Clinical trial NCT05288062
Conditions: Plasma Cell Myeloma Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma Smoldering Plasma Cell Myeloma
Sponsor: Mayo Clinic
Start date: 2022-06-15; Completion date: 2024-07-25
Enrollment: 17 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase II trial studies the effect of immunomodulatory drug(s) in combination with a corticosteroid drug in treating patients with multiple myeloma or smoldering multiple myeloma. Immunomodulatory drugs such as lenalidomide and pomalidomide work through a variety of mechanisms to affect the function of the immune system. They are widely used as treatment for multiple myeloma and remain the backbone of therapy for both newly diagnosed patients and patients that have multiple myeloma that has come back after treatment (relapsed). Corticosteroid drugs like dexamethasone are strong anti-inflammatory agents that are also widely used to treat patients with multiple myeloma. This study may help doctors find out how patients respond to one treatment cycle of immunomodulatory drug(s) in combination with dexamethasone. This may help doctors determine which combinations of drugs work best in treating patients with multiple myeloma or smoldering multiple myeloma.

Detailed description:
PRIMARY OBJECTIVE:

I. To determine response rates (\>= partial response \[PR\]) of prospectively treated multiple myeloma (MM) patients with one cycle of therapy containing a combination of an immunomodulator and dexamethasone.

SECONDARY OBJECTIVE:

I. To identify biomarkers that predict response rates of untreated smoldering MM and MM patients to a combination of an immunomodulator and dexamethasone.

II. To compare response rates of MM among African-Americans (AA) and white patients to a combination of an immunomodulator and dexamethasone.

III. To establish correlation of biomarkers in treated MM patients with the combination of an immunomodulator and dexamethasone to the depth of hematological response observed in new or previously treated patients

OUTLINE: Patients are assigned to 1 of 4 cohorts.

COHORT A: Patients with smoldering multiple myeloma receive lenalidomide orally (PO) once daily (QD) alone on days 1-14 OR in combination with dexamethasone PO QD on days 1, 8 and 15. Treatment for cycle 1 continues for 21 days in the absence of disease progression or unacceptable toxicity. Patients then receive lenalidomide PO QD on days 1-21 alone or in combination with dexamethasone PO QD on days 1, 8, 15, and 22, or in combination with another drug. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.

COHORT B: Patients with newly diagnosed multiple myeloma receive treatment as in Cohort A.

COHORT C: Patients with relapsed or refractory multiple myeloma receive lenalidomide PO QD on days 1-14 in combination with dexamethasone PO QD on days 1, 8 and 15 OR pomalidomide PO QD on days 1-21 in combination with dexamethasone PO QD on days 1, 8 and 15. Treatment for cycle 1 continues for 21 days in the absence of disease progression or unacceptable toxicity. Patients then receive lenalidomide PO QD on days 1-21 in combination with dexamethasone PO QD on days 1, 8, 15, and 22 OR pomalidomide PO QD on days 1-21 in combination with dexamethasone PO QD on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.

COHORT D: Patients with relapsed multiple myeloma after lenalidomide maintenance receive treatment as in Cohort C.

After completion of study treatment, patients are followed up within 7 days.

Arms: arm 1: Patients with smoldering multiple myeloma receive lenalidomide PO QD alone on days 1-14 OR in combination with dexamethasone PO QD on days 1, 8 and 15. Treatment for cycle 1 continues for 21 days in the absence of disease progression or unacceptable toxicity. Patients then receive lenalidomide PO QD on days 1-21 alone or in combination with dexamethasone PO QD on days 1, 8, 15, and 22, or in combination with another drug. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. arm 2: Patients with newly diagnosed multiple myeloma receive treatment as in Cohort A. arm 3: Patients with relapsed or refractory multiple myeloma receive lenalidomide PO QD on days 1-14 in combination with dexamethasone PO QD on days 1, 8 and 15 OR pomalidomide PO QD on days 1-21 in combination with dexamethasone PO QD on days 1, 8 and 15. Treatment for cycle 1 continues for 21 days in the absence of disease progression or unacceptable toxicity. Patients then receive lenalidomide PO QD on days 1-21 in combination with dexamethasone PO QD on days 1, 8, 15, and 22 OR pomalidomide PO QD on days 1-21 in combination with dexamethasone PO QD on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. arm 4: Patients with relapsed multiple myeloma after lenalidomide maintenance receive treatment as in Cohort C.
Interventions: intervention 1: Bone Marrow Biopsy intervention 2: Dexamethasone intervention 3: Lenalidomide intervention 4: Pomalidomide
Intervention descriptions: intervention 1: Undergo bone marrow aspirate/biopsy intervention 2: Given orally intervention 3: Given orally intervention 4: Given orally

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
MC210809 / 21-006597 
 
 
Evaluating Mechanisms of Immunomodulator Sensitivity and 
Resistance in Multiple Myeloma 
 
 
NCT05288062 
 
 
Document Date: 07/18/2023 


MC210809 
Protocol Version Date:13Jun2023 
 
 
                                                               Mayo Clinic Cancer Center 
 
Evaluating Mechanisms of Immunomodulator Sensitivity and Resistance in Multiple Myeloma 
 
Sponsor/Principal Investigators: Wilson I. Gonsalves MD 
Mayo Clinic 
200 First Street SW 
Rochester, MN 55905 
 
                                                      Sikander Ailawadhi MD 
Mayo Clinic 
San Pablo Road South 
Jacksonville, FL 32224 
 
                                                      Rafael Fonseca MD 
Mayo Clinic 
13400 E Shea Boulevard 
Scottsdale, AZ 85259 
 
    Statistician: Gabriela Perez MS 
 
    FDA IND Exempt#:  159997 
 
 
 
Trial Supported by:  
Funding: Mayo Clinic Department of Development (Private Benefactor) 
Drug Availability:  
Commercial Agents: Lenalidomide, Pomalidomide, and Dexamethasone  
 
Study contributor(s) not responsible for patient care 
 
Document History 
(Effective Date) 
 
 
Activation 
March 22, 2022 
Amendment 1 
 November 16, 2022 
Amendment 2 
July 18, 2023 
 
 
 


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Protocol Version Date:13Jun2023 
 
 
Protocol Resources 
 
Questions: 
Contact Name: 
Patient eligibility*, test schedule, 
treatment delays/interruptions/adjustments, 
dose modifications, adverse events, 
forms completion and submission 
Patricia Koenig, Data Manager  
Phone: 507/284-4642 
E-mail: Koenig.patricia@mayo.edu  
Forms completion and submission  
 
Mary Jacobson, CRC (RST) 
Phone: 507/538-6315 
Email: Jacobson.mary@mayo.edu 
 
Stephanie Rizzo, CRC (FL) 
Phone: 904/953-5020 
Email: Rizzo.stephanie@mayo.edu  
 
Cassandra Rivera, CRC (AZ)   
480/574-2412 
Email:  Rivera.Cassandra@mayo.edu     
Protocol document, consent form, 
regulatory issues 
Tracee Shevlin, Research Protocol Specialist  
Phone: 507/293-3276 
Email: Shevlin.tracee@mayo.edu  
Non-paraffin biospecimens  
Stacey Lehman, Laboratory Contact for Correlative Studies  
Phone: 507/284-3805 
Email: Lehman.stacey@mayo.edu 
Serious Adverse Event Reporting 
Patricia G McNamara, SAE Coordinator 
Phone: 507/266-3028 
E-mail: RSTP2CSAES@mayo.edu  
*No waivers of eligibility allowed 
 
 


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Protocol Version Date:13Jun2023 
 
 
Table of Contents 
Protocol Resources ........................................................................................................................................ 2 
Table of Contents .......................................................................................................................................... 3 
Schema .......................................................................................................................................................... 4 
1.0 
Background ................................................................................................................................... 6 
2.0 
Goals ............................................................................................................................................. 8 
3.0 
Registration Patient Eligibility ...................................................................................................... 8 
4.0  
Test Schedule .............................................................................................................................. 10 
5.0 
Grouping Factor .......................................................................................................................... 12 
6.0 
Registration Procedures .............................................................................................................. 12 
7.0 
Protocol Treatment ...................................................................................................................... 14 
8.0 
Dosage Modification Based on Adverse Events ......................................................................... 16 
9.0  
Ancillary Treatment/Supportive Care ......................................................................................... 23 
10.0 
Adverse Event (AE) Monitoring and Reporting ......................................................................... 23 
11.0 
Treatment Evaluation/Measurement of Effect ............................................................................ 33 
12.0 
Descriptive Factors ..................................................................................................................... 40 
13.0 
Treatment/Follow–up Decision at Evaluation of Patient ............................................................ 40 
14.0 
Body Fluid Biospecimens ........................................................................................................... 42 
15.0 
Drug Information ........................................................................................................................ 45 
16.0 
Statistical Considerations and Methodology ............................................................................... 54 
17.0  
Pathology Considerations/Tissue Biospecimens   NA ................................................................ 58 
18.0 
Records and Data Collection Procedures .................................................................................... 58 
19.0  
Budget ......................................................................................................................................... 59 
20.0 
References ................................................................................................................................... 60 
Appendix I  ECOG Performance Status .................................................................................................. 62 
 
 


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Schema 
 
 
Registration 
Cohort B 
Newly Diagnosed MM 
Cohort C 
Relapsed/Refractory MM 
Simultaneous Enrollment in IRB#14-009163 or IRB#521-93 
1# Peripheral Blood and 
Marrow Sample* 
Cycle 1† 
Lenalidomide** 
OR 
Lenalidomide + Dexamethasone** 
Cycle 1† 
Lenalidomide + Dexamethasone** 
OR 
Pomalidomide + Dexamethasone** 
#2 Peripheral Blood and 
Marrow Sample* 
Cycle 2-6† 
Len-Based Regimen** 
Cycle 2-6† 
Len or Pom-based Regimen** 
Optional Peripheral 
Blood and Bone 
Marrow Sample* 
Off Study*** 
*Sample collection under IRB#14-009163, IRB#919-04, or IRB#521-93 
**Dosing and regimen as per section 7 
***Patients who discontinue treatment before completing 6 cycles for any reason will 
go off study (No SFU/CFU).  
†Cycle 1 = 21. Cycles 2 – 6 = 28 days 
Cohort A 
Smoldering MM 
Cohort D  
Relapsed on Len maint 
Events at any time: 
• 
Disease progression1 or Relapse  
• 
Patient refusal 
• 
Intolerable adverse effects 
• 
Subsequent treatment for myeloma 


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Generic name: Lenalidomide 
Brand name(s): Revlimid 
Mayo Abbreviation:  
Availability: Commercial   
Generic name: Pomalidomide 
Brand name(s): Pomalyst 
Mayo Abbreviation:    
Availability: Commercial   
Generic name: Dexamethasone  
Brand name(s):  
Mayo Abbreviation:  
Availability: Commercial   


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1.0 
Background  
Multiple myeloma (MM) is a clonal plasma cell malignancy that tends to affect the older patient 
with a median age at onset of 65-70 years and a slight male predominance. The American Cancer 
Society estimates that about 30,330 new cases of MM will be diagnosed in 2016, and about 
12,650 patients will die of the disease.(1) Patients with MM can experience bone pain, bone 
fractures, fatigue, anemia, infections, hypercalcemia and kidney problems.(2)  Treatment options 
are based on the patient’s disease status.  Standard treatments for MM include combination 
chemotherapy regimens containing proteasome inhibitors (PIs) such as bortezomib and 
carfilzomib, and/or immunomodulatory drugs (IMiDs), such as lenalidomide and pomalidomide, 
in combination with corticosteroids.(3) Alkylating agents such as melphalan and 
cyclophosphamide are also active in MM.(3) Patients under the age of 75, who are free from 
significant comorbidities, are often treated with myeloablative chemotherapy and/or radiation, 
followed by autologous stem cell transplantation (ASCT).(3) These treatments have improved 
outcomes of patients with MM in recent years, both in the relapsed setting as well as at 
diagnosis.(4)  
 
However, despite considerable improvements in therapy, MM relapses remain inevitable and 
mostly incurable making it uniformly fatal with a median overall survival of around 8 years.(5)  
This is because MM cells actively evolve to develop resistance mechanisms against the cytotoxic 
effects of therapies that they are exposed to eventually leading to the exhaustion of all therapeutic 
options. In general, MM patients will receive an average of 4 to 8 different regimens during their 
lifespan utilizing agents such as proteasome inhibitors (e.g., bortezomib, ixazomib and 
carfilzomib), anti-CD38 monoclonal antibodies (e.g., daratumumab and isatuximab), immune 
modulatory agents (e.g., lenalidomide and pomalidomide), etc.(5)  Currently, these 
aforementioned  highly effective drug combinations used are beset with a various degrees of 
toxicity that precludes long-term therapy and also can affect the quality of life metrics. 
Furthermore, we are currently unable to reliably predict in advance whether a particular therapy 
would be effective or not until after administering it to a patient. This exposes patients to 
potential side effects from treatments that may not be beneficial in their case. In order to continue 
the pursuit of improving the overall survival and quality of life of MM patients, it is critical that 
we identify predictive biomarkers of response to therapies that will produce deep and durable 
remissions while at the same time alert patients and physicians of therapies that are unlikely to be 
successful.          
 
1.1       Immunomodulators (IMiDs) as effective therapies in MM 
The immunomodulatory drugs or IMiDs include thalidomide, lenalidomide and pomalidomide. 
These drugs have contributed to improvement in the overall survival of patients with MM. These 
drugs work through a variety of mechanisms due to its pleiotropic effects on multiple myeloma 
cells and the remainder of the cells associated with the immune system. IMiDs are widely used as 
induction therapy for both transplant eligible and ineligible patients, in the post-transplant 
maintenance setting, and for relapsed/refractory disease. As such, they remain the backbone of 
therapy for both newly diagnosed and relapsed disease. 
 
Lenalidomide: The initial phase I study determined the maximal tolerated dose to be 25 mg (6). 
In terms of response rates, in the patients previously treated, studies revealed overall response 
rates of 48–61% and 46–57% in which most patients were previously treated with thalidomide(7-
9). In the newly diagnosed setting, lenalidomide with dexamethasone was found to have an 
overall response rates of 68–91%..(10, 11) As a result, this regimen has replaced the use of 
thalidomide/dexamethasone as one of the most commonly used induction regimens in the United 
States. However, the administration of lenalidomide with dexamethasone changed when a study 


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Protocol Version Date:13Jun2023 
 
 
comparing “high-dose” dexamethasone (40 mg days 1–4, 9–12, 17–20 of a 28-day cycle) to “low-
dose” dexamethasone (40 mg days 1, 8, 15, 22 of a 28-day cycle) in combination with 
lenalidomide revealed a better one-year overall survival rate with an improved side effect profile 
for the low-dose weekly dexamethasone(11). This weekly dosing of dexamethasone is now 
routinely used in almost all myeloma regimens. More recently, the triplet combination of 
lenalidomide, bortezomib, and dexamethasone(12) has become a standard of care of newly 
diagnosed patients as it was found to provide a better progression free survival and overall 
survival compared to just lenalidomide and dexamethasone. In the post-transplant maintenance 
setting, lenalidomide is also widely used. Several randomized phase III studies have been 
performed, all of which have demonstrated significant PFS benefit with lenalidomide (13-15) 
including the CALGB 100104 study which revealed a significant OS benefit (13). A recent meta-
analysis of the three studies assessing maintenance lenalidomide post-transplant confirmed an OS 
benefit(16). 
 
Pomalidomide: This third generation IMiD was approved for the treatment of relapsed/refractory 
myeloma in 2013 for patients who had received at least two prior regimens including 
lenalidomide and bortezomib. This agent has only been evaluated in the previously treated 
setting. In one phase II study, the combination of pomalidomide and dexamethasone where the 
pomalidomide was dosed at 2 mg daily had a 63% overall response rate including 40% ORR in 
lenalidomide-refractory patients and 37% ORR in thalidomide-refractory patients(17). In another 
study which included only lenalidomide-refractory patients, the overall response rate was 
47%(18). An alternative dosing strategy of 4 mg daily for 21 out of 28 days was also explored 
and the ORR was 35–42% (19, 20). 
 
1.2        Rationale for the current trial 
Current treatment regimens in both the upfront and relapsed settings have trended towards 
utilizing combination therapies that include a combination of an IMiD with proteasome inhibitors 
and/or monoclonal antibodies(21, 22). This is largely due to the results of several phase III 
clinical trials demonstrating the overall benefit of three-drug regimens (triplets) containing IMiDs 
and proteasome inhibitors or IMiDs and monoclonal antibodies over two-drug regimens 
(doublets) containing IMiDs alone with dexamethasone in terms of their depth and duration of 
hematological response. However, some patients within these clinical trials as well as in real-
world clinical practice may derive equal depth and duration of therapeutic response to two-drug 
regimens (doublets) containing IMiDs alone with dexamethasone compared to triplets. At this 
time, our gap in knowledge prevents us from apriori identifying those patients who can be spared 
the physical and financial toxicity of adding the additional third or fourth agent such as 
proteasome inhibitors and/or monoclonal antibodies to an IMiD and dexamethasone. Being able 
to develop and validate biomarkers capable of filling this fundamental gap of knowledge could 
have practical implications to the clinical care of patients with MM. As such, this study will 
provide the possibility of obtaining biospecimens from untreated smoldering MM and MM 
patients as well as previously treated MM patients pre- and post-treatment with one cycle of 
therapy containing only an IMiD and dexamethasone. 
 
Furthermore, it has been long hypothesized that there may be a differential response to IMiDs for 
patients belonging to African American (AA) race. Small studies have suggested that AA patients 
may have a better response to IMiDs than whites but receive a lesser access to these agents. This 
has led to the need for a more definitive testing to develop an efficacy profile as well as 
biomarker identification which may help predict the differences in response among AA and white 
patients with MM. 
 
 


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Protocol Version Date:13Jun2023 
 
 
 
2.0 
Goals  
2.1 
Primary Goal 
To determine response rates (>=PR) of prospectively treated MM patients with one cycle 
of therapy containing a combination of an immunomodulator and dexamethasone. 
 
2.2       Secondary Goals 
1. To identify biomarkers that predict response rates of untreated smoldering MM and 
MM patients to a combination of an immunomodulator and dexamethasone. 
2. To compare response rates of MM among AA and white patients to a combination of 
an immunomodulator and dexamethasone. 
3. To establish correlation of biomarkers in treated MM patients with the combination of 
an immunomodulator and dexamethasone to the depth of hematological response 
observed in new or previously treated patients. 
 
3.0 
Registration Patient Eligibility 
3.1 
Registration - Inclusion Criteria 
3.11 
Age ≥18 years 
3.12      Cohort A:  Patient must have untreated smoldering multiple myeloma which is 
defined by the presence of 10% or more but less than 60% clonal 
plasma cells in the bone marrow and the absence of any of the 
following myeloma related symptoms or laboratory and radiographic 
abnormalities: anemia, hypercalcemia, renal insufficiency, 
hypercalcemia, serum free light chain ratio of greater than 100 or 
more than one focal marrow multiple myeloma lesion on MRI 
imaging.  
Cohort B: Patient must have newly diagnosed myeloma requiring treatment and 
no prior therapies  
 Cohort C: Patient must have relapsed or refractory multiple myeloma with at 
least one prior therapy for their multiple myeloma but not refractory 
to all IMiDs 
 Cohort D:  Patient must have relapsed or refractory multiple myeloma with 
Lenalidomide as part of a maintenance regimen as their most recent 
therapy 
3.13 
Measurable disease   as defined in section 11.0 
3.14      Provide written informed consent. 
3.15     Patient must be considered for treatment with an IMiD containing regimen. 
3.16 
ECOG Performance Status (PS) 0, 1, 2 or 3 (Appendix I).  
3.17 
The following laboratory values obtained ≤14 days prior to registration:  
• 
Hemoglobin ≥7.0 g/dL 
• 
Absolute neutrophil count (ANC) ≥1000/mm3 
• 
Platelet count 50,000/mm3 


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Protocol Version Date:13Jun2023 
 
 
• 
Total bilirubin ≤1.5 x upper limit of normal (ULN) unless due to Gilbert’s 
syndrome, in which case the direct bilirubin must be ≤1.5 X ULN.  
• 
Alanine aminotransferase (ALT) and aspartate transaminase (AST)  ≤3 x 
ULN (≤5 x ULN for patients with liver involvement) 
• 
PT/INR/aPTT ≤1.5 x ULN OR if patient is receiving anticoagulant therapy 
and INR or aPTT is within target range of therapy 
• 
Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault 
formula below: 
Cockcroft-Gault Equation: 
Creatinine clearance for males =  
(140 - age)(weight in kg) 
 
(72)(serum creatinine in mg/dL) 
Creatinine clearance for females =  
(140 - age)(weight in kg)(0.85) 
 
(72)(serum creatinine in mg/dL) 
3.18 
Negative pregnancy test done ≤7 days prior to registration, for persons of 
childbearing potential only. 
NOTE: If the urine test is positive or cannot be confirmed as negative, a serum 
pregnancy test will be required.   
3.19a 
Willing to return to enrolling institution for follow-up (during the Active 
 
Monitoring Phase of the study). 
3.19b Willingness to provide mandatory blood and bone marrow specimens for  
 
correlative research (see Section 14.0). 
3.19c 
Willing to follow the requirements of the Pomalyst® REMS program 
 
3.2 
Registration - Exclusion Criteria 
3.21 
An agent that has known genotoxic, mutagenic and teratogenic effects: 
• 
Pregnant persons 
• 
Nursing persons 
• 
Persons of childbearing potential who are unwilling to employ adequate 
contraception 
3.22 
Co-morbid systemic illnesses or other severe concurrent disease which, 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. 
3.23 
Immunocompromised patients and patients known to be HIV positive and 
currently receiving antiretroviral therapy.  
3.24 
Uncontrolled intercurrent illness including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations that would limit compliance 
with study requirements. 
3.25 
Receiving any other investigational agent which would be considered as a 
treatment for the primary neoplasm. 
3.26 
History of myocardial infarction ≤6 months.


