investigator's 
Brochure.  
 
  
 8.5  
Special Reporting Situations  
  
Safety events of interest for a J&J medicinal product that require 
expediting reporting and/or safety evaluation include, but are not limited 
to:  
 
·  Drug exposure during pregnancy (maternal and paternal)  
 
·  Overdose of a J&J medicinal product  
 
·  Exposure to a J&J medicinal product from breastfeeding  
 
·  Suspected abuse/misuse of a J&J medicinal product  

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·  Inadvertent or accidental exposure to a J&J medicinal product  
·  Any failure of expected pharmacological action (i.e., lack of effect) of a 
J&J medicinal product  
·  Medication error involving a J&J medicinal product (with or without 
patient exposure to the J&J medicinal product, e.g., name confusion)  
·    Suspected transmission of any infectious agent via administration of a 
medicinal product  
·  Unexpected therapeutic or clinical benefit from use of a J&J medicinal 
product  
 
  
These safety events may not meet the definition of an adverse event; 
however, from a J&J perspective, they are treated in the same manner as 
adverse events. Special situations should be recorded on the Adverse Event 
page of the CRF.  
  
Any special situation that meets the criteria of a serious adverse event 
should be recorded on a Serious Adverse Event Report Form and be 
reported to J&J within 24 hours of becoming aware of the event.  
  
 
8.6  
Pregnancy  
  
All initial reports of pregnancy must be reported to J&J by the Principal 
Investigator within 24 hours of becoming aware of the event using the 
Serious Adverse Event Form. Abnormal pregnancy outcomes (e.g., 
spontaneous abortion, fetal death, stillbirth, congenital anomaly, ectopic 
pregnancy) are considered serious adverse events and must be reported 
using the Serious Adverse Event Form.  
  
Any subject who becomes pregnant during the study must be promptly 
withdrawn from the study and discontinue further study treatment.  
  
Because the effect of the J&J medicinal product on sperm is unknown, 
pregnancies in partners of male subjects exposed to a J&J medicinal 
product will be reported by the Principal Investigator within 24 hours of their 
knowledge of the event using the Serious Adverse Event Form. Depending 
on local legislation this may require prior consent of the partner.  
  
Follow-up information regarding the outcome of the pregnancy and any 
postnatal sequelae in the infant will be required.  
  
 
8.7  
Maintenance of Safety Information  
  

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All safety data should be maintained in a clinical database in a retrievable 
format. UTMDACC and the Principal Investigator shall provide all adverse 
events, both serious and non-serious, in report format. However, in certain 
circumstances more frequent provision of safety data may be necessary, 
e.g., to fulfill a regulatory request, and as such the data shall be made 
available within a reasonable timeframe at J&J request.  
  
8.8  
Procedures for Reporting Safety Data and Product Quality Complaints (PQCs) 
 
for J&J Medicinal Products to J&J  
  
All adverse events and special situations, whether serious or non-serious,  
related or not related, following exposure to a J&J medicinal product are to 
be documented by the investigator and recorded in the CRF and in the 
subject’s source records. Investigators must record in the CRF their opinion 
concerning the relationship of the adverse event to a J&J medicinal product.  
  
All (serious and non-serious) adverse events reported for a J&J medicinal 
product should be followed-up in accordance with clinical practice.  
  
8.8.1  SAEs, Adverse Events of Special Interest, and Special Reporting 
 
Situations  
  
All serious adverse events that have not resolved by the end of the 
study, or that have not resolved upon discontinuation of the subject's 
participation in the study, must be followed until any of the following 
occurs:  
  
 
·  The event resolves  
 
·  The event stabilizes  
 
·  The event returns to baseline, if a baseline value/status is available  
·  The event can be attributed to agents other than the study drug or to 
factors unrelated to study conduct  
·  It becomes unlikely that any additional information can be obtained 
(subject or health care practitioner refusal to provide additional 
information, lost to follow-up after demonstration of due diligence 
with follow-up efforts)  
  
UTMDACC and the Principal Investigator will transmit all SAEs, 
Adverse Events of Special Interest, and special situations following 
exposure to a J&J product under study in an SAE form provided by 
J&J in accordance within the section titled, Transmission Methods, in 
English within 24-hours of becoming aware of the event(s).  
  

