Kvalheim_EUHaemotology_EU Haematology 09/03/2010 09:13 Page 26
Transplantation
Table 2: Pre-clinical and Clinical Development of Plerixafor
Reference/Clinical Study Topic Trial Phase/
Trial Number Status
Burroughs et al.
58
Plerixafor mobilisation of PBSCs in a canine model Pre-clinical
Larochelle et al.
59
Plerixafor mobilisation of HSCs and long-term repopulating capacity in non-human primates Pre-clinical
Broxmeyer et al.
60
Evaluation in murine and human systems for mobilising capacity, alone and in combination with G-CSF Pre-clinical
Liles et al.
61
Plerixafor mobilisation of HPCs from marrow to peripheral blood in healthy human volunteers Initial clinical
Liles et al.
52
Administration of plerixafor alone and in combination with a standard 5-day G-CSF regimen Phase I
in healthy volunteers
Devine et al.
47
Assessment of safety and clinical effects of plerixafor in MM and NHL Phase I
Flomenberg et al.
48
Evaluation of plerixafor plus G-CSF compared with G-CSF alone in mobilising HPCs and engraftment Stem cell collection trial
Stiff et al.
25
Efficacy and toxicity of combining G-CSF with plerixafor to mobilise stem cells in NHL and MM
Fowler et al.
49
Combined use of plerixafor and G-CSF in patients previously failing to mobilise sufficient PBSCs
Cashen et al.
62
Efficacy and safety of HSC mobilisation with plerixafor in Hodgkin’s lymphoma Phase II
Calandra et al.
35
Plerixafor plus G-CSF mobilisation of CD34
+
cells in NHL, Hodgkin’s disease and MM patients Compassionate
previously failing mobilisation use protocol
DiPersio et al.
50
Safety and efficacy of plerixafor in mobilising HSCs for ASCT in NHL patients. Phase III
DiPersio et al.
51
Safety and efficacy of plerixafor with G-CSF in mobilising HSCs in patients with MM Phase III
NCT00103662
63 ,51
Mobilisation of stem cells with plerixafor in MM patients Completed
NCT00241358
64,65
Plerixafor for transplantation of sibling donor stem cells Active, not recruiting
NCT00665314
66
Addition of plerixafor to a G-CSF mobilisation regimen in NHL and MM Completed
NCT00901225
67
Rescue of poor mobilisers in auto-HSCT Recruiting
NCT00903968
68
Combination plerixafor and bortezomib in MM Recruiting
NCT00822770
69
Plerixafor and G-CSF with busulfan, fluarabine and thymoglobin Recruiting
NCT00838357
70
Plerixafor as a front-line mobilisation agent in combination with G-CSF in NHL or MM Recruiting
NCT00733824
71
Intravenous plerixafor for collection of autologous peripheral blood stem cells in NHL patients Recruiting
NCT00741325
72
Long-term follow-up for NHL patients from 3101 trial Enrolling by invitation
NCT00741780
73
Long-term follow-up for NHL patients from 3102 trial Enrolling by invitation
ASCT = autologous stem cell transplant; G-CSF = granulocyte colony-stimulating factor; HPCs = haematopoietic progenitor cells; HSCs = haematopoietic stem cells; NHL = non-Hodgkin’s
lymphoma; PBSCs = peripheral blood stem cell; MM = multiple myeloma.
risk of mobilisation failure with standard cytokine regimens. The After 12 months of follow-up, results in the plerixafor group were
results showed that all 49 NHL and MM patients mobilised with G- significantly more favourable than those in the placebo group. The
CSF plus plerixafor completed mobilisation and 47 of these patients primary end-point was met by 59.3% of patients in the plerixafor group
(96%) proceeded with transplantation; CD34
+
cells in the circulation and by only 19.6% of the placebo group (p<0.001).
50
In addition,
increased by 2.5-fold after just one dose of plerixafor. A further significantly more patients underwent HSC transplantation after initial
study
49
found that 17 of 20 patients who had previously failed to mobilisation when treated with plerixafor than with placebo (90 and
reach sufficient mobilisation of HSCs achieved successful CD34
+
55%, respectively; p<0.001). Median time to engraftment was similar in
cell mobilisation after one apheresis procedure when treated with both groups, and the most common adverse events associated with
the combination of plerixafor and G-CSF. Two pivotal phase III trials plerixafor were gastrointestinal disorders and injection-site reactions.
of plerixafor were conducted in NHL
50
and MM
51
patients. The first Therefore, relative to G-CSF alone, addition of plerixafor to G-CSF led to
study evaluated the safety and efficacy of plerixafor in mobilising a significantly higher proportion of NHL patients achieving ample
HSCs for auto-HSCT of NHL patients and the second study CD34
+
cell numbers for transplantation in fewer apheresis days.
50
evaluated the safety and efficacy of G-CSF plus plerixafor in
mobilising HSCs in MM patients compared with G-CSF plus placebo. Plerixafor in Multiple Myeloma
Finally, the compassionate use protocol designed to assess the A second phase III multicentre, randomised, double-blind, placebo-
effects of plerixafor in patients who had failed prior mobilisation controlled trial focused on the safety and efficacy of plerixafor plus G-
attempts showed consistent results in rates of successful CD34
+
CSF (n=148) in mobilising HSCs in MM patients compared with
cell remobilisation.
35
G-CSF plus placebo (n=154).
51
Using the same protocol as the previous
phase III trial, the primary end-point was the percentage of patients
Plerixafor in Non-Hodgkin’s Lymphoma who collected ≥6x10
6
CD34
+
cells/kg within two apheresis sessions.
In a phase III multicentre, randomised, double-blind, placebo- Again, significantly more patients receiving plerixafor met the primary
controlled study, 298 NHL patients needing auto-HSCT received end-point than those receiving placebo (71.6 versus 34.4%; p<0.001).
10µg/kg G-CSF subcutaneously daily for up to eight days. On the Furthermore, 54% of the plerixafor-treated group reached the target
evening of day four and for up to four days thereafter, patients were CD34
+
cell level after just one apheresis collection. Both plerixafor
given daily injections of 0.24mg/kg of plerixafor (n=150) or placebo and G-CSF were well tolerated among patients, and the combination
(n=148) subcutaneously. Beginning on day five, patients started proved more effective at mobilising CD34
+
cells than G-CSF alone.
51
daily apheresis for up to four days or until ≥5x10
6
CD34
+
cells/kg
were collected. The primary end-point was the percentage of Safety of Plerixafor
patients from whom ≥5x10
6
CD34
+
cells/kg could be collected in The safety profile of plerixafor has been examined in healthy
four or fewer days.
50
volunteers as well as in patients with haematological diseases. In
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