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Protocol Version Date:13Jun2023 
 
 
 
4.0  
Test Schedule 
 
 
Cycle 1 = 21 
Cycles 2-6 = 28 days   
Footnotes on following page: 
 
 
Tests and procedures 
 
Active Monitoring Phase 
 
 Prior to 
registration  
 
Prior to Day 1 
Cycle 1 
Prior to Day 1  
Cycle 2 
 
 
 
 
Prior to Day 1  
Cycles 3-6 
 
 
 
 
End of 
Treatment 
28 
days 
14 
days 
Window 
 
 
  
±3 days 
 ±3 days 
±7 days 
Complete Medical History  
 
X 
 
 
 
 
Physical exam, Wt, PS 
 
X 
X3 
X 
X 
X 
Adverse event assessment 
 
X 
  
X 
X 
X 
Pregnancy test1 
 
X 
 
 
 
 
Height  
 
X 
 
 
 
 
Hematology group:  
CBC with 5-part differential 
 
X 
X3 
X 
X 
X 
Chemistry group to include 
serum creatinine, calcium, 
T.Bili, D. bili, AST, and ALT  
 
 
X 
X3 
X 
X 
 
X 
LDH,  
Beta-2-microglobulin,  
Plasma cell assessment 
 
 
X 
X3 
 
 
 
PT/PTT/INR 
 
X 
 
 
 
 
TSH 
 
X 
 
 
 
 
Electrophoresis of serum and 
urine 
 
X 
X3,5 
X5 
X5 
X5 
Immunofixation or mass 
fixation of serum and urine 
 
X 
  
X7 
X7 
X7 
Affected Serum 
Immunoglobulin2 
 
X 
X3 
X 
X 
X 
Serum Immunoglobulin free 
light chain 
 
X 
X3 
X 
X 
X 
WBLDCT3 or PET/CT   
X 
 
  
X3 
X3 
 
Bone marrow aspirate and 
biopsy 
X 
 
 
 
 
 
Patient Medication Diary 
(Appendix II) 
 
 
X 
X 
X 
 
Research bone marrow sampleR 
X 
 
  
X6 
 
X4 
Research blood sampleR 
X 
 
  
X6 
 
X4 


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1.   For women of childbearing potential only. Must be done 7 days prior to registration. If the urine test   
is positive or cannot be confirmed as negative, a serum pregnancy test will be required 
2.   Affected immunoglobulin refers to the baseline M-protein type, that is, IgG, IgA, or IgD. Not 
applicable if patient “non-secretory” or if patient has no heavy chain, i.e. light chain myeloma. 
Affected immunoglobulin is required after baseline only if it used for disease monitoring instead of 
SPEP (e.g. IgA myeloma). 
3. Baseline then only if clinically indicated. 
4.   Optional BM sample submission for patients who discontinue treatment due to disease progression or 
 
relapse, intolerable AEs, patient refusal, subsequent treatment for myeloma. 
5 
Urine Electrophoresis required only if used to assess disease response 
6 
Bone marrow aspirate done at the end of Cycle 1 (prior to cycle 2) will be paid for by research.  
7. Immunofixation (IF) only needed in absence of M-Spike to document CR or SCR 
 
R    Collected as part of the IRB# 521-93, IRB# 14-009163 and/or IRB# 919-04   
 
 
4.1 
Survival Follow-up 
 
 
Once a patient completes 6 cycles of therapy and/or is off study due to any reason, no further 
 
clinical and survival follow up is required. 


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5.0 
Grouping Factor 
5.1   
Multiple Myeloma Cohort: Cohort A (Smoldering MM), Cohort B (Newly Diagnosed 
MM), Cohort C (Relapsed/Refractory MM) and Cohort D (Relapsed on Len 
maintenance). 
6.0 
Registration Procedures 
6.1 
Registration:  
6.21 
Registering a patient 
To register a patient, access the Mayo Clinic Research Registration Application 
web page. The registration/ randomization application is available 24 hours a 
day, 7 days a week. Back up and/or system support contact information is 
available on the website. If unable to access the website, call Research Site 
Management at (507) 284-2753 between the hours of 8 a.m. and 4:30 p.m. 
Central Time (Monday through Friday). 
 
The instructions for the registration/randomization application are available on 
the Mayo Clinical Office of Clinical Trials web page 
(https://www.mayo.edu/research/centers-programs/center-clinical-translational-
science/offices/office-of-clinical-trials/research-registration-application) and 
detail the process for completing and confirming patient registration. Prior to 
initiation of protocol treatment, this process must be completed in its entirety and 
an MCCC subject ID number must be available as noted in the instructions. It is 
the responsibility of the individual registering the patient to confirm the process 
has been successfully completed prior to release of the study agent. Patient 
registration via the registration/randomization application can be confirmed in 
any of the following ways: 
• 
Contact Mayo Clinic Research Site Management at (507) 284-2753. If 
the patient was fully registered, the Research Site Management staff can 
access the information from the centralized database and confirm the 
registration. 
• 
Refer to “Instructions for Remote Registration” in section 
“Finding/Displaying Information about A Registered Subject.” 
6.2 
Verification of materials 
Prior to accepting the registration, registration/randomization application will verify the 
following: 
• 
IRB approval at the registering institution 
• 
Patient eligibility 
• 
Existence of a signed consent form 
• 
Existence of a signed authorization for use and disclosure of protected health 
information  
6.3 
Documentation of IRB approval 
Documentation of IRB approval must be on file in the Registration Office before an 
investigator may register any patients.  
In addition to submitting initial IRB approval documents, ongoing IRB approval 
documentation must be on file (no less than annually) with Research Site Management 
(fax: 507-284-0885 or email random01@mayo.edu). If the necessary documentation is 


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not submitted in advance of attempting patient registration, the registration will not be 
accepted and the patient may not be enrolled in the protocol until the situation is resolved. 
When the study has been permanently closed to patient enrollment, submission of annual 
IRB approvals to the Registration Office is no longer necessary. 
6.4 
Correlative Research 
6.41 
Mandatory 
A mandatory correlative research component is part of this study, the patient will 
be automatically registered onto this component (see Sections 3.19b and 14.0).   
6.5 
Treatment start 
Treatment cannot begin prior to registration and must begin 28 days after registration. 
6.6 
Baseline symptoms 
All required baseline symptoms (see Section 10.6) must be documented and graded. 
6.7 
Study Conduct 
The clinical trial will be conducted in compliance with regulations (21 CFR 312, 50, and 
56), guidelines for Good Clinical Practice (ICH Guidance E6), and in accordance with 
general ethical principles outlined in the Declaration of Helsinki; informed consent will 
be obtained from all participating patients; the protocol and any amendments will be 
subject to approval by the designated IRB prior to implementation, in accordance with 
21 CFR 56.103(a); and subject records will be stored in a secure location and subject 
confidentiality will be maintained. The investigator will be thoroughly familiar with the 
appropriate use of the study drug as described in the protocol and Investigator’s 
Brochure. Essential clinical documents will be maintained to demonstrate the validity of 
the study and the integrity of the data collected. Master files should be established at the 
beginning of the study, maintained for the duration of the study and retained according to 
the appropriate regulations. 
 
 
 
 
 


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7.0 
Protocol Treatment 
7.1 
Treatment Schedule 
              Cohort A and B Cycle 1  
        Treatment medication table. Patient may receive Lenalidomide OR Lenalidomide + Dexamethasone.  
Agent 
Dose Level 
Route 
Day 
Re Rx 
Lenalidomide 
 
25 mg* 
Oral 
 
Cycle 1: Day 1-14  
 
 
Cycle 1: 21 days 
 
Dexamethasone 
 
40 mg** 
Oral 
 
Cycle 1: Day 1 ,8, ,15  
 
 
Cycle 1: 21 days 
  
Cycle 1 length = 21 days    
* Starting dose will be determined as per the creatine clearance below (see 7.12) 
**The dose of dexamethasone used can be determined by the treating physician and omitted if    
needed. 
              Cohort C and D Cycle 1  
Treatment medication table. Patient may receive Lenalidomide + Dexamethasone OR Pomalidomide 
+ Dexamethasone. 
Agent 
Dose Level 
Route 
Day 
ReRx 
Lenalidomide 
 
 
25 mg* 
Oral 
 
 
Cycle 1: Day 1-14 
  
 
 
Cycle 1: 21 days 
  
Pomalidomide 
 
 
4 mg 
Oral 
 
 
Cycle 1: Day 1-21 
  
 
 
Cycle 1: 21 days 
  
Dexamethasone 
 
 
40 mg** 
Oral 
 
 
Cycle 1: Day 1 ,8, ,15 
  
 
 
Cycle 1: 21 days 
  
Cycle 1 length = 21 days    
* Starting dose will b determined as per the creatinine clearance below (see 7.12) 
** The dose of dexamethasone used can be determined by the treating physician and omitted if 
needed. 
 
Cohort A and B Cycles 2-6  
 
Treatment Medication Table. Patient may receive Lenalidomide based regimens. 
Agent 
Dose Level 
Route 
Day 
Re Rx 
Lenalidomide 
 
 
25 mg* 
Oral 
 
 
Cycle 2-6: Day 1-21 
 
 
 
Cycles 2-6: 28 days 
  
Dexamethasone 
 
 
40 mg** 
Oral 
 
 
Cycle 2-6: Day 1 ,8, ,15. 22 
 
 
 
 
Cycles 2-6: 28 days 
 
  


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Note: Standard of care agents can be added for cycles 2-6 as long as the regimen contains 
 
lenalidomide 
Cycles 2-6 length = 28 days  
* Any dose-adjustments will be determined as per the creatine clearance below (see 7.12). 
** The dose of dexamethasone used can be determined by the treating physician and omitted if 
needed. 
 
 
Cohort C and D Cycles 2-6 
         Treatment medication table. Patient may receive Lenalidomide based regimen OR Pomalidomide  
based regimen.  
Agent 
Dose Level 
Route 
Day 
ReRx 
Lenalidomide 
 
 
25 mg* 
Oral 
 
 
Cycles 2-6: Day 1-21 
  
 
  
 
Cycles 2-6: 28 days 
 
  
Pomalidomide 
 
 
4 mg 
Oral 
 
 
Cycles 2-6: Day 1-21 
  
 
 
 
Cycles 2-6: 28 days  
 
  
Dexamethasone 
 
 
40 mg** 
Oral 
 
 
Cycle 2-6: Day 1 ,8, ,15, 22 
  
 
 
Cycles 2-6: 28 days  
  
Note: Standard of care agents can be added for cycles 2-6 as long as the regimen contains 
 
lenalidomide or pomalidomide 
 
Cycles 2-6 length = 28 days  
* Any dose-adjustments will be determined as per the creatinine clearance below (see 7.12). 
** The dose of dexamethasone used can be determined by the treating physician and omitted if 
needed. 
 
 
 
7.12 
Creatinine Clearance (CrCl)  
Lenalidomide Dose 
CrCl >60 ml/minute 
25 mg No adjustment required   
CrCl 30-60 ml/minute 
10 mg once daily (may increase to 15 mg once daily 
after 2 cycles if nonresponsive but tolerating 
treatment) 
CrCl <30 ml/minute (non-dialysis dependent) 
15 mg every 48 hours 
7.2        Treatment by local medical doctor (LMD) 
The registering investigator is responsible for all treatment decisions and for the 
collection and submission of the study data in accordance with the approved protocol. 
(Note: Treatment with local MD is allowed as long as the patient is able to come back to 
the registering site for sample collections under IRB # 521-93 or IRB# 14-009163).  
 
When it has been determined that a patient’s malignant disease is stable or objective 
tumor regression has been observed and the patient is tolerating therapy without 
excessive toxicity at a stable dose level, the drug(s) may be sent with the patient for 


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administration by the patient’s Local Medical Doctor (LMD). The registering physician 
retains responsibility for the patient.  
In this case, a written statement outlining drug dosage, method of administration, follow-
up tests required, and telephone number to call to discuss any questions with the 
registering investigator must be sent with the patient to provide necessary information to 
the LMD. The LMD will be required to supervise the administration of the study drugs as 
stipulated in the protocol and provide written documentation that the drug was 
administered.  
The registering investigator is responsible for all treatment decisions and for the 
collection and submission of the study data in accordance with the approved protocol. 
 
The responsible investigator will ensure the integrity of the local physician, facilitate 
drug accountability, and ensure that the LMD can rapidly communicate toxicity.  
 
7.3       End of study 
 
All patients in Cohort A, Cohort B, Cohort C and Cohort D enrolled on this clinical trial 
will be treated on this study only for 6 cycles from the time of registration. After this 
time, they will no longer be part of the study and will be taken off study but can continue 
on their current therapy or any other therapy as deemed appropriate by their physician. 
 
Patients can then continue the therapy instituted beyond cycle 1 with any additional 
therapeutic agents as deemed appropriate by their physician and/or local physician.  
 
8.0 
Dosage Modification Based on Adverse Events 
Any adverse event noted in the study and its resultant dose-modifications should be managed as 
per the prescribing information of lenalidomide, dexamethasone and/or pomalidomide as per 
which of these two drugs the adverse event is attributable to. 
8.1 
Lenalidomide Dose Modifications 
 
 
 
 
 
 
 
 
 
 
Lenalidomide 
(Cycle 1: Day 1-14 
Cycle 2-6: Day 1-21) 
Starting 
dose 
 
25mg 
-1 
10 mg 
-2 
Discontinue 


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→ → Use the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0* 
unless otherwise specified   
CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Investigations 
Platelet count 
decreased 
Grade 4  
Lenalidomide 
*Omit dose until AE has resolved to 
Grade 1 or better 
• Follow CBC weekly 
• If thrombocytopenia <30,000/mm3 
recurs, reduce dose by one dose level 
(by 5 mg) and continue therapy when 
platelet count ≥30,000/mm3 
 
If, after lenalidomide has been 
omitted, and the AE does not return to 
≤Grade 1 within 4 weeks, then the 
patient may continue on remaining  
agent(s) till the completion of 
maintenance and then proceed to off 
study 
 
Neutrophil count 
decreased 
Grade 4  
 
*Omit dose until AE has resolved to 
Grade 2 or better 
• Follow CBC weekly 
* If neutropenia has resolved to 
≤Grade 2, resume dose at one level 
lower  
*If, after lenalidomide has been 
omitted, and the AE does not return to 
≤Grade 2within 4 weeks, then the 
patient may continue on remaining 
agent(s) till the completion of 
maintenance and then proceed to off 
study  
Blood and lymphatic 
system disorders 
Anemia  
Grade 4 
 
*Omit dose until AE has resolved to 
Grade 2 or better 
• Follow CBC weekly 
* If anemia has resolved to ≤Grade 2, 
resume dose at one level lower 
*If, after lenalidomide has been 
omitted, and the AE does not return to 
≤Grade 1 within 4 weeks, then the 
patient may continue on remaining 
agent(s) till the completion of 
maintenance and then proceed to off 
study 
 
Febrile neutropenia 
≥Grade 3 
 
• Omit dose and follow CBC weekly 
• If neutropenia has resolved to 
≤Grade 2, resume dose at same level 
with GCSF support (See Section 9.2 


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CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Cardiac disorders 
Sinus bradycardia/ 
other cardiac 
arrhythmia 
Grade 2 
Lenalidomide 
Omit dose and follow at least weekly 
until resolution 
• If AE resolves to ≤Grade 1, reduce 
dose by one dose level and continue 
therapy 
 
≥ Grade 3 
 
• Discontinue study treatment and go  
off study  
Vascular disorders 
Thromboembolic event 
≥ Grade 3 
 
• Omit dose and start anticoagulation; 
restart at investigator’s discretion 
(maintain dose level) 
Immune system 
disorders 
Allergic reaction 
Grade 2-3 
 
• Omit dose and follow at least 
weekly until resolution 
• If AE resolves to ≤Grade 1, reduce 
dose level and continue therapy 
 
Anaphylaxis 
Grade 4 
 
• Discontinue study treatment and go  
off study 
Skin and 
subcutaneous tissue 
disorders 
Erythema multiforme 
≥Grade 3 
 
Discontinue study treatment and go 
off study 
 
Skin ulceration  
≥Grade 2 
 
Discontinue study treatment and go 
off study  
 
Other: Non-blistering 
rash Grade 3 
 
• If Grade 3 omit dose and follow 
weekly until resolution 
• If AE resolves to ≤Grade 2 continue 
therapy 
 
Other: Non-blistering 
rash Grade 4 
 
• Discontinue study treatment and go 
off study  
Other AEs 
Non-hematologic AE 
assessed as related to 
lenalidomide  
≥Grade 3 
 
• Omit dose and follow at least 
weekly until resolution 
• If the AE resolves to ≤Grade 2, 
implement one dose reduction step 
and continue therapy (per Table 8.1) 
* 
Located at http:/ctep.cancer.gov/protocolDevelopment/electronic applications.ctc.htm     
**  Use the following to describe actions in the Action column: 
➢ Omit = The current dose(s) for the specified drug(s) during a cycle is skipped.  The patient does not 
make up the omitted dose(s) at a later time 
➢ Hold/Delay = The current dose(s) of all drugs during a cycle is delayed.  The patient does make up 
the delayed dose(s) when the patient meets the protocol criteria to restart drugs. 
➢ Discontinue = The specified drug(s) are totally stopped.    
 
8.2 
Standard of Care Agents Dose Modifications (not lenalidomide)  
8.21 
Standard of care dose modifications will be adjusted as per standard of care 
 
guidelines in the prescribing information for multiple myeloma patients.  
 
 
 


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8.3 
Dexamethasone–Related Treatment Modification Guidelines for Adverse Events 
8.31 
Dexamethasone Dose Modifications 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
→ → Use the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0* 
unless otherwise specified   
 
CTCAE SOC 
Adverse event  
Severity 
Action on Dexamethasone 
Gastrointestinal 
disorders 
Dyspepsia, ulcer, or 
gastritis 
Grade 1-2 
Treat with histamine-H2 receptor blockers, 
sucralfate, or proton-pump inhibitors. If 
symptoms persist despite these measures, 
decrease by 1 dose level.  
 
 
≥Grade 3  
Omit dexamethasone until symptoms adequately 
controlled.  
Restart and decrease 1 dose level of current dose 
along with concurrent therapy with histamine-H2 
receptor blockers, sucralfate, or omeprazole.  
If symptoms persist despite these measures, 
discontinue and do not resume 
 
Pancreatitis 
≥Grade 3 
Permanently discontinue 
General disorders 
and administration 
site conditions 
Localized edema 
≥Grade 2 
Intervention indicated (eg, diuretics) as needed 
and decrease by 1 dose level.  
If edema persists despite these measures, decrease 
dose another level at investigator discretion.  
Discontinue and do not resume if symptoms 
persist despite 2nd reduction. 
Psychiatric disorders 
Confusion or  
Agitation 
≥Grade 2 
Omit dexamethasone until symptoms resolve.  
Restart with 1 dose level reduction.  
If symptoms persist despite these measures, 
permanently discontinue dexamethasone. 
Musculoskeletal and 
connective tissue 
disorders 
Generalized muscle 
weakness 
≥Grade 2 
Decrease dexamethasone dose by 1 dose level. If 
weakness persists despite these measures, decrease 
dose further by 1 dose level at investigator 
discretion. 
Permanently discontinue dexamethasone if 
symptoms persist. 
Dose Level 
 
Dexamethasone 
(Cycle 1: Day 1, 8, 15) 
Cycle 2-6: Day 1, 8, 15, 22) 
(Age <75) 
 
Dexamethasone 
(Cycle 1: Day 1, 8, 15) 
Cycle 2-6: Day 1, 8, 15, 22) 
(Age ≥75) 
Starting Dose 
40 mg  
20 mg 
-1 
20 mg 
8 mg 
-2 
8 mg 
 
Discontinue  
-3 
Discontinue 


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CTCAE SOC 
Adverse event  
Severity 
Action on Dexamethasone 
Metabolism and 
nutrition disorders 
Hyperglycemia 
≥Grade 2 
Treatment with insulin or oral hypoglycemia as 
needed.  
If uncontrolled despite these measures, decrease 
dose by 1 dose level until blood glucose levels are 
satisfactory 
Located at http:/ctep.cancer.gov/protocolDevelopment/electronic_applications.ctc.htm 
**  Use the following to describe actions in the Action column: 
➢ Omit = The current dose(s) for the specified drug(s) during a cycle is skipped.  The patient does not 
make up the omitted dose(s) at a later time 
➢ Hold/Delay = The current dose(s) of all drugs during a cycle is delayed.  The patient does make up 
the delayed dose(s) when the patient meets the protocol criteria to restart drugs. 
➢ Discontinue = The specified drug(s) are totally stopped.    
 
8.4 
Pomalidomide–Related Treatment Modification Guidelines for Adverse Events  
 
 
8.41 Pomalidomide Dose Modifications 
 
 
 
 
 
 
 
 
 
 
 
 
 
→ → Use the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0* 
unless otherwise specified   
 
CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Investigations 
Neutrophil count decreased 
If ANC ˂1.0  109/L  
or ANC >1.0  109/L (up to 
LLN) with fever 
(temperature >38.5°C) 
Pomalidomide 
Omit pomalidomide dose. 
Follow CBC weekly. 
If neutropenia has resolved to 
≤Grade 2 prior to Day 21 and 
fever has resolved, restart 
pomalidomide at next lower dose 
level and continue through 
Day 21of a 28-day cycle. 
If febrile neutropenia is the only 
toxicity for which a dose 
reduction is required,  
G-CSF may be used and the 
pomalidomide dose maintained. 
Dose Level 
Pomalidomide 
(Cycle 1: Day 1-21 
Cycle 2-6: Day 1-21) 
Starting dose 
4 mg 
-1 
3 mg 
-2 
2 mg 
-3 
1 mg 
-4 
Discontinue 


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CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Investigations 
Platelet count decreased 
If platelet count ˂30  109/L 
Pomalidomide 
Omit pomalidomide dose 
Follow CBC weekly 
Hold anticoagulation/antiplatelet 
therapy until platelets 
≥50,000/mm³ 
If platelet count resolves to 
≤Grade 2 prior to Day 21, restart 
pomalidomide at next lower dose 
level and continue through 
Day 21 of each cycle 
Skin and 
subcutaneous tissue 
disorders 
Rash maculopapular  
Grade 2 or 3 
Pomalidomide 
Omit pomalidomide dose; follow 
weekly 
If the AE resolves to ≤Grade 1 
prior to Day 21, restart 
pomalidomide at next lower dose 
level and continue through 
Day 21of each cycle 
Grade 3-4 Stevens –Johnson 
Syndrome 
Pomalidomide 
Discontinue pomalidomide and 
remove patient from all study 
treatment 
≥Grade 3 Erythema 
multiforme 
Pomalidomide 
Discontinue pomalidomide and 
remove patient from all study 
treatment 
Erythroderma  
≤Grade 3 
Pomalidomide 
Omit pomalidomide dose; follow 
weekly 
If the AE resolves to ≤Grade 1 
prior to Day 21, restart 
pomalidomide at next lower dose 
level and continue through 
Day 21of the 28-day cycle 
Rash, maculo-papular 
Rash, acneiform 
Grade 4 
Pomalidomide 
Discontinue pomalidomide and 
remove patient from all study 
treatment 
Nervous system 
disorders 
Peripheral sensory 
neuropathy 
Grade 3 
Pomalidomide 
Omit pomalidomide dose and 
follow at least weekly. 
If the AE resolves to ≤Grade 1 
prior to Day 21, restart 
pomalidomide at next lower dose 
level and continue through 
Day 21 
Peripheral sensory 
neuropathy 
Grade 4 
Pomalidomide 
Discontinue pomalidomide and 
remove patient from all study 
treatment 


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CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Immune system 
disorders 
Allergic reaction  
Grade 2-3 
Pomalidomide 
Omit dose and follow at least 
weekly 
If the AE resolves to ≤Grade 1 
prior to Day 15, restart at next 
lower dose level and continue 
through Day 21 
Allergic reaction  
Grade 4 
Pomalidomide 
Discontinue pomalidomide and 
remove patient from all study 
treatment 
Vascular disorders 
Thromboembolic event 
≥ Grade 3 
Pomalidomide 
Omit dose and start 
anticoagulation 
Restart at investigator’s 
discretion (maintain dose level) 
Endocrine disorders 
Hyperthyroidism or 
Hypothyroidism ≥ Grade 2 
Pomalidomide 
Omit pomalidomide for 
remainder of cycle, evaluate 
etiology, and initiate appropriate 
therapy 
   Reduce the dose of 
pomalidomide by 1 dose level. 
Other non-
hematologic adverse 
event 
Other non-hematologic 
≥Grade 3 
Pomalidomide 
If the AE can be attributed to 
either of the drugs, pomalidomide 
should be discontinued at first 
instance    b for recurrence of the 
same toxicity necessitating dose 
modification 
Omit pomalidomide dose. Follow 
at least weekly 
If the toxicity resolves to ≤Grade 2 
prior to Day 21, restart 
pomalidomide at next lower dose 
level and continue through Day 21 
* 
Located at http:/ctep.cancer.gov/protocolDevelopment/electronic_applications.ctc.htm 
**  Use the following to describe actions in the Action column: 
➢ Omit = The current dose(s) for the specified drug(s) during a cycle is skipped. The patient 
does not make up the omitted dose(s) at a later time 
➢ Hold/Delay = The current dose(s) of all drugs during a cycle is delayed. The patient does 
make up the delayed dose(s) when the patient meets the protocol criteria to restart drugs. 
➢ Discontinue = The specified drug(s) are totally stopped. 
 