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In the event the study is blinded, the Principal Investigator will submit an 
unblinded SAE or pregnancy exposure report to J&J.  
  
All follow-up information for serious adverse events that are not 
resolved at the end of the study or by the time of patient withdrawal 
must be reported directly by the Principal Investigator, within 24 hours 
becoming aware, to J&J using the J&J Serious Adverse Event Report  
  
All available clinical information relevant to the evaluation of a related 
SAE, Adverse Events of Special Interest, serious ADR or special 
situation is required.  
  
·  UTMDACC and the Principal Investigator is responsible for 
ensuring that these cases are complete and if not are promptly 
followed-up. A safety report is not considered complete until all 
clinical details needed to interpret the case are received. Reporting 
of follow-up information should follow the same timeline as initial 
reports. 
   
·  Copies of any and all relevant extraordinary (not including routine 
initial or follow-up ICSR submission) correspondences with 
regulatory authorities and ethics committees regarding any and all 
serious adverse events, irrespective of association with the J&J 
Product under study, are to be provided to J&J using a transmission 
method in Section 10 from this Exhibit within 24 hours of such report 
or correspondence being sent to applicable health authorities.  
  
 
8.8.2  Non-Serious AEs  
  
All non-serious adverse events should be reported to J&J according to 
the timeframe outlined in the Research Funding Agreement section 
entitled Reporting of Data.  
 
 8.8.3  PQC Reporting  
  
A PQC may have an impact on the safety and efficacy of the product. 
Timely, accurate, and complete reporting and analysis of PQC 
information from studies are crucial for the protection of patients, 
investigators, and J&J, and are mandated by regulatory agencies 
worldwide. J&J has established procedures in conformity with 
regulatory requirements worldwide to ensure appropriate reporting of 
PQC information. Lot and/or Batch #s shall be collected for any 
reports of failure of expected pharmacological action (i.e., lack of 

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effect). The product should be quarantined immediately and if 
possible, take a picture.  
  
All initial PQCs involving a J&J medicinal product under study must 
be reported to J&J by the Principal Investigator within 24 hours after 
being made aware of the event. The Janssen contact will provide 
additional information/form to be completed.  
  
If the defect for a Janssen medicinal product under study is combined 
with either a serious adverse event or non-serious adverse event, the 
Principal Investigator must report the PQC to J&J according to the 
serious adverse event reporting timelines. A sample of the suspected 
product should be maintained for further investigation if requested by 
J&J.  
   
8.9  Reporting Procedures for Reporting Safety Data and Product Quality Complaints 
 
(PQCs) for Non-Janssen Medicinal Products  
  
For SAEs, special reporting situations and PQCs following exposure to a non-
J&J medicinal product under study, the Principal Investigator should notify the 
appropriate regulatory/competent authority or the manufacturer of that medicinal 
product (in the absence of appropriate local legislation) as soon as possible.  
  
8.10    Transmission Methods  
  
The following methods are acceptable for transmission of safety information 
to J&J:  
  
·  Electronically via J&J SECURE Email service (preferred) IIS-BIO-VIRO-
GCO@its.jnj.com 
 
·  For business continuity purposes, if SECURE Email is non-functional:  
o Facsimile (fax), receipt of which is evidenced in a successful fax 
transmission report 1-866-451-0371  
o Telephone (if fax is non-functional).  
  
Please use the contact information and process information provided by J&J.   
 
