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High-risk LeukemiasPhase 1/2PHINKNCT05304754

"Phase I / II Study on Infusion of Natural Killer Cells After Haploidentical Transplantation in Pediatric Patients"

A Phase 1/2 study testing NK cells stimulated ex vivo with IL-15 and Alloreactive NK cells in people with High-risk Leukemias, run by Instituto de Investigación Hospital Universitario La Paz at 10 sites in Spain.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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 Read more about this study

Who is it for?
Ages Up to 21 years
Conditions the study is for
High-risk Leukemias
What is being tested?
NK cells stimulated ex vivo with IL-15 and Alloreactive NK cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
10 sitesSpain
Study dates
30 Nov 2020to Jul 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients of both sexes with age ≤ 21 years.
  • Not having an identical HLA donor (family or non-family) available in the time needed for the donation of hematopoietic parents.
  • Having a haploidenic donor available
  • Diagnosis of high-risk hematological malignancy. This includes:
  • i. High risk ALL in first complete remission (RC1);
  • ii. ALL in second complete remission (RC2);
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  • iii. ALL in third complete remission (RC3) or later;
  • iv. High risk AML in RC1;
  • v. AML in RC2 or later;
  • vi. Relapsed AML with <25% blasts in bone marrow;
  • vii. AML related to previous treatments in CR> 12 months;
  • viii. Primary or secondary myelodysplastic syndrome
  • ix. NK cell leukemia, biphenotypic or undifferentiated in RC1 or later,
  • x. Chronic myeloid leukemia (CML) in accelerated phase, in chronic phase with persistent molecular positivity, or with intolerance to tyrosine kinase inhibitors
  • xi. Hodgkin's lymphoma in RC2 or later after failure of autologous TPH, or unable to mobilize hematopoietic progenitors for autologous TPH
  • xii. Non-Hodgkin's lymphoma in RC2 or later after failure of autologous TPH, or unable to mobilize hematopoietic progenitors for autologous TPH
  • xiii. Myelomonocytic juvenile leukemia.
  • Positive pre-transplant evaluation
  • i. Left ventricular ejection fraction > 40% or shortening fraction ≥ 25%;
  • ii. Creatinine clearance (ACr) or glomerular filtration rate (TFG) ≥ 50 ml/min/1.73 m2
  • iii. Forced Vital Capacity (FVC) ≥ 50% of predicted value or pulse-oximetry ≥ 92% if the patient cannot perform the pulmonary function tests;
  • iv. Karnofsky or Lansky Index (depending on the patient's age) ≥ 50;
  • v. Bilirubin ≤ 3 times the upper limit of normal for age
  • vi. Alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal for age
  • vii. Women who are not breastfeeding.
  • viii. No uncontrolled bacterial, fungal, or viral infections at the time of inclusion.
  • Women of childbearing potential must have a negative serum or urine pregnancy test performed within 14 days prior to trial inclusion and must agree to use highly effective contraceptive methods (diaphragms plus spermicide or male condom plus spermicide, oral contraceptive combined with a second method of contraceptive implant, injectable contraceptive, permanent intrauterine device, sexual abstinence, or partner with vasectomy) during study participation and for six months after the last trial visit. In the case of male patients with reproductive capacity, they must commit to using an appropriate barrier method for the duration of the study and for up to 6 months thereafter

Who cannot join

  • Patients with an active infectious process or other serious underlying medical condition
  • Patients who, according to the investigator's criteria, have a history of poor compliance with therapy.
  • Patients who after a psycho-social evaluation are advised as not suitable for the procedure:
  • i. Social-family situation that makes correct participation in the study impossible.
  • ii. Patients with emotional or psychological problems secondary to the illness such as post-traumatic stress disorder, phobias, delusions, psychosis, with the need for support from specialists.
  • iii. Evaluation of the involvement of family members in the health of the patient
  • Inability to understand the information about the trial
  • Received an investigational drug within 30 days prior to the start of therapy or within 5 half-lives of receiving an investigational drug, whichever is longer.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Spain10 sites

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28007

  • Hospital Infantil Universitario Niño Jeús

    Madrid, 28009

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Regional Universitario de Málaga (Carlos de Haya)

    Málaga, 29010

  • Hospital Clínico Universitario Virgen de la Arrixaca

    Murcia, 30120

  • Hospital Universitario Central de Asturias

    Oviedo, Principality of Asturias, 33011

  • Hospital Clínico Universitario de Santiago

    Santiago de Compostela, A Coruña, 15706

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Hospital Universitario La Fe

