Clinical trial NCT01547806
Conditions: Plasma Cell Myeloma Multiple Myeloma
Keywords: Autologous Hematopoietic Cell Transplantation Plasma Cell Myeloma Mobilization Apheresis Plerixafor
Sponsor: National Cancer Institute (NCI)
Start date: 2012-02-22; Completion date: 2018-01-11
Enrollment: 49 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Background:

\- One beneficial treatment for plasma cell myeloma is high-dose chemotherapy followed by stem cell transplant. Researchers want to collect stem cells from the blood for later transplant.

Objectives:

\- To collect stem cells for transplant as part of treatment for plasma cell myeloma.

Eligibility:

\- Individuals at least 18 years of age who will have chemotherapy and stem cell transplant for plasma cell myeloma.

Design:

* Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
* Participants will have filgrastim injections for 5 days before collection. This will move stem cells from the bone marrow to the blood.
* Participants will have apheresis to collect the stem cells.
* Participants who need additional apheresis procedures to collect stem cells will have filgrastim and a dose of plerixafor to improve the collection yield.

Detailed description:
Background:

High-dose chemotherapy followed by autologous hematopoietic cell transplant (AHCT) remains a critical part of the Plasma Cell Myeloma (PCM) treatment in subjects eligible for the procedure. The timing of the procedure however, has become more controversial recently. This protocol will allow collection of Hematopoietic Progenitor Cells by Apheresis (HPC, Apheresis) in potential candidates for various PCM protocols at the Clinical Center.

The mobilizing agent plerixafor (Mozobil, Genzyme) has been recently approved by the Food and Drug Administration (FDA) for mobilization in PCM. However, the best and most cost effective strategy for its use remains to be defined.

Objectives:

Evaluate the overall validity of an HPC mobilization strategy (with granulocyte-colony stimulating factor (G-CSF) alone or in combination with plerixafor) using a formula calculating the likelihood of collecting greater than or equal to 5 time 10\^6 cluster of differentiation 34 (CD34) plus cells/kg in a single mobilization cycle.

Collect mobilized Hematopoietic Progenitor Cells by Apheresis (HPC, Apheresis) prior to AHCT for PCM

Eligibility:

Subjects with a possible indication for AHCT for the treatment of newly diagnosed PCM.

Subjects with recurrent or persistent evaluable disease who have not undergone AHCT for the treatment of the PCM.

Design:

Subjects will undergo mobilization and collection of HPC, Apheresis for subsequent use in various clinical protocols.

Mobilization will be provided by a 5-daily administration of filgrastim according to standard procedure.

The need for an additional mobilizing agent (plerixafor) to be given on day 4 of mobilization will be evaluated in real time in each patient, based on the peripheral blood CD34 count on the morning of day 4 of filgrastim administration.

Study accrual over a 3-year period: 70 subjects

Arms: arm 1: Subjects will undergo mobilization and collection of HPC, Apheresis for subsequent use in various clinical protocols.
Interventions: intervention 1: Filgrastim intervention 2: Plerixafor intervention 3: Apheresis
Intervention descriptions: intervention 1: Filgrastim will be administered as a single daily dose in a dose range of 10-16ug/kg/day subcutaneously for 5-7days intervention 2: Plerixafor will be given on day 4, 8-10 hours before the day 5 apheresis, dose calculated according to patient weight intervention 3: The minimum cluster of differentiation 34 (CD34)+ cell dose that must be collected in order to proceed with a single autologous transplantation is 2 x 106 CD34+ cells/kg.

Protocol documents:
Prot_SAP_ICF_000.pdf: 
Amendment
Protocol Number:
12C0074-H
Principal Investigator:Jen Kanakry  
NCI  
ETIB  
301.451.3787  
jennifer.kanakry@nih.gov
(NIH Employee Name, Institute/Branch, Telephone and e-mail)
Reference Number:
373683
Protocol Title:
Mobilization and Collection of Autologous Hematopoietic Progenitor Cell (HPC) for Transplantation (AHCT) for Plasma Cell Myeloma
(PCM)
SIGNATURES
Principal Investigator (*): 
Daniel Fowler - applied signature on 09/22/2017 2:16 PM EDT 
Jen Kanakry - applied signature on 09/22/2017 11:39 AM EDT
Accountable Investigator:
Ronald Gress - applied signature on 09/22/2017 12:17 PM EDT
Branch Chief/CC Department Head (**):
Ronald Gress - applied signature on 09/22/2017 12:18 PM EDT
Medical Advisory Investigator (if applicable):
N/A
Lead Associate Investigator signature:
N/A
Referral Contact signatures:
Jen Kanakry - applied signature on 09/22/2017 11:39 AM EDT
Associate Investigators signatures:
N/A
For Institute/Center Scientific Review Committee:
N/A
Other IC Clinical Director signatures:
N/A
APPROVALS
IRB Chair:
Michael Hamilton - applied signature on 09/23/2017 1:18 PM EDT
Clinical Director:
N/A
CONCURRENCE
OPS Protocol Specialist:
Signature
Print Name
Date
* Signature signifies that investigators on this protocol have  been informed that the collection and use of personally  identifiable information at
the NIH are maintained in a system of record governed under provisions of the Privacy Act of 1974. The information provided is mandatory for
employees of the NIH to perform their assigned duties as related to the administration and reporting of intramural research protocols and
used solely for those purposes.  Questions may be addressed to the Protrak System Owner.
** I have reviewed this research project and considered the NIH Policy for Inclusion of Women and Minorities in Clinical Research. Taking into 
account the overall impact that the project could have on the research field involved, I feel the current plans adequately includes both sex/
gender, minorities, children, and special populations, as appropriate. The current enrollment is in line with the planned enrollment report for 
inclusion of individuals on the basis of their sex/gender, race, and ethnicity and is appropriate and of scientific and technical merit. 
IRB Meeting Date:
Expedited
DEC Clearance Date: 09/22/2017
Protocol Version Date:09/14/2017
Lemuel Clayborn                                                                             AM H                                                     10/04/2017


Abbreviated Title: HPC for AHCT in PCM  
Version date: September 14, 2017 
 
 
                                                                                                                                          Page 1 of 38 
Abbreviated Title: HPC for AHCT in PCM 
CC Protocol Number:  12-C-0074 
NCT#: NCT01547806 
Version Date: September 14, 2017  
Amendment: H 
 
Protocol Title: Mobilization and Collection of Autologous Hematopoietic Progenitor Cell 
(HPC) for Transplantation (AHCT) for Plasma Cell Myeloma (PCM) 
 
NCI Principal Investigator:             Jennifer A. Kanakry, M.D
 A-F 
  
  
  
  
  
Experimental Transplantation and Immunology Branch 
  
  
  
  
 
Center for Cancer Research, NCI   
  
  
  
  
  
10 Center Drive, Building 10, Rm 4-3132 
  
  
  
  
 
Bethesda, MD 20892 
  
  
  
  
  
Phone: 240-760-6172 
                                                             Fax: (301) 451-5667 
  
  
  
  
 
Email: jennifer.kanakry@nih.gov 
 
NIH Associate Investigators: 
Daniele Avila, C.R.N.P., ETIB, CCR A-E 
Dennis Hickstein, MD.,ETIB, CCR 
A-F 
Bazetta  Blacklock  Schuver,  R.N., OCD,  CCR 
A-C 
 Ellen Carroll, R.N., OCD, CCR A-C 
Tracey Chinn, R.N., ETIB, CCR 
A-C 
 Jeremy Rose, M.S, ETIB, CCR E-F 
Constance Yuan, M.D., Ph.D, CCR E-F 
Jennifer Mann, C.R.N.P., ETIB, CCR 
A-E 
Ronald E. Gress, M.D., ETIB, CCR 
A-F 
Steven Pavletic, M.D., ETIB, CCR 
A-F 
Fran Hakim, Ph.D, ETIB, CCR E-F 
Seth Steinberg Ph.D., OCD, CCR B, E 
Brenna Hansen, R.N., OCD, CCR A-C 
Maryalice Stetler-Stevenson, M.D., PhD.,
 CCR 
B, E-F.
4 
 Stephanie Cotton, R.N., OCD, CCRA-C 
David Stroncek, M.D.,DTM, CCR
E-F 
 
Referral contact: Jennifer Kanakry, M.D. 
                             Telephone: 240-760-6172 
  
  
     Email: jennifer.kanakry@nih.gov 
 
                                 
Study Coordinator:  Bazetta Blacklock Schuver, RN 
                                        Phone number: 240-760-6156 
                                     Email: bblacklock@mail.nih.gov 
For each person listed above, roles are identified with the appropriate letter 
A. Obtain information by intervening or interacting with living individuals for research purposes 
B. Obtaining identifiable private information about living individuals 


Abbreviated Title: HPC for AHCT in PCM  
Version date: September 14, 2017 
 
 
                                                                                                                                          Page 2 of 38 
C. Obtaining the voluntary informed consent of individuals to be subjects 
D. Makes decisions about subject eligibility 
E. Studying, interpreting, or analyzing identifiable private information or data/specimens for 
research purposes 
F. Studying, interpreting, or analyzing de-identified data or specimens for research purposes 
G. Some/all research activities performed outside NIH 
 
Investigational Agents: None  
Commercial Agents: Filgrastim and Plerixafor 
  
 


Abbreviated Title: HPC for AHCT in PCM  
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                                                                                                                                          Page 3 of 38 
 
PRÉCIS 
Background:  
• High-dose chemotherapy followed by autologous hematopoietic cell transplant 
(AHCT) remains a critical part of the Plasma Cell Myeloma (PCM) treatment in 
subjects eligible for the procedure. The timing of the procedure however, has become 
more controversial recently.  This protocol will allow collection of Hematopoietic 
Progenitor Cells by Apheresis (HPC, Apheresis) in potential candidates for various 
PCM protocols at the Clinical Center. 
• The mobilizing agent plerixafor (Mozobil®, Genzyme) has been recently approved 
by the FDA for mobilization in PCM. However, the best and most cost effective 
strategy for its use remains to be defined. 
Objectives: 
• Evaluate the overall validity of an HPC mobilization strategy (with G-CSF alone or in 
combination with plerixafor) using a formula calculating the likelihood of collecting 
≥ 5 x 10
6 CD34+ cells/kg in a single mobilization cycle.  
• Collect mobilized Hematopoietic Progenitor Cells by Apheresis (HPC, Apheresis) 
prior to AHCT for PCM 
Eligibility: 
• Subjects with a possible indication for AHCT for the treatment of newly diagnosed 
PCM. 
• Subjects with recurrent or persistent evaluable disease who have not undergone 
AHCT for the treatment of the PCM. 
Design: 
• Subjects will undergo mobilization and collection of HPC, Apheresis for subsequent 
use in various clinical protocols. 
• Mobilization will be provided by a 5-daily administration of filgrastim according to 
standard procedure. 
• The need for an additional mobilizing agent (plerixafor) to be given on day 4 of 
mobilization will be evaluated in real time in each patient, based on the peripheral 
blood CD34 count on the morning of day 4 of filgrastim administration. 
• Study accrual over a 3-year period: 70 subjects 
 
 


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                                                                                                                                          Page 4 of 38 
 
TABLE OF CONTENTS 
PRÉCIS 
....................................................................................................................................... 3 
TABLE OF CONTENTS ............................................................................................................. 4 
1 INTRODUCTION................................................................................................................. 7
 
1.1 
STUDY OBJECTIVES ......................................................................................................... 7 
1.1.1 Primary Objectives 
................................
................................
..................................... 7 
1.1.2 Secondary Objectives 
................................................................................................ 7 
1.2 
BACKGROUND AND RATIONALE....................................................................................... 7
 
1.2.1 Overview of Treatment of MM 
................................................................................... 7 
1.2.2 AMD3100 (Plerixafor, Mozobil™, Genzyme) 
............................................................ 8 
1.2.3 Evaluate the need for systematic use of Plerixafor on day 4 
...................................... 9 
1.2.4 Evaluation of minimal residual disease 
................................................................... 10 
1.2.5 Lack of need for purging of HPC, Apheresis product .............................................. 11
 
1.2.6 Utilization of HPC products in NCI protocols ......................................................... 11 
2 ELIGIBILITY ASSESSMENT AND ENROLLMENT 
.................................................. 12
 
2.1 
ELIGIBILITY CRITERIA ................................................................................................... 12 
2.1.1 Inclusion Criteria 
.................................................................................................... 12 
2.1.2 Exclusion Criteria 
................................................................................................... 12 
2.1.3 Recruitment strategy 
................................
................................
................................. 13 
2.2 
SCREENING EVALUATION .............................................................................................. 13 
2.2.1 History and Physical examination 
................................
............................................ 13 
2.2.2 Laboratory evaluation .............................................................................................. 13 
2.3 
REGISTRATION PROCEDURES 
................................
......................................................... 13 
3 STUDY IMPLEMENTATION 
......................................................................................... 13 
3.1 
STUDY OVERVIEW 
........................................................................................................ 13 
3.2 
TREATMENT SCHEMA 
................................................................................................... 14 
3.3 
DRUG ADMINISTRATION 
................................
................................
................................ 15 
3.3.1 Filgrastim administration 
................................
......................................................... 15 
3.3.2 Plerixafor Administration 
................................
......................................................... 16 
3.3.3 Apheresis 
................................................................................................................. 16 
3.3.4 Inadequate collection 
.............................................................................................. 17 
3.3.5 Salvage collection regimen 
................................
....................................................... 17 
3.4 
DOSE MODIFICATIONS 
................................
................................
................................... 17 
3.5 
STUDY CALENDAR 
................................
................................
......................................... 18 
3.6 
OFF STUDY CRITERIA .................................................................................................... 18 
3.6.1 Criteria for removal from protocol therapy.............................................................. 18 
3.6.2 Off-Study Criteria 
................................
................................
..................................... 18 
3.6.3 Off Protocol Therapy and Off Study Procedure 
....................................................... 19 
4 CONCOMITANT MEDICATIONS/MEASURES 
.......................................................... 19
 