9.0. Data Management and Confidentiality 
 
     9.1  Data Collection and Management Responsibilities 
 
Data Capture: Data will be entered in the MD Anderson institutionally approved 
database (s) Electronic Data Capture Tool, a CFR 21 Part 11 compliant system. All 
eligibility criteria must be documented prior to treatment initiation. 

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All data collected will be used only for research purposes by MDA and J&J. Identifiers 
(name, medical record number, date of birth, treatment diagnosis, imaging tests, 
follow-up and death) may be collected but will be replaced by study numbers in the 
analytic files. Patient identifiers will be confidentially collected and securely 
maintained on a password protected server located behind the institutional firewall. 
Access to identifiers will follow IRB and MDA information security rules and 
regulations. The master database file will be accessible only to the Principal 
Investigator, Financial Supporters, approved collaborators, and research staff 
designated on the delegation of authority log. 
 
Accuracy of Data Collection: The MD Anderson Principal Investigator will be the final 
arbiter of response and toxicity, should a difference of opinion exist. 
 
9.2 Confidentiality 
 
All data and records generated during this study will be kept confidential in 
accordance with Institutional policies and HIPAA on subject privacy and that the 
Investigator and other site personnel will not use such data and records for any 
purpose other than conducting the study. J&J may receive PHI although such access 
to PHI is limited to the terms of the agreement defined in the contract. The contract 
allows for J&J to use the data for research purposes, not limited to this study only. 
 
 

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10.0   References  
1. 
P. Singh, S.K. Kumar, B.R. LaPlant, et al. Lenalidomide maintenance therapy in 
multiple myeloma: a meta-analysis of randomized trials Blood, 122 (2013), p. 407  
2. 
M. Attal, V. Lauwers-Cances, G. Marit, et al. Lenalidomide maintenance after 
stem-cell transplantation for multiple myeloma. N Engl J Med, 366 (2012), pp. 
1782–1791  
3. 
P.L. McCarthy, K. Owzar, C.C. Hofmeister, et al. Lenalidomide after stem-cell 
transplantation for multiple myeloma. N Engl J Med, 366 (2012), pp. 1770–1781  
4. 
A. Palumbo, F. Cavallo, F. Gay, et al. Autologous transplantation and 
maintenance therapy in multiple myeloma. N Engl J Med, 371 (2014), pp. 895– 
905  
5. 
F. Gay, S. Oliva, M.T. Petrucci, et al. Chemotherapy plus lenalidomide versus 
autologous transplantation, followed by lenalidomide plus prednisone versus 
lenalidomide maintenance, in patients with multiple myeloma: a randomised, 
multicentre, phase III trial. Lancet Oncol, 16 (2015), pp. 1617–1629  
6. 
M. Roussel, V. Lauwers-Cances, N. Robillard, et al. Front-line transplantation 
program with lenalidomide, bortezomib, and dexamethasone combination as 
induction and consolidation followed by lenalidomide maintenance in patients with 
multiple myeloma: a phase II study by the Intergroupe Francophone du Myelome 
J Clin Oncol, 32 (2014), pp. 2712–2717  
7. 
M. Attal, V. Lauwers-Cances, C. Hulin, et al. Autologous transplantation for 
multiple myeloma in the era of new drugs: a phase III study of the Intergroupe 
Francophone Du Myelome (IFM/DFCI 2009 Trial) Blood, 126 (2015), p. 391  
8. 
Shah N, Ahmed F, Bashir Q, et al. Durable remission with salvage second auto- 
transplants in patients with multiple myeloma. Cancer. 2012;118:3549–3555.  
9. 
Jimenez-Zepeda VH, Mikhael J, Winter A, et al. Second autologous stem cell 
transplantation as salvage therapy for multiple myeloma: impact on progression- 
free and overall survival. Biol Blood Marrow Transplant. 2012;18:773–779.  
10. Olin RL, Vogl DT, Porter DL, et al. Second auto-SC is safe and effective salvage 
therapy for relapsed multiple myeloma. Bone Marrow Transplant. 2009;43:417– 
422.  
11. Fenk R, Liese V, Neubauer F, et al. Predictive factors for successful salvage 
high- dose therapy in patients with multiple myeloma relapsing after autologous 
blood stem cell transplantation. Leuk Lymphoma. 2011;52:1455–1462.  
12. Alvares CL, Davies FE, Horton C, et al. The role of second autografts in the 
management of myeloma at first relapse. Haematologica. 2006;91:141–142.  
13. Silva Rondon C, Hassoun H, Chimento D, et al. Outcomes following salvage 
autologous stem cell transplant for multiple myeloma. Biol Blood Marrow 
Transplant. 2012;18:S254.  
14. Gonzalvez WI, Gertz MA, Lacy MQ, et al. Second auto stem cell transplant for 
treatment of relapsed multiple myeloma. Bone Marrow Transplant. 2012;10:1–6.  
15. Michaelis LC, Saad A, Zhong X, et al. Savage second hematopoietic cell 
transplantation in myeloma. Biol Blood Marrow Transplant. 2013;19:760–766.  

