Granulocyte Transfusions After Umbilical Cord Blood Transplant

NCT05425043 | Recruiting DMC

• 1 other identifier: 295998
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pediatric Cancer

Keywords

Granulocytes; HSCT; Haematopoietic Stem Cell Transplant; Pediatric; Leukemia

Outcome Measures

Primary Outcomes (2)

• 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.

  2 years

• What is the number of patients with allo-immunisation after the granulocyte infusions?

  This is to access safety of the granulocyte infusions.

  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?

  2 years

• How many patients experience grade II-IV GvHD?

  2 years

• What is the median disease-free and overall survival in this patient cohort?

  2 years

• How many patients enter flow and molecular remission after the transplant?

  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?

  2 years

Study Arms (2)

Granulocytes

EXPERIMENTAL

Patient to receive pooled granulocytes for 7 days concurrently. 20 participants will be approached for this arm.

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.

Interventions

Granulocytes BIOLOGICAL

Receive granulocytes for 7 consecutive days after engraftment post transplant

Granulocytes

Eligibility Criteria

• Age: Up to 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Manchester: lead
• Children's Cancer and Leukaemia Group: collaborator

Study Sites (1)

Royal Manchester Childrens Hospital, MFT

Manchester, M13 9WL, United Kingdom

RECRUITING

Related Publications (18)

• 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.

  PMID: 32196555 BACKGROUND

• Deambrosis 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.

  PMID: 30787020 BACKGROUND

• Lum 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.

  PMID: 28218755 BACKGROUND

• Eapen 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.

  PMID: 28623181 BACKGROUND

• Veys 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.

  PMID: 26728432 BACKGROUND

• Boelens 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.

  PMID: 23493783 BACKGROUND

• Aldenhoven 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.

  PMID: 25708213 BACKGROUND

• Takami 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.

  PMID: 29374826 BACKGROUND

• Milano 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.

  PMID: 27602666 BACKGROUND

• Hiwarkar 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.

  PMID: 26450984 BACKGROUND

• Admiraal 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.

  PMID: 27159172 BACKGROUND

• Chiesa 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.

  PMID: 22224700 BACKGROUND

• Politikos 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.

  PMID: 31935291 BACKGROUND

• Estcourt 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.

  PMID: 27128488 BACKGROUND

• Massey 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.

  PMID: 22591484 BACKGROUND

• Hiwarkar P, Adams S, Gilmour K, Nataraj R, Bonney D, Poulton K, Wynn R. Cord blood CD8+ T-cell expansion following granulocyte transfusions eradicates refractory leukemia. Blood Adv. 2020 Sep 8;4(17):4165-4174. doi: 10.1182/bloodadvances.2020001737.

  PMID: 32886752 BACKGROUND

• Bashir S, Stanworth S, Massey E, Goddard F, Cardigan R. Neutrophil function is preserved in a pooled granulocyte component prepared from whole blood donations. Br J Haematol. 2008 Mar;140(6):701-11. doi: 10.1111/j.1365-2141.2008.06996.x.

  PMID: 18302716 BACKGROUND

• Borrill R, Poulton K, Kusyk L, Routledge A, Bonney D, Hanasoge-Nataraj R, Powys M, Mustafa O, Campbell H, Senthil S, Dillon R, Jovanovic J, Morton S, James B, Rao K, Stanworth S, Konkel J, Wynn R. Granulocyte transfusion during cord blood transplant for relapsed, refractory AML is associated with massive CD8+ T-cell expansion, significant cytokine release syndrome and induction of disease remission. Br J Haematol. 2023 Aug;202(3):589-598. doi: 10.1111/bjh.18863. Epub 2023 May 21.

  PMID: 37211883 DERIVED

MeSH Terms

Conditions

Neoplasms; Leukemia

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Robert Wynn, MD FRCPath

  Royal Manchester Children's Hospital

  STUDY CHAIR

Central Study Contacts

Robert Wynn, MD FRCPath

CONTACT

01617018417; robert.wynn@mft.nhs.uk

Roisin Borrill, MRCPCH

CONTACT

01617018417; roisin.borrill@mft.nhs.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: June 21, 2022
• Study Start: September 14, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 2, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)