8.4 
Standard of Care Agents Dose Modifications (not pomalidomide)  
8.41 
Standard of care dose modifications will be adjusted as per standard of care 
 
guidelines in the prescribing information for multiple myeloma patients.  
 
 


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9.0  
Ancillary Treatment/Supportive Care 
9.1 
Full supportive care  
Patients should receive full supportive care while on this study. This includes blood 
product support, antibiotic treatment, and treatment of other newly diagnosed or 
concurrent medical conditions. All blood products and concomitant medications such as 
antidiarrheals, analgesics, and/or antiemetics received from the first day of study 
treatment administration until 30 days after the final dose will be recorded in the medical 
records. 
9.2 
Blood products and growth factors  
Blood products and growth factors should be utilized as clinically warranted and 
following institutional policies and recommendations. The use of growth factors should 
follow published guidelines of the Journal of Clinical Oncology, Volume 33, No 28 
(October 1), 2015: pp. 3199-3212 (WBC growth factors) AND Journal of Clinical 
Oncology, Volume 28, No 33 (November 20), 2010: pp. 4955-5010 
(darbepoetin/epoetin). 
9.3 
Antiemetics 
Antiemetics may be used at the discretion of the attending physician. 
9.4 
Diarrhea 
Diarrhea could be managed conservatively with loperamide. The recommended dose of 
loperamide is 4 mg at first onset, followed by 2 mg every 2-4 hours until diarrhea free 
(maximum 16 mg/day). 
In the event of Grade 3 or 4 diarrhea, the following supportive measures are allowed: 
hydration, octreotide, and antidiarrheals.  
If diarrhea is severe (requiring intravenous rehydration) and/or associated with fever or 
severe neutropenia (Grade 3 or 4), broad-spectrum antibiotics must be prescribed. 
Patients with severe diarrhea or any diarrhea associated with severe nausea or vomiting 
should be hospitalized for intravenous hydration and correction of electrolyte 
imbalances. 
 
10.0 
Adverse Event (AE) Monitoring and Reporting  
The site principal investigator is responsible for reporting any/all serious adverse events to the 
sponsor as described within the protocol, regardless of attribution to study agent or treatment 
procedure. 
The sponsor/sponsor-investigator is responsible for notifying FDA and all participating 
investigators in a written safety report of any of the following: 
• 
Any suspected adverse reaction that is both serious and unexpected. 
• 
Any findings from laboratory animal or in vitro testing that suggest a significant risk for 
human subjects, including reports of mutagenicity, teratogenicity, or carcinogenicity. 
• 
Any findings from epidemiological studies, pooled analysis of multiple studies, or 
clinical studies, whether or not conducted under an IND and whether or not conducted by 
the sponsor, that suggest a significant risk in humans exposed to the drug 


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• 
Any clinically important increase in the rate of a serious suspected adverse reaction over 
the rate stated in the protocol or Investigator’s Brochure (IB). 
Summary of SAE Reporting for this study  
(please read entire section for specific instructions): 
  
WHO: 
WHAT form: 
WHERE to send: 
  
Mayo Clinic 
Sites  
Pregnancy Reporting 
http://ctep.cancer.gov/protocolDevelopment/electronic_a
pplications/docs/PregnancyReportFormUpdated.pdf 
Mayo Sites – attach to MCCC 
Electronic SAE Reporting Form 
http://livecycle2.mayo.edu/worksp
ace/?startEndpoint=MC4158-
56/Processes/MC4158-56-
Process.MC4158-56 
Will automatically be sent to 
CANCERCROSAFETYIN@mayo
.edu and 
RSTP2CSAES@mayo.edu 
 
Mayo Clinic 
Sites 
Mayo Clinic Cancer Center SAE Reporting Form:  
http://livecycle2.mayo.edu/workspace/?startEndpoint=
MC4158-56/Processes/MC4158-56-Process.MC4158-
56 
Will automatically be sent to 
CANCERCROSAFETYIN@mayo
.edu and 
RSTP2CSAES@mayo.edu 
Mayo Clinic 
Sites 
Mayo Clinic Cancer Center SAE Reporting 
Form:http://livecycle2.mayo.edu/workspace/?startEnd
point=MC4158-56/Processes/MC4158-56-
Process.MC4158-56  
AND attach 
MedWatch 3500A: 
http://www.fda.gov/downloads/AboutFDA/ReportsMa
nualsForms/Forms/UCM048334.pdf 
Will automatically be sent to 
CANCERCROSAFETYIN@mayo
.edu and 
RSTP2CSAES@mayo.edu 
 
 
 
Definitions 
Adverse Event 
Any untoward medical occurrence associated with the use of a drug in humans, whether or 
not considered drug related.  
Suspected Adverse Reaction 
Any adverse event for which there is a reasonable possibility that the drug caused the adverse 
event. 
Expedited Reporting 
Events reported to sponsor within 24 hours, 5 days or 10 days of study team becoming aware 
of the event. 
Routine Reporting 
Events reported to sponsor via case report forms 


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Events of Interest 
Events that would not typically be considered to meet the criteria for expedited reporting, but 
that for a specific protocol are being reported via expedited means in order to facilitate the 
review of safety data (may be requested by the FDA or the sponsor).  
10.1 
Adverse Event Characteristics 
CTCAE term (AE description) and grade: The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting. All appropriate treatment areas should have access 
to a copy of the CTCAE version 5.0 A copy of the CTCAE version 5.0 can be 
downloaded from the CTEP web site: 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm) 
a. Identify the grade and severity of the event using the CTCAE version 5.0. 
b. Determine whether the event is expected or unexpected (see Section 10.2). 
c. Determine if the adverse event is related to the study intervention (agent, treatment or 
procedure) (see Section 10.3). 
d. Determine whether the event must be reported as an expedited report. If yes, 
determine the timeframe/mechanism (see Section 10.4).  
e. Determine if other reporting is required (see Section 10.5). 
f. Note: All AEs reported via expedited mechanisms must also be reported via the 
routine data reporting mechanisms defined by the protocol (see Sections 10.6 and 
18.0). 
NOTE: A severe AE is NOT the same as a serious AE, which is defined in Section 10.4. 
10.2 
Expected vs. Unexpected Events  
Expected events - are those described within the Section 15.0 of the protocol, the study 
specific consent form, package insert (if applicable), and/or the investigator brochure, (if 
an investigator brochure is not required, otherwise described in the general 
investigational plan).  
Unexpected adverse events or suspected adverse reactions are those not listed in Section 
15.0 of the protocol, the study specific consent form, package insert (if applicable), or in 
the investigator brochure (or are not listed at the specificity or severity that has been 
observed); if an investigator brochure is not required or available, is not consistent with 
the risk information described in the general investigational plan. 
Unexpected also refers to adverse events or suspected adverse reactions that are 
mentioned in the investigator brochure as occurring with a class of drugs but have not 
been observed with the drug under investigation. 
An investigational agent/intervention might exacerbate the expected AEs associated with a 
commercial agent. Therefore, if an expected AE (for the commercial agent) occurs with a 
higher degree of severity or specificity, expedited reporting is required. 
NOTE: *The consent form may contain study specific information at the discretion of the 
Principal Investigator; it is possible that this information may NOT be included in the 
protocol or the investigator brochure. Refer to protocol or IB for reporting needs. 
10.3 
Attribution to agent(s) or procedure 
When assessing whether an adverse event (AE) is related to a medical agent(s) medical or 
procedure, the following attribution categories are utilized: 
Definite - The AE is clearly related to the agent(s)/procedure. 
Probable - The AE is likely related to the agent(s)/procedure. 


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Possible - The AE may be related to the agent(s)/procedure. 
Unlikely - The AE is doubtfully related to the agent(s)/procedure. 
Unrelated - The AE is clearly NOT related to the agent(s)/procedure. 
10.31 AEs Experienced Utilizing Investigational Agents and Commercial Agent(s) 
on the SAME (Combination) Arm 
NOTE: When a commercial agent(s) is (are) used on the same treatment arm as 
the investigational agent/intervention (also, investigational drug, biologic, 
cellular product, or other investigational therapy under an IND), the entire 
combination (arm) is then considered an investigational intervention for 
reporting. 
• An AE that occurs on a combination study must be assessed in accordance with the 
guidelines for investigational agents/interventions.  
• An AE that occurs prior to administration of the investigational agent/intervention 
must be assessed as specified in the protocol. In general, only Grade 4 and 5 AEs 
that are unexpected with at least possible attribution to the commercial agent require 
an expedited report, unless hospitalization is required. Refer to Section 10.4 for 
specific AE reporting requirements or exceptions. 
An investigational agent/intervention might exacerbate the expected AEs associated 
with a commercial agent. Therefore, if an expected AE (for the commercial agent) 
occurs with a higher degree of severity or specificity, expedited reporting is 
required. 
• An increased incidence of an expected adverse event (AE) is based on the 
patients treated for this study at their site. A list of known/expected AEs is 
reported in the package insert or the literature, including AEs resulting from a 
drug overdose. 
• Commercial agent expedited reports must be submitted to the FDA via MedWatch 
3500A for Health Professionals (complete all three pages of the form). 
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM0
48334.pdf 
 
10.32 EXPECTED Serious Adverse Events: Protocol Specific Exceptions to 
Expedited Reporting 
For this protocol only, the following Adverse Events/Grades are expected to occur 
within this population and do not require Expedited Reporting. These events must still 
be reported via Routine Reporting (see Section 10.6).* 
*Report any clinically important increase in the rate of a serious suspected 
adverse reaction (at your study site) over that which is listed in the protocol or 
investigator brochure as an expedited event.  
*Report an expected event that is greater in severity or specificity than expected 
as an expedited event. 
*Specific protocol exceptions to expedited reporting should be reported 
expeditiously by investigators ONLY if they exceed the expected grade of the 
event. 
 


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CTCAE 
System Organ Class 
(SOC) 
Adverse event/ Symptoms 
CTCAE Grade at which the event 
will not be reported via expedited 
mechanisms1 
Blood and lymphatic 
system disorders 
Anemia 
≤Grade 4 
Investigations 
Lymphocyte count decreased 
≤Grade 4 
Neutrophil count decreased 
≤Grade 4 
 
Platelet count decreased 
≤Grade 4 
White blood cell count 
decreased 
≤Grade 4 
1 These exceptions only apply if the adverse event does not result in hospitalization. 
If the adverse event results in hospitalization, then the standard expedited adverse 
events reporting requirements must be followed.  
The following hospitalizations are not considered to be SAEs because there is no 
“adverse event” (i.e., there is no untoward medical occurrence) associated with 
the hospitalization: 
● Hospitalizations for respite care 
● Planned hospitalizations required by the protocol 
● Hospitalization planned before informed consent (where the condition 
requiring the hospitalization has not changed post study drug 
administration) 
● Hospitalization for elective procedures unrelated to the current disease and/or 
treatment on this trial 
● Hospitalization for administration of study drug or insertion of access for 
administration of study drug 
● Hospitalization for routine maintenance of a device (e.g., battery replacement) 
that was in place before study entry 
● Hospitalization, or other serious outcomes for signs and symptoms of 
progression of the cancer. 
 
 


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10.4 
Expedited Reporting Requirements for Commercial or Commercial Imaging Agents 
(Non-IND) Agent(s) ONLY:  
10.41 Expedited Reporting Requirements for Adverse Events that Occur in a Non-
IND trial within 30 Days of the Last Administration of a Commercial 
Agent1, 2 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE: Investigators MUST immediately report to the sponsor ANY Serious Adverse Events, whether or not they 
are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
An adverse event is considered serious if it results in ANY of the following outcomes:  
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours  
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) 
A congenital anomaly/birth defect.  
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based upon medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the sponsor within 
the timeframes detailed in the table below. 
Hospitalization 
Grade 1 
Timeframes 
Grade 2 
Timeframes 
Grade 3 Timeframes 
Grade 4 & 5 
Timeframes 
Resulting in 
Hospitalization  
≥24 hrs 
7 Calendar Days 
24-Hour  
3 Calendar 
Days 
Not resulting in 
Hospitalization  
≥24 hrs 
Not required 
7 Calendar Days 
Expedited AE reporting timelines are defined as: 
o “24-Hour; 3 Calendar Days” - The AE must initially be reported within 24 hours of learning of the AE, 
followed by a complete expedited report within 3 calendar days of the initial 24-hour report. 
o “7 Calendar Days” - A complete expedited report on the AE must be submitted within 7 calendar days 
of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows:  
Expedited 24-hour notification followed by complete report within 3 calendar days for: 
• All Grade 4, and Grade 5 AEs 
Expedited 7 calendar day reports for: 
• Grade 2 adverse events resulting in hospitalization or prolongation of hospitalization  
• Grade 3 adverse events 
2 For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half-lives, 
rounded UP to the nearest whole day, after the agent/intervention was last administered. Footnote “1” above 
applies after this reporting period. 
Effective Date: May 5, 2011 
  
 
 NOTE: Refer to Section 10.32 for exceptions to Expedited Reporting 
 


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10.42 General reporting instructions 
The Mayo IND and/or MCCC Compliance will assist the sponsor-investigator in 
the processing of expedited adverse events and forwarding of suspected 
unexpected serious adverse reactions (SUSARs) to the FDA and IRB. 
Use Mayo Expedited Event Report form 
http://livecycle2.mayo.edu/workspace/?startEndpoint=MC4158-
56/Processes/MC4158-56-Process.MC4158-56 for investigational agents or 
commercial/investigational agents on the same arm.  
For commercial agents (for commercial agent(s) on its own arm):  
Attach the MedWatch 3500A form to the Mayo Expedited Event Report form 
http://livecycle2.mayo.edu/workspace/?startEndpoint=MC4158-
56/Processes/MC4158-56-Process.MC4158-56.  
 
10.43 Reporting of re-occurring SAEs 
ALL SERIOUS adverse events that meet the criteria outlined in table10.41 
MUST be immediately reported to the sponsor within the timeframes detailed in 
the corresponding table. This reporting includes, but is not limited to SAEs that 
re-occur again after resolution. 
10.5 
Other Required Reporting 
10.51 Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSOS) 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSOS) in 
general, include any incident, experience, or outcome that meets all of the 
following criteria: 
1. Unexpected (in terms of nature, severity, or frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied; 
2. Related or possibly related to participation in the research (in this guidance 
document, possibly related means there is a reasonable possibility that the 
incident, experience, or outcome may have been caused by the procedures 
involved in the research); and 
3. Suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was 
previously known or recognized. 
Some unanticipated problems involve social or economic harm instead of the 
physical or psychological harm associated with adverse events. In other cases, 
unanticipated problems place subjects or others at increased risk of harm, but no 
harm occurs. 
Note: If there is no language in the protocol indicating that pregnancy is not 
considered an adverse experience for this trial, and if the consent form does not 
indicate that subjects should not get pregnant/impregnate others, then any 
pregnancy in a subject/patient or a male patient’s partner (spontaneously 
reported) which occurs during the study or within 120 days of completing the 
study should be reported as a UPIRTSO. 


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Mayo Clinic Cancer Center (MCCC) Institutions: 
If the event meets the criteria for IRB submission as a Reportable 
Event/UPIRTSO, provide the appropriate documentation and use the Mayo 
Clinic Cancer Center Expedited Event Report form 
http://livecycle2.mayo.edu/workspace/?startEndpoint=MC4158-
56/Processes/MC4158-56-Process.MC4158-56, to submit to 
CANCERCROSAFETYIN@mayo.edu. The Mayo Clinic Compliance Unit will 
review and process the submission to the Mayo Clinic IRB and work with the 
IND Coordinator for submission to FDA. 
 
10.52 Death 
Note: A death on study requires both routine and expedited reporting 
regardless of causality, unless as noted below. Attribution to treatment or 
other cause must be provided. 
Any death occurring within 30 days of the last dose, regardless of attribution to 
an agent/intervention under an IND requires expedited reporting within 24-
hours. 
Any death occurring greater than 30 days with an attribution of possible, 
probable, or definite to an agent/intervention under an IND requires expedited 
reporting within 24-hours. 
Reportable categories of Death  
• 
Death attributable to a CTCAE term. 
• 
Death Neonatal: A disorder characterized by cessation of life during the 
first 28 days of life.  
• 
Death NOS: A cessation of life that cannot be attributed to a CTCAE term 
associated with Grade 5. 
• 
Sudden death NOS: A sudden (defined as instant or within one hour of the 
onset of symptoms) or an unobserved cessation of life that cannot be 
attributed to a CTCAE term associated with Grade 5. 
• 
Death due to progressive disease that cannot be attributed to a CTCAE 
term associated with Grade 5 should be reported as Grade 5 “Disease 
progression” under the system organ class (SOC) of General disorders 
and administration site conditions. Evidence that the death was a 
manifestation of underlying disease (e.g., radiological changes suggesting 
tumor growth or progression: clinical deterioration associated with a 
disease process) should be submitted. 
10.53 Secondary Malignancy 
• 
A secondary malignancy is a cancer caused by treatment for a previous 
malignancy (e.g., treatment with investigational agent/intervention, radiation 
or chemotherapy). A secondary malignancy is not considered a metastasis of 
the initial neoplasm. 
• 
All secondary malignancies that occur following treatment with an agent under 
an IND will be reported. Three options are available to describe the event: 
o Leukemia secondary to oncology chemotherapy (e.g., Acute Myeloctyic 
Leukemia [AML]) 
o Myelodysplastic syndrome (MDS) 


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o Treatment-related secondary malignancy 
• 
Any malignancy possibly related to cancer treatment (including AML/MDS) 
should also be reported via the routine reporting mechanisms outlined in each 
protocol. 
10.54 Second Malignancy 
A second malignancy is one unrelated to the treatment of a prior malignancy (and is 
NOT a metastasis from the initial malignancy). Second malignancies require ONLY 
routine reporting unless otherwise specified. 
 
 
10.55 Pregnancy, Fetal Death, and Death Neonatal  
If a female subject (or female partner of a male subject) taking investigational 
product becomes pregnant, the subject taking should notify the Investigator, and 
the pregnant female should be advised to call her healthcare provider 
immediately. The patient should have appropriate follow-up as deemed necessary 
by her physician. If the baby is born with a birth defect or anomaly, a second 
expedited report is required. 
Prior to obtaining private information about a pregnant woman and her infant, the 
investigator must obtain consent from the pregnant woman and the newborn 
infant’s parent or legal guardian before any data collection can occur. A consent 
form will need to be submitted to the IRB for these subjects if a pregnancy 
occurs. If informed consent is not obtained, no information may be collected. 
In cases of fetal death, miscarriage or abortion, the mother is the patient. In cases 
where the child/fetus experiences a serious adverse event other than fetal death, 
the child/fetus is the patient. 
NOTE: When submitting Mayo Expedited Adverse Event Report reports for 
“Pregnancy”, “Pregnancy loss”, or “Neonatal loss”, the potential risk of exposure 
of the fetus to the investigational agent(s) or chemotherapy agent(s) should be 
documented in the “Description of Event” section. Include any available medical 
documentation. Include this form: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/Pregna
ncyReportFormUpdated.pdf 
10.551 
Pregnancy 
Pregnancy should be reported in an expedited manner as Grade 3 
“Pregnancy, puerperium and perinatal conditions - Other 
(pregnancy)” under the Pregnancy, puerperium and perinatal 
conditions SOC. Pregnancy should be followed until the outcome is 
known. 
10.552 
Fetal Death 
Fetal death is defined in CTCAE as “A disorder characterized by death 
in utero; failure of the product of conception to show evidence of 
respiration, heartbeat, or definite movement of a voluntary muscle after 
expulsion from the uterus, without possibility of resuscitation.” 
Any fetal death should be reported expeditiously, as Grade 4 
“Pregnancy, puerperium and perinatal conditions - Other 
(pregnancy loss)” under the Pregnancy, puerperium and perinatal 
conditions SOC. 
10.553 
Death Neonatal 


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Neonatal death, defined in CTCAE as “A disorder characterized by 
cessation of life occurring during the first 28 days of life” that is felt by 
the investigator to be at least possibly due to the investigational 
agent/intervention, should be reported expeditiously.  
A neonatal death should be reported expeditiously as Grade 4 
“General disorders and administration - Other (neonatal loss)” 
under the General disorders and administration SOC.  
 
10.6 
Required Routine Reporting  
10.61 Baseline and Adverse Events Evaluations 
Pretreatment symptoms/conditions to be graded at baseline and adverse events to 
be graded at each evaluation.  
Grading is per CTCAE v5.0 unless alternate grading is indicated in the table 
below: 
CTCAE  
System/Organ/Class 
(SOC) 
Adverse event/Symptoms 
Baseline 
Each evaluation 
Investigations  
Anemia 
X 
X 
Neutrophil count decreased  
X 
X 
Platelet count decreased  
X 
X 
Gastrointestinal 
Disorders 
Nausea 
X 
X 
Diarrhea 
  
X 
# of stools  
X 
 
Vomiting 
X 
X 
General disorders and 
administration site 
conditions 
Fatigue 
X 
X 
Vascular disorders 
Thromboembolic event 
X 
X 
 
10.62 All other AEs 
Submit via appropriate MCCC Case Report Forms (i.e., paper or electronic, as 
applicable) the following AEs experienced by a patient and not specified in 
Section 10.6: 
10.621 Grade 2 AEs deemed possibly, probably, or definitely related to the study 
treatment or procedure. 
10.622 Grade 3 and 4 AEs regardless of attribution to the study treatment or 
procedure. 
10.623 Grade 5 AEs (Deaths) 
10.6231 
Any death within 30 days of the patient’s last study 
treatment or procedure regardless of attribution to the study 
treatment or procedure. 
10.6232 
Any death more than 30 days after the patient’s last study 
treatment or procedure that is felt to be at least possibly 


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treatment related must also be submitted as a Grade 5 AE, 
with a CTCAE type and attribution assigned. 
 
