Pediatric CancerNCT05425043
Granulocyte Transfusions After Umbilical Cord Blood Transplant
A study testing Granulocytes in people with Pediatric Cancer, run by University of Manchester at 1 site in United Kingdom.
Trial summary
Although most children with leukaemia are cured using drugs (chemotherapy) alone, for some children additional treatments are needed. Stem cell transplant can cure children where chemotherapy and other drugs have failed. In this case, the immune cells of the donor attack the leukaemia cells of the patient. Read more about this study
- Who is it for?
- Ages Up to 16 years
- Conditions the study is for
- Pediatric Cancer
- What is being tested?
- Granulocytes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 14 Sep 2021to 30 Jun 2026
- Phase
- Interventional
- 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 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children, aged <16 years, undergoing a first allogeneic, unrelated donor, T-cell replete, umbilical cord blood HSCT for high risk acute leukaemia.
- Availability of at least a 6/8 allelic matched cord blood, of adequate cell dose, after allele-level matching at HLA (Human Leukocyte Antigen)-A, -B, -C, and -DRB1
- Informed consent by parent or guardian. Age appropriate Assent will also be collected in those Children age 16 and under.
Who cannot join
- Patients participating in other HSCT clinical trial
- The transplant not indicated according to National Health Service England (NHSE) and British Society of Bone Marrow Transplant (BSBMT) Paediatric Transplant Group.
- Pooled Granulocyte Transfusion contraindicated for any reason
- Previous T cell replete unrelated donor cord blood transplant
- Patients with a previous history of sensitivity to granulocyte transfusion will be excluded from the study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Manchester Childrens Hospital, MFT
Manchester, M13 9WL
About this study
Official title: The Use of Granulocyte Transfusions After Umbilical Cord Blood Transplant for Leukaemia: A Prospective, Non-randomised, Single-centre Study to Evaluate Safety and Immune Reconstitution
Although most children with leukaemia are cured using drugs (chemotherapy) alone, for some children additional treatments are needed. Stem cell transplant can cure children where chemotherapy and other drugs have failed. In this case, the immune cells of the donor attack the leukaemia cells of the patient. Cord blood collected from the placenta of unrelated babies is often used as a donor cell source and appears to work well at controlling leukaemia and less likely to cause complications such as when the immune cells also mistakenly attack healthy tissues (called graft versus host disease, GVHD).
The investigators have noticed that during cord blood transplant, the donor immune system appears to recover more quickly and not be associated with GVHD, when a type of blood transfusion containing white cells are also given to the patient. The infused white cells appear to stimulate the donor immune cells to expand much more than usually seen.
During this research, the investigators will study this immune cell expansion during cord blood transplant in children with difficult-to-cure leukaemia who also receive a transfusion of white cells, termed granulocytes. The investigators will assess the safety of the effects of the white cell transfusions and the immune cell expansion on the child, and look at the outcomes on the patient's leukaemia, and whether there is GVHD or not.
Read the detailed description
Most children with acute leukaemia are cured with chemotherapy alone but a few children are either refractory to such therapy, or relapse after it has been administered.
Some of these relapsed or refractory children are given HCT (hematopoietic cell transplantation), and some will be cured with HCT. HCT acts to cure children with leukaemia in two ways:
- There is chemotherapy given before the transplant, to get rid of recipient marrow and the recipient immune system. This chemotherapy is of higher dose than is given in standard chemotherapy protocols, and this dose escalation might overcome the resistance to chemotherapy that is inherent in children with relapsed or refractory disease.
- The engrafting immune system - derived from the HCT donor - recognises the residual leukaemia and rejects it. This is known as graft-versus-leukaemia, and this Is the main way that transplant cures refractory diseases.
Most children with refractory and / or relapsed leukaemia will die of their leukaemia. Transplant offers a chance of cure where conventional therapies will fail. Transplant works through this graft-versus leukaemia effect. This is related to graft-versus-disease (GVHD) and involves a recognition by donor derived T-cells of differences in the host leukaemia cells, and more generally in the recipient.
