Base edited CAR T cells for treating relapsed acute myeloid leukaemia in children

Phase 1 Study of Base Edited CAR T Cells Against AML: Deep Conditioning Ahead of Allogeneic Stem Cell Transplantation

This study is testing a new type of CAR T cell therapy to see if it can help children with relapsed acute myeloid leukaemia feel better and improve their chances of remission before a bone marrow transplant.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 6 Months to 16 Years
• Sex: All
• Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust (Academic / other)
• Drugs / interventions: CAR T, chemotherapy
• Locations: 1 site (London)
• Trial ID: NCT05942599 on ClinicalTrials.gov

What this trial studies

This phase 1 clinical trial is investigating the safety and efficacy of a novel therapy using base edited CAR T cells, known as BE CAR-33, in children aged 6 months to 16 years with relapsed acute myeloid leukaemia (AML). The study involves administering chemotherapy prior to the infusion of these engineered T cells, which are designed to target and eliminate leukaemia cells while minimizing damage to normal cells. Participants will be closely monitored for safety and treatment response through blood and bone marrow tests, with a planned follow-up period extending to 15 years. The ultimate goal is to improve remission rates before a scheduled bone marrow transplant.

Who should consider this trial

Good fit: Ideal candidates are children aged 6 months to 16 years with relapsed acute myeloid leukaemia who are eligible for a planned bone marrow transplant.

Not a fit: Patients with evidence of disease progression after cytoreduction or those with uncontrollable CNS leukaemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly enhance the chances of remission and successful transplantation for children with relapsed AML.

How similar studies have performed: While the use of CAR T cells has shown promise in other studies, this specific approach using base editing is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Male or female patients
* Age ranging between 6 months and \<16 years

Medical and therapeutic criteria

* Relapsed AML ahead of scheduled allogeneic haematopoietic stem cell transplantation (allo-SCT).
* Morphologically confirmed with leukemic blasts in the bone marrow (\>5%) or a quantifiable MRD by multiparameter flow cytometry and/or quantitative polymerase chain reaction (\>10-4)
* CD33+ leukaemia associated immunophenotype (LAIP) on \>95% of blasts
* Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available
* Estimated life expectancy ≥ 12 weeks
* Lansky (age \< 16 years at the time of assent/consent) or performance status ≥ 70;
* Eastern Cooperative Oncology Group ECOG performance status \< 2.

Exclusion Criteria:

* Patients/parents unwilling to undergo follow-up for 15 years
* Foreseeable poor compliance to the study procedures
* Evidence of disease progression after cytoreduction
* Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per
* National Comprehensive Cancer Network guidelines)
* Absence of suitable HLA matched or mismatched donor
* Weight \< 6kgs
* Presence of donor-specific anti-HLA antibodies directed against BE-CAR33
* GvHD requiring systemic therapy
* Systemic steroid therapy prednisolone \>0.5mg/kg/day
* Known hypersensitivity to test materials or related compounds
* Active bacterial, fungal or viral infections not controlled by standard of care anti- microbial or anti-viral treatment. Uncontrolled bacteraemia/ fungaemia is defined as the ongoing detection of bacteria/fungus on blood cultures despite antibiotic or anti-fungal therapy. Uncontrolled viraemia is defined as rising viral loads on two consecutive occasions despite antiviral therapy.
* Risk of pregnancy or non-compliance with contraception (if applicable). Girls of childbearing potential must have been tested negative in a pregnancy test within 14 days prior to inclusion.
* Lactating female participants unwilling to stop breastfeeding
* Prior CAR T cell therapy known to be associated with ≥Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug-related CNS toxicity

Where this trial is running

London

• Great Ormond Street Hospital for Children — London, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Waseem Qasim, Prof — Great Ormond Street Hospital
• Study coordinator: Robert Chiesa, Dr

Conditions Relapsed Acute Myeloid Leukaemia