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16. Sellner L, Heiss C, Benner A, et al. Autologous retransplantation for patients with 
recurrent multiple myeloma. A single-center experience with 200 patients. 
Cancer. 2013;119:2438–2446.  
17. Grövdal M, Nahi H, Gahrton G, et al. Autologous stem cell transplantation versus 
novel drugs or conventional chemotherapy for patients with relapsed multiple 
myeloma after previous ASCT. Bone Marrow Transplant. 2015;50:808–812.  
18. Shah N, Thall P, Milton D, et al. Phase I/II Trial of Lenadliomide and High-Dose 
Melphalan with Autologous Stem Cell Transplantation for Relapsed Myeloma: 
Updated Results. Blood 2016, 128:2269.  
19. Mateos MV, Nahi H, Legiec W, et al: Subcutaneous versus intravenous 
daratumumab in patients with relapsed or refractory multiple myeloma 
(COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. 
Lancet Haematol 7:e370-e380, 2020 
20. Chari A, Suvannasankha A, Fay JW, et al: Daratumumab plus pomalidomide and 
dexamethasone in relapsed and/or refractory multiple myeloma. Blood 130:974-
981, 2017 
21. Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab 
monotherapy in multiple myeloma. N Engl J Med. 2015; 373: 1207–1219.  
22. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients 
with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomized, 
phase 2 trial. Lancet. 2016:1551-60.  
23. Usmani SZ, Weiss BM, Plesner T, et al. Clinical efficacy of daratumumab 
monotherapy in patients with heavily pretreated relapsed or refractory multiple 
myeloma. Blood. 2016: 37-44.  
24. Plesner T, Arkenau H, Gimsing P, et al. Phase I/II study of daratumumab, 
lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood 2016.  
25. Mantel N, Haenszel MW. Statistical aspects of thee analysis of data from 
retrospective studies of disease. J Nat Cancer Inst 2959; 22:719-48.  
26. Fitzmaurice GM, Laird NM, Ware JH. Applied Longitudinal Analysis, 2nd Edition. 
New Jersey: John Wiley and Sons; 2011.  
27. Qiu F, Stein CM, Elston RC; Tuberculosis Research Unit (TBRU). Joint Modeling 
of Longitudinal Data and Discrete-Time Survival Outcome. Stat Methods Med 
Res. 2016 Aug; 25(4):1512-26.  
28. www.clinicaltrials.gov 
29. Zhou Y., Yuan,Y., Lee J.J., Pan,H. (2019). Sample Size Calculation - Time-to-
event Endpoint (V.2.1.0) [Computer software]. Retrieved from 
www.trialdesign.org. 
30. Thall PF, Simon RM, and Estey EH. Bayesian sequential monitoring designs for 
single-arm clinical trials with multiple outcomes. Stat med 1995 Feb 28;14(4):357-
79. 
  
