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

Not Applicable
Terminated
Conditions
DS (Durie/Salmon) Stage I Plasma Cell Myeloma
Refractory Plasma Cell Myeloma
DS Stage II Plasma Cell Myeloma
DS Stage III Plasma Cell Myeloma
Interventions
Biological: Filgrastim
Other: Laboratory Biomarker Analysis
Registration Number
NCT01899326
Lead Sponsor
Albert Einstein College of Medicine
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
10
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (desipramine, filgrastim)Desipramine HydrochlorideParticipants received desipramine hydrochloride PO daily on days -3 to +4 and filgrastim PO BID on days 1-4. Stem cell collection began on day 6.
Treatment (desipramine, filgrastim)Laboratory Biomarker AnalysisParticipants received desipramine hydrochloride PO daily on days -3 to +4 and filgrastim PO BID on days 1-4. Stem cell collection began on day 6.
Treatment (desipramine, filgrastim)FilgrastimParticipants received desipramine hydrochloride PO daily on days -3 to +4 and filgrastim PO BID on days 1-4. Stem cell collection began on day 6.
Primary Outcome Measures
NameTimeMethod
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 TherapyDay 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.

Success Rate of Stem Cell Mobilization (SCM) in Participants Who Completed Filgrastim and Desipramine TherapyDay 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.

Secondary Outcome Measures
NameTimeMethod
Median Time to Neutrophil EngraftmentUp 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.

Incidence of Adverse EventsUp 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 Platelet EngraftmentUp 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.

Median Number of Days of ApheresisUp 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.

Trial Locations

Locations (1)

Albert Einstein College of Medicine

🇺🇸

Bronx, New York, United States

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