In general, the risk of relapse after transplant is:
- Reduced where there is graft versus host disease
- Reduced where the T-cells are left in the graft, a T-cell replete transplant. Often T-cells are removed from the graft - bone marrow, blood, or cord blood - to reduce the risk of GVHD
- Reduced where there is mismatch between the donor and recipient. The investigators and others have shown that it is possible to do T-cell replete, mismatched unrelated donor transplant in umbilical cord transplant.
- The risk of relapse is less in cord blood transplant compared to other cell sources, and this is particularly evident where there is residual disease present, and the risk of treatment failure is highest.
- The risk of chronic GVHD is reduced after cord blood transplant, even where the transplant is T-cell replete and there is mismatch between donor and recipient. Using adult donor-derived, mismatched donor transplant in a T-cell replete setting is associated with a risk of severe acute GVHD and chronic, extensive GVHD which limits quality of life.
- The most meaningful endpoint for children undergoing transplantation for any indication is disease-free and chronic GVHD-free survival. In malignancy this is best achieved using cord blood in a T-cell replete setting.
One of the investigators groups have published data from a xenograft model demonstrating that cord blood T-cells are better at controlling a human leukaemia than adult T-cells, and that the actual cord T-cells infiltrating the xenografted tumour are Cluster of Differentiation 810 (CD810). However, after T-cell replete transplant most of the recovering T-cells are Cluster of Differentiation 4 (CD4) and not Cluster of Differentiation (CD812). Childhood leukaemia is a rapidly proliferative disease, and experience tells us that relapse can happen early, within the first weeks and months. A graft versus tumour effect must be established quickly therefore, to prevent disease recurrence, and death from disease.
In this research, the investigators seek to replicate results that have been described and published prior. Here the investigators demonstrated early, transient, massive Cluster of Differentiation (CD8) T-cell reconstitution after cord blood transplantation without any chronic GVHD, despite early cessation of post-transplant immune suppression.
This observation is important since it incorporates the important components of a clinically meaningful graft-versus-leukaemia, from previous work:
- CD8 biased
- Cord blood
- T-cell replete setting
- Mismatched donors
- No chronic GVHD
This has been recognized by leaders in the field, and as part of the peer review of this work. Milano, an expert in Cord Blood transplant in refractory leukaemia has written that "this is not only economically beneficial but may also result in a paradigm shift for the treatment of patients with high-risk leukaemia's. "
The trial is funded by bone marrow transplant local funds and by funds generated specifically for this research by families, including families with difficult-to-cure, including multiple relapsed and refractory leukaemia. The rationale and patient summaries have been shared with those families, in support of their fundraising efforts. Families of children with such leukaemia understand how transplant works, the risk it generates and the implications when cell therapies also fail where conventional therapy has already failed. They are the best placed of all of us to understand this balance of risk of therapy with risk of treatment failure, and the best placed therefore to understand the rationale and scope of this research.
It is important to replicate the data that the investigators have published. It is important that in a trial setting that the investigators better define the safety of the immune cell expansion, and the nature of the T-cells that are derived. It is important research, for the reasons explained above, and recognised by Milano and other commentators.
There is a control group for T-cell expansion numbers, and for safety evaluations including cytokine release syndrome and engraftment kinetics. This is not an efficacy trial, and the relapsed, refractory leukaemia is rare in children, and so randomisation is not appropriate. The granulocyte doses are standard for children, and what the investigators reported in their preliminary experience.
- Conditions
- Pediatric Cancer
- Being tested
- Granulocytes
- Keywords
- Granulocytes, HSCT, Haematopoietic Stem Cell Transplant, Pediatric, Leukemia
- Medical subject headings
- Neoplasms, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GranulocytesBiological
Receive granulocytes for 7 consecutive days after engraftment post transplant
| Study group | Role | What they receive |
|---|---|---|
| Granulocytes | Experimental | Patient to receive pooled granulocytes for 7 days concurrently. 20 participants will be approached for this arm. Receives: Biological: Granulocytes |
| Control | No intervention | Non-randomised control arm, where patients who are receiving a stem cell transplant, as described in the eligibility criteria, are asked for a blood sample. This is to establish a baseline versus the experimental arm. 20 participants will be approached for this arm. |
What is being measured
The primary outcome is the main question the study is designed to answer.