 
 

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Appendix A.  Treatment and Event Schedule  
  
   
 
Study Visits  
Assessments  
Screening 
Phase  
Treatment Phase (28-day cycles)  
Follow-up Phase  
Cycles 1 & 2  
Cycles 3-6  
Cycles 
7+  
EOTa  
FUPb  
Survivalb, i  
Study Day:  
-28 to -1  
1 
(+/- 3 
days)  
8  
(+/- 3 
days) 
15 
(+/- 3 
days)  
22  
(+/- 3 
days) 
1  
(+/- 3 days) 
15 
(+/- 3 
days)  
1 
(+/- 7 days)  
Post-  
Treatment 7 
days  
(+/- 7 days) 
Post-  
Treatment  
90 (+3) 
days  
q12wks  
(+/- 7 days) 
Informed consent  
 
Subjects must sign the informed consent form before any study-specific procedures are performed  
Eligibility criteria  
X  
   
   
   
   
   
   
   
   
   
   
Forced expiratory volume 
test (subjects with COPD or 
asthma)  
X  
   
   
   
   
   
   
   
   
   
   
Demography/medical history  
X  
   
   
   
   
   
   
   
   
   
   
Physical examination  
X  
Xo  
  
  
  
Xo  
  
Xo 
Xo 
  
  
Weight  
   
X  
   
   
   
X  
   
X  
   
   
   
ECOG performance status  
X  
X  
   
   
   
X  
   
X  
X  
  
   
Blood pressurec and 
temperature  
X  
X  
X  
X  
X  
X  
X  
X  
X  
  
   
Electrocardiogram and 
echocardiogram (The 
echocardiogram performed 
before stem cell transplant 
will be used until the PI 
considers a repeat echo 
before maintenance for 
medical reasons)  
X  
   
   
  
   
   
Adverse event monitoring  
 
Continuous from time of ICF until 30 days after last study treatment   
Treatment-related SAEs  
 

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Study Visits 
Assessments 
Screening 
Phase 
Treatment Phase (28-day cycles) 
Follow-up Phase 
Cycles 1 & 2 
Cycles 3-6 
Cycles 7+ 
EOTa 
FUPb 
Survivalb,i 
Study Day: 
-28 to -1 
1 
(+/- 3 
days) 
8 
(+/- 3 
days) 
15 
(+/- 3 
days) 
22 
(+/- 3 
days) 
1 
(+/- 3 days) 
15 
(+/- 3 
days) 
1 
(+/- 7 days) 
Post- 
Treatment 
7 days 
(+/- 7 days) 
Post- 
Treatment 
90 (+3) days 
q12wks 
(+/- 7 days) 
Dosing 
-28 to -1 
  
  
  
  
  
  
  
  
  
  
  
Pre- and post-infusion 
medicationsd 
 
X 
X 
X 
X 
X 
X 
X 
 
  
  
  
Daratumumab/hyaluronidase-
fihi dosing (SQ)  
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
Pomalidomide 2 mg (PO) 
 
Days 1 – 21 of each 28-day cycle 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessmentse  
-28 to -1 
Cycles 1 & 2 
Cycles 3-6 
Cycles 7+ 
EOTa 
FUPb 
Survivalb,i 
Blood type assessment and 
indirect antiglobulin resultsm 
 x 
 
  
 
  
  
  
  
  
Serum pregnancy test (women 
of childbearing potential only): 
(minimum requirement) 
Xf  
See footnote f 
 
  
  
Biochemistryg 
X 
X 
  
  
  
X 
 
 X 
X 
 X 
  
Hematologyg 
X 
X 
 
 
 
X 
 
 X 
X 
 X 
  
HBV Serologyp 
X 
 
 
 
 
 
 
 
 
 
