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)

. 2020 Sep ; 55 (9) : 1744-1753. [epub] 20200303

Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic

Typ dokumentu klinické zkoušky, fáze I, klinické zkoušky, fáze II, časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid32127657
E-zdroje Online Plný text
Odkazy

PubMed 32127657
PubMed Central PMC7452813
DOI 10.1038/s41409-020-0836-2
PII: 10.1038/s41409-020-0836-2
Knihovny.cz E-zdroje

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.

Zobrazit více v PubMed

DiPersio JF, Uy GL, Yasothan U, Kirkpatrick P. Plerixafor. Nat Rev Drug Discov. 2009;8:105–6. doi: 10.1038/nrd2819. PubMed DOI

Fricker SP, Anastassov V, Cox J, Darkes MC, Grujic O, Idzan SR, et al. Characterization of the molecular pharmacology of AMD3100: a specific antagonist of the G-protein coupled chemokine receptor, CXCR4. Biochem Pharmacol. 2006;72:588–96. doi: 10.1016/j.bcp.2006.05.010. PubMed DOI

Hatse S, Princen K, Bridger G, De Clercq E, Schols D. Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4. FEBS Lett. 2002;527:255–62. doi: 10.1016/S0014-5793(02)03143-5. PubMed DOI

Uy GL, Rettig MP, Cashen AF. Plerixafor, a CXCR4 antagonist for the mobilization of hematopoietic stem cells. Expert Opin Biol Ther. 2008;8:1797–804. doi: 10.1517/14712598.8.11.1797. PubMed DOI

Mohty M, Azar N, Chabannon C, Le Gouill S, Karlin L, Farina L, et al. Plerixafor in poor mobilizers with non-Hodgkin’s lymphoma: a multi-center time-motion analysis. Bone Marrow Transpl. 2018;53:246–54. doi: 10.1038/s41409-017-0033-0. PubMed DOI

Maziarz RT, Nademanee AP, Micallef IN, Stiff PJ, Calandra G, Angell J, et al. Plerixafor plus granulocyte colony-stimulating factor improves the mobilization of hematopoietic stem cells in patients with non-Hodgkin lymphoma and low circulating peripheral blood CD34+ cells. Biol Blood Marrow Transpl. 2013;19:670–5. doi: 10.1016/j.bbmt.2013.01.005. PubMed DOI

Nademanee AP, DiPersio JF, Maziarz RT, Stadtmauer EA, Micallef IN, Stiff PJ, et al. Plerixafor plus granulocyte colony-stimulating factor versus placebo plus granulocyte colony-stimulating factor for mobilization of CD34(+) hematopoietic stem cells in patients with multiple myeloma and low peripheral blood CD34(+) cell count: results of a subset analysis of a randomized trial. Biol Blood Marrow Transpl. 2012;18:1564–72. doi: 10.1016/j.bbmt.2012.05.017. PubMed DOI

Sevilla J, Guillen M, Castillo A, Prudencio M, Gonzalez-Vicent M, Lassaletta A, et al. Defining “poor mobilizer” in pediatric patients who need an autologous peripheral blood progenitor cell transplantation. Cytotherapy. 2013;15:132–7. doi: 10.1016/j.jcyt.2012.10.004. PubMed DOI

Avramova BE, Yordanova MN, Konstantinov DN, Bobev DG. Successful mobilization of peripheral blood stem cells in children with cancer using plerixafor (Mozobil) and granulocyte-colony stimulating factor. Drug Des Dev Ther. 2011;5:407–9. doi: 10.2147/DDDT.S19157. PubMed DOI PMC

Hong KT, Kang HJ, Kim NH, Kim MS, Lee JW, Kim H, et al. Successful mobilization using a combination of plerixafor and G-CSF in pediatric patients who failed previous chemomobilization with G-CSF alone and possible complications of the treatment. J Hematol Oncol. 2012;5:14. doi: 10.1186/1756-8722-5-14. PubMed DOI PMC

Sevilla J, Schiavello E, Madero L, Pardeo M, Guggiari E, Baragano M, et al. Priming of hematopoietic progenitor cells by plerixafor and filgrastim in children with previous failure of mobilization with chemotherapy and/or cytokine treatment. J Pediatr Hematol Oncol. 2012;34:146–50. doi: 10.1097/MPH.0b013e31821c2cb8. PubMed DOI

Teusink A, Pinkard S, Davies S, Mueller M, Jodele S. Plerixafor is safe and efficacious for mobilization of peripheral blood stem cells in pediatric patients. Transfusion. 2016;56:1402–5. doi: 10.1111/trf.13599. PubMed DOI

Maschan AA, Balashov DN, Kurnikova EE, Trakhtman PE, Boyakova EV, Skorobogatova EV, et al. Efficacy of plerixafor in children with malignant tumors failing to mobilize a sufficient number of hematopoietic progenitors with G-CSF. Bone Marrow Transpl. 2015;50:1089–91. doi: 10.1038/bmt.2015.71. PubMed DOI

European Medicines Agency. Mozobil. 2014. https://www.ema.europa.eu/en/medicines/human/EPAR/mozobil. Last accessed 18 February, 2020.

DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009;113:5720–6. doi: 10.1182/blood-2008-08-174946. PubMed DOI

Micallef IN, Stiff PJ, Stadtmauer EA, Bolwell BJ, Nademanee AP, Maziarz RT, et al. Safety and efficacy of upfront plerixafor + G-CSF versus placebo + G-CSF for mobilization of CD34(+) hematopoietic progenitor cells in patients >/=60 and <60 years of age with non-Hodgkin’s lymphoma or multiple myeloma. Am J Hematol. 2013;88:1017–23. doi: 10.1002/ajh.23561. PubMed DOI PMC

Teipel R, Oelschlagel U, Wetzko K, Schmiedgen M, Kramer M, Rucker-Braun E, et al. Differences in cellular composition of peripheral blood stem cell grafts from healthy stem cell donors mobilized with either granulocyte colony-stimulating factor (G-CSF) alone or G-CSF and plerixafor. Biol Blood Marrow Transpl. 2018;24:2171–7. doi: 10.1016/j.bbmt.2018.06.023. PubMed DOI

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01288573

Najít záznam

Citační ukazatele

Možnosti archivace