DS (Durie/Salmon) Stage I Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
Conditions
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.
Interventions
Given PO
BIOLOGICALFilgrastim
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Albert Einstein College of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Ten participants with multiple myeloma between 18-70 years of age eligible for Autologous Stem Cell Transplant (ASCT) were enrolled in the study between September 2013 and July 2014.
Pre-assignment details
Of the 10 participants enrolled, 1 participant dropped out after enrollment and prior to study drug initiation. Of the remaining 9 participants, 6 participants underwent stem cell transplantation and completed the full study protocol.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Desipramine, Filgrastim) Patients received 100mg desipramine hydrochloride PO daily from Day -3 to Day +4 (8 days total) and filgrastim PO BID from Day +1 to Day +4. Complete blood count (CBC) and peripheral blood CD34+ counts were determined on Day +4 and Day +5. Leukapheresis was started when peripheral blood CD34+ count exceeded 10/uL. If CD34+ counts were \<10/uL on Day +5, plerixafor was added as a salvage therapy. Daily leukapheresis was performed with four times the estimated blood volume during each collection until a target cell dose of at least 5x10\^6 cells/kg was reached. If the collected CD34+ cell dose was \<0.5x10\^6 on two consecutive days, aperheris was stopped and the patient was taken off study.
Despiramine hydrochloride: PO Filgrastim: PO | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Disease Relapse (patient with previously undiagnosed relapsing disease) | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Desipramine, Filgrastim) |
|---|---|
| Age, Continuous | 59.5 years |
| Prior chemotherapies >1 prior chemotherapy treatment | 1 participants |
| Prior chemotherapies One prior chemotherapy treatment | 5 participants |
| Prior Lenalidomide therapy No | 2 Participants |
| Prior Lenalidomide therapy Yes | 4 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
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.
Time frame: Day 5
Population: 6 participants underwent stem cell transplantation and completed the full study protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Desipramine, Filgrastim) | Success Rate of Stem Cell Mobilization (SCM) in Participants Who Completed Filgrastim and Desipramine Therapy | 6 Participants |
Primary
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.
Time frame: Day 5
Population: No patients who failed prior mobilization or who were exposed to alkylator therapy or were predicted to be difficult to mobilize were enrolled and as such no data was collected/analyzed for this Outcome Measure.
Secondary
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).
Time frame: Up to 1 week following completion of study treatment, up to 15 days
Population: 6 participants underwent stem cell transplantation and completed the full study protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Desipramine, Filgrastim) | Incidence of Adverse Events | 9 Adverse Events |
Secondary
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.
Time frame: Up to 1 week following completion of study treatment, up to 15 days
Population: 6 participants underwent stem cell transplantation and completed the full study protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Desipramine, Filgrastim) | Median Number of Days of Apheresis | 1.5 Days |
Secondary
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.
Time frame: Up to 1 week following completion of study treatment, up to 15 days
Population: 6 participants underwent stem cell transplantation and completed the full study protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Desipramine, Filgrastim) | Median Time to Neutrophil Engraftment | 12 number of days |
Secondary
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.
Time frame: Up to 1 week following completion of study treatment, up to 15 days
Population: 6 participants underwent stem cell transplantation and completed the full study protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Desipramine, Filgrastim) | Median Time to Platelet Engraftment | 13.5 number of days |