What is the number of patients with grade 1-4 cytokine release syndrome, related to the granulocytes infusions?
This is to access safety of the granulocyte infusions.
Measured: 2 years
What is the number of patients with allo-immunisation after the granulocyte infusions?
This is to access safety of the granulocyte infusions.
Measured: 2 years
Secondary outcomes (5)
What is the median day to neutrophil and to platelet engraftment, and compared with a control group of cord blood transplant recipients not receiving granulocytes?
This is to measure the effect that the granulocyte infusion course have on engraftment and on the disease
Measured: 2 years
How many patients experience grade II-IV GvHD?
This is to measure the effect that the granulocyte infusion course have on engraftment and on the disease
Measured: 2 years
What is the median disease-free and overall survival in this patient cohort?
This is to measure the effect that the granulocyte infusion course have on engraftment and on the disease
Measured: 2 years
How many patients enter flow and molecular remission after the transplant?
This is to measure the effect that the granulocyte infusion course have on engraftment and on the disease
Measured: 2 years
What is the median date of cessation of immune suppression after the transplant, and compared with a control group of cord blood transplant recipients not receiving granulocytes?
This is to measure the effect that the granulocyte infusion course have on engraftment and on the disease
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2022
- Study start14 Sep 2021
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Pediatric CancerStudies of the same condition, open and under way.
- More trials run by University of ManchesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Manchester
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Cancer and Leukaemia Group
- Responsible party
- Sponsor
- Investigators
- Robert Wynn, MD FRCPath, Study chair, Royal Manchester Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05425043
- Sponsor's protocol ID
- 295998
- Status last verified
- Jun 2026
- First submitted
- 17 Dec 2021
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Keating AK, Langenhorst J, Wagner JE, et al. The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia. Blood Adv. 2019;3(7):1118-1128. Blood Adv. 2020 Mar 24;4(6):1081. doi: 10.1182/bloodadvances.2020001753. No abstract available.
PubMed 32196555Deambrosis D, Lum SH, Hum RM, Poulton K, Ogden W, Jones S, Stanworth S, Bonney D, Hiwarkar P, Wynn RF. Immune cytopenia post-cord transplant in Hurler syndrome is a forme fruste of graft rejection. Blood Adv. 2019 Feb 26;3(4):570-574. doi: 10.1182/bloodadvances.2018026963.
PubMed 30787020Lum SH, Miller WP, Jones S, Poulton K, Ogden W, Lee H, Logan A, Bonney D, Lund TC, Orchard PJ, Wynn RF. Changes in the incidence, patterns and outcomes of graft failure following hematopoietic stem cell transplantation for Hurler syndrome. Bone Marrow Transplant. 2017 Jun;52(6):846-853. doi: 10.1038/bmt.2017.5. Epub 2017 Feb 20.
PubMed 28218755Eapen M, Wang T, Veys PA, Boelens JJ, St Martin A, Spellman S, Bonfim CS, Brady C, Cant AJ, Dalle JH, Davies SM, Freeman J, Hsu KC, Fleischhauer K, Kenzey C, Kurtzberg J, Michel G, Orchard PJ, Paviglianiti A, Rocha V, Veneris MR, Volt F, Wynn R, Lee SJ, Horowitz MM, Gluckman E, Ruggeri A. Allele-level HLA matching for umbilical cord blood transplantation for non-malignant diseases in children: a retrospective analysis. Lancet Haematol. 2017 Jul;4(7):e325-e333. doi: 10.1016/S2352-3026(17)30104-7. Epub 2017 Jun 13.