11.0 
Treatment Evaluation/Measurement of Effect  
The International Myeloma Working Group (IMWG) uniform response criteria(23) will be used 
to assess response to therapy. 
11.1  
Terms and definitions 
 
• 
M-protein: synonyms include M-spike, monoclonal protein and myeloma protein, 
paraprotein, M-component. 
 
Serum M-protein level is quantitated using densitometry on SPEP except in cases 
where the SPEP is felt to be unreliable.   
• M-proteins migrating in the -region (usually IgA M-proteins)  
• Cases in which the M-protein is so large and narrow on agarose (some 
specimens >4 g/dL) that they underestimate the actual immunoglobulin level 
(by greater than 1500 mg/dL) due to technical staining properties of the 
agarose gel. 
• Cases in which there are multiple peaks of same M-protein (aggregates or 
dimers) 
 
If SPEP is not available or felt to be unreliable (above examples) for routine M-
protein quantitation, then quantitative immunoglobulin levels derived from 
nephelometry or turbidometry can be accepted, with the exception that quantitative 
IgG may not be used.  However, this must be explicitly reported at baseline, and only 
nephelometry can be used for that patient to assess response. SPEP derived M-protein 
values and quantitative nephelometric immunoglobulin values cannot be used 
interchangeably.   
 
Urine M-protein measurement is estimated using 24-h UPEP only.  Random or 24 h 
urine tests measuring kappa and lambda light chain levels are not reliable and are not 
recommended. 
 
 
FLC estimation is currently carried out using the serum FLC assay (Freelite, The 
Binding Site Limited, UK).  Patients with kappa/lambda FLC ratio <0.26 are defined 
as having monoclonal lambda FLC and those with ratios >1.65 as having a 
monoclonal kappa FLC.  The monoclonal light chain isotype is considered the 
involved FLC isotype, and the opposite light chain type as the uninvolved FLC type.  
 
• 
Response terms: The following response terms will be used: stringent Complete 
Response (sCR), complete response (CR), very good partial response (VGPR), partial 
response (PR), Minimal Response (MR), stable disease (SD), and progressive disease 
(PD).  


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In addition, for each response category, there will be an “unconfirmed” response 
category, which will be for internal use, for the purpose of guiding decision making 
and test ordering. These designations will applied at the time of the first measurement 
at which the quantitative aspect of the response category has been satisfied without 
the confirmation step having been satisfied. The designation “u” will precede the 
standard abbreviations, and will include usCR, uCR, uVGPR, uPR, uMR, uPD.  
 
• 
Measurable disease: Patients who have a measurable serum or urine M-protein.  
 
o Serum M-protein ≥0.5 g/dl  
         NOTE:  Quantitative IgG may not be used for defining measurable disease 
 
o Urine M-protein ≥ 200 mg/24 h 
o Serum FLC assay: Involved FLC level ≥ 10 mg/dl provided serum FLC ratio is 
abnormal 
o Bone marrow plasma cells ≥ 30% 
o Measurable bone or extramedullary disease on imaging. 
 
Measurable disease 
Cohort A 
(Smoldering MM), 
Cohort B 
(Newly Diagnosed 
MM) 
Cohort C 
(Relapsed/Refractory 
MM) 
Cohort D 
(Relapsed on Len 
maintenance) 
 
Patients who have a 
measurable serum or 
urine M-protein.  
 
o 
Serum M-
protein ≥0.5 g/dl  
         NOTE:  
Quantitative IgG may 
not be used for 
defining measurable 
disease 
 
o 
Urine M-
protein ≥ 200 mg/24 
h 
o 
Serum FLC 
assay: Involved FLC 
level ≥ 10 mg/dl 
provided serum FLC 
ratio is abnormal 
o 
Bone 
marrow plasma cells 
Patients who have a 
measurable serum or 
urine M-protein.  
 
o 
Serum M-
protein ≥0.5 g/dl  
         NOTE:  
Quantitative IgG may 
not be used for 
defining measurable 
disease 
 
o 
Urine M-
protein ≥ 200 mg/24 
h 
o 
Serum FLC 
assay: Involved FLC 
level ≥ 10 mg/dl 
provided serum FLC 
ratio is abnormal 
o 
Bone 
marrow plasma cells 
Patients who have a 
measurable serum or 
urine M-protein.  
 
o 
Serum M-
protein ≥0.5 g/dl  
         NOTE:  
Quantitative IgG may 
not be used for 
defining measurable 
disease 
 
o 
Urine M-
protein ≥ 200 mg/24 
h 
o 
Serum FLC 
assay: Involved FLC 
level ≥ 10 mg/dl 
provided serum FLC 
ratio is abnormal 
o 
Bone 
marrow plasma cells 
Patients who have a 
measurable serum or 
urine M-protein.  
 
o 
Serum M-
protein ≥0.5 g/dl  
         NOTE:  
Quantitative IgG may 
not be used for 
defining measurable 
disease 
 
o 
Urine M-
protein ≥ 200 mg/24 
h 
o 
Serum FLC 
assay: Involved FLC 
level ≥ 10 mg/dl 
provided serum FLC 
ratio is abnormal 
o 
Bone 
marrow plasma cells 


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≥ 30% 
o 
Measurable 
bone or 
extramedullary 
disease on imaging. 
≥ 30% 
o 
Measurable 
bone or 
extramedullary 
disease on imaging. 
≥ 30% 
o 
Measurable 
bone or 
extramedullary 
disease on imaging. 
≥ 30% 
o 
Measurable 
bone or 
extramedullary 
disease on imaging. 
 
 
The serum free light chain (FLC) assay is of particular use in monitoring response to 
therapy in patients who have oligo-secretory or non-secretory disease and should be used 
in assessing response only if the baseline serum and/or urine M proteins are not 
“measurable” as above, and the baseline level of the involved FLC is “measurable.”  
When using this assay, it is important to note that the FLC levels vary considerably with 
changes in renal function and in patients with renal insufficiency, the levels of both the 
kappa and lambda may remain elevated, but the ratio normalizes with achievement of 
CR.  Thus, both the level of the involved and the uninvolved FLC isotype (i.e., the 
involved/uninvolved ratio or involved-uninvolved difference) should be considered in 
assessing response.  Patients included on the study on the basis of FLC alone (i.e., no 
measurable serum/urine M-protein) should be the only ones who are evaluated using 
FLC response criteria.  The others should follow usual criteria and ignore FLC results 
with the exception of defining stringent complete response. 
 
• 
Evaluable disease: Patients who do not have a “measurable” serum M-protein, 
serum free light chain, or urine M-protein. 
 
• 
Oligosecretory myeloma: Patient with multiple myeloma who has NEVER had 
“measurable” serum M-protein or urine M-protein, but has had a detectable M-
protein in his/her serum and/or urine and/or measurable serum free light chain.  
 
• 
Non-secretory myeloma: Patient with multiple myeloma who has NEVER had a 
detectable M-protein in his/her serum and/or urine. 
 
11.2 
Confirmed response  
 
In order to be classified as a hematologic response, confirmation of serum M- protein, 
serum immunoglobulin free light chain (when primary determinant of response) and 
urine M- protein (when primary determinant of response) results must be made by 
verification on two consecutive determinations.   
• 
Bone marrow aspirate and biopsy are only required to document CR or sCR, 
except for patients with evaluable disease only, where a bone marrow is required 
to document all response categories including progression. However, a second 
confirmatory bone marrow is not required to confirm response in any case. 
• 
Radiographic studies are not required to satisfy these response requirements; 
however, if radiographic studies were performed there should be no evidence of 
progressive or new bone lesions. 
 


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11.3 
Bone progression  
 
Caution must be exercised to avoid rating progression on the basis of variation of 
radiologic technique alone.  Compression fracture does not exclude continued response 
and may not indicate progression.  When progression is based on skeletal disease alone, it 
should be discussed with the Study Chair before removing the patient from the study.  
 
 11.4 
 Response and Progression 
 
Criteria for response and progression are listed in Table 11.5. Progressive disease for all 
patients as defined in Table 11.5.  
 
 
 


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Table 11.5 
STANDARD IMWG 
RESPONSE 
CATEGORY 
RESPONSE CRITERIA a 
Stringent Complete 
Response (sCR) b 
CR as defined plus 
Normal FLC ratio and 
• Absence of clonal PCs by immunohistochemistry or 2- to 4- color 
flow cytometry i 
Complete Response 
(CR) b 
• Negative immunofixation of serum and urine c and 
• Disappearance of any soft tissue plasmacytoma and 
• <5% PCs in Bone Marrow and 
• If the only measurable disease is FLC, a normal FLC ratio d  
• For patients with extramedullary plasmacytoma present at 
baseline: a) FDG-avid or PET positive prior to therapy: Mass of 
any size permitted if PET negative and b) Variably FDG-avid or 
PET negative: Regression to normal size on CT. For patients with 
only skin involvement, these same criteria apply to skin lesions 
measured with a ruler. 
Very Good Partial 
Response (VGPR)  
• Serum and urine M-protein detectable by immunofixation but not 
on electrophoresis c or 
• ≥90% reduction in serum M-protein and urine M-protein <100 
mg/24 h c 
• If the only measurable disease is FLC, a >90% reduction in the 
difference between involved and uninvolved FLC levels 
• Not applicable for those patients who do not have a “measurable” 
serum M-spike, serum free light chain, or urine M-spike at baseline 
Partial Response (PR) 
• If present at baseline, ≥ 50% reduction of serum M-protein and 
reduction in 24-hour urinary M-protein by ≥90% or to <200 
mg/24hrs c 
• If the only measurable disease is FLC, a ≥50% reduction in the 
difference between involved and uninvolved FLC levels 
• If the only measurable disease is BM, a ≥ 50% reduction in BM 
PCs (provided the baseline PCs was ≥ 30%) 


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• If present at baseline, ≥ 50% reduction in the size (SPD) of soft 
tissue plasmacytomas j 
• For patients with extramedullary plasmacytoma present at 
baseline: ≥50% decrease in SPD of up to 6 largest dominant 
masses and a) FDG-avid or PET positive prior to therapy: one or 
more PET positive at previously involved sites OR b) Variably 
FDG-avid or PET negative: regression on CT or by measurements 
with a ruler in patients with only skin involvement 
Minimal Response (MR)  
• If present at baseline, ≥25% but ≤ 49% reduction of serum M 
protein and reduction in 24-hour urine M-protein by 50-89% 
which still exceeds 200mg/24 hours c and 
• If present at baseline, ≥25% reduction in the size (SPD) of soft 
tissue plasmacytoma j  
Stable Disease (SD) 
• Not meeting criteria for sCR, CR, VGPR, PR, MR or PD 
Progressive Disease 
(PD) b, h 
 
Increase of 25% from lowest value in any of the following f, g: 
• 
Serum M-protein (absolute increase must be ≥ 0.5 g/dL) and/or 
• 
Urine M-protein (absolute increase must be ≥ 200 mg/24 hrs) 
and/or 
• 
If the only measurable disease is FLC, the difference between 
involved and uninvolved FLC levels (absolute increase must be 
>10 mg/dL)  and/or 
• 
If the only measurable disease is BM, bone marrow PC 
percentage (absolute increase must be ≥ 10%) e  
• 
Appearance of a new lesion(s), ≥50% increase from nadir in SPD 
of more than one lesion, or ≥50% increase in longest diameter of 
a previous lesion >1 cm in short axis. Lesions PET positive if 
PET positive prior to therapy  
 
Or any one or more of the following: 
• 
Development of new bone lesion or soft tissue plasmacytoma or 
≥50% increase from nadir in the size (SPD) of existing bone 
lesions or soft tissue plasmacytoma or ≥ 50% increase in the 
longest diameter of a previous lesion >1 cm in short axis j 
• 
50% increase in circulating plasma cells (minimum of 200 cells 
per L) if this is the only measure of disease 


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Clinical Relapse 
One or more of the following direct indicators of increasing 
disease and/or end-organ dysfunction that are considered related 
to the underlying plasma cell proliferative disorder: 
1.  Development of new soft tissue plasmacytomas or bone lesions 
on skeletal survey, magnetic resonance imaging, or other imaging 
2.  Definite increase in the size of existing plasmacytomas or bone 
lesions. A definite increase is defined as a 50% (and at least 1 cm) 
increase as measured serially by the sum of the products of the 
cross-diameters of the measurable lesion 
3.  Hypercalcemia (>11.5 mg/dL; >2.875mM/L) 
4.  Decrease in hemoglobin of more than 2 g/dL (1.25mM) or to less 
than 10 g/dL 
5.  Rise in serum creatinine by more than or equal to 2 mg/dL 
(≥177mM/L) 
6.  Hyperviscosity 
 
 
a All response categories require two consecutive assessments (sCR, CR, VGPR, PR, MR, PD) made at any time 
before the institution of any new therapy.  sCR, CR, VGPR, PR, MR and SD categories require no known evidence 
of progressive or new bone lesions or extramedullary plasmacytomas if radiographic studies were performed. 
However, radiographic studies are not required to satisfy these response requirements. Bone marrow assessments 
need not be confirmed. Each category, except for stable disease, will have a working subcategory of “unconfirmed” 
[prefix ‘u”] to designate first time point at which response category MAY have been achieved if confirmed. The 
date of the initial test is considered as the date of response for evaluation of time dependent outcomes such as 
duration of response. 
 
b CR patient will need to progress at the same level as VGPR and PR patients to be considered a PD.  A positive 
immunofixation alone is not sufficient. 
 
c If more than one M protein spike meets the criteria for measurable disease at baseline, then both need to be 
followed for response.  Otherwise, only follow the measurable M protein spike for response.   
 
d In patients in whom the only measurable disease is by serum FLC levels: CR in such patients indicates a normal 
FLC ratio of 0.26-1.65 in addition to the CR criteria listed above. 
 
e Bone marrow criteria for PD are only to be used in patients without measurable disease by M protein and by FLC;  
 
f A "25% increase" refers to M protein, FLC and bone marrow results and does not refer to bone lesions, soft tissue 
plasmacytoma or hypercalcemia.  The lowest value does not need to be a confirmed value.  If the lowest serum M-
protein is ≥ 5 g/dL, an increase in serum M-protein of ≥ 1 g/dL is sufficient to define disease progression. 
 
g In the case where a value is felt to be a spurious result per physician discretion (for example, a possible lab error), 
that value will not be considered when determining the lowest value. 
 
h Progressive disease should be confirmed on two consecutive evaluations, where the timing of confirmation is per 
the treating physician and can be done immediately within the same cycle or on the next cycle.  However, treatment 
may be discontinued for progressive disease that is unconfirmed per physician discretion.  In this case, an objective 
status of PD should be entered on the measurement form and progressive disease should be reported on the event 
monitoring form. 
 
i Presence/absence of clonal cells is based upon the k/l ratio. An abnormal k/l ratio by immunohistochemistry 
requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting presence of an abnormal clone is 
k/l of 4:1 or 1:2.  
 


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j Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT 
scans where applicable. For patients with only skin involvement, skin lesions should be measured with a ruler. 
Measurement of tumor size will be determined by the sum of the products of the maximal perpendicular diameters 
of measured lesions (SPD). 
 
12.0 
Descriptive Factors  
12.1 
Prior treatment: 0 vs 1 vs 2 vs 3+ 
12.2      Parameters followed for hematologic response: serum monoclonal protein ≥0.5 g/dL and       
urine monoclonal protein ≥200 mg/24 hours vs. serum monoclonal protein ≥0.5 g/dL 
only vs. urine monoclonal protein ≥200 mg/24 hours only vs. serum immunoglobulin free 
light chain ≥10 mg/dL vs. bone marrow plasma cells >= 30% vs. measurable bone or 
extramedullary disease on imaging. Distinguish between SPEP measurements versus 
quantitative IgA measurements versus quantitative IgD measurements for serum 
monoclonal protein. 
12.3 
mSMART FISH risk level: high risk vs low risk vs unknown. 
13.0 
Treatment/Follow–up Decision at Evaluation of Patient  
13.1 
Off protocol treatment 
Patients who go off protocol treatment before completing 6 cycles of treatment will not 
continue to be followed.   
 
13.2  
Criteria for Treatment Discontinuation  
Patients may discontinue treatment for the following reasons:  
• Progressive multiple myeloma (see Section 11.0) 
• Patient withdraws consent to continue in the trial  
• Patient develops an intercurrent illness that precludes further participation, or requires a 
prohibited concomitant treatment  
• The Investigator withdraws the patient in the patient’s best interests  
• Patient is lost to follow-up (defined as the inability to contact the patient on 3 separate 
occasions)  
• Administrative reasons (e.g., the patient is transferred to hospice care)  
• An adverse event, which in the opinion of the investigator precludes further trial 
participation  
 
Patients will be taken off study if they discontinue treatments for any of the reasons 
above.  
 
13.3  
Criteria for Study Discontinuation  
The study may be temporarily or permanently discontinued at any site and at any time.  
Reasons for study discontinuation may include, but are not limited to, the following:  
• Safety concerns  
• Non-compliance with the protocol, Good Clinical Practice guidance or other regulatory 
requirements by the Investigator(s)  
• Request to discontinue the trial by a regulatory or health authority or an IRB  
 
134 
Ineligible 


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A patient is deemed ineligible if after registration, it is determined that at the time of 
registration, the patient did not satisfy each and every eligibility criteria for study entry. 
  
• 
If the patient received treatment, the patient may continue treatment at the discretion 
of the physician as long as there are not safety concerns.  The patient will continue in 
the Active Monitoring/Treatment phase of the study, as per section 4.0 of the 
protocol. 
• 
If the patient never received treatment, on-study material must be submitted. No 
further data submission is necessary.  
 
13.5 
Major violation 
A patient is deemed a major violation, if protocol requirements regarding treatment in 
cycle 1 of the initial therapy are severely violated that evaluability for primary end point 
is questionable. If the patient received treatment, the patient may continue treatment at 
the discretion of the physician as long as there are not safety concerns.  The patient will 
continue in the Active Monitoring/Treatment phase of the study, as per section 4.0 of the 
protocol. 
 
13.6 
Cancel 
A patient is deemed a cancel if he/she is removed from the study for any reason before 
any study treatment is given. On-study material and the End of Protocol 
Treatment/Intervention Form must be submitted. No further data submission is necessary. 


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14.0 
Body Fluid Biospecimens 
  
14.1  
Summary Table of Research Blood and Body Fluid Specimens to be Collected for this Protocol  
Note: Biospecimen Collection will be done under separately established IRB # 521-93 or IRB# 14-009163 or 919-04 
Research  
Specimen Purpose  
(check all that apply) 
Mandatory 
or 
Optional 
Blood or Body 
Fluid being 
Collected 
Type of 
Collection 
Tube (color of 
tube top) 
Volume to 
collect per tube 
(# of tubes to be 
collected) 
Prior to 
D1C1 
 
 
 
Prior to 
D1C2 
 
 
 
End of 
treatment 
(optional) 
Process at 
site? (Yes or 
No) 
Temperatu
re 
Conditions 
for Storage 
/Shipping 
Bone marrow plasma 
☒ Correlative 
☐ Eligibility 
Confirmation 
☐ Banking 
☐ Other  
 
 
Mandatory  
Bone marrow 
aspirate 
EDTA 
(purple) 
4 mL (1) 
X 
X 
 
 
X 
Yes 
Cool Pack 
or Ice 
Bone marrow cells 
☒ Correlative 
☐ Eligibility 
Confirmation 
☐ Banking 
☐ Other  
 
 
Mandatory 
Bone marrow 
aspirate 
ACD (yellow) 
35 mL (1) 
X 
X 
 
 
X 
Yes 
Cool Pack 
or Ice 
Peripheral Blood 
☒ Correlative 
☐ Eligibility 
Confirmation 
☐ Banking 
☐ Other  
 
 
Mandatory 
Whole Blood 
ACD 
(yellow) 
18 mL (1) 
 
X 
X 
 
 
X 
Yes 
Cool Pack 
or Ice 


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14.2 
Shipping and Handling   
 
Kits will not be used. Each site will use their own supply of tubes  
14.22 Shipping 
Bone marrow and blood samples can be shipped with Cool Pak the same 
day they are collected (Monday-Thursday). They should be shipped 
priority overnight taking care to avoid Friday collection and shipping. 
If unavoidable, Friday shipping with Saturday delivery can be arranged 
contacting the laboratory in advance. 
 
Please notify Mayo Clinic by email lehman.stacey@mayo.edu or phone 
(507) 284-3805 to notify laboratory when specimens are being shipped. 
  
Stacey Lehman 
Mayo Foundation  
221 4th Avenue SW 
Stabile 613 
Rochester, MN 55905 
 
14.3 
Metabolomics profiling 
             To determine if specific metabolite profiles within the bone marrow and 
peripheral blood plasma will be reflective of the metabolic phenotype within the 
clonal bone marrow plasma cells that predict for response to therapy with an 
IMiD. 
 
Methodology: For this analysis, bone marrow and peripheral blood plasma will 
undergo large scale, untargeted metabolite profiling via liquid chromatography 
mass spectrometry. Differentially expressed metabolites in responder versus non-
responders will be evaluated for the development of a potential biomarker 
predicting clinical response.   
 
Sample type and timing: Bone marrow aspirate samples will be collected in (1) 
5 ml EDTA (purple top) tube and placed on ice or a cool pack. Samples to be 
collected prior to cycle 1 and then prior to cycle 2.  
 
Sample Destination: 
Stacey Lehman 
Mayo Foundation 
221 4th Ave SW 613 Stabile 
Rochester, MN 55905 
 
14.4     Multiple myeloma cell retrieval  
 
Samples type and timing: For studies utilizing intracellular metabolomics as 
well as genomics and transcriptomics of the MM cells, 35 ml of bone marrow 
aspirate will be obtained in (6) 6 mL ACD (yellow top) tubes in addition to the 5 


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ml of bone marrow aspirate from the (1) 5 mL EDTA (purple top) tube prior to 
cycle 1 and then prior to cycle 2.  
 
Sample Destination: 
Stacey Lehman 
Mayo Foundation 
221 4th Ave SW 613 Stabile 
Rochester, MN 55905 
 


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15.0 
Drug Information 
IND exempt (159997) 
15.1 
Lenalidomide for Oral Administration (Revlimid®) 
 
15.11 Background: Lenalidomide has antineoplastic, immunomodulatory and 
antiangiogenic characteristics via multiple mechanisms. Lenalidomide selectively 
inhibits secretion of proinflammatory cytokines (potent inhibitor of tumor 
necrosis factor-alpha secretion); enhances cell-mediated immunity by stimulating 
proliferation of anti-CD3 stimulated T cells (resulting in increased IL-2 and 
interferon gamma secretion); inhibits trophic signals to angiogenic factors in 
cells. Lenalidomide inhibits the growth of myeloma cells by inducing cell cycle 
arrest and cell death. 
 
