Desipramine Hydrochloride and Filgrastim For Stem Cell Mobilization in Patients With Multiple Myeloma Undergoing Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To study efficacy, safety, harvest kinetics and engraftment kinetics of patients
undergoing autologous stem cell mobilization, mobilized with a combination of granulocyte
colony-stimulating factor (GCSF) (filgrastim) with desipramine (desipramine hydrochloride)
(G+D).

II. To analyze polymorphisms of adrenergic receptor beta 2 (ADRB2) and adrenergic receptor
beta 3 (ADRB3) genes that correlate with mobilization efficiency.

OUTLINE:

Patients receive desipramine hydrochloride orally (PO) daily on days -3 to +4 and filgrastim
PO twice daily (BID) on days 1-4. Stem cell collection begins on day 6.

After completion of study treatment, patients are followed up 1 week after completion of
stem cell collection.

Inclusion Criteria:

- Patients eligible for autologous stem cell transplant for multiple myeloma; planned
use of filgrastim (GCSF) for stem cell mobilization

- Ability to give informed consent

- Glomerular filtration rate (GFR) > 30 ml/minute

- Liver function tests < 2.5 x upper limit of normal (ULN)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 or less

- Based on prior therapy patients will be classified into two categories:

- Initial mobilizers with no exposure to alkylators

- Remobilizers or with prior exposure to alkylators or with greater than 5 cycles
of lenalidomide therapy prior to mobilization

Exclusion Criteria:

- Use of a monoamine oxidase inhibitor (MAO-I) during or within 2 weeks of desipramine
therapy

- Concomitant therapy with any drugs shown to have major interactions with desipramine

- Concurrent use of drugs that are contraindicated with desipramine

- Myocardial infarction in preceding 4 weeks; history of uncontrolled cardiac
arrhythmias or family history of sudden cardiac death; baseline corrected QT (QTc) >
460 msec

- Active alcohol abuse

- Bipolar disorder

- Untreated active major depression

- History of seizures in the past 3 years

- Pregnancy and lactation; refusal to use adequate contraception

- Uncontrolled thyroid disease

- GCSF or pegfilgrastim use within 14 days prior to enrollment

- Bortezomib, Revlimid or thalidomide use within 7 days of enrollment

- Patients with sickle cell disease