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NCT Number: NCT07372885

GRanulocyte Augmented Cord Blood Transplantation for Poor Risk leukaEmia

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.

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Key information

Conditions

Acute Myeloid Leukemia Bone Marrow Diseases Cellular Therapy Cord Blood Stem Cell Transplantation Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Neoplasms Neoplasms by Histologic Type Stem Cell Transplantation Stem Cell Transplantation, Hematopoietic

Age range

16 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Kings College Hospital NHS Trust, London, United Kingdom

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Availability of a suitable cord blood unit
  • Age between 16 and 55 years
  • 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))
  • 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)
  • 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
  • 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

  • AML Secondary to a myeloproliferative neoplasm
  • Active CNS disease
  • Prior allogeneic stem cell transplant
  • 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)
  • History of cardiac arrhythmia
  • Ischaemic heart disease, valvular heart disease or congestive cardiac failure
  • Transient ischaemic attack or cerebrovascular accident
  • Rheumatologic disease (SLE, RA, polymyositis, mixed CTD or polymyalgia rheumatica)
  • Ulcerative colitis or Crohn's disease
  • Liver cirrhosis
  • Presence of an active second malignancy
  • Uncontrolled infection, including viral reactivation (CMV, EBV)
  • HIV positive
  • 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)
  • Pregnancy, breastfeeding, unwilling to use contraception
  • Contraindications to administration of pooled granulocytes
  • Previous history of sensitivity to granulocytes
  • Inability of patient to give informed consent
  • Any other organ dysfunction or co-morbidity that precludes transplant in the opinion of the investigator
  • Any concern by PI

Treatment and study plan

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

Biological

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.

Primary outcomes

  1. Frequency and Severity of Cytokine Release Syndrome (CRS)

    Time frame: Day 0 (day of allograft) to Day 28 post allograft

    Frequency and Severity of Cytokine Release Syndrome (CRS) assessed via ASTCT Consensus Grading for CRS

  2. Frequency and Severity of Acute Graft vs Host Disease

    Time frame: Day 0 (day of allograft) to Day 100 post allograft

    Frequency and Severity of Acute Graft vs Host Disease assessed by modified Glucksberg criteria (revised by MAGIC)

  3. Frequency and Severity of Chronic Graft vs Host Disease

    Time frame: Day 100 post allograft to Day 360 post allograft

    Frequency and Severity of Chronic Graft vs Host Disease assessed by NIH criteria

  4. Frequency of Transplant Related Mortality (TRM)

    Time frame: Day 0 (day of allograft) to Day 100 post allograft

    Frequency of Transplant Related Mortality (TRM) defined as death due to any transplantation-related cause other than disease relapse

  5. Frequency of Primary Graft Failure

    Time frame: Day 0 (day of allograft) to Day 28 post allograft

    Frequency of Primary Graft Failure

  6. Rate of Relapse-Free Survival (RFS)

    Time frame: Day 0 (day of allograft) to Day 360 post allograft

    Relapse-free survival (RFS) rate: number of patients who remain relapse-free and alive within 1 year from transplant

Secondary outcomes

  1. Frequency of Non-Relapse Mortality (NRM)

    Time frame: Day 0 (day of allograft) to Day 360 post allograft

    Non-relapse mortality (NRM): number of patients who die from aetiology not related to disease relapse.

  2. Duration of Overall Survival

    Time frame: Day 0 (day of allograft) to Day 360 post allograft

    Overall survival: time from Day 0 to date of death from any cause. Patients who are alive will be censored at the date of last follow-up.

  3. Duration of GvHD Free Relapse Free Survival (GRFS)

    Time frame: Day 0 (day of allograft) to Day 360 post allograft

    GvHD-free, relapse-free survival (GRFS): time from day to the first occurrence of any of the following events: acute grade III-IV and/or chronic GvHD requiring systemic immune suppressive treatment, disease relapse or progression, or death from any cause. Patients who are alive and free of any of these event will be censored at the date of last follow-up.

Study contacts

Contact information is provided by the study sponsor or research team.

Johnna Ward GRACE Trial Manager

CONTACT

[email protected]

02032999000

Sponsors and collaborators

Lead sponsor

University of Manchester

Other

Collaborators

  • Institute of Cancer Research, United Kingdom
  • King's College Hospital NHS Trust
  • Royal Marsden NHS Foundation Trust
  • The Christie NHS Foundation Trust

Registry information

Official study title

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

Acronym: GRACE

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Jan 28, 2026
Registry last updated
Mar 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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