    Valencia, 46026

Other trials in Spain

About this study

Official title: 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

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

Read the detailed description

Haploidentical hematopoietic stem cell transplantation (haploTPH) constitutes a highly complex but effective procedure for some hematologic malignancies high-risk pediatric patients in the absence of an identical HLA donor. Relapse Post-transplant leukemia is the main problem for survival. Just like reported different expert groups on haploTPH in adults and children, there is a determining role of Natural Killer (NK) cells in haploTPH as inducers powerful graft-versus-leukemia (EIcL) effect. The presence of NK cells allo-reactive is correlated with a lower relapse rate, in addition to favoring the graft, decrease graft versus recipient disease (GVHD) and decrease viral infections. This only occurs in half of the donor-recipient pairs, so that, in its absence, it is necessary to develop other strategies for activating the NK cells. In this sense, the investigational group has extensive experience in research translational with NK cells and is a pioneer in infusing ex vivo activated NK cells with IL-15.

The investigators propose a phase I / II clinical trial with dose escalation, multicenter, framed in the Spanish Group of Hematopoietic Transplantation / Marrow Transplant Bone in Children (GETH / GETMON), to determine the safety and efficacy of a post-haploTPH IL-15 alloreactive / stimulated NK cell infusion in children with malignant blood diseases. The investigators will monitor immune reconstitution, chimerism, Post-transplantation NK cell expansion, phenotype, and function.

Secondarily evaluate the effectiveness of therapy on the incidence of graft failure; EICR; viral reactivations; transplant-related mortality; and relapse of leukemia.

Being tested
NK cells stimulated ex vivo with IL-15, Alloreactive NK cells

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NK cells stimulated ex vivo with IL-15Biological

    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

  • Alloreactive NK cellsBiological

    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

Study groups in NCT05304754
Study groupRoleWhat they receive
KIR mismatch aloreactive NK donor cellsActive comparatorThree patients from each cohort will receive NK aloreactive cells from a KIR mismatch donor
Receives: Biological: Alloreactive NK cells
NK cells stimulated ex vivo with IL-15 from KIR match donorExperimentalThree patients in each cohort will receive ex vivo stimulated NK cells with IL-15 from a KIR match donor.
Receives: Biological: NK cells stimulated ex vivo with IL-15

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 52 weeks

  2. 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.

    Measured: 52 weeks

Secondary outcomes (3)

  1. Efficacy of post haploTPH NK cell therapy

    The efficacy of post haploTPH NK cell therapy will be determined, comparing it with the historical cohort recently reported by GETH/GETMON in the incidence of graft failure, acute/chronic GVHD, viral reactivations (CMV, EBV, HHV-6, adenovirus, BKV), transplant-related mortality (TRM), and leukemia relapse.

    Measured: Week 52

  2. Clinical evolution of patients

    The clinical course of patients will be compared based on the dose of infused NK cells, KIR match vs. KIR mismatch NK cells, expansion, chimerism, and phenotypic and functional characteristics of the infused NK cells, and the speed and characteristics of immune reconstitution post haploTPH.

    Measured: Week 52

  3. Monitor immune reconstitution and characterize NK cells

    Immune reconstitution will be monitored by quantifying immunoglobulins at different times, and characterizing NK cells in patients, at a phenotypic and functional level, for 1 year after haploTPH

    Measured: Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2022
  2. Study start30 Nov 2020
  3. Primary completion30 Jun 2026 (estimated)
  4. Study completionJul 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05304754
Sponsor's protocol ID
PHINK -01/2019
Other IDs
2019-000911-10, 2019
Acronym
PHINK
Status last verified
Apr 2025
First submitted
12 Jan 2022
Last updated
6 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 18606875

  • 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.

    PubMed 11896281

  • 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.

    PubMed 15879158

  • 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.

    PubMed 18176612

  • 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.

    PubMed 18978746

  • 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.

    PubMed 21613256

  • 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.

    PubMed 17442774

  • 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.

    PubMed 19664139

  • 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.

    PubMed 21126598

  • 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.

    PubMed 19700662

  • 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.

    PubMed 21486863

  • 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.

    PubMed 15632206

  • 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.

    PubMed 19212329

  • 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.

    PubMed 28835441

  • 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.

    PubMed 29247781

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NK cells stimulated ex vivo with IL-15 and Alloreactive NK cells in people with High-risk Leukemias, run by Instituto de Investigación Hospital Universitario La Paz at 10 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (TLD) (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05304754, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2025.

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