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.
Brief Title
Desipramine Hydrochloride and Filgrastim For Stem Cell Mobilization in Patients With Multiple Myeloma Undergoing Stem Cell Transplant
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
DS (Durie/Salmon) Stage I Plasma Cell Myeloma
DS Stage II Plasma Cell Myeloma
DS Stage III Plasma Cell Myeloma
Refractory 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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
70 Years
Minimum Age
18 Years
NCT Id
NCT01899326
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2012-230
Overall Status
Terminated
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Pilot Clinical Study of GCSF in Combination With Desipramine for Autologous Stem Cell Mobilization in Multiple Myeloma
Primary Outcomes
Outcome 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.
Outcome Measure
Success Rate of Stem Cell Mobilization (SCM) in Participants Who Completed Filgrastim and Desipramine Therapy
Outcome Time Frame
Day 5
Outcome 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.
Outcome Measure
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
Outcome Time Frame
Day 5
Secondary Ids
Secondary Id
NCI-2013-01212
Secondary Id
11-010
Secondary Id
2012-230
Secondary Id
P30CA013330
Secondary Outcomes
Outcome 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.
Outcome Time Frame
Up to 1 week following completion of study treatment, up to 15 days
Outcome Measure
Median Number of Days of Apheresis
Outcome 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).
Outcome Time Frame
Up to 1 week following completion of study treatment, up to 15 days
Outcome Measure
Incidence of Adverse Events
Outcome 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.
Outcome Time Frame
Up to 1 week following completion of study treatment, up to 15 days
Outcome Measure
Median Time to Neutrophil Engraftment
Outcome Description
Median time (number of days) to platelet engraftment was determined as first of three consecutive days with platelets \> 20,000/ul without transfusion.
Outcome Time Frame
Up to 1 week following completion of study treatment, up to 15 days
Outcome Measure
Median Time to Platelet Engraftment
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
70
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Murali Janakiram
Investigator Email
mjanakir@montefiore.org
Investigator Phone
718-430-4154