PubMed 28623181Veys P, Danby R, Vora A, Slatter M, Wynn R, Lawson S, Steward C, Gibson B, Potter M, de la Fuente J, Shenton G, Cornish J, Gennery A, Snowden JA, Bonney D, Velangi M, Ruggeri A, Gluckman E, Hough R, Rocha V; British Society of Blood and Marrow Transplantation and Eurocord. UK experience of unrelated cord blood transplantation in paediatric patients. Br J Haematol. 2016 Feb;172(3):482-6. doi: 10.1111/bjh.13914. Epub 2016 Jan 5. No abstract available.
PubMed 26728432Boelens JJ, Aldenhoven M, Purtill D, Ruggeri A, Defor T, Wynn R, Wraith E, Cavazzana-Calvo M, Rovelli A, Fischer A, Tolar J, Prasad VK, Escolar M, Gluckman E, O'Meara A, Orchard PJ, Veys P, Eapen M, Kurtzberg J, Rocha V; Eurocord; Inborn Errors Working Party of European Blood and Marrow Transplant group; Duke University Blood and Marrow Transplantation Program; Centre for International Blood and Marrow Research. Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning. Blood. 2013 May 9;121(19):3981-7. doi: 10.1182/blood-2012-09-455238. Epub 2013 Mar 14.
PubMed 23493783Aldenhoven M, Jones SA, Bonney D, Borrill RE, Coussons M, Mercer J, Bierings MB, Versluys B, van Hasselt PM, Wijburg FA, van der Ploeg AT, Wynn RF, Boelens JJ. Hematopoietic cell transplantation for mucopolysaccharidosis patients is safe and effective: results after implementation of international guidelines. Biol Blood Marrow Transplant. 2015 Jun;21(6):1106-9. doi: 10.1016/j.bbmt.2015.02.011. Epub 2015 Feb 20.
PubMed 25708213Takami A. Hematopoietic stem cell transplantation for acute myeloid leukemia. Int J Hematol. 2018 May;107(5):513-518. doi: 10.1007/s12185-018-2412-8. Epub 2018 Jan 27.
PubMed 29374826Milano F, Gooley T, Wood B, Woolfrey A, Flowers ME, Doney K, Witherspoon R, Mielcarek M, Deeg JH, Sorror M, Dahlberg A, Sandmaier BM, Salit R, Petersdorf E, Appelbaum FR, Delaney C. Cord-Blood Transplantation in Patients with Minimal Residual Disease. N Engl J Med. 2016 Sep 8;375(10):944-53. doi: 10.1056/NEJMoa1602074.
PubMed 27602666Hiwarkar P, Qasim W, Ricciardelli I, Gilmour K, Quezada S, Saudemont A, Amrolia P, Veys P. Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells. Blood. 2015 Dec 24;126(26):2882-91. doi: 10.1182/blood-2015-06-654780. Epub 2015 Oct 8.
PubMed 26450984Admiraal R, Chiesa R, Lindemans CA, Nierkens S, Bierings MB, Versluijs AB, Hiwarkar P, Furtado Silva JM, Veys P, Boelens JJ. Leukemia-free survival in myeloid leukemia, but not in lymphoid leukemia, is predicted by early CD4+ reconstitution following unrelated cord blood transplantation in children: a multicenter retrospective cohort analysis. Bone Marrow Transplant. 2016 Oct;51(10):1376-1378. doi: 10.1038/bmt.2016.116. Epub 2016 May 9. No abstract available.
PubMed 27159172Chiesa R, Gilmour K, Qasim W, Adams S, Worth AJ, Zhan H, Montiel-Equihua CA, Derniame S, Cale C, Rao K, Hiwarkar P, Hough R, Saudemont A, Fahrenkrog CS, Goulden N, Amrolia PJ, Veys P. Omission of in vivo T-cell depletion promotes rapid expansion of naive CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant. Br J Haematol. 2012 Mar;156(5):656-66. doi: 10.1111/j.1365-2141.2011.08994.x. Epub 2012 Jan 9.