5 BIOSPECIMEN COLLECTION 
................................
...................................................... 19 


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                                                                                                                                          Page 5 of 38 
5.1 
CORRELATIVE STUDIES FOR RESEARCH/P
HARMACOKINETIC STUDIES .......................... 19
 
5.1.1 Clinical end points 
................................
................................
.................................... 19 
5.1.2 Biologic end points ................................................................................................... 19 
5.2 
SAMPLE STORAGE,
 TRACKING AND DISPOSITION .......................................................... 20
 
5.2.1 Clinical HPC, Apheresis Products ........................................................................... 20 
5.2.2 Storage/Tracking....................................................................................................... 20 
5.2.3 Protocol Completion/Sample Destruction 
................................
................................ 21 
6 DATA COLLECTION AND EVALUATION 
................................
................................. 22 
6.1 
DATA COLLECTION 
...................................................................................................... 22 
6.2 
TOXICITY CRITERIA 
................................
................................
....................................... 23 
7 SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN 
......................................................................................................................................... 23 
7.1 
DATA REPORTING & RECORDS TO BE KEPT 
................................
.................................... 23 
7.2 
DEFINITIONS 
................................
................................
.................................................. 23 
7.2.1 Adverse Event............................................................................................................ 23
 
7.2.2 Suspected adverse reaction 
...................................................................................... 24 
7.2.3 Unexpected adverse reaction 
................................................................................... 24 
7.2.4 Serious....................................................................................................................... 24 
7.2.5 Serious Adverse Event............................................................................................... 24
 
7.2.6 Disability 
................................................................................................................. 25 
7.2.7 Life-threatening adverse drug experience 
................................
................................ 25 
7.2.8 Protocol Deviation (NIH Definition) 
................................
........................................ 25 
7.2.9 Non-compliance (NIH Definition) 
................................
............................................ 25 
7.2.10 Unanticipated Problem 
............................................................................................ 25 
7.3 
NCI-IRB
 AND CLINICAL DIRECTOR REPORTING............................................................ 25
 
7.3.1 NCI-IRB and NCI CD Expedited Reporting of Unanticipated Problems and Deaths
  
25
 
7.3.2 NCI-IRB Requirements for PI Reporting at Continuing Review 
.............................. 26 
7.3.3 Exceptions to reporting: ........................................................................................... 26 
7.4 
DATA AND SAFETY MONITORING PLAN 
........................................................................ 26 
7.4.1 Principal Investigator/Research Team 
................................
..................................... 26 
8 STATISTICAL CONSIDERATIONS 
................................
.............................................. 27 
9 HUMAN SUBJECTS PROTECTIONS 
........................................................................... 28 
9.1 
RATIONALE FOR SUBJECT SELECTION 
................................
........................................... 28 
9.2 
PARTICIPATION OF CHILDREN 
................................
........................................................ 28 
9.3 
PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT 
............................................. 28
 
9.4 
EVALUATION OF BENEFITS AND RISKS/D
ISCOMFORTS 
................................................... 28
 
9.5 
RISKS/B
ENEFITS ANALYSIS............................................................................................ 28
 
9.6 
CONSENT AND ASSENT PROCESS AND DOCUMENTATION............................................... 29
 
9.6.1 Telephone re-consent procedure............................................................................... 29 
9.6.2 Short form consent process for non-English speaking patients 
................................ 29 
9.7 
SUBJECT INFORMATION AND CONFIDENTIALITY 
............................................................ 30
 
10 PHARMACEUTICAL INFORMATION 
........................................................................ 30 


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                                                                                                                                          Page 6 of 38 
10.1 FILGRASTIM (N
EUPOGEN ®,G-CSF) ............................................................................... 30 
10.1.1 Source ....................................................................................................................... 30 
10.1.2 Adverse effects .......................................................................................................... 30 
10.1.3 Formulation, Storage, and Stability.......................................................................... 30 
10.1.4 Administration........................................................................................................... 30
 
10.2 PLERIXAFOR (M
OZOBIL®) 
............................................................................................. 31 
10.2.1 Source ....................................................................................................................... 31 
10.2.2 Adverse effects .......................................................................................................... 31 
10.2.3 Formulation, Storage, and Stability.......................................................................... 31 
10.2.4 Administration........................................................................................................... 31
 
10.2.5 Pharmacokinetics 
.................................................................................................... 31 
11 REFERENCES 
.................................................................................................................. 32 
12 APPENDIX 1: ON-STUDY CHECK LIST 
..................................................................... 36 
13 APPENDIX 2: DATA COLLECTION ELEMENTS REQUIRED BY PROTOCOL 
. 37
 
13.1 PATIENT ENROLLMENT 
................................
................................
.................................. 37 
13.2 STUDY DRUG ADMINISTRATION 
................................
..................................................... 37 
13.3 LABORATORY AND DIAGNOSTIC TEST DATA 
................................
................................. 37 
13.4 ADVERSE EVENTS 
........................................................................................................ 37 
13.5 CONCOMITANT MEASURES 
................................
............................................................ 37 
13.6 OFF STUDY 
................................................................................................................... 38 
 


Abbreviated Title: HPC for AHCT in PCM  
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                                                                                                                                          Page 7 of 38 
 
1 INTRODUCTION 
1.1 STUDY OBJECTIVES 
1.1.1 Primary Objectives 
• Evaluate the overall validity of an HPC mobilization strategy (with G-CSF alone or in 
combination with plerixafor) using a formula calculating the likelihood of collecting ≥ 5 
x 106 CD34+ cells/kg in a single mobilization cycle.   
• Collect and cryopreserve “HPC Apheresis” products for subsequent use in AHCT in 
subjects with Plasma Cell Myeloma (PCM).  
1.1.2 Secondary Objectives 
• Determine the proportion of subjects requiring addition of plerixafor to the G-CSF 
mobilization regimen. 
• Determine the proportion of subjects achieving the target or optimum goal of ≥ 5 x 
106 CD34+ cells/kg in a single mobilization cycle with or without Plerixafor. 
• Determine the proportion of subjects achieving the minimum goal of ≥ 2 but <5 x 10
6 
CD34+ cells/kg in a single mobilization cycle with or without Plerixafor. 
• Determine the degree of tumor cell contamination in the final product. 
• Determine the impact of plerixafor in the degree of tumor cell contamination in the 
final product. 
1.2 BACKGROUND AND RATIONALE 
1.2.1 Overview of Treatment of MM 
Approximately 20,000 new cases of Plasma Cell Myeloma (PCM) are diagnosed each year in the 
United States.  In the general population, the incidence of PCM is 5 per 100,000 with an average 
age of onset around 70 years. Rates are higher in African Americans and in men. It is the second 
most common hematologic malignancy in the United States. There are an estimated 45,000 
people living with PCM in this country and it is estimated that there were 19,900 new diagnoses 
and 10,790 deaths due to MM in 2007
[1]. The median survival of patients with MM was less than 
one year before introduction of alkylating agents (melphalan) in the 1960s which resulted in 
improved survival but still in a very limited number of complete responses and in no curative 
effect. 
For many years dexamethasone (Dex) alone or in combination with oral melphalan (MP) or with 
vincristine and doxorubicin (VAD)[2] has been the mainstay of induction therapy for newly 
diagnosed PCM.  Recently, several agents with novel mechanisms of action have shown superior 
activity in PCM. Thalidomide in combination with Dex was found to be superior to Dexalone as 
well as superior to VAD in randomized trials[3, 4].  Additionally, bortezomib, a proteosome 
inhibitor, has been shown to be superior to VAD as induction therapy in randomized trial
[5].  
Two phase III studies show an increased overall survival with oral lenalidomide plus Dex 


Abbreviated Title: HPC for AHCT in PCM  
Version date: September 14, 2017 
 
 
                                                                                                                                          Page 8 of 38 
compared to Dex plus placebo in previously treated PCM patients[6, 7].  Phase II studies in newly 
diagnosed patients corroborate these findings.  Therefore, significant progress has been made in 
the last decade in the management of PCM with the advent of therapy with thalidomide, 
bortezomib and more recently lenalidomide[8] and their combination in strategies including high-
dose chemotherapy followed by autologous hematopoietic stem cell transplantation(AHCT).  In 
patients not exposed to this new generation of drugs, the median survival following relapse after 
AHCT is about 18 months while in patients exposed to these drugs following relapse after 
AHCT, the median survival has almost doubled to 36 months.  Overall, in a recent study from 
Mayo Clinic, the median overall survival for subjects diagnosed in the last decade was 44.8 
months (95% CI; 39.6,50) compared with 29.9 months (95% CI; 28.3, 31.6) p< .001,for those 
diagnosed earlier[9].  These successes have allowed moving these agents to front line therapy in 
newly diagnosed subjects with significant improvement in response rates and EFS[10-12].  The 
multiple improved therapeutic options now available as induction therapy for MM were recently 
reviewed
[13]and are available as standard of care for newly diagnosed MM.  Guidelines are 
described and regularly up-dated by the National Comprehensive Cancer Network   
(http://www.nccn.org/professionals/physician_gls/f_guidelines.asp).
 
Prior to the present era of novel therapeutic agents for PCM, AHCT has been shown to 
significantly increase the complete remissions (CR) rate to almost 50% in selected patients 
(versus 1–13% CR with conventional dose therapy), but the disease recurs almost without 
exception
[14-16].  AHCT increases the CR rate and time-to-progression and has shown a survival 
improvement
[17, 18] though not consistently
[19, 20].  In a meta-analysis of 2411 subjects on 9 
randomized trials, Koreth et al. showed progression free survival (PFS) benefit but not overall 
survival (OS) benefit for AHCT with single autologous transplantation performed early in 
multiple myeloma over chemotherapy alone[18]. 
Of note, prior to the present era of novel agents, there was no advantage in delaying AHCT until 
disease progression. The treatment duration was overall shorter in patients transplanted upfront 
following induction chemotherapy
[21].  In the present era of more effective induction therapy 
though, this assertion needs to be revisited and at least two randomized trials are presently 
ongoing to address the question of upfront versus delayed AHCT following induction with novel 
agents. 
Of significance, to the present day, achievement of a CR continues to be the single most 
predictive factor for EFS and OS for PCM[22].  Better responses lead to better response durations. 
Outcomes of 4,990 AHCT patients according to their best tumor response were reported in two 
meta-analyses of 21 studies (10 prospective and 11 retrospective). Both meta-analyses indicated 
highly significant association between maximal response (CR/VGPR) during or after AHCT and 
long-term outcomes (OS and EFS) as well as a highly significant associations between maximal 
response following induction therapy and EFS/OS
[23].   Therefore, improvement of the initial CR 
rate continues to be at the forefront of clinical research in PCM. 
1.2.2 AMD3100 (Plerixafor, Mozobil™, Genzyme) 
Plerixafor is a small molecule reversible inhibitor of the binding of SDF-1αto its cognate 
receptor CXCR4 and mobilizes hematopoietic stem cells from the marrow to the blood
[24, 25].  
Plerixafor clinical experience and toxicity have been recently reviewed[26, 27]. 


Abbreviated Title: HPC for AHCT in PCM  
Version date: September 14, 2017 
 
 
                                                                                                                                          Page 9 of 38 
Maximal mobilization of CD34+ cells occurs 8-10 h after dosing
[26]. There is a highly synergistic 
interaction of G-CSF and AMD3100 on mobilization
[28].The combination plerixafor/ G-CSF is 
more effective than G-CSF alone for CD34
+ cell mobilization. In a study of stem cell 
mobilization for AHCT for PCM, the percentage of patients who collected ≥ 6 x 10
6 CD34+  
cells/kg in ≤ 2 aphereses was 71.6% (106 of 148 patients) in the G-CSF + plerixafor group and  
34.4% (53 of 154) in the G-CSF + placebo group (p < .001). 54% of G-CSF + plerixafor-treated 
patients reached target after one apheresis, whereas 56% of the G-CSF + placebo-treated patients 
required 4 aphereses to reach target
[29].  Similar results were found in a phase III randomized 
placebo controlled study in non-Hodgkin’s lymphoma[30]. 
Plerixafor (Mozobil™) received FDA approval in December 2008 for use in stem-cell 
mobilization in NHL and PCM. This was based on the results of two placebo-controlled clinical 
trials. In both studies, the subjects were randomized to receive either plerixafor 0.24 mg/kg or 
placebo on each evening prior to apheresis. They received daily morning doses of G-CSF 10 
mcg/kg for 4 days prior to the first dose of plerixafor or placebo and on each morning prior to 
apheresis. Study 1[30] enrolled 298 NHL subjects. Fifty nine percent of the subjects mobilized 
with plerixafor and G-CSF collected ≥ 5 x 106 CD34+ cells/kg from the peripheral blood in four 
or fewer apheresis sessions, compared with 20% of subjects mobilized with placebo and G-CSF 
(p < 0.001). The median number of apheresis days to collect ≥ 5 x 10
6 CD34+ cells/kg was 3 
days for the plerixafor group and not evaluable for the placebo group. Study 2[29] enrolled 302 
MM subjects. Seventy two percent of patients mobilized with plerixafor and G-CSF collected ≥ 
6 x 106 CD34+ cells/kg from the peripheral blood in two or fewer apheresis sessions, compared 
with 34% of patients mobilized with placebo and G-CSF (p < 0.001). The median number of 
apheresis days to collect ≥ 6 x 10
6 CD34+ cells/kg was 1 day for the plerixafor group and 4 days 
for the placebo group. 
More recent experience has now also been acquired in using plerixafor alone as a mobilization 
agent prior to AHCT for PCM
[31]and prior to allo BMT
[32]. 
1.2.2.1 Plerixafor pharmacokinetics 
Peak plasma concentrations occur about 30 to 60 minutes after a subcutaneous dose. It is about 
58% bound to plasma proteins and largely confined to the extravascular fluid space. About 70% 
of a dose is eliminated in the urine within 24 hours after a dose, and the terminal half-life is 
about 3 to 5 hours.  
In moderate and severe renal impairment (creatinine clearance 50 ml/min or less) the dose of 
plerixafor should be reduced to 160 micrograms/kg, given by subcutaneous injection about 10 
hours before apheresis, for up to 4 consecutive days. The daily dose should not exceed 27 mg. 
complete information is available at the following web site: 
http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/C8B255/DUPLICATIO
NSHIELDSYNC/257110/ND_PG/PRIH/ND_B/HCS/SBK/1/ND_P/Main/PFActionId/hcs.comm
on.RetrieveDocumentCommon/DocId/20551-
p/ContentSetId/30/SearchTerm/mozobil/SearchOption/BeginWith 
1.2.3 Evaluate the need for systematic use of Plerixafor on day 4 
Based on recent work from the Department of Transfusion Medicine of the Clinical Center, the 
yield of an apheresis procedure could be accurately predicted on the basis of a pre-procedure 


