Plerixafor as a Salvage Regimen to Mobilize Allogeneic Stem Cells in Healthy Volunteers (MOBIL1)

With a standard mobilization regimen using G-CSF, approximately 5% of allogeneic donors does not mobilize enough CD34+ cells to reach an optimal dose for transplantation and are therefore called "poor mobilizers". A generally accepted optimum CD34+ PBSC dose for allogeneic transplantation is > 4.5 x 106/kg body weight of the recipient. The minimum total CD34+ PBSC dose certainly amounts to 2 x 106/kg body weight of the recipient.The objective of this trial is to assess the efficacy of a single dose of Plerixafor as salvage procedure in allogeneic stem cell donors with a poor CD34+ cell yield after the first day of peripheral blood stem cell collection.

Study Overview

• Status: Completed
• Conditions: Blood Stem Cell Harvest Failure
• Intervention / Treatment: Drug: Plerixafor

Detailed Description

In this trial the administration of a single dose of Plerixafor 240 µg/kg body weight of the donor SC in the evening at 10 PM after frustraneous stem cell apheresis on day 1 will be provided. The apheresis on day 2 is performed according to standard recommendations.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Cellex Gesellschaft für Zellgewinnung mbH Dresden
  • Dresden, Germany, 01307
    • Universitätsklinikum Dresden, Medizinische Klinik I
  • Köln, Germany, 50670
    • Cellex Gesellschaft für Zellgewinnung mbH Köln

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Donor age between 18 years and 75 years
• Eligibility of the donor for allogeneic PBSC donation according to German Guidelines (Richtlinien Hämotherapie Bundesärztekammer 2005) preceding the application of G-CSF
• The donor has understood and signed the donor information. Written informed consent has been obtained.
• Donation of less than 2.0 x 106 CD34 cells/kg recipient body weight after one apheresis following five days of stem-cell mobilization with Lenograstim 7.5 to 10 µg/kg donor body weight
• First leukapheresis according to standard recommendations with a processing of 3 x donor's blood volume ± 10% using either of the following three devices: Cobe Spectra (Terumo BCT) Spectra Optia (Terumo BCT) Fresenius COM.TEC

Exclusion Criteria:

• Pain or any discomfort in the left upper square of the abdomen during physical examination immediately prior to study inclusion or any spontaneous complaint about abdominal discomfort without an ultrasound investigation which rules out splenomegaly.
• Palpitations or any thoracic discomfort in the absence of an ECG which shows normal results
• Platelet count < 80 x 109/l
• Serum creatinine > 80 µmol/l for female donors or > 106 µmol/l for male donors. If serum creatinine is elevated then the estimated creatinine clearance has to be > 50 ml/min. Estimation by the Modification of Diet in Renal Disease equation where predicted GFR(ml/min/1.73m2) = 186 x (Serum Creatinine in mg/dL)-1.154 x (age in years)-0.203 x (0.742 if patient is female) x (1.212 if patient is black) or GFR(ml/min/1.73m2) = 186 x 176 (Serum Creatinine in µmol/l)-1.154 x (age in years)-0.203 x (0.742 if patient is female) x (1.212 if patient is black)
• Contraindications against a second leukapheresis, such as severe side effects during 1st leukapheresis (intolerable pain, severe circulatory disorder, severe citrate intolerance)
• Missing written approval by the transplant center that the transplantation of the Plerixafor-mobilized graft is being considered
• Treatment with any known non-marketed drug substance or experimental therapy within 4 weeks prior to enrolment or participation in any other interventional clinical study
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise donor safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
• Female donors of childbearing potential unable or unwilling to use adequate contraception methods for three months after the administration of the study drug. Adequate methods for contraception in female donors are sexual abstinence, the use of condoms by their partners, vasectomy of the partner or hormonal contraception.
• Male donors unable or unwilling to use adequate contraception methods for one month after the administration of the study drug. Adequate methods for contraception for males are sexual abstinence or the use of condoms.
• Known intolerance to Plerixafor

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: Plerixafor, Mozobil; Administration of a single dose of Plerixafor 240 µg/kg body weight of the donor SC in the evening at 10 PM after frustraneous stem cell apheresis on day 1.	Drug: Plerixafor; Administration of a single dose of Plerixafor 240 µg/kg body weight of the donor SC in the evening at 10 PM after frustraneous stem cell apheresis on day 1.; Other Names: Mozobil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of donation success	A generally accepted optimum CD34+ PBSC dose for allogeneic transplantation is > 4.5 x 10e6/kg body weight of the recipient. The minimum total CD34+ PBSC dose certainly amounts to 2 x 10e6/kg body weight of the recipient.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of donor safety and tolerability based on self-reporting on a questionnaire, clinical findings, and laboratory evaluations; and evaluation of the cellular composition of the apheresis products collected with and without Plerixafor application.	The composition of apheresis products collected after filgrastim or filgrastim plus Plerixafor will be characterized with respect to: CD34+ cell subsets (differential expression of prominin1/CD133+)33; Regulatory T-cells34; Dendritic cells; Myeloid-derived suppressor cells	30 days

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: University Hospital Carl Gustav Carus; Cellex Gesellschaft für Zellgewinnung mbH Dresden; Cellex Gesellschaft für Zellgewinnung mbH Köln
• Investigators: Principal Investigator: Kristina Hölig, Dr. med., Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I, 01307 Dresden

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: September 27, 2013
• First Submitted That Met QC Criteria: September 27, 2013
• First Posted (Estimate): October 7, 2013

Study Record Updates

• Last Update Posted (Estimate): September 19, 2016
• Last Update Submitted That Met QC Criteria: September 16, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: donor; Plerixafor; PBSC; allogeneic peripheral stam cell donation; poor donors
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Plerixafor
• Other Study ID Numbers: TUD-MOBIL1-056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO