GRanulocyte Augmented Cord Blood Transplantation for Poor Risk leukaEmia

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.

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.

Sponsors & Collaborators

• King's College Hospital NHS Trust

  collaborator OTHER

• Institute of Cancer Research, United Kingdom

  collaborator OTHER

• The Christie NHS Foundation Trust

  collaborator OTHER

• Royal Marsden NHS Foundation Trust

  collaborator OTHER

• University of Manchester

  lead OTHER

Principal Investigators

• Mark Williams, BA MB BChir PhD MRCP FRCPath · University of Manchester

• Mili N Shah, BSc MBBS MRCP FRCPath · Kings College Hospital NHS Trust

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

16 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-09

Primary Completion

2028-12-31

Completion

2029-12-31

Countries

• United Kingdom

Study Locations