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

Condition(s) targeted: DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Intervention: Desipramine Hydrochloride (Drug); Filgrastim (Biological); Laboratory Biomarker Analysis (Other)

Phase: N/A

Status: Active, not recruiting

Sponsored by: Albert Einstein College of Medicine of Yeshiva University

Official(s) and/or principal investigator(s):
Murali Janakiram, Principal Investigator, Affiliation: Albert Einstein College of Medicine of Yeshiva University

This pilot clinical trial studies how well desipramine hydrochloride and filgrastim works for stem cell mobilization in patients with multiple myeloma undergoing stem cell transplant. Giving colony-stimulating factors, such as filgrastim, and other drugs, such as desipramine hydrochloride, helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored.

Official title: Pilot Clinical Study of GCSF in Combination With Desipramine for Autologous Stem Cell Mobilization in Multiple Myeloma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Success rate of stem cell mobilization (SCM) using filgrastim and desipramine to collect > 5 x 10^6 cluster of differentiation (CD)34/kg in patients with multiple myeloma (MM) who are first time mobilizers or unexposed to alkylating agents

Success rate of SCM using filgrastim and desipramine to achieve a total collection of > 5 x 10^6 CD34/kg in patients with MM who failed prior mobilization or were exposed to alkylator therapy or are predicted to be difficult to mobilize

Secondary outcome:

Average number of days of apheresis required to collect > 5 x 10^6 CD34+/kg

Incidence of adverse events graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4

Time to neutrophil engraftment: first of three consecutive days with absolute neutrophil count (ANC) > 500/ul or first day with ANC > 1000/ul in the absence of growth factor support

Time to platelet engraftment: first of three days of platelets > 20,000/ul without transfusion

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

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

Albert Einstein College of Medicine, Bronx, New York 10461, United States

Starting date: December 2012
Last updated: March 5, 2015