PubMed 22224700Politikos I, Lavery JA, Hilden P, Cho C, Borrill T, Maloy MA, Giralt SA, van den Brink MRM, Perales MA, Barker JN. Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin. Blood Adv. 2020 Jan 14;4(1):191-202. doi: 10.1182/bloodadvances.2019000836.
PubMed 31935291Estcourt LJ, Stanworth SJ, Hopewell S, Doree C, Trivella M, Massey E. Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction. Cochrane Database Syst Rev. 2016 Apr 29;4(4):CD005339. doi: 10.1002/14651858.CD005339.pub2.
PubMed 27128488Massey E, Harding K, Kahan BC, Llewelyn C, Wynn R, Moppett J, Robinson SP, Green A, Lucas G, Sadani D, Liakopoulou E, Bolton-Maggs P, Marks DI, Stanworth S. The granulocytes in neutropenia 1 (GIN 1) study: a safety study of granulocytes collected from whole blood and stored in additive solution and plasma. Transfus Med. 2012 Aug;22(4):277-84. doi: 10.1111/j.1365-3148.2012.01152.x. Epub 2012 May 16.
PubMed 22591484
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Granulocyte Transfusions After Umbilical Cord Blood Transplant for Leukaemia: A Prospective, Non-randomised, Single-centre Study to Evaluate Safety and Immune Reconstitution
- ClinicalTrials.gov ID
- NCT05425043
- Acronym / sponsor ID
- 295998
- Conditions
- Pediatric Cancer
- Keywords
- Granulocytes, HSCT, Haematopoietic Stem Cell Transplant, Pediatric, Leukemia
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of ManchesterUniversity, hospital or other
- Collaborators
- Children's Cancer and Leukaemia Group
- Study start
- 14 Sep 2021 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 21 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Although most children with leukaemia are cured using drugs (chemotherapy) alone, for some children additional treatments are needed. Stem cell transplant can cure children where chemotherapy and other drugs have failed. In this case, the immune cells of the donor attack the leukaemia cells of the patient. Cord blood collected from the placenta of unrelated babies is often used as a donor cell source and appears to work well at controlling leukaemia and less likely to cause complications such as when the immune cells also mistakenly attack healthy tissues (called graft versus host disease, GVHD).
The investigators have noticed that during cord blood transplant, the donor immune system appears to recover more quickly and not be associated with GVHD, when a type of blood transfusion containing white cells are also given to the patient. The infused white cells appear to stimulate the donor immune cells to expand much more than usually seen.
During this research, the investigators will study this immune cell expansion during cord blood transplant in children with difficult-to-cure leukaemia who also receive a transfusion of white cells, termed granulocytes. The investigators will assess the safety of the effects of the white cell transfusions and the immune cell expansion on the child, and look at the outcomes on the patient's leukaemia, and whether there is GVHD or not.
Detailed description
Most children with acute leukaemia are cured with chemotherapy alone but a few children are either refractory to such therapy, or relapse after it has been administered.
Some of these relapsed or refractory children are given HCT (hematopoietic cell transplantation), and some will be cured with HCT. HCT acts to cure children with leukaemia in two ways:
- There is chemotherapy given before the transplant, to get rid of recipient marrow and the recipient immune system. This chemotherapy is of higher dose than is given in standard chemotherapy protocols, and this dose escalation might overcome the resistance to chemotherapy that is inherent in children with relapsed or refractory disease.
- The engrafting immune system - derived from the HCT donor - recognises the residual leukaemia and rejects it. This is known as graft-versus-leukaemia, and this Is the main way that transplant cures refractory diseases.
Most children with refractory and / or relapsed leukaemia will die of their leukaemia. Transplant offers a chance of cure where conventional therapies will fail. Transplant works through this graft-versus leukaemia effect. This is related to graft-versus-disease (GVHD) and involves a recognition by donor derived T-cells of differences in the host leukaemia cells, and more generally in the recipient.
In general, the risk of relapse after transplant is:
- Reduced where there is graft versus host disease
- Reduced where the T-cells are left in the graft, a T-cell replete transplant. Often T-cells are removed from the graft - bone marrow, blood, or cord blood - to reduce the risk of GVHD
- Reduced where there is mismatch between the donor and recipient. The investigators and others have shown that it is possible to do T-cell replete, mismatched unrelated donor transplant in umbilical cord transplant.