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                                                                                                                                          Page 10 of 38 
peripheral blood CD34+ cells content determination[33].  However, this work was done prior to 
the use of plerixafor in mobilization and in a population of healthy donors for allogeneic 
transplantation.   
This study will seek to validate the formula developed by DTM that calculates the likelihood of 
collecting ≥ 5 million CD34+ cells/kg in a single apheresis after 5 days of G-CSF alone (without 
plerixafor). The equation is based on the circulating blood CD34+cell concentration in healthy 
subjects on the morning of day 
5 (after 4 evening doses of G-
CSF); see Figure and Table. 
Therefore, with the knowledge 
of the pre-procedure peripheral 
blood CD34+ cell count after 4 
doses of G-CSF, the patient’s 
weight and the blood volume 
that can be processed during a 
single apheresis procedure, it 
should be possible to predict 
which subjects would most 
likely achieve a collection of 5 
x 106 CD34+ cells/kg with a 
single apheresis. These subjects 
would not need to receive 
plerixafor on day 4 of mobilization but would receive day 5 of G-CSF as planned. 
Table 1 
Prediction of Need for Plerixafor based on Pre-Apheresis CD34 Count 
  
Target 
Minimum CD34 
x106/L  
Minimum 
required 
Minimum acceptable D4  
Pt Kg  
CD34 
processed yield   
 pre-apheresis  
CD34 count (predicted)  
Wgt 
x 106 
in 25 L procedure 
CD34/uL 
w/o plerixafor 
≤60 
300 
12 
21 
24 
61-65 
325 
13 
23 
26 
66-70 
350 
14 
26 
28 
71-75 
375 
15 
28 
31 
76-80 
400 
16 
31 
33 
81-85 
425 
17 
33 
35 
86-90 
450 
18 
36 
38 
91-95 
475 
19 
38 
40 
≥96 
500 
20 
40 
42 
 
1.2.4 Evaluation of minimal residual disease 
• Residual disease evaluation will be performed using high resolution detection methods:  
• Multicolor Flow cytometry[34-38] 
y = 0.4079x + 3.501
R² = 0.7654
0
10
20
30
40
50
60
70
80
90
100
110
0
20
40
60
80
100 120 140 160 180 200
CD34 Cell Yield (x106)
Per Liter Processed
Preapheresis CD34 Count (cells/uL)
CD34 Cell Y
ield/Net Liter Processed vs Preapheresis 
CD34 Count 
in 240 NMDP Donors 


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                                                                                                                                          Page 11 of 38 
• Molecular Pathology 
• Idiotype-specific PCR[39-42]. 
High sensitivity detection methods may be used for the determination of the degree of tumor cell 
contamination in the HPC, Apheresis product and/or as a surrogate marker for treatment efficacy 
comparing pre-treatment values with those of best response.  Furthermore, clinical relapse may 
be anticipated.  In a study using IgH PCR with patient-specific probes, increase of clonotypic 
cells in PB was detectable a median of 3 months before clinical relapse
[43]. 
1.2.5 Lack of need for purging of HPC, Apheresis product 
Multiple studies have been performed in an attempt to improve the EFS post-transplant by 
purging the “HPC, Apheresis” product from myeloma cells.  Results have been conflicting at 
best, but mostly disappointing [44]. 
Two phase 3 randomized trials compared patients with PCM who received autografts purged of 
tumor cells (CD34+-selected PBSC) with those with unselected PBSCs[45, 46]. Both studies used a 
highly sensitive, tumor-specific PCR technique to identify the Ig heavy chain sequence of the 
myeloma clone and determine the level of tumor cell contamination. Both studies achieved a 
large reduction in tumor burden (approximately 1 to 6 log tumor load reduction), but no 
significant differences were observed between the 2 groups in terms of response, EFS/PFS, or 
OS. 
These disappointing results clearly demonstrate that the residual tumor burden in the patient and 
the inability to eradicate it at the time of the High-Dose chemotherapy are the primary cause for 
treatment failure post-AHCT and should remain the primary focus for improving transplant 
outcome. There is much hope, however, that the combination of novel agents and AHCT will 
achieve much greater disease burden reduction than previously achieved in the randomized 
studies cited above. Therefore, tumor cell contamination of HPC products may then become an 
impediment to prolonged disease free survival.  It will be important then to have knowledge of 
the potential contribution of each mobilization strategy to HPC tumor cell contamination.  This 
protocol offers a great opportunity to compare the contribution of G-CSF and plerixafor to HPC 
product tumor cell contamination. 
1.2.6 Utilization of HPC products in NCI protocols 
The cellular products collected on this protocol are extremely likely to be subsequently used in a 
CCR protocol.  HPC collection for subsequent AHCT is a recommendation of the International 
Myeloma Working Group for all patients treated for PCM. This position is echoed in several 
recent reviews
[47-49].  
ETIB has presently one protocol open which includes AHCT for PCM (11-C-0016).  
The Myeloma Program is presently accruing 2 to 3 patients per week, the majority of whom are 
either already eligible for protocol11-C-0016 at the time of their enrollment on the Lymphoid 
Malignancies Branch (LYMB) studies or are likely to become eligible.  The ETIB protocol in 
preparation is also likely to capture a large number LYMB recruited subjects as AHCT continues 
to play a large role in PCM therapy in spite of the recent therapeutic advances with the use of 
novel agents.  At this point it is expected that more than 80% of subjects who would undergo 
HPC collection under this protocol would undergo AHCT as part of a CCR study. 


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                                                                                                                                          Page 12 of 38 
2 ELIGIBILITY ASSESSMENT AND ENROLLMENT 
2.1 ELIGIBILITY CRITERIA 
2.1.1 Inclusion Criteria 
2.1.1.1 Multiple Myeloma criteria 
• Subjects with an indication for AHCT for the treatment of PCM as determined by the 
PI or LAI. 
o Subjects following induction treatment for PCM 
o Subjects with recurrent or persistent evaluable disease who have not undergone 
AHCT for the treatment of the PCM. 
2.1.1.2 Other eligibility criteria 
• Age >18 years and less than or equal to 75 years.  In subjects between 65 and 75 years of 
age, physiologic age and co-morbidity will be thoroughly evaluated before enrolling.  
• Karnofsky performance status of 70% or greater (ECOG 0 or 1)  
• Ejection fraction (EF) by MUGA or 2-D echocardiogram within institution normal limits.  In 
case of low EF, the subject may remain eligible after a stress echocardiogram is performed if 
the EF is more than 35% and if the increase in EF with stress is estimated at 10% or more. 
• Hgb > 8g/dl (transfusion acceptable) 
• No history of abnormal bleeding tendency. 
• Patients must be able to give informed consent 
2.1.2 Exclusion Criteria 
• Prior allogeneic stem cell transplantation 
• Hypertension not adequately controlled by 3 or less medications. 
• Clinically significant cardiac pathology: myocardial infarction within 6 months prior to 
enrollment, Class III or IV heart failure according to NYHY, uncontrolled angina, severe 
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or 
acute conduction system abnormalities. Specifically, any history of cardio-vascular 
pathology or symptoms, not clearly fitting this exclusion criterion will prompt an evaluation 
by a Clinical Center Cardiologist and eligibility will be considered on a case-by-case basis.  
Should the cardiologist deem the patient’s findings on work-up to be not clinically significant 
pathology, the patient will have met this exclusion criterion.  
• Patients with a history of coronary artery bypass grafting or angioplasty will receive a 
cardiology evaluation and be considered on a case-by-case basis. 
• Active hepatitis B or C infection 
• HIV seropositive, with positive confirmatory nucleic acid test 
• Patients known or found to be pregnant.  
• Patients of childbearing age who are unwilling to practice contraception. 
• Patients may be excluded at the discretion of the PI/LAI if it is deemed that allowing 
participation would represent an unacceptable medical or psychiatric risk. 


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                                                                                                                                          Page 13 of 38 
2.1.3 Recruitment strategy 
It is anticipated that internal recruitment from CCR subjects will be likely sufficient for the 
expected accrual. 
2.2 SCREENING EVALUATION 
2.2.1 History and Physical examination 
All patients must have a complete history, review of systems and physical examination within 4 
weeks of study entry date.  Appropriate consultations may also be obtained as indicated for best 
clinical care. 
2.2.2 Laboratory evaluation 
The following laboratory studies must be performed within the specified period prior to study 
entry date:  
• Studies performed at diagnosis to establish the diagnosis of PCM (or subsequent studies 
demonstrating the presence of disease) must be available for review and diagnostic 
confirmation at the NCI.  
• CBC with differential and platelet count (1 week), 
• Acute, Hepatic and Mineral panels (1 week), 
• PT/PTT, fibrinogen (1 week), 
• ABO typing (4 weeks), 
• Serology for hepatitis B and C virus, HIV-1/2, HTLV I/II, T. Cruzi (4 weeks), Nucleic acid 
testing (NAT) for transmissible disease agents, per DTM policy (4 weeks), 
• β-HCG or urine pregnancy test in non-menopausal women only (1 week), 
• ECG (4 weeks) 
2.3 REGISTRATION PROCEDURES 
All patients must be registered on study once study consent has been obtained. This is typically 
done after eligibility has been confirmed. Authorized staff must register an eligible candidate 
with Central Registration within 24 hours after the candidate signing informed consent.  A 
registration checklist from the web site 
(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) must be completed and sent via 
encrypted email to:  NCI Central Registration Office ncicentralregistration-l@mail.nih.gov.  The 
Central Registration Office will send a confirmation of eligibility and will call Pharmacy to 
advise them of the acceptance of the patient on the protocol prior to the release of any 
investigational agents.  Verification of Registration will be forwarded electronically via e-mail.  
For questions regarding registration, authorized individuals should call the Central Registration 
Office between the hours of 8:30AM and 5:00PM, Monday – Friday: phone (301) 402-1732.  
Voicemail is available during non-business hours. 
3 STUDY IMPLEMENTATION 
3.1 STUDY OVERVIEW 
• Subjects will undergo mobilization and collection of peripheral blood stem cells for 
subsequent use in various clinical protocols. 


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                                                                                                                                          Page 14 of 38 
• The  need  for  an  additional  mobilizing  agent  (plerixafor)  to  be  given  on  day 4  of 
mobilization  will  be  evaluated  
in  
real  
time  
in  each  patient, based  on  
the  peripheral 
blood CD34 count on the morning of day 4 of G-CSF administration. 
o Patients with a peripheral CD 34+ cells count of greater  
than or equal to 42 cells/μl 
performed on  the  morning  of  day  4,  a  minimum  of  3  hours  after    the  4th  G-CSF 
administration will not receive plerixafor but will receive a fifth dose of filgrastim in 
the morning of day 5. The apheresis will start that morning, day 5 of mobilization, a 
minimum of 3 hours after the 5th G-CSF administration. 
o Patients with a peripheral CD 34+ cells count of less than 42 cells/μl on the morning 
of  day 4 of  G-CSF  administration may receive either  filgrastim  alone on  day  5  of 
mobilization or both plerixafor in evening of day 4 and filgrastim in the morning of 
day 5 of mobilization, depending on their weight and their circulating CD34 count, as 
described in Table 1. The apheresis will start that morning, day 5 of mobilization, a 
minimum of 3 hours after the administration of the 5th G-CSF dose (and plerixafor, if 
indicated). 
• The  collection  target  dose  is  5  x  106 CD34+ cells/kg, to  be  sufficient  for  a  double 
AHCT if  clinically  indicated (or  for  a  rescue  procedure  as  required  on  some 
transplant protocols) (minimum dose is 4 x 10
6 CD34+ cells/kg for a double transplant 
and 2 x 10
6 CD34+ cells/kg for a single autologous transplant). 
3.2 TREATMENT SCHEMA 
 
 
 
* G-CSF 10-16μg/kg/dose (according to DTM algorithm in section 3.3.1) subcutaneously 
** Plerixafor240 mcg/kg, not to exceed 24,000 mcg total 
 
Mobilization 
Day 1:  - G-CSF 10-16 μg/kg/dose *(at 9 am +/- 1 h) 
Day 2:  - G-CSF 10-16 μg/kg/dose *(at 9 am +/- 1 h) 
Day 3:  - G-CSF 10-16 μg/kg/dose *(at 9 am +/- 1 h) 
Day 4: - G-CSF 10-16 μg/kg/dose *(at 6 am +/- 1 h) 
 