15.12 Formulation and Dispensing: Commercially available for oral administration 
as: Capsules: 5 mg, 10 mg, 15 mg and 25 mg  
 
Lenalidomide is approved for marketing only under a FDA approved, restricted 
distribution program called RevAssist. Physicians, pharmacies, and patients must 
be registered; a maximum 28-day supply may be dispensed; a new prescription is 
required each time it is filled; pregnancy testing is required for females of 
childbearing potential. 
 
15.13 Preparation, storage, and stability: Store oral capsules at controlled 
room temperature between 15ºC and 30ºC (59 ºF and 86 ºF). Refer to 
labeling on the bottle for expiration date of the commercial tablets. 
  
15.14 Administration:  Refer to the treatment section for specific administration 
instructions. Administer with water. Swallow capsule whole; do not break, open, 
or chew. 
 
 
15.15 Pharmacokinetic information: 
Absorption: Rapid 
Metabolism: Approximately two-thirds of Lenalidomide is eliminated 
unchanged through urinary excretion.  
Protein binding: ~30% 
Time to peak, plasma: Healthy volunteers: 0.6-1.5 hours; Myeloma 
patients: 0.5-4 hours 
Half-life elimination: ~3 hours 
Excretion: Urine (~67% as unchanged drug) 
 
 
15.16 Potential Drug Interactions: 
Increased Effect/Toxicity: Abatacept and Anakinra may increase the risk 
of serious infection when used in combination with Lenalidomide. 
Lenalidomide may increase the risk of infections associated with vaccines 
(live organism). 
Decreased Effect: Lenalidomide may decrease the effect of vaccines 
(dead organisms). 
Herb/Nutraceutical Interactions: Avoid echinacea (has 
immunostimulant properties; consider therapy modifications). 


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15.17 Known potential adverse events: Consult the package insert for the most 
current and complete information.  
 
 
Boxed Warnings:  
1. Potential for human birth defects 
2. Hematologic toxicity (neutropenia and thrombocytopenia) 
3. Deep Venous Thrombosis and Pulmonary Embolism 
 
Common known potential toxicities, > 10%:   
Cardiovascular: Peripheral edema  
Central nervous system: Fatigue, pyrexia, dizziness, headache 
Dermatologic: Pruritus, rash, dry skin 
Endocrine & metabolic: Hyperglycemia, hypokalemia 
Gastrointestinal: Diarrhea, constipation, nausea, weight loss, dyspepsia, 
anorexia, taste perversion, abdominal pain 
Genitourinary: Urinary tract infection 
Hematologic: Thrombocytopenia, neutropenia, anemia, myelosuppression 
is dose-dependent and reversible with treatment interruption and/or dose 
reduction 
Infection, especially when white blood cell count is low 
Neuromuscular & skeletal: Muscle cramp, arthralgia, back pain, tremor, 
weakness, paresthesia, limb pain, muscle spasms 
Ocular: Blurred vision 
Respiratory: Nasopharyngitis, cough, dyspnea, pharyngitis, epistaxis, 
upper respiratory infection, pneumonia, shortness of breath 
 
Less common known potential toxicities, 1% - 10%:  
Cardiovascular: Edema, deep vein thrombosis, hypertension, chest pain, 
palpitation, atrial fibrillation, syncope 
Central nervous system: Insomnia, hypoesthesia, pain, depression 
Dermatologic: Bruising, cellulitis, erythema 
Endocrine & metabolic: Hypothyroidism, hypomagnesemia, hypocalcemia 
Gastrointestinal: Vomiting, xerostomia, loose stools 
Genitourinary: Dysuria 
Hematologic: Leukopenia, febrile neutropenia, Lymphopenia 
Hepatic: ALT increased, abnormal hepatic function tests 
Neuromuscular & skeletal: Myalgia, rigors, neuropathy 
Respiratory: Sinusitis, rhinitis, bronchitis, pulmonary embolism 
Miscellaneous: Night sweats, diaphoresis, fever 
 
Rare known potential toxicities, <1% (Limited to important or life-
threatening):  
Angioedema, Stevens-Johnson Syndrome and Toxic Epidermal 
Necrolysis, Tumor Lysis Syndrome, Graft vs. Host Disease, 
rhabdomyolysis, Kidney damage which may require dialysis 
 
15.18 Drug procurement:  Commercial supplies. Pharmacies or clinics shall obtain 
supplies from normal commercial supply chain or wholesaler. 
 
 


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As a requirement of the REMS program, access to Lenalidomide is restricted. 
Lenalidomide is approved for marketing only under a FDA approved, restricted 
distribution program called REVLIMID REMS (www.REVLIMIDREMS.com) 
formerly known as the RevAssist program. Physicians, pharmacies, and patients 
must be registered; a maximum 28-day supply may be dispensed; a new 
prescription is required each time it is filled; pregnancy testing is required for 
females of childbearing potential. 
 
15.19- Nursing Guidelines-Lenalidomide 
 
15.191 Myelosuppression is dose-dependent and reversible with treatment 
interruption and/or dose reduction. Monitor CBC w/diff regularly. 
Instruct patient to report any unusual bruising or bleeding 
(thrombocytopenia); signs and symptoms of infection (neutropenia); and 
energy conserving lifestyle (anemia). 
15.192 Lenalidomide can have thrombotic adverse events (i.e DVT and PE). 
Instruct patient to report any limb swelling or pain, and to seek medical 
attention for shortness of breath or chest pain. 
15.193 Because of the potential for birth defects patients should be instructed in 
effective methods of birth control. Female patients should use 2 forms of 
birth control during treatment and for 4 weeks after discontinuing 
therapy. Males must be instructed to use a latex condom during any 
sexual contact with a woman of child bearing potential (even if they have 
had a vasectomy), because it is unknown if lenalidomide is present in 
semen. 
15.194 Patents may experience pruritus, rash and dry skin. Because of the rare 
risk of Steven’s Johnson Syndrome, patients should immediately report 
any rash to their provider. 
15.195 Drug may cause hyperglycemia. Patients with diabetes or impaired 
fasting glucose may need to have their glucose levels monitored more 
closely. 
15.196 Gastrointestinal side effects (diarrhea, constipation, nausea, dyspepsia, 
anorexia, etc) are commonly seen. Manage patent symptomatically and 
monitor for effectiveness. 
15.197 Patients may experience myalgias, arthralgias, parasthesias and other 
generalized pain. Administer analgesics as ordered and monitor for their 
effectiveness. Rarely infective bursitis and arthritis have been reported. 
Instruct patients to report any joint pain or redness to study team 
immediately. 
15.198 Upper respiratory symptoms (nasopharyngitis, cough, epistaxis, etc.) can 
be seen. Manage symptomatically and monitor for effectiveness. 
15.199 Agent may cause fatigue, dizziness, vertigo or blurred vision. Instruct 
patients to use caution when driving or operating machines.  
15.200 Monitor LFT’s and report any elevations to the study team. Instruct 
patient to report abdominal pain and/or jaundice to the study team. 
15.201 All prescribers and patients must be enrolled into the REVLIMID REMS 
program. Only enough lenalidomide for one cycle of therapy will be 
supplied to the patient each cycle. 


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15.202 Rarely secondary malignancies have been seen after lenolidamide 
therapy, including MDS, squamous/basal cell carcinomas of the skin, T-
cell type acute leukemia. 
15.203  Monitor Renal function, renal failure has been reported. 
15.204 Acute GVHD following Allo Transplant has been seen.  
15.205 Rarely tumor lysis syndrome has been seen. Monitor appropriate TLS 
labs and report any abnormalities to the study team. 
 
15.2 
Pomalidomide (CC-4047, Pomalyst®) 
 
15.21 Background: Pomalidomide (CC-4047) is a novel drug in the class of 
immunomodulatory agents known as IMiDs compounds.  Pomalidomide binds to 
its molecular target cereblon (CRBN), a protein that is part of an E3 ubiquitin 
ligase complex, which is responsible for the polyubiquitination of substrate 
proteins, targeting them for subcellular redistribution and destruction by the 
proteasome. The pharmacologic properties of pomalidomide are of potential 
therapeutic benefit in the treatment of various hematologic neoplasms (such as 
multiple myeloma and myeloproliferative neoplasm-associated myelofibrosis), 
non-neoplastic hematologic disorders (such as β-thalassemia and sickle cell 
disease) and non-hematologic disorders such as systemic sclerosis, as well as 
solid tumor neoplasms. 
 
15.22 Formulation:  Pomalidomide capsules can be 0.5-mg gelatin capsules (size 4 
reddish brown), 1-mg hard gelatin capsules (size 4 reddish brown), 2-mg (size 2 
reddish-brown), 3-mg and 4-mg hard gelatin capsules (size 2 reddish-brown), and 
5-mg hard gelatin capsules (size 1 reddish-brown), containing pomalidomide, 
mannitol, pregelatinized starch, and sodium stearyl fumarate.  
  
Pomalidomide capsules are supplied in high density polyethylene (HDPE) 
containers fitted with induction seals and child-resistant plastic closures or 
PVC/PCTFE blister with push-through foil. 
 
 
15.23 Preparation and storage:  Store drug at controlled room temperature, 
between 68-77 ºF (20-25ºC) or as indicated on the manufacturer’s label.  
The expiration date is indicated on the label. 
 
 
Only enough study drug for one month of therapy may be dispensed. 
 
15.24 Administration:  Pomalidomide is administered by mouth at approximately the 
same time each day.  Capsules should be swallowed whole, and should not be 
broken, chewed or opened. If a dose of pomalidomide is missed, it should be 
taken as soon as possible on the same day. If it is missed for the entire day, it 
should not be made up.  Patients should be instructed never to give this medicinal 
product to another person and to return any unused capsules to the study doctor at 
the end of treatment.  Patients who take more than the prescribed dose of 
pomalidomide should be instructed to seek emergency medical care if needed 
and contact study staff immediately.   
 
15.25 Pharmacokinetic information:  
a)  Absorption – oral absorption has been moderately rapid with first dose Cmax 
occurring in 1.5 to 4 hrs. More than 70% of the pomalidomide dose is absorbed 


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in humans.  A high fat meal decreased the rate of absorption but had minimal 
effect on overall extent of absorption; therefore drug may be administered 
without regard to food intake. 
b)  Distribution – Apparent volume of distribution in healthy subjects 
ranged from 74-138 L across a dose range of 1 to 10 mg daily.  
Pomalidomide protein binding in human plasma is low to moderate 
(15.8% for R-enantiomer, 42.2% for S-enantiomer) and the binding is 
concentration independent in the concentration range of 30 and 1000 
ng/mL.  Drug distributes into semen. 
 
c)  Metabolism – Eight metabolites were detected in plasma, each at 
exposures < 10% of the plasma pomalidomide.  CYP-dependent 
metabolites accounted for approximately 43% of the excreted 
radioactivity, while non-CYP dependent hydrolytic metabolites accounted 
for 25%, and excretion of unchanged pomalidomide accounted for 10%. 
d)  Excretion – In healthy patients, 72.8% of the dose was recovered in 
urine and 15.5% was recovered in feces. Less than 3% of the dose is 
excreted as unchanged pomalidomide in the urine.  The geometric mean 
terminal elimination half-life (t1/2) of pomalidomide was approximately 7.5 
hours. 
 
In pomalidomide renal studies, no dose adjustment was required for subjects with 
renal impairment. On hemodialysis days, subjects were instructed to take 
pomalidomide following hemodialysis.  No dose adjustment of pomalidomide is 
required for patients with hepatic impairment as defined by the Child-Pugh 
criteria. 
 
15.26 Potential Drug Interactions:  Pomalidomide is partially metabolized by 
CYP1A2 and CYP3A4/5.  Pomalidomide is also a substrate for P-glycoprotein 
(P-gp). Coadministration of pomalidomide with the strong CYP3A4/5 and P-gp 
inhibitor ketoconazole, or the strong CYP3A4/5 inducer carbamazepine, had no 
clinically relevant effect on exposure to pomalidomide.  Coadministration of the 
strong CYP1A2 inhibitor fluvoxamine with pomalidomide increased mean 
exposure to pomalidomide by 125% compared to pomalidomide alone. If strong 
inhibitors of CYP1A2 are coadministered with pomalidomide, the pomalidomide 
dose by should be reduced 50%. 
Smoking: Administration of pomalidomide in smokers, with smoking tobacco 
known to induce the CYP1A2 isoform, had no clinically relevant effect on 
exposure to pomalidomide relative to that exposure to pomalidomide observed in 
non-smokers. 
Dexamethasone: Co-administration of multiple doses of 4 mg pomalidomide 
with 20 mg to 40 mg dexamethasone (a weak inducer of CYP3A) to patients with 
multiple myeloma had no effect on the pharmacokinetics of pomalidomide 
compared with pomalidomide administered alone. 
 
15.27  Known potential toxicities:   
Very common known potential toxicities, ≥ 10%:   
Anemia, leukopenia, neutropenia, thrombocytopenia, constipation, diarrhea, 
nausea, fatigue, peripheral edema, pyrexia, bronchitis, pneumonia, upper 
respiratory tract infection, decreased appetite, bone pain, muscle spasm, 
dizziness, peripheral neuropathy, blood creatinine increased, acute renal failure, 


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cough, dyspnea, pruritis 
 
Common known potential toxicities, ≥1% - <10%:  
Febrile neutropenia, pancytopenia, vertigo, vomiting, gastrointestinal 
hemorrhage, hemorrhoidal hemorrhage, rectal hemorrhage, hematochezia, 
gingival bleeding, bronchopneumonia, herpes zoster, nasopharyngitis, 
neutropenic sepsis, respiratory tract infection, alanine aminotransferase 
increased, increased liver function test, aspartate aminotransferase increased, 
gamma-glutamyltransferase increased, neutrophil count decreased, platelet count 
decreased, white blood cell count decreased, hyperkalemia, hyponatremia, 
depressed level of consciousness, peripheral sensory neuropathy, paresthesia, gait 
disturbance, polyneuropathy, hypoesthesia, neuralgia, peripheral motor 
neuropathy, tremor, confusional state, renal failure, renal impairment, 
hypercreatininemia, urinary retention, pelvic pain, pulmonary embolism, pruritus 
generalized, rash, swelling face, face edema, deep vein thrombosis 
 
Uncommon and rare known potential toxicities, <1%:  
Melena, Mallory-Weiss syndrome, upper gastrointestinal hemorrhage, mucosal 
hemorrhage, hyperbilirubinemia, blood bilirubin increased, transaminases 
increased, blood alkaline phosphates increased, liver function test abnormal, basil 
cell carcinoma, dysesthesia, areflexia, motor dysfunction, sensory disturbance, 
burning sensation, muscle atrophy, blood urea increased, creatinine renal 
clearance decreased, oliguria, glomerular filtration rate decreased, renal tubular 
necrosis, acute prerenal failure, azotemia, pneumonitis, interstitial lung disease, 
pruritis generalized, angioedema, urticarial, eyelid edema,  
 
Frequency not defined:  
Hepatitis, hepatitis B viral reactivation, tumor lysis syndrome, squamous cell 
carcinoma of skin, eye swelling, periorbital edema, lip swelling, swollen tongue, 
mouth edema, pharyngeal edema, Stevens-Johnson syndrome, toxic epidermal 
necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS) 
 
All study participants must be registered into the mandatory POMALYST 
REMS™ program, and be willing and able to comply with the requirements of 
the POMALYST REMS™ program.  Females of reproductive potential must 
adhere to the scheduled pregnancy testing.  Females of childbearing potential 
should not handle or administer pomalidomide unless they are wearing gloves. 
 
15.28 Drug procurement:   Commercial supplies. Pharmacies or clinics shall obtain 
supplies from normal commercial supply chain or wholesaler. 
 
   
Per the standard   POMALYST REMS™ program requirements, all 
physicians who prescribe pomalidomide for research subjects enrolled into 
this trial, and all research subjects enrolled into this trial, must be 
registered in and must comply with all requirements of the POMALYST 
REMS™ program.   
 
15.29  Nursing Guidelines 
 
15.259 Agent is known to be teratogenic in rabbits.  Therefore all women who 
are pregnant or who could become pregnant, should not handle the agent 


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outside of the original packaging. Chemotherapy gloves should be worn 
if contact is necessary. 
 
15.260 Because of the similarity of this agent to thalidomide certain precautions 
MUST be employed by all subjects on protocol and for 4 weeks after 
discontinuation of agent. Instruct patients the following must be adhered 
to: No donation of tissue/blood/semen/sperm; sexually active males/ 
females must use protocol-specific contraception (regardless of fertility 
status-i.e. history of vasectomy). 
 
15.261 Cytopenias are common (neutropenia most common). Monitor CBC 
closely and instruct patient to report any signs/symptoms of infection or 
unusual bruising or bleeding to the study team. 
 
 
15.262 Thrombotic events have been reported. Anticoagulation prophylaxis may 
be recommended. Instruct patients to report any problems with bleeding, 
extremity pain or swelling, or shortness of breath to the study team 
immediately.  
 
15.263 Patients may experience cough, URI, pneumonia, or sinusitis. Instruct 
patients to report respiratory symptoms to the study team. 
 
 
15.264 Gastrointestinal side effects consisting of diarrhea, constipation, 
stomatitis, nausea, decreased appetite, and abdominal pain have been 
seen. Treat symptomatically and monitor for effectiveness. 
 
15.265 Drug should be taken without food (at least 2 hours before or 2 hours 
after a meal). Do not open or crush capsules. 
 
 
15.266 Patients may experience myalgias and muscle spasms. Treat 
symptomatically and monitor for effectiveness. 
 
15.267 Fatigue is common. Instruct patient in energy conserving lifestyle. 
 
5.199b Warn patients about the possibility of peripheral neuropathy, headache, 
confusion, and dizziness. 
 
15.199c Patients may experience URI, pneumonia, dyspnea, and cough. Instruct 
patients to report respiratory symptoms to the study team.  
 
15.199d Severe dermatologic reactions have been seen (including urticaria). 
Instruct patient to report and rash or skin changes to the study team. 
 
15.199e All patients must be registered in the POMALYST REMS program. See 
protocol for more details. 
 
15.99f Monitor creatinine, as patients may experience elevated creatinine levels, 
with rare reports of renal failure. 


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15.199g  Rare reports of GI bleeding have been seen. Instruct patient to report 
any hematochezia, or melena to the study team immediately.  
 
 
15.3 
Dexamethasone for Oral Administration (DXM) 
 
15.31 Background: Dexamethasone is an adrenal corticosteroid compound. 
Dexamethasone decreases inflammation by suppression of neutrophil migration, 
decreased production of inflammatory mediators, and reversal of increased 
capillary permeability; suppresses normal immune response. Dexamethasone’s 
mechanism of antiemetic activity is unknown. 
 
15.32 Formulation: Commercially available for oral administration as:  
 
Tablets [scored]: 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 4 mg, and 6 mg 
 
Solution, oral: 0.5 mg/5 mL (500 mL) 
Solution, oral concentrate: Dexamethasone Intensol: 1 mg/mL (30 mL) 
 
15.33 Preparation, storage, and stability: Refer to package insert for complete 
preparation and dispensing instructions. Store oral tablets at room 
temperature between 20ºC to 25ºC (60ºF to 77ºF). Protect from moisture. 
Dispense in a well-closed, light-resistant container as defined in the 
USP/NF. Store oral liquid at room temperature, do not freeze. Do not use 
if solution contains a precipitate. Refer to commercial package for drug 
expiration date. 
 
15.34 Administration:  Refer to the treatment section for specific administration 
instructions. May be taken with meals to decrease GI upset.  
 
 
15.35 Pharmacokinetic information: 
Onset of action: Prompt 
Duration of metabolic effect: 72 hours 
Metabolism: Hepatic 
Half-life elimination: Normal renal function: 4 ± 0.9 hours; Biological 
half-life: 36-54 hours 
Time to peak, serum: Oral: 1-2 hours 
Excretion: Urine (~10%) 
 
 
15.36 Potential Drug Interactions: 
Cytochrome P450 Effect: Substrate of CYP3A4 (major), P-
glycoprotein/ABCB1; Induces CYP2A6 (weak/moderate), 2C9 
(weak/moderate), 3A4 (weak), UGT1A1 
Increased Effect/Toxicity: Aprepitant, azole antifungals, calcium channel 
blockers, cyclosporine, estrogens, and macrolides may increase the serum 
levels of corticosteroids. Corticosteroids may increase the hypokalemic 
effects of amphotericin B or potassium-wasting diuretics (loop or 
thiazide); monitor. Refer to the package insert for a listing of other drugs. 
Decreased Effect: Antacids and bile acid sequestrants may reduce the 
absorption of corticosteroids, separate administration by 2 hours. 
Aminoglutethimide, barbiturates, and CYP3A4 inducers may reduce the 
serum levels/effects of dexamethasone.  Serum concentrations of isoniazid 


MC210809 
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Protocol Version Date:13Jun2023 
 
 
may be decreased by corticosteroids. Corticosteroids may lead to a 
reduction in warfarin effect. Corticosteroids may suppress the response to 
vaccinations. 
Ethanol/Nutrition/Herb Interactions:  
Ethanol: Avoid ethanol (may enhance gastric mucosal irritation). 
Food: Dexamethasone interferes with calcium absorption. Limit caffeine. 
Herb/Nutraceutical: Avoid cat’s claw, Echinacea (have immunostimulant 
properties) 
 
15.37 Known potential adverse events: Consult the package insert for the most 
current and complete information.  
 
Common known potential toxicities, frequency not defined:   
Fluid and electrolyte disturbances, congestive heart failure in susceptible 
persons, hypertension, euphoria, personality changes, insomnia, 
exacerbation of infection, exacerbation or symptoms of diabetes, 
psychosis, muscle weakness, osteoporosis, vertebral compression 
fractures, pancreatitis, esophagitis, peptic ulcer, dermatologic disturbances, 
convulsions, vertigo and headache, endocrine abnormalities, ophthalmic 
changes, and metabolic changes. Some patients have experienced itching 
and other allergic, anaphylactic or hypersensitivity reactions. Withdrawal 
from prolonged therapy may result in symptoms including fever, myalgia 
and arthralgia. 
 
15.38 Drug procurement:  Commercial supplies. Pharmacies or clinics shall obtain 
supplies from normal commercial supply chain or wholesaler. 
 
15.39 Nursing Implications: 
 
15.391 Monitor regularly for hypertension, CHF and other evidence of fluid 
retention. 
 
15.392 Advise patient of possible mood or behavioral changes, i.e., depression, 
euphoria, insomnia, even psychosis.  Instruct patient to report any 
suspected changes to healthcare team. 
 