- The risk of relapse is less in cord blood transplant compared to other cell sources, and this is particularly evident where there is residual disease present, and the risk of treatment failure is highest.
- The risk of chronic GVHD is reduced after cord blood transplant, even where the transplant is T-cell replete and there is mismatch between donor and recipient. Using adult donor-derived, mismatched donor transplant in a T-cell replete setting is associated with a risk of severe acute GVHD and chronic, extensive GVHD which limits quality of life.
- The most meaningful endpoint for children undergoing transplantation for any indication is disease-free and chronic GVHD-free survival. In malignancy this is best achieved using cord blood in a T-cell replete setting.
One of the investigators groups have published data from a xenograft model demonstrating that cord blood T-cells are better at controlling a human leukaemia than adult T-cells, and that the actual cord T-cells infiltrating the xenografted tumour are Cluster of Differentiation 810 (CD810). However, after T-cell replete transplant most of the recovering T-cells are Cluster of Differentiation 4 (CD4) and not Cluster of Differentiation (CD812). Childhood leukaemia is a rapidly proliferative disease, and experience tells us that relapse can happen early, within the first weeks and months. A graft versus tumour effect must be established quickly therefore, to prevent disease recurrence, and death from disease.
In this research, the investigators seek to replicate results that have been described and published prior. Here the investigators demonstrated early, transient, massive Cluster of Differentiation (CD8) T-cell reconstitution after cord blood transplantation without any chronic GVHD, despite early cessation of post-transplant immune suppression.
This observation is important since it incorporates the important components of a clinically meaningful graft-versus-leukaemia, from previous work:
- CD8 biased
- Cord blood
- T-cell replete setting
- Mismatched donors
- No chronic GVHD
This has been recognized by leaders in the field, and as part of the peer review of this work. Milano, an expert in Cord Blood transplant in refractory leukaemia has written that "this is not only economically beneficial but may also result in a paradigm shift for the treatment of patients with high-risk leukaemia's. "
The trial is funded by bone marrow transplant local funds and by funds generated specifically for this research by families, including families with difficult-to-cure, including multiple relapsed and refractory leukaemia. The rationale and patient summaries have been shared with those families, in support of their fundraising efforts. Families of children with such leukaemia understand how transplant works, the risk it generates and the implications when cell therapies also fail where conventional therapy has already failed. They are the best placed of all of us to understand this balance of risk of therapy with risk of treatment failure, and the best placed therefore to understand the rationale and scope of this research.
It is important to replicate the data that the investigators have published. It is important that in a trial setting that the investigators better define the safety of the immune cell expansion, and the nature of the T-cells that are derived. It is important research, for the reasons explained above, and recognised by Milano and other commentators.
There is a control group for T-cell expansion numbers, and for safety evaluations including cytokine release syndrome and engraftment kinetics. This is not an efficacy trial, and the relapsed, refractory leukaemia is rare in children, and so randomisation is not appropriate. The granulocyte doses are standard for children, and what the investigators reported in their preliminary experience.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Granulocytes | Experimental | Biological: GranulocytesPatient to receive pooled granulocytes for 7 days concurrently. 20 participants will be approached for this arm. |
| Control | No intervention | –Non-randomised control arm, where patients who are receiving a stem cell transplant, as described in the eligibility criteria, are asked for a blood sample. This is to establish a baseline versus the experimental arm. 20 participants will be approached for this arm. |
Who may qualify
- Ages
- Up to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Children, aged <16 years, undergoing a first allogeneic, unrelated donor, T-cell replete, umbilical cord blood HSCT for high risk acute leukaemia.
- Availability of at least a 6/8 allelic matched cord blood, of adequate cell dose, after allele-level matching at HLA (Human Leukocyte Antigen)-A, -B, -C, and -DRB1
- Informed consent by parent or guardian. Age appropriate Assent will also be collected in those Children age 16 and under.