Day 4:  - circulating blood CD 34 cell count, drawn a minimum of 3 hours 
after the G-CSF dose 
  
- if Day 4 CD 34 < 42 cells/μl, refer to Table 1 for decision:  
 
-Plerixafor**as indicated in Table 1 to be given at 10pm on day 
4 
Day 5:  - G-CSF 10-16 μg/kg/dose * 3 hours prior to apheresis (at 6 am) 
  
 
- start apheresis #1 the same day 
  
 
 


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                                                                                                                                          Page 15 of 38 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3.3 DRUG ADMINISTRATION 
• Filgrastim will be administered as a single daily dose in a dose range of 10-
16ug/kg/day subcutaneously for 5-7days (see Table below for sliding-scale filgrastim 
dose schedule).  
• The filgrastim doses for days 1-3 are to be given at approximately 9:00 a.m.(+/- 1 h). 
On day 4, the filgrastim dose is to be given at 6:00 a.m. (+/- 1h). 
• The filgrastim dose to be administered on day 5 (and if necessary days 6 and 7) may 
be combined with a concurrent day 4 dose of plerixafor 240 mcg/kg subcutaneously 
based on the peripheral blood CD34+ cell count (see Table 1 for prediction of need 
for plerixafor based on patient weight and circulating CD34
+ cell count).   
• On days 5, 6 or 7, filgrastim (or both drugs) must be given approximately 3 hours 
prior to starting apheresis.  
• It is not anticipated that a fourth consecutive apheresis procedure will be required; 
however, there may be circumstances, such as technical problems during apheresis or 
damage to a product during processing that require an additional procedure.  In this 
case, the same mobilization regimen given prior to the previous apheresis procedures 
will be given again.  The maximum number of consecutive apheresis procedures 
performed in any patient will be 4.  
3.3.1 Filgrastim administration 
Filgrastim will be administered according to a vial-based algorithm to reduce wastage and 
increase the total filgrastim dose given to lighter weight donors in order to improve CD34 
yields[33]. The weight on day 1 will be used for all calculations 
Not reached;   
<4 x106 CD34/kg 
collected 
Not reached;   
> 4 but <5 
x106 CD34/kg 
 
Minimum  
dose reached 
May proceed 
to 2
nd 
mobilization 
cycle 
• Cryopreserve 
• Proceed to AHCT 
Apheresis 
Target dose: 5 x 10
6CD34+cells / kg 
Following apheresis #1, proceed to apheresis #2 / #4: 
Give 8-10 hours prior to apheresis #2/ #4 
o -Plerixafor 240 μg/kg 
Give 3 hours prior to apheresis #2/ #4: 
  
    -G-CSF 10-16 μg/kg  
 
  
  
 
Target dose reached? 
reached 
After apheresis 1/2 
After apheresis 3 


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                                                                                                                                          Page 16 of 38 
 
Subject Weight 
Total Filgrastim Dose 
Dose /kg (range)  
 
  
38 - <49 kg 
600 mcg   
(12.5 to 15.8 mcg/kg)   
  
49 - < 57 kg      
780 mcg   
(13.9 to 15.9 mcg/kg)  
  
57 - <61 kg  
900 mcg   
(15.0 to 15.8 mcg/kg) 
  
61 - <68 kg       
960 mcg   
(14.3 to 15.7 mcg/kg) 
  
68 - <109 kg    
1080 mcg  
(10.0 to 15.9 mcg/kg)   
  
> 109 kg      
1200 mcg  
(11.0 or less)   
 
3.3.2 Plerixafor Administration 
If plerixafor is necessary, it will be given on day 4, 8-10 hours before the day 5 apheresis 
Subject Weight 
Total Plerixafor Dose 
< 90 kg   
 
calculate dose at 240 mcg/kg 
> 90 kg  
  
24,000 mcg (flat dose, equal to one full 1.2-mL vial) 
 
3.3.3 Apheresis 
HPC, Apheresis collection will be performed in the Dowling Apheresis Clinic of the Department 
of Transfusion Medicine (DTM).  A DTM physician is within the immediate vicinity of the 
procedure or available within one minute by pager. The minimum CD34+ cell dose that must be 
collected in order to proceed with a single autologous transplantation is 2 x 10
6 CD34+ cells/kg.  
As standard of care not infrequently calls for tandem transplants in multiple myeloma and as 
some NCI protocols require that a backup product be collected in cases of single transplants , a 
higher dose of  > 5 x106 CD34+ cells/kg will be targeted, to permit more than one cycle of high 
dose chemotherapy with autologous stem cell rescue.  Based on the mobilization response of 
individual subjects, this may require additional collections even if the minimum required for a 
single transplant (2x10
6 CD34 cells/kg) has been collected in a single apheresis procedure.  
The volume processed per apheresis procedure will be determined by DTM medical staff on the 
day of apheresis, based on peak CD34+ cell mobilization response to filgrastim and optimum and 
minimum CD34 cell dose needed. In general, volume processed will range from 12 to 30 liters 
per procedure for 1 to3 consecutive daily procedures, not to exceed a total of 60 liters over 
3days.  If the minimal cell dose necessary to proceed with a single autologous transplant (≥2 
x106 CD34+ cells/kg) is not achieved with 3 daily large volume leukapheresis procedures, then it 
is exceedingly unlike that a fourth consecutive apheresis procedure will reach this goal. The 
patient in such cases is likely to have minimal marrow reserve and not mobilize progenitor cells 
in response to pharmacologic agents.  In contrast, if a technical mishap occurs during apheresis, 
or product contamination occurs during processing, resulting in inadvertent product loss, then a 
fourth daily procedure may be considered. 
All decisions about the need for a third day of collection will be made in concert between PI/LAI 
and DTM physicians. 
 Collections will be performed with use of a dual-access continuous-flow apheresis device 
(Spectra Apheresis System, Caridian). Many subjects will require a central double lumen 
apheresis catheter. Subjects will receive continuous intravenous calcium prophylaxis to prevent 
citrate toxicity during apheresis, in accordance with standard DTM policies. 


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                                                                                                                                          Page 17 of 38 
The products will be cryopreserved in the Cell Processing Section, DTM, CC and will be stored 
in the vapor phase of liquid nitrogen.  
3.3.4 Inadequate collection 
If, after 3 or 4 consecutive daily procedures, the total number of CD34+ cells collected is: 
• Greater or equal to 4x106/kg; the subject will not be offered a 2nd collection cycle and 
will come off study. 
• Less than 4x106/kg; on a case by case basis, the subject may be offered a 2
nd 
collection cycle on study. 
All decision about the need for an additional cycle of collection will be made in concert between 
PI/LAI and DTM physicians. 
3.3.5 Salvage collection regimen 
Subjects with an inadequate collection as defined above may be offered a 2
ndmobilization and 
collection cycle.  The following regimen is suggested; 
Day 1:  - G-CSF 10-16 μg/kg/dose *(approximately at 9am, +/- 1h) 
Day 2:  - G-CSF 10-16 μg/kg/dose *(approximately at 9 am, +/- 1h) 
Day 3:  - G-CSF 10-16 μg/kg/dose *(approximately at 9 am, +/- 1h) 
Day 4:  - G-CSF 10-16 μg/kg/dose *(approximately at 6 am, +/- 1h) 
  
- Plerixafor** (at 8-10 pm) 
Day 5:  - 3 hours prior to apheresis (approximately at 6 am) 
  
  - G-CSF 10-16 μg/kg/dose*   
- Plerixafor** (at 8-10 pm) 
Day 6:  - 3 hours prior to apheresis (approximately at 6 am) 
  
  - G-CSF 10-16 μg/kg/dose* 
  
 
- Plerixafor** (at 8-10 pm) 
 
Day 7:  - 3 hours prior to apheresis (approximately at 6 am) 
  
  - G-CSF 10-16 μg/kg/dose* 
  
    
The salvage regimen may start no sooner than 4 weeks after the last apheresis procedure. 
If, after a second collection, the cumulative CD34
+cell number collected during the two 
collections is less than 2x10
6 cells / kg, the product may be discarded since no transplant will be 
performed.  
3.4 DOSE MODIFICATIONS 
See dosage algorithm above in sections 3.3.1and 3.3.2 
There are no planned dose modifications. 


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                                                                                                                                          Page 18 of 38 
 
3.5 STUDY CALENDAR 
 
 
ON 
STUDY Day 1 Day 2 Day 3 Day 4 
Day 5 
Day 6 
Day 7 
Day post 
last apheresis 
History & Physical  (2 week) 
X 
 
 
 
 
 
 
 
X 
CBC, diff, plts (1 week) 
X 
 
 
 
 
 
 
 
X 
Chemistries (1 week) 
X 
 
 
 
 
 
 
 
X 
PT/PTT, fibrinogen (1 week) 
X 
 
 
 
 
 
 
 
 
Serology: HBV, HCV, HIV, 
HTLV, T.Cruzi (4 weeks) 
X 
 
 
 
 
 
 
 
 
ABO typing (4 weeks) 
X 
 
 
 
 
 
 
 
 
DTM  NAT testing (4 weeks) 
X 
 
 
 
 
 
 
 
 
β-HCG / urine pregnancy test 
non menopausal women only 
 (1 week) 
X 
 
 
 
 
 
 
 
 
ECG (4 weeks) 
X 
 
 
 
 
 
 
 
 
Mobilization therapy 
 
 
 
 
 
 
 
 
 
G-CSF (given in the morning) 
 
X 
X 
X 
X 
X 
X (or not) X (or not) 
 
Plerixafor (given in the evening) 
 
 
 
 
X (or not) 
X (or 
not) 
X (or not) X (or not)  
Apheresis 
 
 
 
 
 
X 
X (or not) X (or not) 
 
Peripheral CD34* count (in am) 
 
 
 
 
X 
X 
pre-
apheresis 
X (or not) X (or not) 
 
Peripheral Blood MRD  
(FACS & molecular) 
X 
 
 
 
X 
X (pre) X (or not) X (or not) 
 
Apheresis product MRD 
(FACS & molecular) 
 
 
 
 
 
X 
X (or not) 
 
 
 
3.6 OFF STUDY CRITERIA 
3.6.1 Criteria for removal from protocol therapy 
• Subject’s decision 
• Adverse event related to the filgrastim or plerixafor administration which, in the 
opinion of the PI/LAI, warrants discontinuation of the treatment. 
3.6.2 Off-Study Criteria 
• Adequate collection of > 4x 106 CD34+ cells/kg: subject will be evaluated the day 
following the last apheresis procedure.  If no significant complication from the 
procedure has arisen, the subject will be taken off study. 
• Completed a second mobilization/collection cycle (“salvage cycle”), regardless of the 
total number of cells collected 
• Any grade >2 adverse event possibly, probably or definitely related to the procedure 
will be followed until resolution or clinical stabilization before the subject is taken off 
study. 


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                                                                                                                                          Page 19 of 38 
• Death 
• PI decision to end this study 
 
3.6.3 Off Protocol Therapy and Off Study Procedure 
Authorized staff must notify Central Registration Office (CRO) when a subject is off protocol 
therapy and when a subject is taken off-study. A Participant Status Update Form from the web 
site (http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) main page must be completed and 
sent via encrypted email to:  NCI Central Registration Office ncicentralregistration-
l@mail.nih.gov. 
4 CONCOMITANT MEDICATIONS/MEASURES 
Analgesic medications may be needed during filgrastim therapy. 
5 BIOSPECIMEN COLLECTION 
5.1 CORRELATIVE STUDIES FOR RESEARCH/P
HARMACOKINETIC STUDIES 
5.1.1 Clinical end points 
• Determination of the proportion of subjects requiring addition of plerixafor to the 
mobilization regimen 
• Determination of the proportion of subjects achieving the target goal of 5 x 106 cells / 
Kg with one or two apheresis procedures with or without Plerixafor. 
5.1.2 Biologic end points 
• Determination of the degree of tumor cell contamination in the final product. 
• Determination of the impact of plerixafor in the degree of tumor cell contamination of 
the final product. 
5.1.2.1 Peripheral blood 
- 20 cc in Green Top tube to the NCI Clinical Flow Cytometry core (Flow cytometry) 
- 20 cc in Lavender Top tube to Dr. Figg’s lab for processing and storage 
- Time points: 
- At baseline,  
- day 4 (collected after the 4th dose of G-CSF), 
- day 5, pre-apheresis 
- and days 6, 7, if collected on these days. 
5.1.2.2 Apheresis Product 
For each day of apheresis  
- 1-2 cc in red top tube to the NCI Clinical Flow Cytometry core (Flow cytometry) 
- 1-2 cc in red top tube to Dr. Figg’s lab for processing and storage+ 
Note for Figg’s lab blood collection: Please e-mail Julie Barnes at Julie.barnes@nih.gov and 
Paula Carter pcartera@mail.nih.gov at least 24 hours before transporting samples (the Friday 
before is preferred). 


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                                                                                                                                          Page 20 of 38 
For sample pickup, page 102-11964qaaas. 
For immediate help, call 240-760-6180 (main blood processing core number) or, if no answer, 
240-760-6190 (main clinical pharmacology lab number). 
For questions regarding sample processing, contact Julie Barnes by e-mail or at 240-760-6044. 
 
