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

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

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.

Study Overview

• Status: Terminated
• Conditions: Refractory Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; DS (Durie/Salmon) Stage I Plasma Cell Myeloma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Desipramine Hydrochloride; Biological: Filgrastim

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (desipramine, filgrastim); Participants 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Desipramine Hydrochloride; Given PO; Other Names: Norpramin; Pertofrane; Biological: Filgrastim; Given PO; Other Names: G-CSF; r-metHuG-CSF; Nivestim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success Rate of Stem Cell Mobilization (SCM) in Participants Who Completed Filgrastim and Desipramine Therapy	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.	Day 5
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	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.	Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Number of Days of Apheresis	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.	Up to 1 week following completion of study treatment, up to 15 days
Incidence of Adverse Events	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).	Up to 1 week following completion of study treatment, up to 15 days
Median Time to Neutrophil Engraftment	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.	Up to 1 week following completion of study treatment, up to 15 days
Median Time to Platelet Engraftment	Median time (number of days) to platelet engraftment was determined as first of three consecutive days with platelets > 20,000/ul without transfusion.	Up to 1 week following completion of study treatment, up to 15 days

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Murali Janakiram, Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: July 11, 2013
• First Submitted That Met QC Criteria: July 11, 2013
• First Posted (Estimate): July 15, 2013

Study Record Updates

• Last Update Posted (Actual): March 28, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Desipramine
• Other Study ID Numbers: 2012-230 (Other Identifier: Albert Einstein College of Medicine); P30CA013330 (U.S. NIH Grant/Contract); NCI-2013-01212 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 11-010