Key exclusion criteria (5 listed)
- Patients participating in other HSCT clinical trial
- The transplant not indicated according to National Health Service England (NHSE) and British Society of Bone Marrow Transplant (BSBMT) Paediatric Transplant Group.
- Pooled Granulocyte Transfusion contraindicated for any reason
- Previous T cell replete unrelated donor cord blood transplant
- Patients with a previous history of sensitivity to granulocyte transfusion will be excluded from the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GranulocytesReceive granulocytes for 7 consecutive days after engraftment post transplant | Biological | Granulocytes |
Primary outcome
What is the number of patients with grade 1-4 cytokine release syndrome, related to the granulocytes infusions?
Time frame: 2 years
This is to access safety of the granulocyte infusions.
What is the number of patients with allo-immunisation after the granulocyte infusions?
Time frame: 2 years
This is to access safety of the granulocyte infusions.
5 secondary outcomes
What is the median day to neutrophil and to platelet engraftment, and compared with a control group of cord blood transplant recipients not receiving granulocytes?
Time frame: 2 years
How many patients experience grade II-IV GvHD?
Time frame: 2 years
What is the median disease-free and overall survival in this patient cohort?
Time frame: 2 years
How many patients enter flow and molecular remission after the transplant?
Time frame: 2 years
What is the median date of cessation of immune suppression after the transplant, and compared with a control group of cord blood transplant recipients not receiving granulocytes?
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Background: PubMed 32196555Keating AK, Langenhorst J, Wagner JE, et al. The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia. Blood Adv. 2019;3(7):1118-1128. Blood Adv. 2020 Mar 24;4(6):1081. doi: 10.1182/bloodadvances.2020001753. No abstract available.
- Background: PubMed 30787020Deambrosis D, Lum SH, Hum RM, Poulton K, Ogden W, Jones S, Stanworth S, Bonney D, Hiwarkar P, Wynn RF. Immune cytopenia post-cord transplant in Hurler syndrome is a forme fruste of graft rejection. Blood Adv. 2019 Feb 26;3(4):570-574. doi: 10.1182/bloodadvances.2018026963.
- Background: PubMed 28218755Lum SH, Miller WP, Jones S, Poulton K, Ogden W, Lee H, Logan A, Bonney D, Lund TC, Orchard PJ, Wynn RF. Changes in the incidence, patterns and outcomes of graft failure following hematopoietic stem cell transplantation for Hurler syndrome. Bone Marrow Transplant. 2017 Jun;52(6):846-853. doi: 10.1038/bmt.2017.5. Epub 2017 Feb 20.
- Background: PubMed 28623181Eapen M, Wang T, Veys PA, Boelens JJ, St Martin A, Spellman S, Bonfim CS, Brady C, Cant AJ, Dalle JH, Davies SM, Freeman J, Hsu KC, Fleischhauer K, Kenzey C, Kurtzberg J, Michel G, Orchard PJ, Paviglianiti A, Rocha V, Veneris MR, Volt F, Wynn R, Lee SJ, Horowitz MM, Gluckman E, Ruggeri A. Allele-level HLA matching for umbilical cord blood transplantation for non-malignant diseases in children: a retrospective analysis. Lancet Haematol. 2017 Jul;4(7):e325-e333. doi: 10.1016/S2352-3026(17)30104-7. Epub 2017 Jun 13.
- Background: PubMed 26728432Veys P, Danby R, Vora A, Slatter M, Wynn R, Lawson S, Steward C, Gibson B, Potter M, de la Fuente J, Shenton G, Cornish J, Gennery A, Snowden JA, Bonney D, Velangi M, Ruggeri A, Gluckman E, Hough R, Rocha V; British Society of Blood and Marrow Transplantation and Eurocord. UK experience of unrelated cord blood transplantation in paediatric patients. Br J Haematol. 2016 Feb;172(3):482-6. doi: 10.1111/bjh.13914. Epub 2016 Jan 5. No abstract available.