5.2 SAMPLE STORAGE,
 TRACKING AND DISPOSITION 
5.2.1 Clinical HPC, Apheresis Products 
The cryopreserved HPCs will be stored in the Cell Processing laboratory until they are infused 
for autologous transplantation. In the event a subject wishes to undergo AHCT at an outside 
institution, the HPC product may be shipped to that institution in accordance with regulations 
and DTM Standard Operating Procedures. If all or part of the HPC products is no longer needed 
for autologous transplantation, the cells with either be issued to the investigator for IRB 
approved research or disposed of.  
5.2.2 Storage/Tracking 
Samples will be ordered in CRIS and tracked through a Clinical Trial Data Management system.  
Should a CRIS screen not be available, the CRIS downtime procedures will be followed.  
Research samples will not be sent outside NIH without IRB notification and an executed MTA. 
5.2.2.1 Labeling of Samples 
All specimens are to be labeled per the local site’s standard procedures. The following 
information, if not provided on the specimen label, must be linked to the specimen label and 
provided on the inventory sheet:  
- patient study ID #  
- sample type 
- date/time of draw (DD/MMM/YY 24:00) 
- timepoint (ex. Day 4, 5, 6, 7, etc.) 
- any collection issues (short draw, delayed processing, etc.) 
- protocol title/number 
- institute name 
- contact information 
Do not include the patient name, medical record number, or initials. 
5.2.2.2 Sample Data Collection 
All samples sent to the Clinical Pharmacology Program (CPP) will be barcoded, with data 
entered and stored in the Patient Sample Data Management System (PSDMS) utilized by the 
CPP. This is a secure program, with access to the PSDM System limited to defined CPP 
personnel, who are issued individual user accounts. Installation of PSDMS is limited to 
computers specified by Dr. Figg. These computers all have a password restricted login screen. 


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                                                                                                                                          Page 21 of 38 
All CPP personnel with access to patient information annually complete the NIH online 
Protection of Human Subjects course.  
PSDMS creates a unique barcode ID for every sample and sample box, which cannot be traced 
back to patients without PSDMS access. The data recorded for each sample includes the patient 
ID, name, trial name/protocol number, time drawn, cycle time point, dose, material type, as well 
as box and freezer location. Patient demographics associated with the clinical center patient 
number are provided in the system. For each sample, there are notes associated with the 
processing method (delay in sample processing, storage conditions on the ward, etc.). 
5.2.2.3 Sample Storage 
Barcoded samples are stored in barcoded boxes in a locked freezer at either -20 or -80°C 
according to stability requirements.  These freezers are located onsite in the CPP  and offsite at 
NCI Frederick Central Repository Services in Frederick, MD. Visitors to the laboratory are 
required to be accompanied by laboratory staff at all times.  
Access to stored clinical samples is restricted. Samples will be stored until requested by a 
researcher named on the protocol. All requests are monitored and tracked in the PSDM System. 
All researchers are required to sign a form stating that the samples are only to be used for 
research purposes associated with this trial (as per the IRB approved protocol) and that any 
unused samples must be returned to the CPP. It is the responsibility of the NCI Principal 
Investigator to ensure that the samples requested are being used in a manner consistent with IRB 
approval. 
Following completion of this study, samples will remain in storage as detailed above. Access to 
these samples will only be granted following IRB approval of an additional protocol, granting 
the rights to use the material.  
If, at any time, a patient withdraws from the study and does not wish for their existing samples to 
be utilized, the individual must provide a written request. Following receipt of this request, the 
samples will be destroyed (or returned to the patient, if so requested), and reported as such to the 
IRB. Any samples lost (in transit or by a researcher) or destroyed due to unknown sample 
integrity (i.e. broken freezer allows for extensive sample thawing, etc.) will be reported as such 
to the IRB. 
Sample barcodes are linked to patient demographics and limited clinical information. This 
information will only be provided to investigators listed on this protocol, via registered use of the 
PSDMS. It is critical that the sample remains linked to patient information such as race, age, 
dates of diagnosis and death, and histological information about the tumor, in order to correlate 
genotype with these variables. 
5.2.3 Protocol Completion/Sample Destruction 
Once primary research objectives for the protocol are achieved, researchers can request access to 
remaining samples, providing they have both approval of the Principal Investigator of the 
original protocol under which the samples or data were collected and either an IRB approved 
protocol and patient consent or the OSHRP Authorization Form stipulating that the activity is 
exempt from IRB review.  


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Samples, and associated data, can only be permanently archived if the subject has provided 
informed consent. If researchers have samples remaining once they have completed all studies 
associated with the protocol, they must be returned to the Preclinical Service laboratory. 
The Preclinical Service staff will report to the Principal Investigators any destroyed samples, if 
samples become unsalvageable because of environmental factors (e.g. broken freezer or lack of 
dry ice in a shipping container), lost in transit between facilities or misplaced by a researcher. 
The Principal Investigators will annually report this information to the IRB. 
6 DATA COLLECTION AND EVALUATION 
6.1 DATA COLLECTION 
The PI will be responsible for overseeing entry of data into an in-house password protected 
electronic system and ensuring data accuracy, consistency and timeliness. The principal 
investigator, associate investigators/research nurses and/or a contracted data manager will assist 
with the data management efforts. All data obtained during the conduct of the protocol will be 
kept in secure network drives or in approved alternative sites that comply with NIH security 
standards. Primary and final analyzed data will have identifiers so that research data can be 
attributed to an individual human subject participant. 
End of study procedures: Data will be stored according to HHS and, FDA regulations and NIH 
Intramural Records Retention Schedule as applicable.  
Loss or destruction of data: Should we become aware that a major breach in our plan to protect 
subject confidentiality and trial data has occurred, the IRB will be notified. 
• All patients’ data must be recorded in the progress notes and flow sheets of the patient 
chart maintained by the Medical Records Department of participating institutions or available 
electronically on the CRIS system of the NIH Clinical Center.  Duplicate of key data may be 
kept in a research folder maintained by the Experimental Transplantation & Immunology 
Branch or the research office of participating institutions. 
• Patient’s demographics will be collected. 
• No specific toxicity data or adverse event related to the myeloma therapy will be 
collected for study purposes.  
• Data on Adverse Events requiring IRB reporting (see section7.3) following filgrastim and 
plerixafor administration will be collected. 
• All clinical data pertaining to a subject’s death while on protocol will be collected. 
• Data will be prospectively collected and entered in real time into the Cancer Central 
Clinical Data System database (NCI C3D; information at http://ccrtrials.nci.nih.gov). It is 
expected that clinical data be entered into C3D no later than after 10 business days of the 
occurrence.  The NCI PI and research nurse will have access to this data via web access. 
• All patient records will be kept confidential according to individual institution policies 
and procedures concerning patient information.  
• All grade 3 and grade 4 non hematologic adverse events will be recorded (see section 
7.3.2 for exceptions).
 


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6.2 TOXICITY CRITERIA 
The following adverse event management guidelines are intended to ensure the safety of each 
patient while on the study.  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE 
reporting.  All appropriate treatment areas should have access to a copy of the CTCAE version 
4.0.  A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40).  
7 SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN 
7.1 DATA REPORTING & RECORDS TO BE KEPT 
 All clinical data will be recorded in the patient’s chart as per institutions’ practices (maintained 
by the NIH Clinical Center Department of Medical Records and on the electronic chart CRIS 
system).  The patient records will be maintained by the Clinical Associate and other protocol 
personnel.  Each patient’s NIH Clinical Center medical record must reflect all of the following 
information: 
• The patient met all eligibility criteria. 
• Signed Informed Consent document was obtained before treatment. 
• Specific dates and times of all treatments specified in the protocol, doses administered, 
and documentation for the reason for any dose modification.  
• Documentation of all toxicities with grading according to NCI CTCAE version 4.0 as 
specified in the protocol. 
• Documentation of all follow-ups as specified in the protocol. 
7.2 DEFINITIONS 
7.2.1 Adverse Event 
An adverse event is defined as any reaction, side effect, or untoward event that occurs during the 
course of the clinical trial associated with the use of a drug in humans, whether or not the event 
is considered related to the treatment or clinically significant. For this study, AEs will include 
events reported by the patient, as well as clinically significant abnormal findings on physical 
examination or laboratory evaluation. A new illness, symptom, sign or clinically significant 
laboratory abnormality or worsening of a pre-existing condition or abnormality is considered an 
AE.  All AEs must be recorded on the AE case report form unless otherwise noted above in 
Section 6.1. 
All AEs, including clinically significant abnormal findings on laboratory evaluations, regardless 
of severity, will be followed until return to baseline or stabilization of event. Serious adverse 
events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of at least possibly related to the agent/intervention 
should be recorded and reported as per section 7.3 
  An abnormal laboratory value will be considered an AE if the laboratory abnormality is 
characterized by any of the following: 


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• Results in discontinuation from the study 
• Is associated with clinical signs or symptoms  
• Requires treatment or any other therapeutic intervention 
• Is associated with death or another serious adverse event, including hospitalization.  
• Is judged by the Investigator to be of significant clinical impact 
• If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome. 
7.2.2 Suspected adverse reaction 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event. A suspected adverse reaction implies a lesser degree of 
certainty about causality than adverse reaction, which means any adverse event caused by a drug. 
7.2.3 Unexpected adverse reaction 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in 
the investigator brochure or is not listed at the specificity or severity that has been observed; or, 
if an investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. 
"Unexpected”, also refers to adverse events or suspected adverse reactions that are mentioned in 
the investigator brochure as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring with the 
particular drug under investigation. 
7.2.4 Serious 
An Unanticipated Problem or Protocol Deviation is serious if it meets the definition of a Serious 
Adverse Event or if it compromises the safety, welfare or rights of subjects or others. 
7.2.5 Serious Adverse Event 
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following: 
• Death, 
• A life-threatening adverse drug experience 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant disability/incapacity 
• A congenital anomaly/birth defect. 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 


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7.2.6 Disability 
A substantial disruption of a person’s ability to conduct normal life functions. 
7.2.7 Life-threatening adverse drug experience 
Any adverse event or suspected adverse reaction that places the patient or subject, in the view of 
the investigator or sponsor, at immediate risk of death from the reaction as it occurred, i.e., it 
does not include a reaction that had it occurred in a more severe form, might have caused death. 
7.2.8 Protocol Deviation (NIH Definition) 
Any change, divergence, or departure from the IRB approved research protocol.  
7.2.9 Non-compliance (NIH Definition) 
The failure to comply with applicable NIH Human Research Protections Program (HRPP) 
policies, IRB requirements, or regulatory requirements for the protection of human research 
subjects. 
7.2.10 Unanticipated Problem 
Any incident, experience, or outcome that: 
•  Is unexpected in terms of nature, severity, or frequency in relation to  
(a) the research risks that are described in the IRB-approved research protocol and 
informed consent document; Investigator’s Brochure or other study documents, and 
(b) the characteristics of the subject population being studied; AND 
• Is related or possibly related to participation in the research; AND 
• Suggests that research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
7.3 NCI-IRB AND CLINICAL DIRECTOR REPORTING 
As subjects will be enrolled on protocol at the time they are receiving concurrent, off-protocol, 
standard of care therapy with expected toxicity, the toxicity of any concurrent therapy will not be 
reported for this study.  Adverse Event reporting will be limited to events occurring during or 
immediately following the apheresis procedure. 
7.3.1 NCI-IRB and NCI CD Expedited Reporting of Unanticipated Problems and Deaths 
The Protocol PI will report in the NIH Problem Form to the NCI-IRB and NCI Clinical Director: 
• All deaths, except deaths due to progressive disease  
• All Protocol Deviations 
• All Unanticipated Problems 
• All non-compliance 
 


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Reports must be received within 7 days of PI awareness via iRIS. 
7.3.2 NCI-IRB Requirements for PI Reporting at Continuing Review 
The protocol PI will report to the NCI-IRB:  
1. A summary of all protocol deviations in a tabular format to include the date the deviation 
occurred, a brief description of the deviation and any corrective action. 
2. A summary of any instances of non-compliance 
3. A tabular summary of the following adverse events: 
• All Grade 2 unexpected events that are possibly, probably or definitely related to the 
research;  
• All Grade 3 and 4 events that are possibly, probably or definitely related to the 
research;  
• All Grade 5 events regardless of attribution;  
• All Serious Events regardless of attribution.  
NOTE: Grade 1 events are not required to be reported.  
7.3.3 Exceptions to reporting: 
The following events that are possibly, probably or definitely related to the research will 
not be reported: 
o Of any grade: Leukocytosis or neutrophilia, elevated LDH, paresthesias, bone pain, 
fever, fatigue, muscle cramps, back/leg pain, splenomegaly 
o Of grade <3: Thrombocytopenia, anemia, hypocalcemia, hypomagnesemia, elevated 
transaminases or alkaline phosphatase, diarrhea, nausea, vomiting, flatulence, fatigue, 
arthralgia, headache and dizziness, mild injection site reactions. 
7.4 DATA AND SAFETY MONITORING PLAN 
7.4.1 Principal Investigator/Research Team  
In order to assure optimal concordance between the protocol requirements and the best possible 
clinical care of the patients, the PI/LAI or designate will co-sign a patient registration check list 
(Section 12). 
The clinical research team will meet on a weekly basis when patients are being actively treated 
on the trial to discuss each patient. Decisions about dose level enrollment and dose escalation if 
applicable will be made based on the toxicity data from prior patients.  
All data will be collected in a timely manner and reviewed by the principal investigator or 
designate. Adverse events will be reported as required above. Any safety concerns, new 
information that might affect either the ethical and or scientific conduct of the trial, or protocol 
deviations will be immediately reported to the IRB using iRIS.  
The Principal Investigator will review adverse event and response data on each patient to ensure 
safety and data accuracy. The Principal Investigator will personally conduct or supervise the 


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investigation and provide appropriate delegation of responsibilities to other members of the 
research staff. 
8 STATISTICAL CONSIDERATIONS 
The primary clinical purpose of this protocol is to permit collection of apheresis products as 
needed in connection with AHCT in subjects with Plasma Cell Myeloma (PCM). The overall 
success rate of the algorithm shown in Table 1and in section 3.1 will be evaluated and will be 
considered the primary scientific endpoint for the study.  In addition, as a descriptive study, the 
percent of patients achieving either of two levels of CD34+ cell collection (optimum collection 
of  ≥ 5 x 10
6 CD34+ cells/kg, or minimum collection of ≥ 2 but < 5 x 10
6 CD34+ cells/kg) in one 
apheresis procedure, in two procedures, and in greater than two procedures will be determined 
according to whether patients have received filgrastim alone versus filgrastim plus plerixafor.  
Based on the algorithm shown in table 1 and in section 3.1, patients either will or will not receive 
plerixafor to potentially boost the CD34 processed yield.  
 
