Collection of Transplant Stem Cells for Plasma Cell Myeloma

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

- INCLUSION CRITERIA:

Multiple Myeloma Criteria:

Subjects with an indication for autologous hematopoietic cell transplant (AHCT) for the
treatment of PCM as determined by the principal investigator (PI) or lead associate
investigator (LAI).

- Subjects following induction treatment for plasma cell myeloma (PCM)

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

Other Eligibility Criteria:

Age greater than or equal to 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 (Eastern Cooperative Oncology Group ((ECOG)
0 or 1)

Ejection fraction (EF) by multigated acquisition scan (MUGA) or 2-D echocardiogram within
institution normal limits. In case of low ejection fraction (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.

Hemoglobin (Hgb) greater than or equal to 8 g/dl (transfusion acceptable)

No history of abnormal bleeding tendency.

Patients must be able to give informed consent

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 New York Heart Association (NYHA),
uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic
evidence of acute ischemia or active 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 patients 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

Human immunodeficiency virus (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 principal investigator (PI)/lead
associate investigator (LAI) if it is deemed that allowing participation would represent an
unacceptable medical or psychiatric risk.