 
HBV DNA Testsp 
X 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Visits 
Assessments 
Screening 
Phase 
Treatment Phase (28-day cycles) 
Follow-up Phase 
Cycles 1 & 2 
Cycles 3-6 
Cycles 7+ 
EOTa 
FUPb 
Survivalb,i 
Study Day: 
-28 to -1 
1 
(+/- 3 
days) 
8 
(+/- 3 
days) 
15 
(+/- 3 
days) 
22 
(+/- 3 
days) 
1 
(+/- 3 days) 
15 
(+/- 3 days) 
1 
(+/- 7 days) 
Post- 
Treatment 
7 days 
(+/- 7 days) 
Post- 
Treatment 
90 (+3) days 
q12wks 
(+/- 7 days) 
 
 
 
 
Disease Evaluations 
(Blood/Urine)e 
-14 to -1 
Cycles 1 & 2 
Cycles 3-6 
Cycles 7+ 
EOTa 
FUPb 
Survivalb,i 
Serum beta 2-microglobulin 
X 
  
  
  
  
  
  
QIg (IgA, IgM, IgG, IgD, IgE)n 
X 
 
Every 2-3 cycles during treatment (+/-7 days) 
  
  
  
SPEP 
X 
X 
Xb 
  
UPEP (24-hr urine sample) 
X 
X 
Xb 
  
Serum calcium corrected for 
albumin 
X 
X 
Xb 
  
Serum FLC & serum/urine 
immunofixation 
X 
X 
X 
 
Disease Evaluations (Other) 
-42 to -1 
  
  
Bone marrow aspirate/biopsy 
and assessment of MRD 
X 
 
To confirm CR (including sCR) j 
Bone marrow biopsy examination with NGF-based MRD testing at 6 months from the start of maintenance (+/- 2 
weeks) then as clinically indicated  
  
Skeletal survey 
As clinically 
indicated 
As clinically indicated   
  

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Study Visits 
Assessments 
Screening 
Phase 
Treatment Phase (28-day cycles) 
Follow-up Phase 
Cycles 1 & 2 
Cycles 3-6 
Cycles 7+ 
EOTa 
FUPb 
Survivalb,i 
Study Day: 
-28 to -1 
1 
(+/- 3 
days) 
8 
(+/- 3 days) 
15 
(+/- 3 
days) 
22 
(+/- 3 
days) 
1 
(+/- 3 days) 
15 
(+/- 3 days) 
1 
(+/- 7 days) 
Post- 
Treatment 
7 days 
(+/- 7 days) 
Post- Treatment 90 
(+3) days 
q12wks 
(+/- 7 
days) 
Assess extramedullary 
plasmacytomas 
Xk 
Measurable sites every 4 weeks (if applicable) (for physical examination) 
and   every 12 weeks  (for radiologic examination) for subjects with a history of plasmacytomas or 
as clinically indicated for others 
Xl 
  
Abbreviations: COPD=chronic obstructive pulmonary disease; CR=complete response; CT=computed tomography; ECOG=Eastern Cooperative Oncology Group; EORTC=European 
Organization for Research and Treatment of Cancer; EOT=End-of-Treatment; FFPE= formalin-fixed paraffin embedded; FLC=free light chain; FUP=Follow-up Phase; ICF=informed 
consent form; IV=intravenous; QIg=quantitative immunoglobulins; MRD=minimal residual disease; MRI=magnetic resonance imaging; PBMCs=peripheral blood mononuclear cells; 
PK=pharmacokinetics; PD=progressive disease; PFS=progression-free survival; SAE=serious adverse event; sCR=stringent CR; SPEP=Serum M- protein quantitation by electrophoresis; 
UPEP=urine M-protein quantitation by electrophoresis 
Note: Study drug is defined as daratumumab and pomalidomide. 
a)   To occur within 7 days after discontinuation of all study treatment. 
b)   In the 90 (+3) days after the last dose of daratumumab for safety follow-up visits. For subjects who discontinue study treatment before PD, disease evaluations should continue to 
be performed at the frequency specified below until confirmed PD, death, start of a new anticancer treatment, withdrawal of consent to study participation, or end of the study, 
whichever occurs first. Once PD is confirmed, subsequent disease evaluation time points are not required. 
-     Every 8-12 weeks (±3 days), at clinician’s discretion:  SPEP and 24-hour UPEP assessments, and serum calcium corrected for albumin 
-     Every 4 weeks (±3 days), or at clinician’s discretion:  physical examination of extramedullary plasmacytomas if applicable 
-     Every 12 weeks (±14 days), or at clinician’s discretion:   radiologic imaging of extramedullary plasmacytomas if applicable  
-     When CR is suspected or maintained: serum FLC, serum and urine immunofixation 
-     As clinically indicated: skeletal survey 

