PHINK
Phase I / II Study on Infusion of Alloreactive or Stimulated Natural Killer Cells With IL-15 ex Vivo After Haploidentical Transplantation of Hematopoietic Progenitors in Pediatric Patients With Hematological Neoplasms
Sponsor study identifier
Secondary identifiers
EUDRACT_NUMBER
NIH
interventional
18
1 country
10
Study Start
November 30, 2020
Actual (reported)Primary Completion
June 30, 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
Study Completion
July 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
Phase I / II study on infusion of alloreactive or stimulated Natural Killer cells with IL-15 ex vivo after haploidentical transplantation of hematopoietic progenitors in pediatric patients with hematologic malignancies (PHINK
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
July 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
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Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
November 30, 2020
Actual (reported)January 12, 2022
Actual (reported)March 31, 2022
Actual (reported)June 30, 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
July 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
Dose-limiting toxicity (TLD)
To determine dose-limiting toxicity (TLD) of a single infusion of aloreactive NK cells or ex vivo IL-15-stimulated NK cells after haploTPH in pediatric patients with high-risk leukemias.
52 weeks
Maximum tolerated dose (MTD)
To determine maximum tolerated dose (MTD) of a single infusion of aloreactive NK cells or ex vivo IL-15-stimulated NK cells after haploTPH in pediatric patients with high-risk leukemias.
52 weeks
Efficacy of post haploTPH NK cell therapy
Week 52
Clinical evolution of patients
Week 52
Monitor immune reconstitution and characterize NK cells
Week 52
Three patients from each cohort will receive NK aloreactive cells from a KIR mismatch donor
Three patients in each cohort will receive ex vivo stimulated NK cells with IL-15 from a KIR match donor.
When patient and donor are KIR-HLA match, the patient submits all HLA class I molecules, or in the absence of any, your donor does not have this molecule, or having it lacks the corresponding KIR receiver. For more information detailed information on the product under investigation, reference is made to the Dossier of the Research Product (IMPD): PEI 09-008
Hospital Clínico Universitario de Santiago
Santiago de Compostela, A Coruña, 15706, Spain
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Hospital Infantil Universitario Niño Jeús
Madrid, 28009, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Regional Universitario de Málaga (Carlos de Haya)
Málaga, 29010, Spain
Ciceri F, Labopin M, Aversa F, Rowe JM, Bunjes D, Lewalle P, Nagler A, Di Bartolomeo P, Lacerda JF, Lupo Stanghellini MT, Polge E, Frassoni F, Martelli MF, Rocha V; Acute Leukemia Working Party (ALWP) of European Blood and Marrow Transplant (EBMT) Group. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood. 2008 Nov 1;112(9):3574-81. doi: 10.1182/blood-2008-02-140095. Epub 2008 Jul 7.
Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002 Mar 15;295(5562):2097-100. doi: 10.1126/science.1068440.
First Submitted
January 12, 2022
First Posted
March 31, 2022
Study Start
November 30, 2020
Actual (reported)Primary Completion
June 30, 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
When the patient lacks the HLA class I molecule and his donor has this molecule and also the donor NK cells have the KIR receptor that recognizes the absence of the corresponding HLA class I ligand
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Contact the study team to confirm eligibility.
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia, 30120, Spain
Hospital Universitario Virgen del Rocío
Seville, 41013, Spain
Hospital Universitario La Fe
Valencia, 46026, Spain
Leung W, Iyengar R, Triplett B, Turner V, Behm FG, Holladay MS, Houston J, Handgretinger R. Comparison of killer Ig-like receptor genotyping and phenotyping for selection of allogeneic blood stem cell donors. J Immunol. 2005 May 15;174(10):6540-5. doi: 10.4049/jimmunol.174.10.6540.
Aversa F. Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States. Bone Marrow Transplant. 2008 Mar;41(5):473-81. doi: 10.1038/sj.bmt.1705966. Epub 2008 Jan 7.
Lang P, Handgretinger R. Haploidentical SCT in children: an update and future perspectives. Bone Marrow Transplant. 2008 Oct;42 Suppl 2:S54-9. doi: 10.1038/bmt.2008.285.
Leung W, Campana D, Yang J, Pei D, Coustan-Smith E, Gan K, Rubnitz JE, Sandlund JT, Ribeiro RC, Srinivasan A, Hartford C, Triplett BM, Dallas M, Pillai A, Handgretinger R, Laver JH, Pui CH. High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia. Blood. 2011 Jul 14;118(2):223-30. doi: 10.1182/blood-2011-01-333070. Epub 2011 May 25.
Handgretinger R, Chen X, Pfeiffer M, Mueller I, Feuchtinger T, Hale GA, Lang P. Feasibility and outcome of reduced-intensity conditioning in haploidentical transplantation. Ann N Y Acad Sci. 2007 Jun;1106:279-89. doi: 10.1196/annals.1392.022. Epub 2007 Apr 18.
Moretta A, Pende D, Locatelli F, Moretta L. Activating and inhibitory killer immunoglobulin-like receptors (KIR) in haploidentical haemopoietic stem cell transplantation to cure high-risk leukaemias. Clin Exp Immunol. 2009 Sep;157(3):325-31. doi: 10.1111/j.1365-2249.2009.03983.x.
