Desipramine Hydrochloride and Filgrastim For Stem Cell Mobilization in Patients With Multiple Myeloma Undergoing Stem Cell Transplant
Primary Purpose
DS (Durie/Salmon) Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma
Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Desipramine Hydrochloride
Filgrastim
Laboratory Biomarker Analysis
Sponsored by
About this trial
This is an interventional treatment trial for DS (Durie/Salmon) Stage I Plasma Cell Myeloma
Eligibility 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
Sites / Locations
- Albert Einstein College of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (desipramine, filgrastim)
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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).
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.
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.
Full Information
NCT ID
NCT01899326
First Posted
July 11, 2013
Last Updated
March 2, 2023
Sponsor
Albert Einstein College of Medicine
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01899326
Brief Title
Desipramine Hydrochloride and Filgrastim For Stem Cell Mobilization in Patients With Multiple Myeloma Undergoing Stem Cell Transplant
Official Title
Pilot Clinical Study of GCSF in Combination With Desipramine for Autologous Stem Cell Mobilization in Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
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.
Study Start Date
September 2013 (Actual)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Albert Einstein College of Medicine
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
DS (Durie/Salmon) Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (desipramine, filgrastim)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Desipramine Hydrochloride
Other Intervention Name(s)
Norpramin, Pertofrane
Intervention Description
Given PO
Intervention Type
Biological
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF, Nivestim, r-metHuG-CSF
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Success Rate of Stem Cell Mobilization (SCM) in Participants Who Completed Filgrastim and Desipramine Therapy
Description
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.
Time Frame
Day 5
Title
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
Description
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.
Time Frame
Day 5
Secondary Outcome Measure Information:
Title
Median Number of Days of Apheresis
Description
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.
Time Frame
Up to 1 week following completion of study treatment, up to 15 days
Title
Incidence of Adverse Events
Description
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).
Time Frame
Up to 1 week following completion of study treatment, up to 15 days
Title
Median Time to Neutrophil Engraftment
Description
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.
Time Frame
Up to 1 week following completion of study treatment, up to 15 days
Title
Median Time to Platelet Engraftment
Description
Median time (number of days) to platelet engraftment was determined as first of three consecutive days with platelets > 20,000/ul without transfusion.
Time Frame
Up to 1 week following completion of study treatment, up to 15 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Murali Janakiram
Organizational Affiliation
Albert Einstein College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Desipramine Hydrochloride and Filgrastim For Stem Cell Mobilization in Patients With Multiple Myeloma Undergoing Stem Cell Transplant
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