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NCT07372885

PHASE1/PHASE2

GRanulocyte Augmented Cord Blood Transplantation for Poor Risk leukaEmia

Sponsor: University of Manchester

View on ClinicalTrials.gov

Summary

Allogeneic stem cell transplantation is the only potentially curative therapy for patients with high-risk Acute Myeloid Leukaemia, but relapse is common and remains the leading cause of death. Patients with certain mutations and those transplanted without first clearing their disease have very poor outcomes with most relapsing soon after transplant, and then surviving only a few months. A recent trial at the Royal Manchester Children's Hospital used cord blood stem cells alongside a type of white blood cell called 'granulocytes' and produced surprisingly good outcomes for children with very resistant leukaemia. GRACE is a clinical trial for adults (\<55 years) with Acute Myeloid Leukaemia that has not responded to chemotherapy or harbours mutations that predict a very poor response to conventional transplant. Participants will receive a transplant using umbilical cord blood and be given additional infusions of white blood cells, called granulocytes. The trial will be split into two parts:-The first will study the safety of this new approach. The experience of the investigators in children is that granulocyte infusions cause a fever, rash and expansion of another type of white blood cell called lymphocytes. Children that did not have this reaction did not respond to treatment. The investigators therefore believe that the reaction is necessary for the treatment to work, but the investigators must ensure that it is safe in adult patients. The trial design allows the investigators to determine the dose of granulocytes that is best tolerated and most likely to be effective. The aim of the second part is to demonstrate that the new treatment is more effective than conventional transplantation. The study will be conducted in three NHS transplant centres. Patients will be recruited over 36 months and followed up for a minimum of 1 year. The study is funded by Blood Cancer UK.

Official title: A Multi-centre Phase I/II Trial of Granulocyte-augmented Cord Blood Transplantation for Young Adults With Very Poor Risk Acute Myeloid Leukaemia.

Key Details

Gender

All

Age Range

16 Years - 55 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-02-09

Completion Date

2029-12-31

Last Updated

2026-03-11

Healthy Volunteers

Conditions

Acute Myeloid Leukemia Stem Cell Transplantation Stem Cell Transplantation, Hematopoietic Cord Blood Stem Cell Transplantation Cellular Therapy

Interventions

BIOLOGICAL

Cord blood transplantation + conditioning + granulocytes of variable days according to study design

All participants will receive a T replete cord blood transplant with a standardised conditioning regimen involving Fludarabine, Cyclophosphamide, Thiotepa, and TBI. A single pool of irradiated granulocytes will be given daily to all participants- but for a variable number of days starting on the day of transplant according to study design (1,3,5 or 7 days). The study consists of two phases- Phase 1 has two components (dose escalation and dose optimisation) to identify the Recommended Phase II Dose (RP2D) of granulocytes. Phase 2 will assess preliminary efficacy based Relapse Free Survival at 1 year.

INCLUSION CRITERIA: 1. Availability of a suitable cord blood unit 2. Age between 16 and 55 years 3. Primary diagnosis of Acute Myeloid Leukaemia (AML) or MDS/AML (as defined by ICC 2022) fitting one or more of the following criteria: * TP53 mutation (single- or multi-hit) * Presence of inv(3) (q21.3q26.2) or t(3;3)(q21.3;q26.2) * Adverse risk (as per ICC 2022) and \>0.1% MRD by flow cytometry after 2 cycles of induction * AML (any risk) with partial remission (\<10% blasts) after 2 cycles induction * Early relapse (\<6 months) after chemotherapy alone (excluding t(16;16), inv(16) or t(8;21)) 4. Bone marrow performed within 28 days of starting conditioning chemotherapy demonstrates either: * \<10% blasts * \>10% blasts with a hypocellular background (must be discussed with the trial team) 5. Suitable fitness and organ function as per the following criteria: * Glomerular filtration rate \>50 mL/min/1.73m2 * Ejection fraction \>50% * FEV1 \>65% without dyspnoea on mild activity * AST/ALT \<3 x ULN * Bilirubin \<1.5 x ULN (excluding Gilbert's syndrome) * Performance Status (ECOG) of 0 or 1 6. Females of and male patients of reproductive potential (i.e., not post-menopausal or surgically sterilised) must agree to use appropriate, highly effective, contraception from the point of commencing therapy until 12 months after transplant EXCLUSION CRITERIA: 1. AML Secondary to a myeloproliferative neoplasm 2. Active CNS disease 3. Prior allogeneic stem cell transplant 4. Participation in another clinical trial that would alter any aspect of the transplant protocol or that aims to reduce the subsequent risk of relapse (discuss with trial team if unsure) 5. History of cardiac arrhythmia 6. Ischaemic heart disease, valvular heart disease or congestive cardiac failure 7. Transient ischaemic attack or cerebrovascular accident 8. Rheumatologic disease (SLE, RA, polymyositis, mixed CTD or polymyalgia rheumatica) 9. Ulcerative colitis or Crohn's disease 10. Liver cirrhosis 11. Presence of an active second malignancy 12. Uncontrolled infection, including viral reactivation (CMV, EBV) 13. HIV positive 14. Hepatitis B/C active infection with measurable viral load (patients with chronic hepatitis B or C infection require clear documentation of absence of cirrhosis by either fibroscan or biopsy, regardless of viral load) 15. Pregnancy, breastfeeding, unwilling to use contraception 16. Contraindications to administration of pooled granulocytes 17. Previous history of sensitivity to granulocytes 18. Inability of patient to give informed consent 19. Any other organ dysfunction or co-morbidity that precludes transplant in the opinion of the investigator 20. Any concern by PI

Locations (3)

Kings College Hospital NHS Trust

London, United Kingdom

The Royal Marsden Hospital NHS Foundation Trust