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-     Evidence of clinical relapse will also be documented at the time at which it is first detected. 
After PD is determined, patient will be taken off study and no further study evaluations will be needed. 
c)   Blood pressure is to be measured at the following time points on Cycle 1 Days 1: immediately pre-administration, at the end of administration, 30 minutes post administration, 60 
minutes post administration, and then hourly until 6 hours post administration. On Cycle 1 Day 8: immediately pre-administration, at the end of administration, 30 minutes post 
administration, 60 minutes post administration, and 120 minutes post administration. On Cycle 1 Day 15 onward: immediately pre-administration, at the end of administration, 15 
minutes post administration.  Infusion observation times and vital signs may be adjusted per PI discretion. 
d)   Pre-infusion medications to be given before all daratumumab infusions (if necessary, oral pre-infusion medications may be administered at the subject’s home on the day of the 
infusion, provided they are given within 3 hours prior to the infusion) 
e)   Unless otherwise stated, all blood and urine samples must be obtained before administration of study treatment. 
f)    During Screening, to be performed within 10-14 days prior to dosing and then again within 24 hours prior to dosing.  During the Treatment Phase, to be performed weekly during 
Cycle 1 and then monthly in subsequent cycles in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles. 
g)    Results of these laboratory tests must be evaluated before each study treatment administration. At Cycle 1 Day 1, these tests do not need to be repeated if they have been 
performed within 7 days. 
h)   Samples must be sent to the clinical laboratory at MDACC.  
i)   Following the primary PFS analysis, efficacy assessments will be performed according to the standard of care for subjects without disease progression.  
j)         Bone marrow biopsy examination with NGF-based MRD testing at 6 months (+/- 2 weeks) from the start of maintenance then yearly as clinically indicated.       
k)   Should be assessed for all subjects with a history of plasmacytomas or if clinically indicated at Screening, by clinical examination or radiologic imaging. 
l)   At 6 months after the subject’s first dose, the timing of radiologic assessment of extramedullary plasmacytomas should follow the standard of care. 
m)    It is recommended that in addition to ABO and Rh blood typing, indirect antiglobulin test (also  known  as  indirect  Coombs  test)  be performed and that the subject carries a card 
with the blood antigen profile at all times during the study. 
 
n)   Testing for IgD and IgE will only be performed for subjects with IgD and IgE-type myeloma. 
o)  Patients will be evaluated either in person or remotely via telemedicine or telephone. If patient is seen remotely via telemedicine or telephone physical exam, vital signs, and 
weight are not required.. 
p)   Hepatitis Tests: 
- 
HBV Serology:  All subjects will be tested locally for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (Anti-HBs), and hepatitis B core antibody (Anti-HBc) at 
Screening.  
-        HBV DNA Tests: Subjects who are positive for Anti-HBc or Anti-HBs will undergo testing for hepatitis B DNA by PCR. Subjects with serologic findings suggestive of HBV vaccination 
(Anti-HBs positivity as the only serologic marker) and a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR. During and following study 

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treatment, subjects who have history of HBV infection will be closely monitored for clinical and laboratory signs of reactivation of HBV.  Where required by local law, the results of 
HBV testing may be reported to the local health authorities.