Trial Outcomes & Findings for Desipramine Hydrochloride and Filgrastim For Stem Cell Mobilization in Patients With Multiple Myeloma Undergoing Stem Cell Transplant (NCT NCT01899326)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

10 participants

Primary outcome timeframe

Day 5

Results posted on

2023-03-28

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Treatment (Desipramine, Filgrastim) Participants 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
Overall Study STARTED	10
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Desipramine, Filgrastim) Participants 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
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	2
Overall Study Disease Relapse (patient with previously undiagnosed relapsing disease)	1

Baseline Characteristics

Age range of the 6 patients who completed the study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Desipramine, Filgrastim) n=6 Participants 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
Age, Continuous	59.5 years n=5 Participants • Age range of the 6 patients who completed the study.
Sex: Female, Male Female	4 Participants n=5 Participants • Gender of the 6 patients who completed the study.
Sex: Female, Male Male	2 Participants n=5 Participants • Gender of the 6 patients who completed the study.
Region of Enrollment United States	6 participants n=5 Participants • Region of enrollment of the 6 patients who completed the study.
Prior Lenalidomide therapy Yes	4 Participants n=5 Participants • Number of patients who had received Lenalidomide prior to the trial who completed the study.
Prior Lenalidomide therapy No	2 Participants n=5 Participants • Number of patients who had received Lenalidomide prior to the trial who completed the study.
Prior chemotherapies One prior chemotherapy treatment	5 participants n=5 Participants • Number of prior chemotherapy treatments for the study participants who completed the trial.
Prior chemotherapies >1 prior chemotherapy treatment	1 participants n=5 Participants • Number of prior chemotherapy treatments for the study participants who completed the trial.

PRIMARY outcome

Timeframe: Day 5

Population: 6 participants underwent stem cell transplantation and completed the full study protocol.

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 measures

Outcome measures
Measure	Treatment (Desipramine, Filgrastim) n=6 Participants 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, apheresis was stopped and the patient was taken off study. Despiramine hydrochloride: PO Filgrastim: PO
Success Rate of Stem Cell Mobilization (SCM) in Participants Who Completed Filgrastim and Desipramine Therapy	6 Participants

PRIMARY outcome

Timeframe: 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.

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 measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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 measures

Outcome measures
Measure	Treatment (Desipramine, Filgrastim) n=6 Participants 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, apheresis was stopped and the patient was taken off study. Despiramine hydrochloride: PO Filgrastim: PO
Median Number of Days of Apheresis	1.5 Days Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: 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.

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 measures

Outcome measures
Measure	Treatment (Desipramine, Filgrastim) n=6 Participants 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, apheresis was stopped and the patient was taken off study. Despiramine hydrochloride: PO Filgrastim: PO
Incidence of Adverse Events	9 Adverse Events

SECONDARY outcome

Timeframe: 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.

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 measures

Outcome measures
Measure	Treatment (Desipramine, Filgrastim) n=6 Participants 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, apheresis was stopped and the patient was taken off study. Despiramine hydrochloride: PO Filgrastim: PO
Median Time to Neutrophil Engraftment	12 number of days Interval 11.8 to 12.0

SECONDARY outcome

Timeframe: 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.

Median time (number of days) to platelet engraftment was determined as first of three consecutive days with platelets \> 20,000/ul without transfusion.

Outcome measures

Outcome measures
Measure	Treatment (Desipramine, Filgrastim) n=6 Participants 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, apheresis was stopped and the patient was taken off study. Despiramine hydrochloride: PO Filgrastim: PO
Median Time to Platelet Engraftment	13.5 number of days Interval 12.0 to 14.6

Adverse Events

Treatment (Desipramine, Filgrastim)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment (Desipramine, Filgrastim) n=6 participants at risk 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
Gastrointestinal disorders Nausea	50.0% 3/6 • Number of events 3 • Subjects were monitored for incidence of Adverse Events up to 1 week following completion of treatment, for a total of up to 15 days
General disorders Fatigue	16.7% 1/6 • Number of events 1 • Subjects were monitored for incidence of Adverse Events up to 1 week following completion of treatment, for a total of up to 15 days
General disorders Pain	16.7% 1/6 • Number of events 1 • Subjects were monitored for incidence of Adverse Events up to 1 week following completion of treatment, for a total of up to 15 days
Skin and subcutaneous tissue disorders Dry Mouth	16.7% 1/6 • Number of events 1 • Subjects were monitored for incidence of Adverse Events up to 1 week following completion of treatment, for a total of up to 15 days
Ear and labyrinth disorders Vertigo	33.3% 2/6 • Number of events 2 • Subjects were monitored for incidence of Adverse Events up to 1 week following completion of treatment, for a total of up to 15 days
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 1 • Subjects were monitored for incidence of Adverse Events up to 1 week following completion of treatment, for a total of up to 15 days

Additional Information

Dr. Amit Verma

Albert Einstein College of Medicine

Phone: 718-430-4091

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place