15.393 Assess for symptoms of gastric ulcer, heartburn, or gastritis.  Suggest 
antacids.  Instruct patient to report symptoms to healthcare team if unable 
to control. 
 
15.394 Evaluate signs of infection, particularly local candidal infections and 
treat appropriately. 
 
15.395 Monitor blood glucose frequently. 
 
15.396 Instruct patient to report frequent, unrelenting headaches or visual 
changes to healthcare team. 
 
15.397 Advise patient that easy bruising is a side effect. 
 


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16.0 
Statistical Considerations and Methodology  
16.1 
Overview:   
 
This is a pilot study to determine the response rates (>PR) of the combination of an 
immunomodulator and dexamethasone in Multiple Myeloma (MM) patients of each 
clinically relevant biomarker. This combination will be evaluated in four cohorts: Cohort 
A (Smoldering MM), Cohort B (Newly Diagnosed MM), Cohort C (Relapsed/Refractory 
MM) and Cohort D (Relapsed on Len maintenance). This study will not utilize a formal 
statistical design but will focus more on estimation rather than hypothesis testing. 
 
16.11  Primary Endpoint: The primary endpoint of this trial is to estimate (>PR)  
response rates (RR) after one cycle of treatment. Biomarkers of interest will be 
identified and categorized into clinically relevant groups (e.g. positive vs. 
negative) by evaluating baseline and post treatment (after cycle one) 
biospecimens. RR will be estimated within each biomarker.  
 
 
16.2  
Statistical Design 
 
Due to the lack of data to identify relevant biomarkers, the estimation of RR would be of 
interest. In each group, the response rates will be examined to see if there’s any 
preliminary evidence to suggest further studies. This study will not utilize a formal 
statistical design. 
  
For each biomarker category, the RR will be estimated by the number of patients who 
achieve a PR or better divided by the total number of evaluable patients in each cohort. 
Exact binomial 95% confidence intervals for these rates will be calculated. 
 
16.22 Sample Size: A maximum of 30 evaluable patients will be accrued in cohort A 
and B and 60 patients in cohort C and D respectively. We anticipate accruing an 
additional 2 in cohort A and B and 3 in cohort C and D to account for 
ineligibility, cancellation, major treatment violation, or other reasons. Therefore, 
the maximum projected accrual is 190 patients (A: 32, B: 32, C: 63 and D: 63).  
 
16.23  Accrual Rate and Study Duration: The anticipated accrual rate is 6 evaluable 
patients per month. Therefore, the accrual period for this pilot study is expected 
to be approximately 32 months. The final analysis can begin approximately 35 
months after the trial begins, i.e. as soon as the last patient has been observed for 
1 months and allowing 2 months for data entry.  
 
16.24  Other considerations: Adverse events, quality/duration of response, and patterns 
of treatment failure observed in this study, as well as scientific discoveries or 
changes in standard care will be taken into account in any decision to terminate 
the study 
 
16.3 
Analysis Plan.    
 
The analysis for this study is planned to start after data maturity has occurred. It 
is anticipated that the earliest date in which the result will be available via 
manuscript, abstract or presentation after the last registered patient has been 
followed for at least 1 month.  


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16.31    Primary Outcome Analyses: 
 
Each cohort (A-D) will be evaluated separately and independently.  
 
16.311 Definition:  
The primary endpoint of this study is RR after 1 cycle of treatment. RR 
is defined as a binary variable. A success will be defined as patient who 
achieve a response of a PR or better using the IMWG criteria (Section 
11.0) after one cycle of treatment. All patients meeting eligibility criteria 
who have signed a consent form, who complete at least one cycle of 
treatment and have successfully submitted biospecimens (pre and post 
treatment) will be evaluable for the endpoint. 
 
Estimation: For each biomarker of interest, RR will be calculated by the number 
of successes divided by the total number of evaluable patients in each cohort. 
 
16.32     Secondary Outcome Analyses 
 
16.321 Biomarkers and RR will be analyzed using logistic regressions to identify 
 
predictive biomarkers. 
 
16.322  RR among African American (AA) patients and white MM patients will 
 
be evaluated after one cycle of treatment. Chi-Square (or Fischer Exact) 
 
test and 95% confidence intervals will be estimated to compared AA and 
 
white patients descriptively. 
 
16.323  Correlation between the depth of hematological responses and 
biomarkers will be estimated. Logistic regressions and chi square (or 
Fischer exact) testing will be utilized.   
 
16.33 Data & Safety Monitoring:    
 
The principal investigator(s) and the study statistician will review the study at 
least twice a year to identify accrual, adverse event, and any endpoint problems 
that might be developing. The Mayo Clinic Cancer Center (MCCC) Data Safety 
Monitoring Board (DSMB) is responsible for reviewing accrual and safety data 
for this trial at least twice a year, based on reports provided by the MCCC 
Statistical Office.  
 
Adverse Event Stopping Rules: (Each cohort will be analyzed separately) The 
stopping rules specified below are based on the knowledge available at study 
development. We note that the Adverse Event Stopping Rule may be adjusted in 
the event of either (1) the study re-opening to accrual or (2) at any time during 
the conduct of the trial and in consideration of newly acquired information 
regarding the adverse event profile of the treatment(s) under investigation. The 
study team may choose to suspend accrual because of unexpected adverse event 
profiles that have not crossed the specified rule below.  
 
Accrual will be temporarily suspended to this study if at any time we observe 
events considered at least possibly related to study treatment (i.e. an adverse 


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Protocol Version Date:13Jun2023 
 
 
event with attribute specified as “possible”, “probable”, or “definite”) that satisfy 
either of the following:  
 
• If 3 or more out of the first 10 treated patients experience grade 4+ non-
hematological toxicities  
• If after the first 10 patients have been treated, 30% of patients experience grade 
4+ non-hematologic toxicities  
 
We note that we will review grade 5 adverse events deemed “unrelated” or 
“unlikely to be related”, to verify their attribution and to monitor the 
emergence of a previously unrecognized treatment-related adverse event. 
 
16.4 
Inclusion of Women and Minorities 
 
16.41 This study will be available to all eligible patients, regardless of race, gender, or 
ethnic origin. 
 
16.42 There is no information currently available regarding differential effects of this 
regimen in subsets defined by race, gender, or ethnicity, and there is no reason to 
expect such differences to exist. Therefore, although the planned analysis will, as 
always, look for differences in treatment effect based on racial and gender 
groupings, the sample size is not increased in order to provide additional power 
for subset analyses. 
 
16.43 Based on prior studies involving similar disease sites, we expect about 3-5% of 
patients will be classified as minorities by race. However, we are aiming to 
increase these percentages and accrue 15% of African American patientsto meet 
our secondary endpoints. If efforts to accrue in this racial category are not 
fruitful, the study will continue to accrue patients in the other racial categories. . 
Expected sizes of racial by gender subsets are shown in the following table: 
 


MC210809 
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Protocol Version Date:13Jun2023 
 
 
Accrual Estimates by Gender/Ethnicity/Race 
 
Ethnic Category 
Sex/Gender 
Females 
Males 
Unknown 
Total 
Hispanic or Latino 
0 
6 
0 
6 
Not Hispanic or Latino 
64 
120 
0 
184 
Unknown 
0 
0 
0 
0 
Ethnic Category: Total of all subjects 
64 
125 
0 
190 
Racial Category 
 
American Indian or Alaskan Native 
0 
0 
0 
0 
Asian 
0 
0 
0 
0 
Black or African American 
9 
20 
0 
29 
Native Hawaiian or other Pacific Islander 
0 
0 
0 
00 
White 
56 
105 
0 
161 
More than one race 
0 
0 
0 
0 
Unknown 
0 
0 
0 
0 
Racial Category: Total of all subjects 
64 
125 
0 
190 
 
Ethnic 
Categories: 
Hispanic or Latino – a person of Cuban, Mexican, Puerto Rican, South or Central 
American, or other Spanish culture or origin, regardless of race. The term “Spanish 
origin” can also be used in addition to “Hispanic or Latino.” 
Not Hispanic or Latino 
Racial 
Categories: 
American Indian or Alaskan Native – a person having origins in any of the original 
peoples of North, Central, or South America, and who maintains tribal affiliations or 
community attachment. 
Asian – a person having origins in any of the original peoples of the Far East, 
Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, 
India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and 
Vietnam. (Note: Individuals from the Philippine Islands have been recorded as Pacific 
Islanders in previous data collection strategies.)  
Black or African American – a person having origins in any of the black racial 
groups of Africa.  
Native Hawaiian or other Pacific Islander – a person having origins in any of the 
original peoples of Hawaii, Guam, Samoa, or other Pacific Islands. 
White – a person having origins in any of the original peoples of Europe, the Middle 
East, or North Africa. 


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17.0  
Pathology Considerations/Tissue Biospecimens   NA 
18.0 
Records and Data Collection Procedures  
18.1 
Submission Timetable 
Data submission instructions for this study can be found in the Data Submission 
Schedule. 
18.2 
Survival Follow-up 
N/A. See Section 4.  
18.3 
CRF completion 
This study will use Medidata Rave for remote data capture (rdc) of all study data. Data 
collection for this study will be done exclusively through the Medidata Rave clinical data 
management system. Access to the trial in Rave is granted through the iMedidata 
application to all persons with the appropriate roles assigned in Regulatory Support 
System (RSS). To access Rave via iMedidata, the site user must have an active account 
and the appropriate Rave role (Rave CRA, Read-Only, Site Investigator) on either the 
organization roster at the enrolling site. 
18.4 
Site responsibilities 
Each site will be responsible for ensuring that all materials contain the patient’s initials, 
MCCC registration number, and MCCC protocol number. Patient’s name must be 
removed. 
18.5 
Supporting documentation  
This study requires supporting documentation for diagnosis for all cohorts and relapse 
prior to study entry for Cohort C and Cohort D. These documents should be submitted 
within 14 days of registration. 
 
Supporting documentation for diagnosis will include either a pathology report or a 
laboratory report demonstrating multiple myeloma (including SPEP, UPEP, FLC, Serum 
and Urine Immunofixation, Bone Marrow Biopsy and Aspirate, skeletal bone survey, 
PET scan, Plasma Cell Proliferation and Assessment and FISH). These reports should be 
uploaded into the Supporting Documentation: Baseline form within 14 days of 
registration. 
 
For relapse of disease prior to study entry, supporting documentation includes the 
evidence needed to determine the patient’s relapse prior to enrollment. These documents 
should be uploaded into the Supporting Documentation: Baseline form within 14 days of 
registration. 
 
For response to treatment, supporting documentation may include SPEP, UPEP, FLC, 
Serum and Urine Immunofixation, Bone Marrow Biopsy and aspirate, skeletal bone 
survey, and PET scan. These documents should be uploaded into the Supporting 
Documentation form. 
 
For patients who progress after study therapy supporting documentation may include any 
of the following: SPEP, UPEP, FLC, serum and urine immunofixation, bone marrow 
biopsy and aspirate, skeletal bone survey, and PET scan. These documents should be 
uploaded into the Supporting Documentation form. 


MC210809 
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Protocol Version Date:13Jun2023 
 
 
18.6 
Labeling of materials 
Each site will be responsible for ensuring that all materials contain the patient’s initials, 
MCCC registration number, and MCCC protocol number. Patient’s name must be 
removed. 
18.7 
Overdue lists 
A list of overdue forms and outstanding queries will be available in Rave through the 
Rave Task Summary. In addition to this, the Overdue Materials report will be distributed  
monthly by the data manager. 
19.0  
Budget 
19.1 
Costs charged to patient: routine clinical care 
 
19.2 
Tests to be research funded: Research testing on blood and tissue specimens. Bone 
marrow aspirate done at the end of Cycle 1 (prior to cycle 2) will be paid for by research.  
19.3 
Other budget concerns: Private benefactor funds through the Department of Development 
will provide Mayo Clinic with funding to support the costs of running this study. 


MC210809 
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Protocol Version Date:13Jun2023 
 
 
20.0 
References 
1. 
R. L. Siegel, K. D. Miller, A. Jemal, Cancer statistics, 2016. CA Cancer J Clin 66, 7-30 (2016). 
2. 
R. A. Kyle et al., Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin 
Proc 78, 21-33 (2003). 
3. 
V. Rajkumar, Myeloma today: Disease definitions and treatment advances. Am J Hematol 91, 965 
(2016). 
4. 
S. K. Kumar et al., Improved survival in multiple myeloma and the impact of novel therapies. 
Blood 111, 2516-2520 (2008). 
5. 
W. I. Gonsalves et al., Clinical course and outcomes of patients with multiple myeloma who 
relapse after autologous stem cell therapy. Bone Marrow Transplant 51, 1156-1158 (2016). 
6. 
P. G. Richardson et al., Immunomodulatory drug CC-5013 overcomes drug resistance and is well 
tolerated in patients with relapsed multiple myeloma. Blood 100, 3063-3067 (2002). 
7. 
D. M. Weber et al., Lenalidomide plus dexamethasone for relapsed multiple myeloma in North 
America. N Engl J Med 357, 2133-2142 (2007). 
8. 
J. Hou et al., A multicenter, open-label, phase 2 study of lenalidomide plus low-dose 
dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial. 
J Hematol Oncol 6, 41 (2013). 
9. 
M. Dimopoulos et al., Lenalidomide plus dexamethasone for relapsed or refractory multiple 
myeloma. N Engl J Med 357, 2123-2132 (2007). 
10. 
S. V. Rajkumar et al., Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for 
newly diagnosed myeloma. Blood 106, 4050-4053 (2005). 
11. 
S. V. Rajkumar et al., Lenalidomide plus high-dose dexamethasone versus lenalidomide plus 
low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label 
randomised controlled trial. Lancet Oncol 11, 29-37 (2010). 
12. 
P. G. Richardson et al., Lenalidomide, bortezomib, and dexamethasone combination therapy in 
patients with newly diagnosed multiple myeloma. Blood 116, 679-686 (2010). 
13. 
P. L. McCarthy et al., Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl 
J Med 366, 1770-1781 (2012). 
14. 
M. Attal et al., Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. 
N Engl J Med 366, 1782-1791 (2012). 
15. 
A. Palumbo et al., Autologous transplantation and maintenance therapy in multiple myeloma. N 
Engl J Med 371, 895-905 (2014). 
16. 
P. L. McCarthy et al., Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in 
Newly Diagnosed Multiple Myeloma: A Meta-Analysis. J Clin Oncol 35, 3279-3289 (2017). 
17. 
M. Q. Lacy et al., Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed 
multiple myeloma. J Clin Oncol 27, 5008-5014 (2009). 
18. 
M. Q. Lacy et al., Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active 
and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia 24, 1934-1939 
(2010). 
19. 
P. G. Richardson et al., Phase 1 study of pomalidomide MTD, safety, and efficacy in patients 
with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood 121, 
1961-1967 (2013). 
20. 
X. Leleu et al., Pomalidomide plus low-dose dexamethasone is active and well tolerated in 
bortezomib and lenalidomide-refractory multiple myeloma: Intergroupe Francophone du 
Myelome 2009-02. Blood 121, 1968-1975 (2013). 
21. 
D. Dingli et al., Therapy for Relapsed Multiple Myeloma: Guidelines From the Mayo 
Stratification for Myeloma and Risk-Adapted Therapy. Mayo Clin Proc 92, 578-598 (2017). 
22. 
S. V. Rajkumar, S. Kumar, Multiple myeloma current treatment algorithms. Blood Cancer J 10, 
94 (2020). 


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23. 
S. Kumar et al., International Myeloma Working Group consensus criteria for response and 
minimal residual disease assessment in multiple myeloma. Lancet Oncol 17, e328-e346 (2016). 
 
 
 


MC210809 
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Protocol Version Date:13Jun2023 
 
 
Appendix I  ECOG Performance Status 
 
 
ECOG PERFORMANCE STATUS* 
Grade ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair. 
5 
Dead 
*As published in Am. J. Clin. Oncol.: 
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity 
And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982. 
The ECOG Performance Status is in the public domain therefore available for public use. To duplicate the 
scale, please cite the reference above and credit the Eastern Cooperative Oncology Group, Robert Comis 
M.D., Group Chair. 
From http://www.ecog.org/general/perf_stat.html  
 
 
 

ICF_001.pdf: 
 
 
 
 
 
MC210809 / 21-006597 
 
 
Evaluating Mechanisms of Immunomodulator Sensitivity and 
Resistance in Multiple Myeloma 
 
 
NCT05288062 
 
 
Document Date: 01/24/2024 


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
IRB#: 21-00659700         E-sign AS 
Page 1 of 31 
IRB Doc. Ctrl # 10013.35 
 
 
 
 
 
 
 
Name and Clinic Number 
 
RESEARCH PARTICIPANT CONSENT AND PRIVACY 
AUTHORIZATION FORM 
 
Study Title: MC210809, Evaluating Mechanisms of Immunomodulator Sensitivity and 
Resistance in Multiple Myeloma 
 
IRB#:  
21-006597  
 
Principal Investigator: Wilson Gonsalves, M.D., and Colleagues 
 
 
Key Study Information 
 
 
This section provides a brief summary of the study.  It is important for you to understand why 
the research is being done and what it will involve before you decide.  Please take the time to 
read the entire consent form carefully and talk to a member of the research team before 
making your decision.  You should not sign this form if you have any questions that have not 
been answered. 
It’s Your Choice 
This is a research study.  Being in this research study is your choice; 
you do not have to participate.  If you decide to join, you can still stop 
at any time.  You should only participate if you want to do so. You 
will not lose any services, benefits or rights you would normally have 
if you choose not to take part. 
Research Purpose 
The purpose of this study is to find out how patients will respond to 
one cycle of standard treatment with a type of drug called an 
immunomodulatory drug (sometimes referred to as IMiDs), combined 
with a corticosteroid drug. Examples of an immunomodulatory drug 
include lenalidomide and pomalidomide. These drugs work through a 
variety of mechanisms to affect the function of the immune system. 
They are widely used as treatment for multiple myeloma and remain 
the backbone of therapy for both newly diagnosed patients and 
patients that have relapsed disease. 
 
An example of a corticosteroid drug is dexamethasone. 
Dexamethasone is a strong anti-inflammatory agent and is also widely 
used to treat patients with multiple myeloma.  


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
IRB#: 21-00659700         E-sign AS 
Page 2 of 31 
IRB Doc. Ctrl # 10013.35 
 
 
 
 
 
 
 
Name and Clinic Number 
You have been asked to take part in this research because you have 
been diagnosed with multiple myeloma or smoldering myeloma. 
What’s Involved 
For each patient (study participant), the study will be conducted in 3 
periods: screening period, treatment period, and follow-up period. You 
will be required to come to the study site for study visits; this is 
similar to making an appointment with your study doctor. In addition 
to your regular appointments and procedures, you will be asked to 
have a bone marrow aspirate/biopsy done for research at the end of 
Cycle 1. This will be paid for by the research study. You will also be 
asked to participate in another study that will ask about the use of your 
blood and bone marrow biopsy samples. You and your study doctor 
will plan as many visits as needed to complete the study assessments 
and procedures for the protocol. 
Key Information 
All the study drugs are approved by the FDA for treatment of patients 
with multiple myeloma or smoldering myeloma, this includes patients 
who are newly diagnosed and haven’t yet received treatment, as well 
as patients who have already received treatment.  
 
There are risks to the study drugs that are described later in this 
document. Some of the very common side effects are fatigue, nausea, 
low platelet count, low hemoglobin count, infections, decreased 
appetite, vomiting, and diarrhea.   
 
Many side effects go away shortly after the treatment is stopped, but 
in some cases side effects can be serious, long lasting problems, or 
may never go away. There may be side effects that are unknown. The 
risks associated with study participation are completely described later 
in this form. It is important to review the risk section carefully. 
 
It is not known whether this treatment will be better or worse for you 
than what your doctor would normally choose.  By participating in 
this research study, you may help doctors answer this question. 
You do not have to participate in this study to receive treatment for 
your condition. Your study doctor will discuss the risks and benefits 
of other treatments with you before you decide whether or not you 
want to participate in this study. 


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
IRB#: 21-00659700         E-sign AS 
Page 3 of 31 
IRB Doc. Ctrl # 10013.35 
 
 
 
 
 
 
 
Name and Clinic Number 
Learn More 
If you are interested in learning more about this study, read the rest of 
this form carefully. The information in this form will help you decide 
if you want to participate in this research or not.  A member of our 
research team will talk with you about taking part in this study before 
you sign this form.  If you have questions at any time, please ask us.    
 
 
Making Your Decision 
 
 
Taking part in research is your decision.  Take your time to decide.  Feel free to discuss the study 
with your family, friends, and healthcare provider before you make your decision.  Taking part in 
this study is completely voluntary and you do not have to participate. 
 
If you decide to take part in this research study, you will sign this consent form to show that you 
want to take part. We will give you either a printed or electronic copy of this form to keep. A 
copy of this form will be put in your medical record. 
 
For purposes of this form, Mayo Clinic refers to Mayo Clinic in Arizona, Florida and Rochester, 
Minnesota; Mayo Clinic Health System; and all owned and affiliated clinics, hospitals, and 
entities. 
 
 
 


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
IRB#: 21-00659700         E-sign AS 
Page 4 of 31 
IRB Doc. Ctrl # 10013.35 
 
 
 
 
 
 
 
Name and Clinic Number 
 
Contact Information 
 
 
If you have questions about … 
You can contact … 
 Study tests and procedures 
 Materials you receive 
 Research-related appointments  
 Research-related concern or complaint 
 Research-related injuries or emergencies 
 Withdrawing from the research study 
Principal Investigator:  
Wilson Gonsalves, M.D. 
Phone: 507-284-2511 
 
Institution Name and Address: 
Mayo Clinic 
200 First Street SW 
Rochester, MN 55905 
 
Co-Principal Investigator: 
Sikander Ailawadhi, M.D.  
Phone: (904) 953-2000 
 
Institution Name and Address: 
Mayo Clinic Hospital  
Jacksonville, FL 32224 
 
Co-Principal Investigator: 
Rafael Fonseca, M.D.  
Phone: (480) 301-8000 
 
Institution Name and Address: 
Mayo Clinic Hospital 
5777 E Mayo Blvd 
Phoenix, AZ 85054 
 Rights of a research participant 
Mayo Clinic Institutional Review Board (IRB)  
Phone: (507) 266-4000 
 
Toll-Free: (866) 273-4681 
 Rights of a research participant 
 Any research-related concern or complaint 
 Use of your Protected Health Information 
Research Participant Advocate (RPA) 
(The RPA is independent of the Study Team) 
Phone: (507) 266-9372 
Toll-Free: (866) 273-4681 


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
IRB#: 21-00659700         E-sign AS 
Page 5 of 31 
IRB Doc. Ctrl # 10013.35 
 
 
 
 
 
 
 
Name and Clinic Number 
If you have questions about … 
You can contact … 
 Stopping your authorization to use your 
Protected Health Information 
 Withdrawing from the research study 
 
E-mail: researchparticipantadvocate@mayo.edu 
 Billing or insurance related to this research 
study 
Patient Account Services 
Toll-Free: (844) 217-9591 
 
Other Information:   
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
 
 
Why are you being asked to take part in this research study? 
 
