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 participants 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:

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

After completion of study treatment, participants were followed up to 1 week after completion of stem cell collection.

• Desipramine Hydrochloride (Drug), also known as Norpramin, Pertofrane: Given PO
• Filgrastim (Biological), also known as G-CSF, Nivestim, r-metHuG-CSF: Given PO
• Laboratory Biomarker Analysis (Other): Correlative studies

Primary outcomes

• Success Rate of Stem Cell Mobilization (SCM) in Participants Who Completed Filgrastim and Desipramine Therapy [Day 5]: Success rate was assessed as the number of participants with Multiple Myeloma (MM) who were first time mobilizers or unexposed to alkylating agents who completed the full course of filgrastim and desipramine and achieved the target collection of >=5 x 10\^6 CD34+ cells/kg.
• Success Rate of Stem Cell Mobilization (SCM) in Participants Who Failed Prior Mobilization or Who Were Exposed to Alkylator Therapy or Who Were Predicted to be Difficult to Mobilize Who Completed Filgrastim and Desipramine Therapy [Day 5]: Success rate was assessed as the number of participants with Multiple Myeloma (MM) who Failed Prior Mobilization or who were Exposed to Alkylator Therapy or who were Predicted to be Difficult to Mobilize who completed the full course of filgrastim and desipramine and achieved the target collection of >=5 x 10\^6 CD34+ cells/kg.

Secondary outcomes

• Median Number of Days of Apheresis [Up to 1 week following completion of study treatment, up to 15 days]: Median number of days of apheresis required to collect >=5 x 10\^6 CD34+ cells/kg. Standard descriptive statistics were used to summarize the data.
• Incidence of Adverse Events [Up to 1 week following completion of study treatment, up to 15 days]: Incidence of adverse events up to 1 week following completion of study treatment. Adverse events were graded using Version 4.0 of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
• Median Time to Neutrophil Engraftment [Up to 1 week following completion of study treatment, up to 15 days]: Median time (number of days) to neutrophil engraftment was determined as 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.
• Median Time to Platelet Engraftment [Up to 1 week following completion of study treatment, up to 15 days]: Median time (number of days) to platelet engraftment was determined as first of three consecutive days with platelets > 20,000/ul without transfusion.

Sex: All, ages: 18 Years to 70 Years

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

Participant flow

Outcome results

• Success Rate of Stem Cell Mobilization (SCM) in Participants Who Completed Filgrastim and Desipramine Therapy (Primary), Count of participants, Participants: Treatment (Desipramine, Filgrastim) 6
• Success Rate of Stem Cell Mobilization (SCM) in Participants Who Failed Prior Mobilization or Who Were Exposed to Alkylator Therapy or Who Were Predicted to be Difficult to Mobilize Who Completed Filgrastim and Desipramine Therapy (Primary)
• Median Number of Days of Apheresis (Secondary), Median, Days: Treatment (Desipramine, Filgrastim) 1.5 (1 to 2)
• Incidence of Adverse Events (Secondary), Number, Adverse Events: Treatment (Desipramine, Filgrastim) 9
• Median Time to Neutrophil Engraftment (Secondary), Median, number of days: Treatment (Desipramine, Filgrastim) 12 (11.8 to 12)
• Median Time to Platelet Engraftment (Secondary), Median, number of days: Treatment (Desipramine, Filgrastim) 13.5 (12 to 14.6)

Adverse events

Time frame: Subjects were monitored for incidence of Adverse Events up to 1 week following completion of treatment, for a total of up to 15 days

Other adverse events by term

Limitations and caveats: Target enrollment (n=20) was not reached. The study was stopped during the interim analysis due to low accrual after the widespread use of plerixafor for multiple myeloma in the United States.

• Murali Janakiram, Principal investigator, Albert Einstein College of Medicine

NIH grants: P30CA013330