Plerixafor combined with standard regimens for hematopoietic stem cell mobilization in pediatric patients with solid tumors eligible for autologous transplants: two-arm phase I/II study (MOZAIC)

Abstract

This study (NCT01288573) investigated plerixafor's safety and efficacy in children with cancer. Stage 1 investigated the dosage, pharmacokinetics (PK), pharmacodynamics (PD), and safety of plerixafor + standard mobilization (G-CSF ± chemotherapy). The stage 2 primary endpoint was successful mobilization (doubling of peripheral blood CD34+ cell count in the 24 h prior to first apheresis) in patients treated with plerixafor + standard mobilization vs. standard mobilization alone. In stage 1, three patients per age group (2-<6, 6-<12, and 12-<18 years) were treated at each dose level (160, 240, and 320 µg/kg). Based on PK and PD data, the dose proposed for stage 2 was 240 µg/kg (patients 1-<18 years), in which 45 patients were enrolled (30 plerixafor arm, 15 standard arm). Patient demographics and characteristics were well balanced across treatment arms. More patients in the plerixafor arm (24/30, 80%) met the primary endpoint of successful mobilization than in the standard arm (4/14, 28.6%, p = 0.0019). Adverse events reported as related to study treatment were mild, and no new safety concerns were identified. Plerixafor + standard G-CSF ± chemotherapy mobilization was generally well tolerated and efficacious when used to mobilize CD34+ cells in pediatric cancer patients.

A multicenter report on the safety and efficacy of plerixafor based stem cell mobilization in children with malignant disorders

“…In the phase I part of their study (n = 27), Morland et al determined the dose of plerixafor in children to be 240 μg/kg which was the dose received by majority of patients in our cohort. Previous studies have reported a median 3.2 to 13-fold 3,7,21,22 increase in PB CD34+ count following plerixafor administration, we observed a median 4-fold increase in PB CD34+ counts using this agent. In phase II study from Europe, 80% of children who received plerixafor upfront with SM achieved doubling of PB CD34+ vs 28.6% of those who received SM alone.…”

“…Plerixafor was administered along with the SM in Group A patients at the discretion of the treating physician. As described in previous studies, 3,7,8,21,22 SM was defined as inadequate if the peripheral blood (PB) CD34+ cell count was <20 cells/cu.mm pre-apheresis. Following this inadequate PB CD34+ count, plerixafor was added to the mobilization regimen at the initial apheresis attempts in Group B1 patients.…”

Plerixafor‐based mobilization in pediatric healthy donors with unfavorable donor/recipient body weight ratio resulted in a better CD34+ collection yield: A retrospective analysis

“…It is worth mentioning the association that was found between exposure to the drug, with age and weight. Interestingly, they observed that the exposure to medication (area under the curve and maximum serum concentration) depended on both age and weight, leading to a twofold lower exposure in the group aged <6 years compared with the group aged 12 to 18 years and a more than twofold lower exposure in the <15 kg weight cohort compared with the >40 kg cohort, which could explain the lower rate of adverse effects in relation to mobilization in this group of donors 39 …”

“…Interestingly, they observed that the exposure to medication (area under the curve and maximum serum concentration) depended on both age and weight, leading to a twofold lower exposure in the group aged <6 years compared with the group aged 12 to 18 years and a more than twofold lower exposure in the <15 kg weight cohort compared with the >40 kg cohort, which could explain the lower rate of adverse effects in relation to mobilization in this group of donors. 39 To obtain sufficient yields of ≥2 to 5 × 10 6 CD34 + cells/kg per recipient body weight with a single leukapheresis procedure, success rates between 83% and 92% have been reported. 40 A large single institution report from the MD.…”

Mesenchymal Stromal Cells in Neuroblastoma: Exploring Crosstalk and Therapeutic Implications

“…Similarly, AMD3100 diminished adhesion of MM cells to BM stromal cells (identity not further clarified) in vitro and promoted mobilization of tumor cells into the circulation in vivo, subsequently sensitizing them to bortezomib [ 208 ]. However, AMD3100 presents a nonspecific way of targeting tumor cells in the BM, as it is also used for mobilizing HSPCs from the BM before stem cell transplantation [ 209 ]. All AMD3100-effects must, therefore, be considered during its application, but it might be beneficial in sensitization of NB cells to therapy and specific targeting of dormant NB cells to lower the risk for relapse.…”