 
You are being asked to take part in this study because you have been diagnosed with a type of 
blood cancer called Multiple Myeloma or Smoldering Myeloma that requires treatment. 
 
The plan is to have about 190 take part in this study at Mayo Clinic.  
 
 
Why is this research study being done? 
 
 
The purpose of this study is to find out how patients will respond to 1 cycle of treatment with a 
type of drug called an immunomodulatory drug (sometimes referred to as IMiDs), combined 
with a corticosteroid drug. Examples of an immunomodulatory drug include lenalidomide and 
pomalidomide. These drugs work through a variety of mechanisms to affect the function of the 
immune system. They are widely used as treatment for multiple myeloma and remain the 
backbone of therapy for both newly diagnosed patients and patients that have relapsed disease. 
An example of a corticosteroid drug is dexamethasone. Dexamethasone is a strong anti-
inflammatory agent and is also widely used to treat patients with multiple myeloma.  
 
All the drugs used in this research study are FDA approved.  
 
 


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
IRB#: 21-00659700         E-sign AS 
Page 6 of 31 
IRB Doc. Ctrl # 10013.35 
 
 
 
 
 
 
 
Name and Clinic Number 
 
Information you should know 
 
 
Who is Funding the Study? 
This study is being funded by a philanthropic foundation that supports cancer research. They will 
pay the institution to cover costs related to running the study.  
 
Information Regarding Conflict of Interest: 
Your healthcare provider may be referring you to this research study.  If your healthcare provider 
is also an investigator on this study, there is the chance that his or her responsibilities for the 
study could influence his or her recommendation for your participation.  If you prefer, your 
healthcare provider will be happy to refer you to another investigator on the research study team 
for you to decide if you want to participate in the study and to see you for the research study 
activities while you are in the study.   
 
 
How long will you be in this research study? 
 
 
You will be in the study for up to 6 months (cycles). If your multiple myeloma 
worsens or you have side effects from the study medications you may not be in the study for 6 
months (cycles).   
 
 
What will happen to you while you are in this research study? 
 
 
If you agree to take part in this study, we will ask you to sign this consent form to see if you are 
eligible. Routine tests for your cancer will be done.   
 
Screening Period 
Prior to starting treatment on this trial, you will have specific procedures and tests to make sure 
you are eligible to be in this study.  
 
 


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
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They include:  
• Medical history (including any medications that you are taking now or have taken in the 
past) 
• Review of your current medical condition(s) 
• Physical examination (including height and weight) 
• Vital signs (blood pressure, heart rate, temperature) 
• Whole body low dose CT scan or PET/CT if deemed necessary 
• Routine blood tests (including CBC, chemistry panel, INR/PT and TSH) 
• Blood tests done specifically to assess your disease 
• Urine tests done specifically to assess your disease 
• Pregnancy test if you are able to become pregnant 
• Bone marrow aspirate and biopsy 
 
These tests are part of regular care for your cancer. If some of these tests have been done 
recently, you may not need to repeat them. 
 
If you qualify to participate in the study, and agree to participate you will receive the study 
treatment.   
 
Treatment Period  
This study consists of 4 groups (also called cohorts): 
   
Group A (cohort A) 
This group is for patients who have been diagnosed with smoldering multiple myeloma.  
 
Group B (cohort B)  
This group is for patients who have been newly diagnosed with multiple myeloma and haven’t 
received any treatment yet.  
 
Group C (cohort C) 
This group is for patients who have been diagnosed with multiple myeloma and have already 
received initial treatment, but their multiple myeloma has gotten worse (called relapsed and/.or 
refractory).  
 
Group D (cohort D) 
This group is for patients who have been diagnosed with multiple myeloma and their multiple 
myeloma is getting worse while on treatment with lenalidomide which is being used as a 
maintenance treatment (relapsed after lenalidomide maintenance).  
 


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
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Please note: If you choose to participate in this study, those enrolled in groups (cohorts) B, C, or 
D will not have standard of care treatment for cycle 1. For example, patients with multiple 
myeloma that is newly diagnosed (Cohort B), relapsed and refractory (Cohort C) or relapsed 
after lenalidomide maintenance (Cohort D) will receive at least one cycle of a doublet (2 drugs) 
based therapy alone that includes either lenalidomide or pomalidomide with dexamethasone 
instead of conventional standard of care regimens that include a combination of triplet (3 drugs) 
or quadruplets (4 drugs) drug combination regimens.  After the first cycle, participants will be 
able to receive conventional standard of care regimens for cycles 2 and beyond.   
 
Treatment is given in either 21- or 28-day cycles.  Cycle 1 is 21 days and cycles 2-6 are 28 days.   
You will receive the following treatment:  
 
Groups A and B Cycle 1 
You may receive lenalidomide or lenalidomide and dexamethasone, your doctor will tell you 
what you should take. The directions for taking the lenalidomide are below and your doctor will 
give you the directions for the other treatment drugs.  
 
• Lenalidomide is taken by mouth Days 1-14 
o Lenalidomide is a capsule and should be taken at about the same time each day. 
The capsules should not be opened, broken or chewed. The capsules should be 
swallowed whole, preferably with water, either with or without food.  
o If you miss a dose of lenalidomide: If less than 12 hours has passed since missing 
a dose, you can take the dose. If more than 12 hours has passed since missing a 
dose at the normal time, you should not take the dose, but take the next dose at the 
normal time on the following day. If you miss a dose let your study doctor know. 
 
You will have the following tests/visits:  
• After Cycle 1 (before Cycle 2), you will have a research bone marrow biopsy.  
• After Cycle 1 (before Cycle 2), you will have a research blood sample, about 4 
tablespoons (i.e., 60 mL).  
 
Groups A and B Cycles 2-6 
You may receive lenalidomide or lenalidomide and dexamethasone, or lenalidomide and another 
agent. Your doctor will tell you what you should take. The directions for taking the lenalidomide 
are below and your doctor will give you the directions for the other treatment drugs. 
  
• Lenalidomide is taken by mouth Days 1-21 
o Lenalidomide is a capsule and should be taken at about the same time each day. 
The capsules should not be opened, broken or chewed. The capsules should be 
swallowed whole, preferably with water, either with or without food.  


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
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o If you miss a dose of lenalidomide: If less than 12 hours has passed since missing 
a dose, you can take the dose. If more than 12 hours has passed since missing a 
dose at the normal time, you should not take the dose, but take the next dose at the 
normal time on the following day. If you miss a dose let your study doctor know. 
 
Groups C and D Cycle 1 
You will receive lenalidomide and dexamethasone or pomalidomide and dexamethasone. Your 
doctor will tell you what you should take.  
 
• Lenalidomide is taken by mouth Days 1-14 
o Lenalidomide is a capsule and should be taken at about the same time each day. 
The capsules should not be opened, broken or chewed. The capsules should be 
swallowed whole, preferably with water, either with or without food.  
o If you miss a dose of lenalidomide: If less than 12 hours has passed since missing 
a dose, you can take the dose. If more than 12 hours has passed since missing a 
dose at the normal time, you should not take the dose, but take the next dose at the 
normal time on the following day. If you miss a dose let your study doctor know. 
• 
Pomalidomide is taken by mouth Days 1-21 
o The capsules should be taken about the same time each day. The tablets should 
not be broken or chewed. The tablets should be swallowed whole with water. 
o If a dose of pomalidomide is missed, it should be taken as soon as possible on the 
same day. If it is missed for the entire day, it should not be made up. 
o As part of your clinical care, you will automatically be enrolled in the Pomalyst® 
REMS program in order to obtain pomalidomide. Before you can be enrolled in 
this program, you must read and agree to all the instructions. Due to the risks of 
the drug, pomalidomide is only available through this program. More information 
is available on this website http://www.pomalystrems.com/patient.html 
• Dexamethasone is taken by mouth Days 1, 8, and 15 
o The tablets should be taken about the same time each day. The tablets should not 
be broken or chewed. The tablets should be swallowed whole with water. 
o If you forget a dose, take it as soon as you remember it. However, if more than 12 
hours have passed since missing a dose at the normal time skip the missed dose. 
Do not take a double dose (two doses at the same time) to make up for a forgotten 
 
You will have the following tests/visits:  
• After Cycle 1 (before Cycle 2), you will have a research bone marrow biopsy 
• After Cycle 1 (before Cycle 2), you will have a research blood sample , about 4 
tablespoons (i.e., 60 mL).  
 
 


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
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Groups C and D Cycles 2-6: 
You will receive lenalidomide plus dexamethasone or pomalidomide plus dexamethasone, Your 
doctor will tell you what to take. 
• Lenalidomide is taken by mouth Days 1-21 
o Lenalidomide is a capsule and should be taken at about the same time each day. 
The capsules should not be opened, broken or chewed. The capsules should be 
swallowed whole, preferably with water, either with or without food.  
o If you miss a dose of lenalidomide: If less than 12 hours has passed since missing 
a dose, you can take the dose. If more than 12 hours has passed since missing a 
dose at the normal time, you should not take the dose, but take the next dose at the 
normal time on the following day. If you miss a dose let your study doctor know. 
• 
Pomalidomide is taken by mouth Days 1-21 
o The capsules should be taken about the same time each day. The tablets should 
not be broken or chewed. The tablets should be swallowed whole with water. 
o If a dose of pomalidomide is missed, it should be taken as soon as possible on the 
same day. If it is missed for the entire day, it should not be made up. 
o As part of your clinical care, you will automatically be enrolled in the Pomalyst® 
REMS program in order to obtain pomalidomide. Before you can be enrolled in 
this program, you must read and agree to all the instructions. Due to the risks of 
the drug, pomalidomide is only available through this program. More information 
is available on this website http://www.pomalystrems.com/patient.html 
 
For all groups, during cycles 2-6, you may receive an additional anti-myeloma agent at the 
discretion of your physician.  It would be given to you as standard of care if your doctor thinks 
this will help your treatment. Your doctor may determine that it is beneficial to you to continue 
on the treatment regimen even after the 6th cycle when you would have completed the study.   
 
All groups:  
You will have the following tests/visits:  
• Medical history (including any medications that you are taking now or have taken in the 
past) 
• Review of your current medical condition(s) every cycle  
• Physical examination (including height and weight) every cycle  
• Vital signs (blood pressure, heart rate, temperature) every cycle 
• Routine blood tests every cycle (including CBC, chemistry panel) 
• Blood tests done specifically to assess your disease  
• Urine tests done specifically  to assess your disease  
• Pregnancy test every cycle (if you are able to become pregnant) 
• Clinical bone marrow aspirate and biopsy (as clinically indicated) 


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
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Name and Clinic Number 
{{$QNS1Y}} 
{{$QNS1N}}
{{$QNS1IN}} 
{{$QNS1D                                                                                                    }} 
• Medication Diary to be completed every cycle     
• Research blood test  before cycle 1. This will only be done if you agree to participate in 
another research study, IRB#521-93, 919-04 or 14-009163 and sign a consent form for 
that study)  
• Research bone marrow aspirate and biopsy before cycle 1. This will only be done if you 
agree to participate in another research study, IRB#521-93, 919-04, or 14-009163 and 
sign a consent form for that study) (before cycle 1) 
 
Follow-up Period  
There will be a follow-up visit within 7 days after you finish the study treatment.  
 
You will have the following tests/visits while receiving treatment:  
• Medical history (including any medications that you are taking now or have taken in the 
past) 
• Review of your current medical condition(s)  
• Physical examination (including height and weight) 
• Vital signs (blood pressure, heart rate, temperature)  
• Whole body low dose CT scan or PET/CT  
• Routine blood tests   (including CBC, chemistry panel) 
• Blood tests done specifically to assess your disease  
• Urine tests done specifically to assess your disease  
• Clinical bone marrow aspirate and biopsy (if clinically indicated) 
• Optional research bone marrow and aspirate   
• Optional research blood sample   
 
Optional research bone marrow biopsy and aspirate and blood sample  
 
After you have completed treatment, we would like to request a sample of bone marrow for 
research.  This would be done at the same time as your clinical bone marrow biopsy.  
 
Please check one. 
I agree to provide a bone marrow sample for this optional biopsy: 
 
  Yes 
  No  
Please initial here: ________Date: ________ 
 
After you complete treatment, we would like to request a blood sample for research.  This would 
be done at the same time as your clinical blood draw.  


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
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{{$QNS2Y}} 
{{$QNS2N}} 
{{$QNS2IN}} 
{{$QNS2D                                                                                                  }} 
Please check one. 
I agree to provide a blood sample for this optional blood test   
 
  Yes 
  No  
Please initial here: ________Date: ________ 
 
Tests done only for research purposes are not meant to provide clinical information or help care 
for you. The results are only important for research. Therefore, the results of tests done with your 
information and samples will not be provided to you. In the rare event that a finding might affect 
the health of you or your family, we will contact you and you can choose whether to receive or 
refuse the information. If you decide to follow up and further medical testing or care is needed, 
the costs will be billed to you or your insurance. 
 
 
What are the possible risks or discomforts from being in this research study? 
 
 
Many side effects go away shortly after the study drugs are stopped, but in some cases side 
effects can be serious, long lasting, or may never go away. There may be a risk of death.  Some 
side effects may not be known.  Side effects may range from mild to life-threatening. Other 
drugs may be given to make side effects less serious and less uncomfortable.  Talk to the study 
doctor about side effects and ask any other questions.  
 
It is possible that the symptoms of your condition will not improve during the study or may even 
worsen. Treatment with the study treatment may also involve risks to your future health that we 
currently do not know about. You will be closely monitored for any side effects that may occur. 
Side effects that have been reported with the study treatments are described below. If you have 
any questions about these, please ask the study doctor.  
 
As with all research, there is a chance that confidentiality could be compromised; however, we 
take precautions to minimize this risk.  
Lenalidomide  
 
The following are likely risks of lenalidomide:  
• Low white blood cells (neutropenia) and lymphopenia or a decrease in white blood cells 
that can make you more prone to infections 
• Low platelets (thrombocytopenia) have been observed which may require reduction or 
interruption of the dose of lenalidomide that you receive.  


 
 
Approval Date:  
January24, 2024 
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• Deep venous thrombosis (blood clots in veins, usually in your calf) and lung emboli 
(blood clot in lungs). You need to seek medical care if you experience shortness of 
breath, chest pain, or arm or leg swelling.  
• Fatigue or feeling tired 
• Constipation or difficulty moving your bowels 
• Diarrhea or loose/frequent bowel movements 
• Infections involving various organs 
• Peripheral neuropathy, causing numbness or tingling in extremities 
 
Less likely risks of lenalidomide (events occurring less than or equal to 20% of the time) 
• Allergic reaction and tumor lysis syndrome have been reported. Tumor lysis syndrome 
refers to disturbances of your electrolytes which is caused by rapid killing of cancer cells 
in the blood. This may be seen after initiation of cancer treatment and may result in 
kidney damage and heart problems such as an abnormal heartbeat.  
• Diarrhea 
• Fatigue, lack of energy 
• Low red blood cells (anemia) 
• Constipation 
• Swelling of hands, feet or limbs 
• Difficulty sleeping 
• Muscle cramp/spasms 
• Back pain 
• Joint pain  
• Nausea 
• Fever 
• Infection of the nose, sinuses, and/or throat 
• Cough 
• Rash 
• Itching and dry skin  
• Lack or loss of strength  
• Shortness of breath 
• Dizziness 
• Headache  
• Decreased appetite 
• Tremor 
• Abnormal thyroid function or inflammation of thyroid gland 
• Abdominal pain or distension  
• Gastrointestinal bleeding  


 
 
Approval Date:  
January24, 2024 
Not to be used after: January 23, 2025 
 
 
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• Bowel obstruction  
• Abnormalities of liver tests 
• Allergic reactions to drug 
• Abnormalities of mineral levels in blood 
• Heartburn 
 
Serious side effects occurring in 1% or more of patients and not listed in bold above 
• Neutropenia associated with a fever 
• Pulmonary embolism or blood clot in or around the lungs 
• Deep vein thrombosis or blood clots in a larger blood vessel 
• Atrial fibrillation or irregular heartbeat 
• Progression of the disease being studied including multiple myeloma 
• Pneumonia or an infection of the lungs 
• Sepsis or an infection of the blood 
• Dehydration  
• Kidney failure which can cause increases or decreases in the amounts of chemicals in 
your blood which can cause irregular heartbeats, muscle twitching, seizures, and/or death.  
• Myocardial infarction (heart attack) 
• Stroke (bleeding in the brain or clotting) 
 
Rare cases of the following events have been reported: 
• Angioedema- an allergic skin disease characterized by patches of swelling involving the 
skin and/or the lining of your nose, mouth, and gastrointestinal tract. 
• Anaphylaxis- serious potentially life-threatening type of allergic reaction that may cause 
breathing difficulty, dizziness, low blood pressure, and loss of consciousness. 
• Stevens-Johnson syndrome and toxic epidermal necrolysis- serious allergic skin reactions 
that begin as a rash in one area and later cover more of the body leading to detachment of 
the top layer of skin (could be body-wide).  Medical journals have reported patients with 
allergic skin reaction with thalidomide who also developed the same type of reaction with 
lenalidomide 
• Drug reaction with eosinophilia and systemic symptoms (DRESS). This is a drug reaction 
and may cause fever, rash, hepatitis, nephritis, pneumonitis, myocarditis, and/or 
pericarditis 
 
 


 
 
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• Tumor lysis syndrome- metabolic complication that can occur during or without 
treatment of cancer.  These complications are caused by the break-down products of 
dying cancer cells and include hyperkalemia (high potassium), hyperphosphatemia (high 
phosphorus), hyperuricemia and hyperuricosuria (high uric acid in blood and urine), 
hypocalcemia (low calcium), and consequent acute uric acid nephropathy and acute renal 
failure (kidney damage). 
• Tumor Flare reaction- a condition that involves any of the following increase in the size 
of the cancerous lymph nodes, rash and slight fever. 
• Rhabdomyolysis- a serious condition involving the destruction of skeletal muscle that can 
lead to kidney failure. Signs and symptoms include dark, red, or cola colored urine and 
muscle tenderness, stiffness, aching (myalgia) or weakness. 
• Increase in blood levels of lipase due to inflammation of pancreas gland. 
• Abnormalities of blood clotting 
• Bone marrow failure 
• Decrease in lymphocytes (type of white blood cells) 
• Enlarged spleen 
• Abnormal heart rhythms 
• Congestive heart failure (condition where the heart becomes weak and cannot pump 
enough blood to the rest of the body 
• Decreased function of adrenal gland 
• Decreased hearing 
• Vision abnormalities 
• Clotting in blood vessels of intestines 
• Seizures 
• Graft-versus-host disease (when transplanted donor tissue attacks the tissues of the 
recipient's body) (graft vs. host disease) 
 
Also Reported on Lenalidomide Trials but with the Relationship to Lenalidomide Still 
Undetermined:   
• Tissue swelling (angioedema)  
• Rhabdomyolysis is a breakdown of muscle fibers. It occurs when muscle cells die and 
release cell contents into the blood stream. It can cause muscle pain and a number of 
health problems, including damage to the kidneys. If severe, this could be life threatening 
(rhabdomyolysis) 
 
These events have the potential to be fatal. 
 


 
 
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Your health care team may give you medicines to help lessen side effects. Many side effects go 
away soon after you stop taking study drug.  In some cases, side effects can be serious, long 
lasting or may never go away. 
 
You should talk to your study doctor about any side effects that you have while taking part in the 
study.  
 
Hematological Toxicity 
Lenalidomide is associated with significant neutropenia (decrease in white blood cells that help 
fight infection) and thrombocytopenia (decrease in platelets that help with blood clotting). You 
will have your blood counts checked frequently when starting treatment with lenalidomide. 
 
Deep Vein Thrombosis and Pulmonary Embolism 
Lenalidomide has demonstrated an increased risk of deep vein thrombosis (DVT, blood clot in a 
larger blood vessel) and pulmonary embolism (PE, a blood clot in or around the lungs) in some 
people with certain medical conditions. The study staff will ask you about any risk factors you 
may have.  [If you have a history of blood clots your doctor will prescribe either heparin or 
coumadin for the first four months of the study treatment.  The doctor may continue to prescribe 
the medication or aspirin for the remainder of your course of study treatment.  All other patients 
will receive (at the discretion of the treating physician) either oral low–dose aspirin or another 
treatment to prevent blood clotting during study participation.]  Patients unable or unwilling to 
undergo treatment for prevention of blood clots will not be eligible to participate in this study.  
You will be instructed on the signs and symptoms of DVT and PE and if symptoms occur you 
should contact your study doctor promptly. 
 
Second new cancers  
According to researchers, patients with cancer have a higher risk of developing a second new 
cancer when compared to people without cancer.  In clinical studies of newly diagnosed multiple 
myeloma, a higher number of second cancers were reported in patients treated with induction 
therapy (treatment as first step to reducing number of cancer cells) and/or bone marrow 
transplant then lenalidomide for a long period of time compared to patients treated with 
induction therapy and/or bone marrow transplant then placebo (a capsule containing no 
lenalidomide).  Patients should make their doctors aware of their medical history and any 
concerns they may have regarding their own increased risk of other cancers. 
 
Other Risks 
If any physician other than the study doctor prescribes medication for you for another condition 
or you are taking any over-the-counter medications or vitamins, you must inform the study staff.  
This is important because the interaction of some medications may cause serious side effects. 


 
 
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Lenalidomide has been shown to increase the level of digoxin in the blood in some patients; 
please tell your doctor if you are taking digoxin. 
 
Your condition may not get better or may become worse while you are in this study. 
 
Risks Associated with Pregnancy 
 
Lenalidomide is related to thalidomide.  Thalidomide is a known to cause severe life-threatening 
human birth defects.  Findings from a monkey study indicate that lenalidomide caused birth 
defects in the offspring of female monkeys who received the drug during pregnancy. If 
lenalidomide is taken during pregnancy, it may cause birth defects or death to any unborn baby.  
Females must not become pregnant while taking lenalidomide.  You have been informed that the 
risk of birth defects is unknown. If you are female, you agree not to become pregnant while 
taking lenalidomide. 
 
Lenalidomide is detected in trace quantities in human semen according to a study. The risk to the 
fetus in females of childbearing potential whose male partner is receiving lenalidomide is 
unknown at this time.  For these reasons male patients receiving lenalidomide must use a latex 
condom while taking lenalidomide, when temporarily stopping lenalidomide, and for 28 days 
after permanently stopping lenalidomide treatment during any sexual contact with a pregnant 
female or a female of childbearing potential even if you have undergone a successful vasectomy.  
 
Patients should not donate blood during treatment therapy or for 28 days following 
discontinuation of lenalidomide. 
 
You must NEVER share lenalidomide with anyone else. 
 