Sixty patients or more will be enrolled on this study during a three year period, and based on 
historical data, it is anticipated that approximately 75% will not need plerixafor (45) and 25% 
will need plerixafor (15). The overall success of the algorithm (percent of patients achieving 
optimum collection of  5 x 10
6 CD34+ cells/kg in one mobilization cycle, who were predicted 
to do so using the algorithm) will be determined as follows. If 60 total patients are enrolled and if 
50 or more of 60 have a successful collection, then the probability of this occurring will be 
96.6% if the true rate of success were 90% while it would be 1.4% if the true rate of success 
were 70%. Thus, if a high fraction (50+/60) has a successful collection, there is a much greater 
likelihood that the true rate of overall success with the algorithm is 90% as opposed to 70%.  
In addition, the success rate of the algorithm will be evaluated separately for those who do and 
do not receive plerixafor. If 41/45 not receiving plerixafor have a successful collection in one 
cycle, the associated 95% CI will extend from approximately 79 to 98%. Among those receiving 
plerixafor, if 13/15 have a successful collection in one apheresis, the 95% CI ranges from 60% to 
98%. The overall success rate of the algorithm, as described above, and ideally, the fractions that 
have a successful collection would be high and success rates would be similar to one another in 
both groups, but the success rates will only be compared descriptively since there is limited 
power for any comparison. In addition to the fractions who have successful collections, the total 
number of apheresis procedures per patient and the total number of liters processed per patient 
during the collection course to achieve either the optimum or the minimum CD34+ cell dose will 
be reported and informally compared between patients receiving filgrastim alone versus 
filgrastim plus plerixafor.  
 
As an exploratory, secondary analysis, if sufficient data are available, a multivariable  logistic 
regression analysis may be performed, using patient and disease characteristics (available data 
potentially, but not mandatorily, from among: gender, race, age, weight, baseline hemoglobin, 
total WBC, neutrophil, monocyte, lymphocyte, and platelet count, number of prior cycles of 
cytotoxic chemotherapy, total prior dose of lenalidomide and similar agents per kg) to construct 
a model for risk of acceptable vs. non-acceptable CD34 mobilization with filgrastim alone. 


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Because of an expectation of limited patients, construction of a similar model for risk of poor 
mobilization with use of combined filgrastim plus plerixafor will not likely be attempted.  
It is expected that up to 3 years may be required to obtain 60 evaluable subjects on this protocol.  
The accrual ceiling will be set at 70 patients to allow for flexibility. 
9 HUMAN SUBJECTS PROTECTIONS 
9.1 RATIONALE FOR SUBJECT SELECTION 
The study is open to all subjects with a clinical indication for autologous stem cell 
transplant for the treatment of multiple myeloma 
9.2 PARTICIPATION OF CHILDREN 
Children will not be enrolled on this study as PCM is not a disease seen in the pediatric 
population. 
9.3 PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT 
Adults unable to give consent are excluded from enrolling in the protocol. However re-consent 
may be necessary and there is a possibility, though unlikely, that subjects could become 
decisionally impaired. For this reason and because there is a prospect of direct benefit from 
research participation (section 0, all subjects ≥ age 18 will be offered the opportunity to fill in 
their wishes for research and care, and assign a substitute decision maker on the “NIH Advance 
Directive for Health Care and Medical Research Participation” form so that another person can 
make decisions about their medical care in the event that they become incapacitated or 
cognitively impaired during the course of the study. Note: The PI or AI will contact the NIH 
Ability to Consent Assessment Team for evaluation.  For those subjects that become 
incapacitated and do not have pre-determined substitute decision maker, the procedures 
described in MEC Policy 87-4 for appointing a surrogate decision maker for adult subjects who 
are (a) decisionally impaired, and (b) who do not have a legal guardian or durable power of 
attorney, will be followed. 
9.4 EVALUATION OF BENEFITS AND RISKS/D
ISCOMFORTS 
Subjects undergoing apheresis for collection of a mobilized HPC, Apheresis product may 
experience headache, bone and joint pain due to filgrastim, nausea and abdominal pain due to 
plerixafor, bleeding and pain due to the discomfort of central line insertion, hypocalcemic 
symptoms due to the citrate anticoagulant used during apheresis, and vasovagal events including 
bradycardia, hypotension, syncope and very rarely, seizures, associated with reflex neurovascular 
reactions to apheresis. Rarely, cardiovascular events may occur due to previously present but 
undiagnosed coronary or cerebrovascular occlusive conditions.  
The benefit is to be able to undergo an autologous stem cell transplant which is known to 
improve outcome in PCM. 
9.5 RISKS/B
ENEFITS ANALYSIS 
The potential benefits outweigh the risk for a procedure considered worldwide a standard 
practice for the treatment of PCM. 


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9.6 CONSENT AND ASSENT PROCESS AND DOCUMENTATION 
Prior to receiving any therapy, patients must have their eligibility confirmed and must have 
signed an informed consent.  The Principal Investigator or Lead Associate Investigator will 
review orders for mobilizing agent administration. 
The investigational nature and research objectives of this trial, the procedures and treatments 
involved and their attendant risks and discomforts and benefits, and potential alternative 
therapies will be carefully explained to the subjects during the Informed Consent process.  A 
signed Informed Consent document will be obtained prior to entry onto the study by the 
Principal Investigator or an Associate Investigator. 
All patients must have a copy of their signed Informed Consent document maintained in the 
chart during therapy. 
 Results of the study or of individual patients may be reported at meetings or in scientific 
publications with removal of specific patient identifiers. 
9.6.1 Telephone re-consent procedure 
Reconsent on this study may be obtained via telephone according to the following procedure: the 
informed consent document will be sent to the subject.  An explanation of the study will be 
provided over the telephone after the subject has had the opportunity to read the consent form.  
The subject will sign and date the informed consent. A witness to the subject’s signature will 
sign and date the consent. 
The original informed consent document will be sent back to the consenting investigator who 
will sign and date the consent form with the date the consent was obtained via telephone.  A fully 
executed copy will be returned via mail for the subject’s records.  The informed consent process 
will be documented on a progress note by the consenting investigator and a copy of the informed 
consent document and note will be kept in the subject’s research record. 
9.6.2 Short form consent process for non-English speaking patients 
If there is an unexpected enrollment of a research participant for whom there is no translated 
extant IRB approved consent document, the principal investigator and/or those authorized to 
obtain informed consent will use the Short Form Oral Consent Process as described in MAS 
Policy M77-2, OHSRP SOP 12, 45 CFR 46.117 (b) (2) and 21 CFR 50.27 (b) (2).  The summary 
that will be used is the English version of the extant IRB approved consent document.  Signed 
copies of both the English version of the consent and the translated short form will be given to 
the subject or their legally authorized representative and the signed original will be filed in the 
medical record. 
Unless the PI is fluent in the prospective subject’s language, an interpreter will be present to 
facilitate the conversation.  Preferably someone who is independent of the subject (i.e., not a 
family member) will assist in presenting information and obtaining consent. Whenever possible, 
interpreters will be provided copies of the relevant consent documents well before the consent 
conversation with the subject (24 to 48 hours if possible).  
We request prospective IRB approval of the use of the short form process and will notify the IRB 
at the time of continuing review of the frequency of the use of the Short Form. 


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9.7 SUBJECT INFORMATION AND CONFIDENTIALITY 
As information is gathered from this trial, clinical results will be shared with patients.  
Any new significant observation(s) found during the course of the research, which may affect a 
patient’s willingness to participate further would be explained.   
Confidentiality of information concerning participants will be maintained including in all 
publications and presentations resulting from this study.  Names of participants or material 
identifying participants will not be released without permission, except as such release is 
required by law.  Records at the National Cancer Institute are maintained according to current 
legal requirements, and are made available for review, as required by the Food and Drug 
Administration or other authorized users, only under the guidelines established by the Federal 
Privacy Act.   
See section 5.2 for specifics of sample management and storage.  
10 PHARMACEUTICAL INFORMATION 
10.1 FILGRASTIM (N
EUPOGEN ®,G-CSF) 
Neupogen® (filgrastim, G-CSF)is a human granulocyte colony-stimulating factor (G-
CSF) produced by recombinant DNA technology. Neupogen
 ® is indicated to decrease the 
incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid 
malignancies receiving myelosuppressive anti-cancer drugs associated with a significant 
incidence of severe neutropenia with fever.  
10.1.1 Source 
Neupogen ® will be obtained from the commercial supply in the Clinical Center 
Pharmacy. 
10.1.2 Adverse effects 
Bone pain, which can sometimes be severe.  Other adverse reactions include fever, 
fatigue, muscle cramps, back/leg pain, splenomegaly, thinning hair, allergic reactions and flare 
of known auto-immune disease. 
10.1.3 Formulation, Storage, and Stability 
Recombinant granulocyte-colony stimulating factor (G-CSF) manufactured by Amgen 
(Thousand Oaks, CA) is supplied as a clear sterile solution of 300 mcg/mL packaged into either 
1-mL (300 mcg) or 1.6-mL (480 mcg) vials.  Neupogen ® should be stored in the refrigerator at 
2° to 8°C (36° to 46°F). Avoid shaking. Prior to injection, Neupogen ® may be allowed to reach 
room temperature for a maximum of 24 hours. Any vial or prefilled syringe left at room 
temperature for greater than 24 hours should be discarded. Do not freeze. G-CSF is stable for at 
least 1 year when refrigerated. 
10.1.4 Administration 
G-CSF will be administered as a subcutaneous injection to mobilize peripheral blood 
stem cells for collection by apheresis. See Section 3.3.1for sliding scale G-CSF dosing algorithm 
for mobilization. 


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Patients may be instructed on the self-administration of G-CSF. 
10.2 PLERIXAFOR (M
OZOBIL®) 
Plerixafor is a CXCR4 chemokine receptor antagonist that blocks the binding of stromal 
cell-derived factor 1α (SDF-1α). It inhibits the retention of hematopoietic stem cells in bone 
marrow, and increases their number in peripheral blood. It is used with granulocyte colony-
stimulating factor (G-CSF) to mobilize stem cells for collection and subsequent autologous 
transplantation. 
10.2.1 Source 
 Mozobil
® will be obtained from the commercial supply in the Clinical Center Pharmacy. 
10.2.2 Adverse effects 
Common adverse effects include diarrhea, nausea, vomiting, flatulence, fatigue, 
arthralgia, headache and dizziness, mild injection site reactions.  
Less commonly, insomnia or systemic reactions occurring about 30 minutes after 
injection (urticaria, periorbital swelling, dyspnea, and hypoxia).  
Some cases of vasovagal reactions, orthostatic hypotension, and syncope, within 1 hour 
of injection, have also been reported.  
10.2.3 Formulation, Storage, and Stability 
  
Subcutaneous Solution: 20 mg/ml 
 
Inspect vial for particulate matter and discoloration prior to administration; do not use if 
particulate matter present or solution is discolored. (Prod Info MOZOBIL(R) subcutaneous 
injection, 2008). 
Store at controlled room temperature, 25 degrees C (77 degrees F), with excursions 
permitted between 15 and 30 degrees C (59 and 86 degrees F). 
10.2.4 Administration 
Plerixafor 240µg/kg will be administered for one to three consecutive days as a 
subcutaneous injection to mobilize peripheral blood stem cells for collection by apheresis.  
Plerixafor will be administered on day 4 and possibly day 5 and 6 of filgrastim 
administration, 8 to 10 hours before apheresis begins.  
10.2.5 Pharmacokinetics 
Peak plasma concentrations of plerixafor occur about 30 to 60 minutes after a 
subcutaneous dose. It is about 58% bound to plasma proteins and largely confined to the 
extravascular fluid space. About 70% of a dose is eliminated in the urine within 24 hours after a 
dose, and the terminal half-life is about 3 to 5 hours.  
 
Plerixafor is not metabolized using human liver microsomes or human primary 
hepatocytes. Additionally, plerixafor does not exhibit inhibitory activity towards the major drug 
metabolizing cytochrome P450 enzymes nor did it induce CYP1A2, CYP2B6, or CYP3A4. 


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Dimopoulos, M., et al., Lenalidomide plus dexamethasone for relapsed or refractory 
multiple myeloma. The New England journal of medicine, 2007. 357(21): p. 2123-32. 
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Richardson, P., Management of the relapsed/refractory myeloma patient: strategies 
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Kumar, S.K., et al., Improved survival in multiple myeloma and the impact of novel 
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Front-Line Therapy for Patients with Multiple Myeloma (MM): Preliminary Results of a 
Phase 1/2 Study. Blood (ASH Annual Meeting Abstracts), 2007. 110(11): p. 187. 
12.  Zonder, J.A., et al., Superiority of Lenalidomide (Len) Plus High-Dose Dexamethasone 
(HD) Compared to HD Alone as Treatment of Newly-Diagnosed Multiple Myeloma 
(NDMM): Results of the Randomized, Double-Blinded, Placebo-Controlled SWOG Trial 
S0232. Blood (ASH Annual Meeting Abstracts), 2007. 110(11): p. 77. 
13.  Palumbo, A. and S.V. Rajkumar, Treatment of newly diagnosed myeloma. Leukemia, 
2008. 


