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Acute Myeloid LeukemiaPhase 1/2GRACENCT07372885

GRanulocyte Augmented Cord Blood Transplantation for Poor Risk leukaEmia

A Phase 1/2 study testing Cord blood transplantation + conditioning + granulocytes of variable days according to study design in people with Acute Myeloid Leukemia and Stem Cell Transplantation, run by University of Manchester at 3 sites in United Kingdom.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 16 to 55 years
What is being tested?
Cord blood transplantation + conditioning + granulocytes of variable days according to study design
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
3 sitesUnited Kingdom
Study dates
9 Feb 2026to 31 Dec 2029
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 16 to 55 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Johnna Ward GRACE Trial Manager contact

02032999000

kch-tr.gracestudy@nhs.net

United Kingdom3 sites

  • Kings College Hospital NHS Trust

    London

    Johnna Ward Trial Manager/Research Nurse, +44 (0) 20 3299 9000, kch-tr.gracestudy@nhs.net

    Mili N Shah, BSc MBBS MRCP FRCPath

  • The Royal Marsden Hospital NHS Foundation Trust

    London

    Francesca Temple-Brown Senior Trials Manager- Transplant, 0044 20 3186 5004, francesca.temple-brown@rmh.nhs.uk

    Chloe Anthias

  • The Christie NHS Foundation Trust

    Manchester

    Jake Healey Senior Trial Coordinator, jake.healey@nhs.net

    John Chadwick, MBBS, MRes, PhD

Other trials in United Kingdom

About this study

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.

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.

Read more

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.

Being tested
Cord blood transplantation + conditioning + granulocytes of variable days according to study design
Keywords
Grace, granulocyte-augmented cord blood transplantation, poor risk acute myeloid leukaemia, Cord Blood Transplantation, Myelodysplastic Syndrome, TP53, MECOM
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

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

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

    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.

Study groups in NCT07372885
Study groupRoleWhat they receive
Phase I: T replete cord blood transplant + conditioning + 1 day GranulocytesActive comparatorAll 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 to participants for 1 day starting on the day of transplant.
Receives: Biological: Cord blood transplantation + conditioning + granulocytes of variable days according to study design
Phase I: T replete cord blood transplant + conditioning + 3 day GranulocytesActive comparatorAll 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 participants for 3 days starting on the day of transplant.
Receives: Biological: Cord blood transplantation + conditioning + granulocytes of variable days according to study design
Active Comparator: Phase I: T replete cord blood transplant + conditioning + 5 day GranulocytesActive comparatorAll 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 participants for 5 days starting on the day of transplant.
Receives: Biological: Cord blood transplantation + conditioning + granulocytes of variable days according to study design
Active Comparator: Phase I: T replete cord blood transplant + conditioning + 7 day GranulocytesActive comparatorAll 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 participants for 7 days starting on the day of transplant.
Receives: Biological: Cord blood transplantation + conditioning + granulocytes of variable days according to study design
Phase II: T replete cord blood transplant + conditioning + Granulocytes at Recommended Phase II DoseExperimentalAll 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- at the Recommended Phase II Dose (RP2D)
Receives: Biological: Cord blood transplantation + conditioning + granulocytes of variable days according to study design

What is being measured

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

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

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

    Measured: Day 0 (day of allograft) to Day 28 post allograft

  2. Frequency and Severity of Acute Graft vs Host Disease

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

    Measured: Day 0 (day of allograft) to Day 100 post allograft

  3. Frequency and Severity of Chronic Graft vs Host Disease

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

    Measured: Day 100 post allograft to Day 360 post allograft

  4. Frequency of Transplant Related Mortality (TRM)

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

    Measured: Day 0 (day of allograft) to Day 100 post allograft

  5. Frequency of Primary Graft Failure

    Frequency of Primary Graft Failure

    Measured: Day 0 (day of allograft) to Day 28 post allograft

  6. Rate of Relapse-Free Survival (RFS)

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

    Measured: Day 0 (day of allograft) to Day 360 post allograft

Secondary outcomes (3)

  1. Frequency of Non-Relapse Mortality (NRM)

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

    Measured: Day 0 (day of allograft) to Day 360 post allograft

  2. Duration of Overall Survival

    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.

    Measured: Day 0 (day of allograft) to Day 360 post allograft

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

    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.

    Measured: Day 0 (day of allograft) to Day 360 post allograft

Timeline

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

  1. First posted28 Jan 2026
  2. Study start9 Feb 2026 (estimated)
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2029 (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
Randomised
Intervention model
Sequential
Model description
This trial utilises an innovative early phase seamless design, integrating dose-escalation and randomised dose-optimisation which is built on latest FDA and MDICT guidance. Phase I (up to 30 patients) will include two components: dose-escalation and dose-optimisation to identify the Recommended Phase II Dose (RP2D). In the dose-escalation component, a modified 2-stage Bayesian Time-to-event Continual Reassessment Method (TITE-CRM) will be used to determine the maximum tolerated dose and tolerable doses among 4 dose schedules. In the dose optimisation, subsequent patients will be randomised to selected tolerable doses to determine final RP2D based on tolerability, activity and other key secondary endpoints in consultation with the integrated TSC/DMC. Phase II will assess preliminary efficacy at the RP2D, based on relapse free survival at 1 year using a single-stage Bayesian design.
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07372885
Sponsor's protocol ID
357519
Acronym
GRACE
Status last verified
Jan 2026
First submitted
20 Nov 2025
Last updated
11 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cord blood transplantation + conditioning + granulocytes of variable days according to study design in people with Acute Myeloid Leukemia and Stem Cell Transplantation, run by University of Manchester at 3 sites 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 19 inclusion and 20 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: opening soon, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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.

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?

Contact Johnna Ward GRACE Trial Manager (02032999000, kch-tr.gracestudy@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency and Severity of Cytokine Release Syndrome (CRS) (time frame: Day 0 (day of allograft) to Day 28 post allograft). The study lists 6 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 NCT07372885.

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 11 Mar 2026.

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