- Background: PubMed 23493783Boelens JJ, Aldenhoven M, Purtill D, Ruggeri A, Defor T, Wynn R, Wraith E, Cavazzana-Calvo M, Rovelli A, Fischer A, Tolar J, Prasad VK, Escolar M, Gluckman E, O'Meara A, Orchard PJ, Veys P, Eapen M, Kurtzberg J, Rocha V; Eurocord; Inborn Errors Working Party of European Blood and Marrow Transplant group; Duke University Blood and Marrow Transplantation Program; Centre for International Blood and Marrow Research. Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning. Blood. 2013 May 9;121(19):3981-7. doi: 10.1182/blood-2012-09-455238. Epub 2013 Mar 14.
- Background: PubMed 25708213Aldenhoven M, Jones SA, Bonney D, Borrill RE, Coussons M, Mercer J, Bierings MB, Versluys B, van Hasselt PM, Wijburg FA, van der Ploeg AT, Wynn RF, Boelens JJ. Hematopoietic cell transplantation for mucopolysaccharidosis patients is safe and effective: results after implementation of international guidelines. Biol Blood Marrow Transplant. 2015 Jun;21(6):1106-9. doi: 10.1016/j.bbmt.2015.02.011. Epub 2015 Feb 20.
- Background: PubMed 29374826Takami A. Hematopoietic stem cell transplantation for acute myeloid leukemia. Int J Hematol. 2018 May;107(5):513-518. doi: 10.1007/s12185-018-2412-8. Epub 2018 Jan 27.
- Background: PubMed 27602666Milano F, Gooley T, Wood B, Woolfrey A, Flowers ME, Doney K, Witherspoon R, Mielcarek M, Deeg JH, Sorror M, Dahlberg A, Sandmaier BM, Salit R, Petersdorf E, Appelbaum FR, Delaney C. Cord-Blood Transplantation in Patients with Minimal Residual Disease. N Engl J Med. 2016 Sep 8;375(10):944-53. doi: 10.1056/NEJMoa1602074.
- Background: PubMed 26450984Hiwarkar P, Qasim W, Ricciardelli I, Gilmour K, Quezada S, Saudemont A, Amrolia P, Veys P. Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells. Blood. 2015 Dec 24;126(26):2882-91. doi: 10.1182/blood-2015-06-654780. Epub 2015 Oct 8.
- Background: PubMed 27159172Admiraal R, Chiesa R, Lindemans CA, Nierkens S, Bierings MB, Versluijs AB, Hiwarkar P, Furtado Silva JM, Veys P, Boelens JJ. Leukemia-free survival in myeloid leukemia, but not in lymphoid leukemia, is predicted by early CD4+ reconstitution following unrelated cord blood transplantation in children: a multicenter retrospective cohort analysis. Bone Marrow Transplant. 2016 Oct;51(10):1376-1378. doi: 10.1038/bmt.2016.116. Epub 2016 May 9. No abstract available.
- Background: PubMed 22224700Chiesa R, Gilmour K, Qasim W, Adams S, Worth AJ, Zhan H, Montiel-Equihua CA, Derniame S, Cale C, Rao K, Hiwarkar P, Hough R, Saudemont A, Fahrenkrog CS, Goulden N, Amrolia PJ, Veys P. Omission of in vivo T-cell depletion promotes rapid expansion of naive CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant. Br J Haematol. 2012 Mar;156(5):656-66. doi: 10.1111/j.1365-2141.2011.08994.x. Epub 2012 Jan 9.
- Individual participant dataSharing planned: No
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Knowledge, Attitudes, Practice
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Wynn, MD FRCPath study chair
Royal Manchester Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Granulocytes in people with Pediatric Cancer, run by University of Manchester at 1 site in United Kingdom.
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 3 inclusion and 5 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 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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.
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?
What is the number of patients with grade 1-4 cytokine release syndrome, related to the granulocytes infusions? (time frame: 2 years). 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 NCT05425043, which also lists 18 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 9 Jun 2026.