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).
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
14
01
2020
accepted:
03
02
2020
pubmed:
5
3
2020
medline:
22
6
2021
entrez:
5
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32127657
doi: 10.1038/s41409-020-0836-2
pii: 10.1038/s41409-020-0836-2
pmc: PMC7452813
doi:
Substances chimiques
Benzylamines
0
Cyclams
0
Heterocyclic Compounds
0
plerixafor
S915P5499N
Banques de données
ClinicalTrials.gov
['NCT01288573']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1744-1753Références
DiPersio JF, Uy GL, Yasothan U, Kirkpatrick P. Plerixafor. Nat Rev Drug Discov. 2009;8:105–6.
doi: 10.1038/nrd2819
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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