Ciurea SO, Mulanovich V, Jiang Y, Bassett R, Rondon G, McMannis J, de Lima M, Shpall EJ, Champlin RE. Lymphocyte recovery predicts outcomes in cord blood and T cell-depleted haploidentical stem cell transplantation. Biol Blood Marrow Transplant. 2011 Aug;17(8):1169-75. doi: 10.1016/j.bbmt.2010.11.020. Epub 2010 Nov 30.
Leen AM, Christin A, Myers GD, Liu H, Cruz CR, Hanley PJ, Kennedy-Nasser AA, Leung KS, Gee AP, Krance RA, Brenner MK, Heslop HE, Rooney CM, Bollard CM. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood. 2009 Nov 5;114(19):4283-92. doi: 10.1182/blood-2009-07-232454. Epub 2009 Aug 21.
Distler E, Bloetz A, Albrecht J, Asdufan S, Hohberger A, Frey M, Schnurer E, Thomas S, Theobald M, Hartwig UF, Herr W. Alloreactive and leukemia-reactive T cells are preferentially derived from naive precursors in healthy donors: implications for immunotherapy with memory T cells. Haematologica. 2011 Jul;96(7):1024-32. doi: 10.3324/haematol.2010.037481. Epub 2011 Apr 12.
Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, Orchard PJ, Blazar BR, Wagner JE, Slungaard A, Weisdorf DJ, Okazaki IJ, McGlave PB. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005 Apr 15;105(8):3051-7. doi: 10.1182/blood-2004-07-2974. Epub 2005 Jan 4.
Triplett BM, Horwitz EM, Iyengar R, Turner V, Holladay MS, Gan K, Behm FG, Leung W. Effects of activating NK cell receptor expression and NK cell reconstitution on the outcomes of unrelated donor hematopoietic cell transplantation for hematologic malignancies. Leukemia. 2009 Jul;23(7):1278-87. doi: 10.1038/leu.2009.21. Epub 2009 Feb 12.
Ciurea SO, Schafer JR, Bassett R, Denman CJ, Cao K, Willis D, Rondon G, Chen J, Soebbing D, Kaur I, Gulbis A, Ahmed S, Rezvani K, Shpall EJ, Lee DA, Champlin RE. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. Blood. 2017 Oct 19;130(16):1857-1868. doi: 10.1182/blood-2017-05-785659. Epub 2017 Aug 23.
Wanquet A, Bramanti S, Harbi S, Furst S, Legrand F, Faucher C, Granata A, Calmels B, Lemarie C, Picard C, Chabannon C, Weiller PJ, Castagna L, Blaise D, Devillier R. Killer Cell Immunoglobulin-Like Receptor-Ligand Mismatch in Donor versus Recipient Direction Provides Better Graft-versus-Tumor Effect in Patients with Hematologic Malignancies Undergoing Allogeneic T Cell-Replete Haploidentical Transplantation Followed by Post-Transplant Cyclophosphamide. Biol Blood Marrow Transplant. 2018 Mar;24(3):549-554. doi: 10.1016/j.bbmt.2017.11.042. Epub 2017 Dec 13.
Perez-Martinez A, Fernandez L, Valentin J, Martinez-Romera I, Corral MD, Ramirez M, Abad L, Santamaria S, Gonzalez-Vicent M, Sirvent S, Sevilla J, Vicario JL, de Prada I, Diaz MA. A phase I/II trial of interleukin-15--stimulated natural killer cell infusion after haplo-identical stem cell transplantation for pediatric refractory solid tumors. Cytotherapy. 2015 Nov;17(11):1594-603. doi: 10.1016/j.jcyt.2015.07.011. Epub 2015 Sep 1.
Perez-Martinez A, Iyengar R, Gan K, Chotsampancharoen T, Rooney B, Holladay M, Ramirez M, Leung W. Blood dendritic cells suppress NK cell function and increase the risk of leukemia relapse after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011 May;17(5):598-607. doi: 10.1016/j.bbmt.2010.10.019. Epub 2010 Oct 25.
Van Elssen CHMJ, Ciurea SO. NK cell therapy after hematopoietic stem cell transplantation: can we improve anti-tumor effect? Int J Hematol. 2018 Feb;107(2):151-156. doi: 10.1007/s12185-017-2379-x. Epub 2017 Dec 1.
Vela M, Corral D, Carrasco P, Fernandez L, Valentin J, Gonzalez B, Escudero A, Balas A, de Paz R, Torres J, Leivas A, Martinez-Lopez J, Perez-Martinez A. Haploidentical IL-15/41BBL activated and expanded natural killer cell infusion therapy after salvage chemotherapy in children with relapsed and refractory leukemia. Cancer Lett. 2018 May 28;422:107-117. doi: 10.1016/j.canlet.2018.02.033. Epub 2018 Feb 23.
Fernandez L, Leivas A, Valentin J, Escudero A, Corral D, de Paz R, Vela M, Bueno D, Rodriguez R, Torres JM, Diaz-Almiron M, Lopez-Collazo E, Martinez-Lopez J, Perez-Martinez A. How do we manufacture clinical-grade interleukin-15-stimulated natural killer cell products for cancer treatment? Transfusion. 2018 Jun;58(6):1340-1347. doi: 10.1111/trf.14573. Epub 2018 Mar 14.
Study Completion
July 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
Last Updated
April 6, 2025
Record last verified: 2025-04
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