Abbreviated Title: HPC for AHCT in PCM  
Version date: September 14, 2017 
 
 
                                                                                                                                          Page 33 of 38 
14. 
Vesole, D.H., et al., High-dose therapy for refractory multiple myeloma: improved 
prognosis with better supportive care and double transplants. Blood, 1994. 84(3): p. 950-
956. 
15.  Attal, M., et al., Single versus double autologous stem-cell transplantation for multiple 
myeloma. New England Journal of Medicine, 2003. 349(26): p. 2495-2502. 
16.  Child, J.A., et al., High-dose chemotherapy with hematopoietic stem-cell rescue for 
multiple myeloma. New England Journal of Medicine, 2003. 348(19): p. 1875-1883. 
17. 
Levy, V., et al., A meta-analysis on data from 575 patients with multiple myeloma 
randomly assigned to either high-dose therapy or conventional therapy. Medicine 
(Baltimore), 2005. 84(4): p. 250-260. 
18.  Koreth, J., et al., High-dose therapy with single autologous transplantation versus 
chemotherapy for newly diagnosed multiple myeloma: A systematic review and meta-
analysis of randomized controlled trials. Biol.Blood Marrow Transplant., 2007. 13(2): p. 
183-196. 
19.  Segeren, C.M., et al., Overall and event-free survival are not improved by the use of 
myeloablative therapy following intensified chemotherapy in previously untreated 
patients with multiple myeloma: a prospective randomized phase 3 study. Blood, 2003. 
101(6): p. 2144-2151. 
20. 
Barlogie, B., et al., Standard chemotherapy compared with high-dose chemoradiotherapy 
for multiple myeloma: final results of phase III US Intergroup Trial S9321. J.Clin.Oncol., 
2006. 24(6): p. 929-936. 
21.  Fermand, J.P., et al., High-dose therapy and autologous peripheral blood stem cell 
transplantation in multiple myeloma: up-front or rescue treatment? Results of a 
multicenter sequential randomized clinical trial. Blood, 1998. 92(9): p. 3131-6. 
22.  Gay, F., et al., Complete response correlates with long-term progression-free and overall 
survivals in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood, 
2010: p. blood-2010-09-307645. 
23.  van de Velde, H.J., et al., Complete response correlates with long-term survival and 
progression-free survival in high-dose therapy in multiple myeloma. Haematologica, 
2007. 92(10): p. 1399-406. 
24.  Hatse, S., et al., Chemokine receptor inhibition by AMD3100 is strictly confined to 
CXCR4. FEBS Lett, 2002. 527(1-3): p. 255-62. 
25.  Rosenkilde, M.M., et al., Molecular mechanism of AMD3100 antagonism in the CXCR4 
receptor: transfer of binding site to the CXCR3 receptor. J Biol Chem, 2004. 279(4): p. 
3033-41. 
26.  Devine, S.M., et al., Rapid mobilization of CD34+ cells following administration of the 
CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's 
lymphoma. J Clin Oncol, 2004. 22(6): p. 1095-102. 
27.  DiPersio, J.F., et al., Plerixafor. Nat Rev Drug Discov, 2009. 8(2): p. 105-107. 


Abbreviated Title: HPC for AHCT in PCM  
Version date: September 14, 2017 
 
 
                                                                                                                                          Page 34 of 38 
28.  Flomenberg, N., et al., The use of AMD3100 plus G-CSF for autologous hematopoietic 
progenitor cell mobilization is superior to G-CSF alone. Blood, 2005. 106(5): p. 1867-
74. 
29.  DiPersio, J.F., et al., Plerixafor and G-CSF versus placebo and G-CSF to mobilize 
hematopoietic stem cells for autologous stem cell transplantation in patients with 
multiple myeloma. Blood, 2009. 113(23): p. 5720-6. 
30.  DiPersio, J.F., et al., Phase III prospective randomized double-blind placebo-controlled 
trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus 
granulocyte colony-stimulating factor for autologous stem-cell mobilization and 
transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol, 2009. 27(28): 
p. 4767-73. 
31.  Flomenberg, N., et al., Plerixafor (Mozobil) alone to mobilize hematopoietic stem cells 
from multiple myeloma patients for autologous transplantation. Biol Blood Marrow 
Transplant, 2010. 16(5): p. 695-700. 
32.  Devine, S.M., et al., Rapid mobilization of functional donor hematopoietic cells without 
G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood, 2008. 
112(4): p. 990-8. 
33.  Vasu, S., et al., Donor demographic and laboratory predictors of allogeneic peripheral 
blood stem cell mobilization in an ethnically diverse population. Blood, 2008. 112(5): p. 
2092-100. 
34. 
San Miguel, J.F., et al., Immunophenotypic evaluation of the plasma cell compartment in 
multiple myeloma: a tool for comparing the efficacy of different treatment strategies and 
predicting outcome. Blood, 2002. 99(5): p. 1853-6. 
35.  Rawstron, A.C., et al., Flow cytometric disease monitoring in multiple myeloma: the 
relationship between normal and neoplastic plasma cells predicts outcome after 
transplantation. Blood, 2002. 100(9): p. 3095-100. 
36.  Liu, H., et al., Flow cytometric minimal residual disease monitoring in patients with 
multiple myeloma undergoing autologous stem cell transplantation: a retrospective 
study. Leuk Lymphoma, 2008. 49(2): p. 306-14. 
37.  Paiva, B., et al., Multiparameter flow cytometric remission is the most relevant 
prognostic factor for multiple myeloma patients who undergo autologous stem cell 
transplantation. Blood, 2008. 112(10): p. 4017-23. 
38.  Paiva, B., et al., Multiparameter flow cytometry quantification of bone marrow plasma 
cells at diagnosis provides more prognostic information than morphological assessment 
in myeloma patients. Haematologica, 2009. 94(11): p. 1599-602. 
39.  Cavo, M., et al., Molecular monitoring of minimal residual disease in patients in long-
term complete remission after allogeneic stem cell transplantation for multiple myeloma. 
Blood, 2000. 96(1): p. 355-7. 
40.  Lemoli, R.M., et al., Engraftment, clinical, and molecular follow-up of patients with 
multiple myeloma who were reinfused with highly purified CD34+ cells to support single 
or tandem high-dose chemotherapy. Blood, 2000. 95(7): p. 2234-9. 


Abbreviated Title: HPC for AHCT in PCM  
Version date: September 14, 2017 
 
 
                                                                                                                                          Page 35 of 38 
41. 
Martinelli, G., et al., Polymerase chain reaction-based detection of minimal residual 
disease in multiple myeloma patients receiving allogeneic stem cell transplantation. 
Haematologica, 2000. 85(9): p. 930-4. 
42. 
Martinelli, G., et al., Molecular remission after allogeneic or autologous transplantation 
of hematopoietic stem cells for multiple myeloma. J Clin Oncol, 2000. 18(11): p. 2273-81. 
43.  Fenk, R., et al., Levels of minimal residual disease detected by quantitative molecular 
monitoring herald relapse in patients with multiple myeloma. Haematologica, 2004. 
89(5): p. 557-66. 
44.  DiPersio, J.F., et al., Relevance and Clinical Implications of Tumor Cell Mobilization in 
the Autologous Transplant Setting. Biology of Blood and Marrow Transplantation, 2011. 
17(7): p. 943-955. 
45.  Stewart, A.K., et al., Purging of autologous peripheral-blood stem cells using CD34 
selection does not improve overall or progression-free survival after high-dose 
chemotherapy for multiple myeloma: Results of a multicenter randomized controlled 
trial. Journal of Clinical Oncology, 2001. 19(17): p. 3771-3779. 
46.  Bourhis, J.-H., et al., Relapse risk after autologous transplantation in patients with newly 
diagnosed myeloma is not related with infused tumor cell load and the outcome is not 
improved by CD34+ cell selection: long term follow-up of an EBMT phase III 
randomized study. Haematologica, 2007. 92(8): p. 1083-1090. 
47.  Attal, M. and J.L. Harousseau, The role of high-dose therapy with autologous stem cell 
support in the era of novel agents. Semin Hematol, 2009. 46(2): p. 127-32. 
48.  Dimopoulos, M.A. and M. Attal, Multiple myeloma in the era of novel agents. Semin 
Hematol, 2009. 46(2): p. 107-9. 
49.  Palumbo, A. and S.V. Rajkumar, Multiple myeloma: chemotherapy or transplantation in 
the era of new drugs. Eur J Haematol, 2010. 84(5): p. 379-90. 
 




Abbreviated Title: HPC for AHCT in PCM  
Version date: September 14, 2017 
 
 
                                                                                                                                          Page 37 of 38 
13 APPENDIX 2: DATA COLLECTION ELEMENTS REQUIRED BY PROTOCOL 
All of the following elements will be recorded in the C3D database. 
13.1 PATIENT ENROLLMENT 
• Date of birth, age, gender, race, ethnicity 
• Height 
• Weight 
• Performance Status 
• Date of original diagnosis 
• Stage at diagnosis 
• Stage at study entry 
• Tumor Histology and date of confirmation 
• Date of Informed Consent signature, consent version and date of registration 
• Baseline History/Physical 
• Baseline Symptoms 
• Number prior chemotherapy courses and anti-myeloma medications administered  
13.2 STUDY DRUG ADMINISTRATION 
• Doses of filgrastim and plerixafor 
13.3 LABORATORY AND DIAGNOSTIC TEST DATA 
• All Clinical laboratory and diagnostic test results done at screening 
• Data collected by the DTM pertaining to the HPC, Apheresis collection 
• All tests done to document resolution of adverse events  
13.4 ADVERSE EVENTS 
• All Grade 2 unexpected events that are possibly, probably or definitely related to the 
research. 
• All grade 3 and 4 adverse events that are possibly, probably or definitely related to the 
research will be recorded. 
Exceptions to reporting: 
The following events that are possibly, probably or definitely related to the research will 
not be reported: 
o Of any grade: Leukocytosis or neutrophilia, elevated LDH, paresthesias, bone pain, 
fever, fatigue, muscle cramps, back/leg pain, splenomegaly, 
o Of grade <3: Thrombocytopenia, anemia, hypocalcemia, hypomagnesemia, elevated 
transaminases, diarrhea, nausea, vomiting, flatulence, fatigue, arthralgia, headache 
and dizziness, mild injection site reactions. 
13.5 CONCOMITANT MEASURES 
• Baseline medications  
• Therapy for recorded adverse events 


Abbreviated Title: HPC for AHCT in PCM  
Version date: September 14, 2017 
 
 
                                                                                                                                          Page 38 of 38 
13.6 OFF STUDY 
• Date and reason for off study 
• Date and cause of death 
• PI decision to end this study 
 


 
 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD  
               •  Adult Patient or     •  Parent, for Minor Patient 
 
 
 
INSTITUTE: 
National Cancer Institute 
 
 
STUDY NUMBER: 
12-C-0074 
PRINCIPAL INVESTIGATOR:  Jennifer A. Kanakry, 
M.D. 
 
 
STUDY TITLE:   
Mobilization and collection of Autologous Stem cell for transplantation (ASCT) for  
 
 
Plasma Cell Myeloma (PCM) 
 
 
Continuing Review Approved by the IRB on 08/07/17  
  
  
  
 
Amendment Approved by the IRB on 09/23/17 (H)    
 
Date Posted to Web: 10/05/17 
Standard 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (1) 
 
 
 
INTRODUCTION 
 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
 
First, we want you to know that: 
 
Taking part in NIH research is entirely voluntary. 
 
  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
 
  
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of 
medical or research treatments they would want to receive (such as blood transfusions).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional. 
 
Why are you being asked to take part in this study? 
 
You are being invited to participate in a study to collect Hematopoietic Progenitor Cells (HPCs) 
from your blood for later use in the treatment of your Plasma Cell Myeloma (PCM).    
 
You have been told by your doctors that high-dose chemotherapy followed by Autologous Stem 
Cell Transplant (ASCT) may be of benefit in the treatment of your Plasma Cell Myeloma.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 12-C-0074 
CONTINUATION: page 2 of 10 pages 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
Why is this study being done? 
 
The main goal of the study is to collect your HPCs and to evaluate the best drug combination 
(one or two drugs) to use for “mobilizing” them out of your bone marrow into your bloodstream 
where they will be collected.  HPCs are collected from the blood in a procedure called apheresis.  
After collection, they will be stored frozen until you are ready to undergo the ASCT procedure 
for the treatment of PCM. 
 
Both drugs, filgrastim (Neupogen) and plerixafor (Mozobil) are approved by the FDA for use in 
mobilization in subjects with PCM.  They are not experimental.  Mobilization with filgrastim 
alone is considered to be the standard of care at this point. It has been shown that adding 
plerixafor to filgrastim increases the yield of the apheresis procedure.  This study will try to 
determine what proportion of subjects may be adequately mobilized with a single drug 
(Neupogen) for the most efficient HPC collection and what proportion would benefit from 
adding plerixafor.   
 
Description of Research Study 
 
You will undergo HPC mobilization with a standard regimen of filgrastim: one injection under 
the skin for 5 days in a row.  On the morning of the fourth day a special blood test will be 
performed to determine how many HPCs are in your blood stream. Based on previous research 
done at the Department of Transfusion Medicine (DTM) of NIH, the result of this test allows us 
to make a fairly accurate prediction of whether you would be likely to complete your HPC 
collection with a single apheresis procedure or if it is likely that you would need several 
procedures.  If the DTM doctors believe, based on the blood test, that you are likely to need a 
second day of apheresis, you would be given a single dose of plerixafor on that evening, along 
with the fifth dose of filgrastim the next day. We believe that this would greatly increase your 
chances of completing the HPC collection with a single apheresis. 
 