Lenalidomide will hurt unborn babies. The manufacturer of this drug has a pregnancy prevention 
program for any patient who takes this drug. Your doctor can explain to you such a program. 
There are additional side effects that have been seen in patients that have taken lenalidomide.  
Please ask your study doctor for information regarding these side effects. 
 
POTENTIAL DISCOMFORTS AND RISKS OF POMALIDOMIDE (CC-4047, 
Pomalyst®) 
 
Likely risks of pomalidomide (events occurring greater than 20% of the time) 
• A low number of white blood cells, which are the infection fighting cells, which could 
put you at risk for infection (neutropenia or leukopenia) 
• A low number of a particular white blood cell, which is important to the immune system 
(lymphopenia) 


 
 
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• Feeling tired (fatigue) 
• Difficulty passing stool (constipation) 
• Feeling sick to your stomach (nausea) 
• Decreased number of blood cells (platelets) that help to clot the blood (which could put 
you at increased risk of bleeding (thrombocytopenia) 
• Decrease in red blood cells, which are the oxygen carrying cells, which could make you 
feel tired (anemia) 
• Back pain 
• Shortness of breath or difficulty breathing (dyspnea) 
• Loose stools (diarrhea) 
• Bronchitis 
• Upper respiratory tract infection 
• Pneumonia 
• Dizziness 
• Nerve damage (peripheral neuropathy) 
• Decreased appetite 
• Swelling of limbs (peripheral edema) 
• Fever (Pyrexia) 
• Bone pain 
• Muscle spasm 
• Cough 
• Kidney failure (renal failure) 
• Increased blood creatinine which is associated with kidney failure 
• Sudden onset of kidney failure (Acute renal failure) 
• Nausea 
• Generalized weakness (asthenia) 
• Itchiness (Pruritus) 
 
Less likely risks of pomalidomide (events occurring less than or equal to 20% of the time) 
• When pomalidomide or related drugs (i.e. thalidomide and lenalidomide) have been used 
along with corticosteroids and certain other chemotherapy drugs, there has been an 
increased risk of individuals developing blood clots including blood clots in the big veins 
of the limbs (deep vein thrombosis) or in the lungs (pulmonary embolism).  Your doctor 
may request or require that you take aspirin or another blood thinner in this situation. 
• Abdominal pain 
• Sore mouth, nose, or throat (nasopharyngitis) 
• Drop in blood pressure  
• Headache 


 
 
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• Chest pain 
• Feeling shaky (tremor) 
• Infections including potentially life threatening infections 
• Muscle aches  
• Muscle weakness 
• Nerve damage with numbness and abnormal sensations (peripheral sensory neuropathy) 
• Abnormal sensations (Paresthesia) 
• Abnormal balance (Gait disturbance) 
• Damage to multiple nerves (Polyneuropathy) 
• Decreased sensations (Hypoesthesia) 
• Pain due to nerve damage or irritation (Neuralgia) 
• Nerve damage with difficulty in movement (peripheral motor neuropathy) 
• Joint swelling or achiness 
• Dry or itchy skin 
• Blushing or redness to face (flushing) 
• Decreased function of the thyroid gland, which can result in feeling tired and weight gain 
that may first show up as an increased levels of thyroid stimulating hormone 
(hypothyroidism). If your thyroid function becomes abnormal, your doctor may have you 
take a thyroid replacement pill daily. 
• Difficulty emptying the bladder (urinary retention) 
• Pelvic pain 
• Rash 
• Throwing up (vomiting) 
• Decreased sodium levels in the blood (hyponatremia) 
• Abnormally high calcium in the blood stream, that can result in fatigue, confusion, 
feeling sick to your stomach, throwing up, difficulty passing stool, abnormal heartbeat, 
coma, and death (hypercalcemia) 
• Abnormally low calcium in the blood stream, that can result in muscle cramps, 
abdominal cramps, spasms (hypocalcemia) 
• Abnormal levels of potassium in the blood (hyper- or hypokalemia) 
• Death 
• Excessive sweating (hyperhidrosis) 
• High blood sugar (hyperglycemia) 
• Gastrointestinal bleeding 
• Airway and lung infection (bronchopneumonia) 
• Shingles (Herpes zoster) 
• Severe infection secondary to low neutrophil count (neutropenic sepsis) 
• Fever related to low neutrophil count (Neutropenic fever) 


 
 
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• Respiratory tract infection 
• Pneumonia caused by Pneumocystis jiroveci 
• Pneumonia caused by respiratory syncytial virus 
• Pneumonia with involvement of lobes of lungs (Lobar pneumonia) 
• Pneumonia caused by streptococcal bacteria (Streptococcal pneumonia) 
• Elevated liver enzymes (alanine aminotransferase elevation, Aspartate aminotransferase 
elevation, Gamma-glutamyltransferase elevation) 
• Elevated liver function test 
• Confusion 
• Depressed level of consciousness 
• Drop in all blood counts resulting in anemia, low white blood cell count (leucopenia), and 
low platelet count (thrombocytopenia) (pancytopenia) 
• Spinning sensation (vertigo) 
• Nosebleed (epistaxis) 
• General physical health deterioration 
• Swelling face (Face edema) 
• Generalized itchiness (Generalized pruritus) 
• Impairment of kidney function (Renal impairment) 
• Loss of protein in urine (Proteinuria) 
• Bleeding in gastrointestinal tract (Gastrointestinal hemorrhage) 
• Bleeding from hemorrhoids (Hemorrhoidal hemorrhage) 
• Bleeding from rectum (Rectal hemorrhage) 
• Bleeding gum (Gingival bleeding) 
• Passage of fresh blood per anus (Hematochezia) 
 
Rare but serious risks of pomalidomide (events occurring less than 2-3% of the time) 
• Chest wall pain 
• Inability of the heart to properly pump blood to the lungs (right ventricular failure) 
• Bleeding from the stomach large intestine and/or small intestine (gastrointestinal 
bleeding) 
• Narrowing of the stomach or intestines (gastrointestinal stenosis) 
• Chest pain that occurs when your heart doesn't get enough oxygen, which can be a 
warning sign of a heart attack (angina - unstable) 
• An irregular heartbeat that results from the top/upper chambers of the heart “quivering” 
instead of beating normally (atrial fibrillation) 
• Fast heart rate (tachycardia) or slow heart rate (bradycardia) 
• Decrease in the ability of the heart to pump blood, because of weakening of the heart 
muscle (congestive heart failure) 


 
 
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• Lack of oxygen to the heart muscle which can cause damage to the heart (heart attack) 
• Feeling like your heart is “fluttering or skipping” (heart palpitations) 
• Bleeding in the brain (cerebral hemorrhage) 
• Lack of oxygen to the brain caused by either bleeding in the brain or blood clot. Also 
called a stroke (cerebral vascular accident) 
• Memory impairment 
• Blood creatinine increased 
• Excessive or abnormal loss of body fluids (dehydration) 
• Failure to thrive 
• Anxiety 
• Feeling sad or blue (depression)  
• Difficulty falling or staying asleep (insomnia) 
• Changes in mood 
• Kidney stones (nephrolithiasis) 
• Collection of fluid in the space around the lung (pleural effusion) 
• Inability of the lungs to function properly (respiratory failure) 
• High blood pressure (hypertension) or low blood pressure (hypotension) 
• Acute inflammation of the liver including hepatitis, liver failure, jaundice (yellowing of 
skin and whites of eyes)  (hyperbilirubinemia) 
• Inflammation of supporting tissue of the lungs (interstitial lung disease) 
• Possible second cancer with prolonged use 
• Blurred vision 
• Decreased level of phosphorus in the blood (hypophosphatemia) 
• Decreased albumin in the blood (hypoalbuminemia) 
• Low levels of magnesium in the blood (hypomagnesemia) 
• Night sweats 
• Changes in the voice or hoarseness (dysphonia) 
• Nosebleed (epistaxis) 
• Very sleepy, difficulty arousing (lethargy) 
• Fainting (syncope) 
• Excessive sleepiness (somnolence/depressed level of consciousness) 
• Change in taste sensation (dysgeusia) 
• Dry mouth 
• Chills 
• Recurrent areas of skin or mucosal swelling of sudden onset, usually disappearing within 
24 hours; an allergic reaction to the medication (angioedema and urticaria) an 
exaggerated or inappropriate immune response (hypersensitivity) to pomalidomide  
• Hepatitis B viral activation 


 
 
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• Hepatitis 
• Kidney failure and blood chemistry abnormalities secondary to destruction of cancer cells 
by anti-cancer treatment (tumor lysis syndrome) 
• Skin cancer (basal cell carcinoma and squamous cell carcinoma) 
• Development of a new cancer during cancer treatment (second primary malignancies) 
including blood and bone marrow cancers (Hematologic malignancies), solid organ 
tumors (solid tumors), and skin cancers.  
• Inflammation of the lungs  
• Inflammation of lung tissue (pneumonitis) 
• Pneumonia caused by staphylococcal bacteria 
• Pneumonia caused by fungi 
• Pneumonia caused by viruses 
• Pneumonia caused by influenza virus 
• Increased blood urea level which can be related to kidney failure 
• Decreased creatinine renal clearance which is related to kidney failure 
• Decreased glomerular filtration rate which is related to kidney failure 
• Decreased urine output (Oliguria) which can be related to kidney failure 
• Destruction of kidney tubules (Renal tubular necrosis) 
• Kidney failure of sudden onset mostly related to dehydration (Acute pre-renal failure) 
• Chemical changes in body related to kidney failure (Azotemia) 
• Eyelid edema 
• Eye swelling or swelling around eyes (Periorbital edema) 
• Lip swelling 
• Swollen tongue 
• Swelling in the mouth (Edema mouth) 
• Swelling in the throat (Pharyngeal edema) 
• Severe skin reaction with wide-spread fluid sac (bullous) formation and skin shedding 
(Stevens-Johnson syndrome) 
• Severe skin reaction with wide-spread skin destruction and shedding (Toxic epidermal 
necrolysis) 
• Drug reaction with eosinophilia and systemic symptoms 
• Itchiness due to drug allergy (Allergic pruritus) 
 
Risks Associated with Pregnancy 
 
Pomalidomide is related to thalidomide. Thalidomide is a known to cause severe life-threatening 
human birth defects. If pomalidomide is taken during pregnancy, it may cause birth defects or 
death to any unborn baby. Females must not become pregnant while taking pomalidomide.  


 
 
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You have been informed that the risk of birth defects is unknown. If you are female, you agree 
not to become pregnant while taking pomalidomide. 
 
Pomalidomide is detected in trace quantities in human semen according to a study. The risk to 
the fetus in females of childbearing potential whose male partner is receiving pomalidomide is 
unknown at this time. For these reasons male patients receiving pomalidomide must use a latex 
condom while taking pomalidomide, when temporarily stopping pomalidomide, and for 90 days 
after permanently stopping pomalidomide treatment during any sexual contact with a pregnant 
female or a female of childbearing potential even if you have undergone a successful vasectomy.  
 
Patients should not donate blood during treatment therapy or for 28 days following 
discontinuation of pomalidomide. 
 
You must NEVER share pomalidomide with anyone else. 
 
Female subjects of childbearing potential must be willing to use 2 methods of birth control or be 
surgically sterile or abstain from heterosexual activity for 28 days prior to starting 
pomalidomide, during the course of the study, and through 30 days after last dose of 
pomalidomide and carfilzomib. Female subjects of childbearing potential are those who 1) have 
achieved menarche at some point, 2) have not undergone a hysterectomy or bilateral 
oophorectomy or 3) have not been naturally postmenopausal (amenorrhea following cancer 
therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had 
menses at any time in the preceding 24 consecutive months). Note: Abstinence is acceptable if 
this is the usual lifestyle and preferred contraception for the subject. 
 
Male subjects must agree to practice abstinence or use an effective barrier method of 
contraception starting with the first dose of pomalidomide through 6 months after last dose of 
pomalidomide and carfilzomib if sexually active with a female of childbearing potential. Note: 
Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 
Other acceptable methods of contraception are condoms with contraceptive foam, oral, 
implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm 
with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. 
 
All subjects must agree to follow the local requirements for pomalidomide counseling, 
pregnancy testing, and birth control; and be willing and able to comply with the local 
requirements (for example, periodic pregnancy tests, safety labs, etc.). 
 
 
 


 
 
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Dexamethasone 
 
Likely risks of dexamethasone (events occurring greater than 20% of the time): 
• Stomach and throat ulcers or worsening of any ulcers you had before treatment 
• Swelling and pain of the pancreas 
• Weight gain around the stomach 
• Puffiness (especially in the face) 
• Buildup of fluids and a rise in blood pressure 
• Possible rise in your blood sugar 
• Changes in the blood levels of potassium 
• Infection  
 
Less likely risks of dexamethasone (events occurring less than or equal to 20% of the time) 
• Muscle weakness 
• Brittle bones 
• Menstrual changes 
• Itching, and other allergic reactions, some severe 
 
Rare but serious risks of dexamethasone (events occurring less than 2-3% of time) 
• Mood swings 
• Depression 
• Trouble sleeping 
• Changes in personality 
• Seizures 
• Dizziness 
• Patients who are more likely to get heart disease may have heart failure 
 
As with any medication, allergic reactions are a possibility.   
 
Pregnancy risk 
If you are a female of childbearing potential, you must agree to the following: 
• abstain from heterosexual intercourse   
OR  
• to use birth control as follows:  
o Two methods of reliable birth control (one method that is highly effective and one 
additional barrier method), beginning 4 weeks before starting treatment and 
continuing for 4 months after completing treatment.  
 


 
 
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You must also agree not to donate eggs for the purpose of reproduction during treatment and 
continuing for 4 months after completing treatment.  
If you are a male, you must agree to the following:  
• Refrain from donating sperm 
• Abstain from heterosexual intercourse   
OR 
• Agree to use contraception/barrier as follows:  
o Agree to use a male condom, even if you have undergone a successful vasectomy, 
and your female partner must use an additional highly effective contraceptive 
method   
 
 
As with all research, there is a chance that confidentiality could be compromised; however, we 
take precautions to minimize this risk.  
 
Standard of Care risks 
Your doctor will discuss the risks of bone marrow aspirate and biopsy, blood draw, and 
WBLDCT (or PET/CT), as these tests and procedures are part of your standard clinical care. 
You will be exposed to radiation from the WBLDCT or PET/CT. The amount of radiation has a 
low risk of harmful effects. 
 
If your doctor prescribes another treatment drug for you to receive during cycles 2-6, they will 
discuss those risks.  
 
 
Are there reasons you might leave this research study early? 
 
 
Taking part in this research study is your decision. You may decide to stop at any time. You 
should tell your study doctor if you decide to stop and you will be advised whether any 
additional tests may need to be done for your safety. 
 
In addition, your doctor, the researchers, or Mayo Clinic may stop you from taking part in this 
study at any time: 
• If it is in your best interest, 
• If you do not follow the study rules, 
• If the study is stopped. 
 
If you leave this research study early, or are withdrawn from the study, no more information 
about you will be collected; however, information already collected about you in the study may 


 
 
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continue to be used. 
We will tell you about any new information that may affect your willingness to stay in the 
research study. 
 
 
What if you are injured from your participation in this research study? 
 
 
Where to get help: 
If you think you have suffered a research-related injury, you should promptly notify the Principal 
Investigator listed in the Contact Information at the beginning of this form. Mayo Clinic will 
offer care for research-related injuries, including first aid, emergency treatment and follow-up 
care as needed. 
 
Who will pay for the treatment of research related injuries? 
Care for such research-related injuries will be billed in the ordinary manner, to you or your 
insurance. You will be responsible for all treatment costs not covered by your insurance, 
including deductibles, co-payments and coinsurance. 
 
 
What are the possible benefits from being in this research study? 
 
 
The treatment being used in the trial contains medicines that are typically used for treatment of 
myeloma. We hope the information learned from this study will benefit other people with 
multiple myeloma in the future. 
 
 
What alternative do you have if you choose not to participate in this research 
study? 
 
 
You do not have to be in this study to receive treatment for your condition. Your other choices 
may include the commonly used treatment regimens that include the currently approved drugs.  
You should talk to the researcher and your regular physician about each of your choices before 
you decide if you will take part in this study. 
 
 
 


 
 
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What tests or procedures will you need to pay for if you take part in this research 
study? 
 
 
You won’t need to pay for tests and procedures which are done just for this research study.  
These are:  
• Research bone marrow aspirate done at the end of Cycle 1 
 
You and/or your insurance will need to pay for all other tests and procedures that you would 
have as part of your clinical care. These tests and procedures are: 
• Medical history (including any medications that you are taking now or have taken in the 
past) 
• Review of your current medical condition(s) 
• Physical examination (including height and weight) 
• Vital signs (blood pressure, heart rate, temperature) 
• Whole body low dose CT scan or PET/CT 
• Routine blood tests   
•  Blood tests to assess your disease  
• Urine tests to assess your disease  
• Pregnancy test if you are able to become pregnant 
• Bone marrow aspirate and biopsies that are done as part of your routine care 
• Standard of care drugs, Lenalidomide, Pomalidomide and Dexamethasone 
• Any other standard of care drug prescribed by your doctor  
 
You will also be responsible for any co-payments and deductibles. Before you take part in this 
study, you should call your insurer to find out if the cost of these tests and/or procedures will be 
covered. You will have to pay for any costs not covered by your insurance. 
 
If you have questions about any costs to you that may result from taking part in the research, 
please speak with the Principal Investigator. If you wish, arrangements can be made for you to 
speak with someone in Patient Financial Services about these costs. 
 
If you have billing or insurance questions call Patient Account Services at the telephone 
number provided in the Contact Information section of this form. 
 
 
 


 
 
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Will you be paid for taking part in this research study? 
 
 
You will not be paid for taking part in this study. 
 
There is a very small chance that some commercial value may result from the use of your 
sample. This could include new products like a drug or a test to diagnose a disease. If that 
happens, you will not be offered a share in any profits. 
 
 
Will your information or samples be used for future research? 
 
 
Your samples will be used for this study. When the study is done, they will be destroyed. 
 
Your information or samples collected for this study will not be used or shared for future 
research studies even if the identifiable information such as your name, Mayo Clinic number or 
date of birth is removed. 
 
 
How will your privacy and the confidentiality of your records be protected? 
 
 
Mayo Clinic is committed to protecting the confidentiality of information obtained about you in 
connection with this research study. All of your research samples given to Mayo Clinic will be 
labeled with a code number and kept in locked storage. Only your study team will be able to link 
your samples with your identity. No one working with your samples will know your identity. If 
the results of the research are made public, information that identifies you will not be used. 
 
During this research, information about your health will be collected.  Under Federal law called 
the Privacy Rule, health information is private.  However, there are exceptions to this rule, and 
you should know who may be able to see, use and share your health information for research and 
why they may need to do so.  Information about you and your health cannot be used in this 
research study without your written permission.  If you sign this form, it will provide that 
permission (or “authorization”) to Mayo Clinic. 
 
 
 


 
 
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Your health information may be collected from: 
• Past, present and future medical records. 
• Research procedures, including research office visits, tests, interviews and 
questionnaires. 
 
Your health information will be used and/or given to others to: 
• Do the research. 
• Report the results. 
• See if the research was conducted following the approved study plan, and applicable rules 
and regulations. 
 
Your health information may be used and shared with: 
• Mayo Clinic research staff involved in this study.  
• Other Mayo Clinic staff involved in your clinical care.  
• The sponsor(s) of this study and the people or groups hired by the sponsor(s) to help 
perform this research. 
• The Mayo Clinic Institutional Review Board that oversees the research.  
• Federal and State agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health and other United States 
agencies) or government agencies in other countries that oversee or review research. 
• A group that oversees the data (study information) and safety of this research.   
 
How your information may be shared with others: 
While taking part in this study, you will be assigned a code that is unique to you, but does not 
include information that directly identifies you. This code will be used if your study information 
is sent outside of Mayo Clinic. The groups or individuals who receive your coded information 
will use it only for the purposes described in this consent form. 
 
If the results of this study are made public (for example, through scientific meetings, reports or 
media), information that identifies you will not be used. 
 
In addition, individuals involved in study oversight and not employed by Mayo Clinic may be 
allowed to review your health information included in past, present, and future medical and/or 
research records. This review may be done on-site at Mayo Clinic or remotely (from an off-site 
location). These records contain information that directly identifies you. However, the 
individuals will not be allowed to record, print, or copy (using paper, digital, photographic or 
other methods), or remove your identifying information from Mayo Clinic. 
 
 
 


 
 
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Is your health information protected after it has been shared with others? 
Mayo Clinic asks anyone who receives your health information from us to protect your privacy; 
however, once your information is shared outside Mayo Clinic, we cannot promise that it will 
remain private and it may no longer be protected by the Privacy Rule. 
 
 
Your Rights and Permissions 
 
 
Participation in this study is completely voluntary. You have the right not to participate at all.  
Even if you decide to be part of the study now, you may change your mind and stop at any time.  
You do not have to sign this form, but if you do not, you cannot take part in this research study. 
 
Deciding not to participate or choosing to leave the study will not result in any penalty.  Saying 
‘no’ will not harm your relationship with your own doctors or with Mayo Clinic. 
 
If you cancel your permission for Mayo Clinic to use or share your health information, your 
participation in this study will end and no more information about you will be collected; 
however, information already collected about you in the study may continue to be used. 
 
You can cancel your permission for Mayo Clinic to use or share your health information at any 
time by sending a letter to the address below: 
 
Mayo Clinic 
Office for Human Research Protection 
ATTN:  Notice of Revocation of Authorization 
PL 3-02 
200 1st Street SW 
Rochester, MN  55905 
 
Alternatively, you may cancel your permission by emailing the Mayo Clinic Research 
Participant Advocate at: researchparticipantadvocate@mayo.edu. 
 
Please be sure to include in your letter or email: 
• The name of the Principal Investigator, 
• The study IRB number and /or study name, and 
• Your contact information. 
 


 
 
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{{$prtPartName                                          }} 
{{$dteParticipantSig                                }} 
{{!$sigWitness}} 
{{$sigParticipant                    }} 
{{$prtPOCName                                       }} 
{{$dtePOCSig                                        }} 
{{$sigPOC                                 }} 
Your permission for Mayo Clinic to use and share your health information lasts until the end of 
this study, unless you cancel it.  The study does not end until all data has been collected, checked 
(or audited), analyzed, and reported. Because research is an ongoing process, we cannot give you 
an exact date when the study will end. Sometimes this can be years after your study visits and/or 
activities have ended. 
 
 
Enrollment and Permission Signatures 
 
 
Your signature documents your permission to take part in this research.  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
Printed Name  
 
 
Date (mm/dd/yyyy) 
 
 
Time (hh:mm am/pm)  
 
 
 
 
 
 
 
 
_______________________________ 
Signature 
 
 
 
Person Obtaining Consent  
• I have explained the research study to the participant. 
• I have answered all questions about this research study to the best of my ability. 
 
 
 
Printed Name  
 
 
Date (mm/dd/yyyy) 
 
 
Time (hh:mm am/pm) 
 
 
_______________________________ 
Signature