How many people will take part in this study? 
 
A total of 60 people will be enrolled in this study.   
  
What are the experimental procedures? 
 
There is no experimental procedures in this study.  The apheresis procedure has been widely 
accepted for many years as the standard procedure to collect HPCs (see details below). 
 
What will happen if you take part in this research study? 
 
To enter this study, you will need to undergo blood tests and an ECG to ensure that you can 
undergo the apheresis procedures safely.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 12-C-0074 
CONTINUATION: page 3 of 10 pages 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
• A blood test will be done to determine if you have had exposure to the human 
immunodeficiency virus (HIV) associated with the acquired immunodeficiency syndrome 
(AIDS).  If you are infected with HIV, you will not be able to participate in this study. We 
will tell you what the results mean, how to find care, how to avoid infecting others, how we 
report HIV infection, and the importance of informing your partners at possible risk because 
of your HIV infection. 
• Your blood will be tested for many other infectious agents (mostly viruses), including: 
Human T-lymphotrophic virus, T. Cruzi, and hepatitis B and C viruses.  ABO typing will 
also be performed.   
• Approximately 4 tablespoons of blood will be taken for these tests. You may not be allowed 
to participate in this study if you test positive for some of these viruses.   
• All non-menopausal women entering the study will have either a blood or urine test for 
pregnancy. You will not be allowed to participate in this study if you are pregnant, or if you 
are not willing to stop breast feeding. 
 
In addition to the tests listed above, you may need to have the following as part of this 
study: 
 
• Insertion of a catheter placed into a large vein (central venous catheter) that will remain in 
place throughout the apheresis procedures.  The catheter is placed under local (or sometimes 
general) anesthesia and you will be asked to sign a separate consent for this procedure.   
• The DTM staff will determine based on the size of the veins in your arms if you will need a 
central venous catheter. 
 
Apheresis Procedure 
 
The collection of some of your own white blood cells (HPCs) from your blood is done through a 
procedure called apheresis.  The collected HPCs may be stored frozen for the months that you 
complete your standard treatment.  This procedure is quite routine; normal blood donor 
volunteers routinely undergo apheresis for platelets donation in Blood Centers (Red Cross or 
others). The procedure will take from three to five hours during which time you will have to 
remain in a bed or a reclining chair. You do not need to be hospitalized for the procedure.  
However, if you need a certain type of central venous catheter and require multiple apheresis 
procedures to complete the HPC collection, you would need to stay in the hospital overnight (in 
between the procedures). 
 
Apheresis is done in the NIH Blood Bank (Department of Transfusion Medicine; DTM) and is 
supervised by Blood Bank physicians.  During apheresis, blood is removed continuously through 
a vein in your arm (or your catheter), goes through the machine where the white blood cells are 
separated from the red blood cells and plasma and the red blood cells and most of plasma are 
returned continuously to you through the other line.   
 
In some cases, the intravenous catheter placed to receive chemotherapy can be used for the 
apheresis procedure.  However, you may be asked to have two intravenous lines placed, one in 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 12-C-0074 
CONTINUATION: page 4 of 10 pages 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
each arm.  On occasion, you may be asked to have a single, larger temporary intravenous line 
placed in a vein in your groin until the apheresis procedure is finished.   
Apheresis will be performed daily until a sufficient number of cells is collected. Most people 
will need one or two apheresis to collect the desired cell number. The maximum number of 
apheresis procedures to be performed is 4. 
 
The length of treatment  
 
The total length of the study is about one week but depends on the number of apheresis 
procedures required to collect enough HPCs. You will need to be evaluated the day after the last 
apheresis.   
 
When you are taken off this protocol, your care will return to your referring doctor (or your NCI 
treatment team if you are on an NIH protocol or will enroll on another one).  
 
Participation in this study does not constitute an agreement for NIH to provide long-term 
medical care for your cancer or other medical needs at the NIH Clinical Center. 
 
Risks or Discomforts of Participation 
 
Medications sides effects: 
 
Medications 
Possible side effects 
 
Likely 
Less Likely 
Rare 
Filgrastim 
• Bone pain, which 
can sometimes be 
severe.   
• Fatigue 
• Muscle cramps, 
back/leg pain 
• Headache  
• Pain at the needle site  
• fevers  
• Tiredness 
• Thinning hair 
• Filgrastim can 
cause rupture of the 
spleen, which can 
cause death 
Plerixafor 
(Mozobil
®) 
 
• Diarrhea, nausea, 
vomiting, flatulence  
• Fatigue, joint pain, 
headache and 
dizziness  
• Mild injection site 
reactions 
• Trouble sleeping 
• Hives 
• Swelling around the 
eyes 
• Shortness of breath, 
and low oxygen levels 
in your blood 
(occurring about 30 
minutes after injection) 
• Low blood pressure 
and fainting (within 1 
hour of injection). 
 
Central Venous Catheter:  The general risks of placing this type of catheter include bleeding, 
infection, blood clots, a hole in the lung (called pneumothorax, causing breathing difficulties and 
possibly requiring placement of a tube to re-inflate the lung), and the risks of local or general 
anesthesia. 
 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 12-C-0074 
CONTINUATION: page 5 of 10 pages 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Apheresis: discomfort at the insertion sites of the catheters, bleeding, low blood pressure, 
fatigue, numbness or tingling in the extremities or the face. Numbness or tingling that you may 
experience during apheresis would be expected to go away after the procedure.  Blood infections 
from contamination of the apheresis machine are a remote possibility, but this has not occurred 
at the NIH.  Individuals with bleeding disorders can be harmed by this procedure and you will be 
evaluated for such a condition before apheresis is done.  All attempts will be made to protect you 
from any complications. 
 
Reproductive Risks:  It is unknown what effects this experimental procedure may have on an 
unborn child.  If you are a woman who is unwilling to stop breast-feeding or pregnant, you may 
not take part in the study because we don’t know how this medicine would affect your baby or 
your unborn child. If you are a woman who can become pregnant, or are the partner of a woman 
who can become pregnant, you will need to practice an effective form of birth control before 
starting study experimental procedure, during study experimental procedure, and for 6 months 
after you finish study experimental procedure.  If you think that you or your partner is pregnant, 
you should tell your study doctor or nurse immediately.   
 
Effective forms of birth control include: 
• abstinence  
• intrauterine device (IUD) 
• hormonal [birth control pills, injections, or implants] 
• tubal ligation 
• vasectomy 
 
Other Possible Hazards / Discomforts  
 
Blood sampling: For medical management, you will be asked to give blood samples multiple 
times. The blood samples (about 1 to 5 tablespoons each time) are not expected to produce any 
important decrease in the total amount of blood in your body.  These will be collected from your 
central line or by simple needle-stick from a vein in your arm in the same fashion as routine 
blood tests.  Venipuncture can be associated with pain, bruising, and rarely bleeding or infection.  
Additionally, some patients can experience light-headedness or fainting during insertion of the 
needle.  The samples collected will be used to both to monitor your medical condition and for 
research purposes.  The total amount of blood which may be taken from you will not exceed 450 
ml (one pint) every six weeks.  Some of this blood may be obtained through apheresis (see above 
“apheresis procedure”).  
 
Potential Benefits of Participation 
 
Collection of HPCs for later use in a transplant for the treatment of your PCM. 
 
 
 
 
 
 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 12-C-0074 
CONTINUATION: page 6 of 10 pages 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Alternative Treatments 
 
The standard of care treatment that you should / will receive for your multiple myeloma is not 
part of this study.   
 
Instead of being in this study, you have these options: 
• Getting HPC collection for the care for your PCM done at another facility without being 
in a study 
• Taking part in another study 
 
Please talk to your doctor about these and other options. 
 
 
Research Subject’s Rights 
 
What are the costs of taking part in this study?  
 
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
• You  will  receive  the study treatment  at  no  charge  to  you.  This  may 
include medicines  and  laboratory  testing done  at  the  Clinical  Center, 
National Institutes of Health (NIH).  
• There  are  limited  funds  available  to  cover  the  cost  of  some tests  and 
procedures performed outside the Clinical Center, NIH.  You may have 
to  pay  for  these  costs  even  if  they  are  not  covered  by  your  insurance 
company. 
• Medicines that are not part of the study will not be provided or paid for 
by the Clinical Center, NIH. 
• Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
 
Will your medical information be kept private? 
 
We will do our best to make sure that the personal information in your medical record will be 
kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or 
copy your medical records for research, quality assurance, and data analysis include: 
• The  National  Cancer  
Institute  
(NCI)  and  other  government  agencies,  
like  
the  Food  and 
Drug Administration (FDA), which are involved in keeping research safe for people. 
• National Cancer Institute Institutional Review Board 
 
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. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 12-C-0074 
CONTINUATION: page 7 of 10 pages 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
 
Stopping Therapy  
 
Your doctor may decide to stop your therapy for the following reasons: 
• if he/she believes that it is in your best interest 
• if new information shows that another treatment would be better for you 
• If you have side effects from the treatment that your doctor thinks are too severe 
• if the study doctor decides to end the study 
 
If this is the case, you will be informed of the reason therapy is being stopped. 
 
Participation in this research study is voluntary.  You may stop your participation in the study at 
any time.  There are no penalties for withdrawing from the study.  However, if you decide to stop 
taking part in the study, we would like you to talk to the study doctor and your regular doctor 
first. If you decide at any time to withdraw your consent to participate in the trial, we will not 
collect  any  additional  medical  
information  about  you.  
If  you  withdraw  your  consent  and leave 
the trial, any samples of yours that have been obtained for the study and stored at the NCI can be 
destroyed  upon  
request.  However,  any samples  and  data  generated  
from the samples that have 
already  been  distributed  to  other  researchers  or  placed  in  the  research  databases  cannot  be 
recalled and destroyed. 
 
Conflict of Interest 
 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide. You may ask your research 
team for a copy of the Protocol Review Guide or for more information. Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study. This is allowed under federal rules and is not a 
conflict of interest.  
Use of Specimens and Data for Future Research 
To advance science, it is helpful for researchers to share information they get from studying 
human samples.  They do this by putting it into one or more scientific databases, where it is 
stored along with information from other studies. A researcher who wants to study the 
information must apply to the database and be approved.  Researchers use specimens and data 
stored in scientific databases to advance science and learn about health and disease.   
We plan to keep some of your specimens and data that we collect and use them for future 
research and share them with other researchers. We will not contact you to ask about each of 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 12-C-0074 
CONTINUATION: page 8 of 10 pages 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
these future uses.  These specimens and data will be stripped of identifiers such as name, address 
or account number, so that it may be used for future research on any topic and shared broadly for 
research purposes. Your specimens and data will be used for research purposes only and will not 
benefit you.  It is also possible that the stored specimens and data may never be used.  Results of 
research done on your specimens and data will not be available to you or your doctor.  It might 
help people who have cancer and other diseases in the future.   
If you do not want your stored specimens and data used for future research, please contact us in 
writing and let us know that you do not want us to use your specimens and/or data.  Then any 
specimens that have not already been used or shared will be destroyed and your data will not be 
used for future research. However, it may not be possible to withdraw or delete materials or data 
once they have been shared with other researchers. 
 
 
 
 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or  
• Parent, for Minor Patient 
STUDY NUMBER: 12-C-0074 
CONTINUATION: page 9 of 10 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
OTHER PERTINENT INFORMATION 
1. Confidentiality.  When results of an NIH research study are reported in medical journals or 
at scientific meetings, the people who take part are not named and identified.  In most cases, the 
NIH  will  not  release  any  information  about  your  research  involvement  without  your  written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information  might  affect  (either  favorably  or  unfavorably)  the  willingness  of  the  insurance 
company to sell you insurance. 
 
The  Federal  Privacy  Act  protects  
the  confidentiality  of  your  NIH  medical  
records.  
  However, 
you  should  know  that  the  Act  allows  release  of  some  information  from  your  medical  record 
without  your  permission,  for  example,  
if  
it  
is  required  by  
the  Food  and  Drug  Administration 
(FDA),  members  of  Congress,  law  enforcement  officials,  or  authorized hospital  accreditation 
organizations. 
 
2. Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-term 
medical  care  
for  any  
injury  
resulting  
from  your  participation  
in  
research  here.  
  
In  general,  no 
long-term medical care or financial compensation for research-related injuries will be provided 
by the National Institutes of Health, the Clinical Center, or the Federal Government.  However, 
you have the right to pursue legal remedy if you believe that your injury justifies such action. 
 
3. Payments.   The  amount  of  payment  to  research  volunteers  is  guided  by  the  National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies 
at  
the  National  
Institutes  of  Health.  
 Reimbursement  of  
travel  and  subsistence  will  be  offered 
consistent with NIH guidelines. 
 
4. Problems or Questions.  If you have any problems or questions about this study, or about 
your rights as a research participant, or about any research-related injury, contact the Principal 
Investigator: Jennifer Kanakry, M.D., Building 10, Room 3-3132, Telephone:  240-760-6172. If 
you have any questions about the use of your specimens or data for future research studies, you 
may contact the Office of the Clinical Director, NCI, telephone: 240-760-6070.  You may also 
call the Clinical Center Patient Representative at 301-496-2626. 
 
5. Consent Document.  Please keep a copy of this document in case you want to read it again. 
 
 
 
 
 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or  
• Parent, for Minor Patient 
STUDY NUMBER: 12-C-0074 
CONTINUATION: page 10 of 10 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
  
 
Signature of Adult Patient/ 
Legal Representative 
Date 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The  information  in  the  above  consent  was  described  to  my  child  and  my  child  agrees  to 
participate in the study. 
 
 
 
 
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM AUGUST 07, 2017 THROUGH AUGUST 06, 2018. 
 
 
  
  
  
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name