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

NCT05942599 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 18IC13
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

In this phase 1 clinical trial, the investigators are testing an experimental medicine in children aged 6 months up to 16 years with acute myeloid leukaemia (AML), which has come back (relapsed). The new product is made from white blood cells (T cells) collected from a healthy donor and changed so they can kill leukaemia cells. These 'ready-made' CAR T cells have been made using a new technique called Base Editing to modify their DNA code and have been given the code name 'BE CAR-33'. This technique allows them to work after chemotherapy and also disarms them to prevent effects against normal cells. The main purpose of this study is to assess the safety of the 'BE CAR-33' therapy and to see if ready-made CAR T cells can get rid of Acute Myeloid Leukaemia ahead of a planned bone marrow transplant that will hopefully prevent the leukaemia from returning.

Conditions

Relapsed Acute Myeloid Leukaemia

Outcome Measures

Primary Outcomes (1)

• Frequency and description of adverse events after BE-CAR33 Infusion

  Incidence of grade 3-5 toxicities occurring from infusion up to one year follow-up. Severe Adverse reactions of special interest will be CRS, ICANS, GvHD and VOD. American Society of Bone Marrow transplantation grading scales for CRS/ICANS, National institute of health criteria for GvHD and EBMT criteria for VOD will be applied. Common terminology criteria for adverse event (CTCAE) nomenclature will be used to grade other adverse events.

  1 Year

Secondary Outcomes (1)

• Number of patients achieving disease remission ahead of allo-SCT

  28 Days

Study Arms (1)

Single dose intravenous infusion of a banded dose of CAR33+ T Cells/Kg BECAR33

EXPERIMENTAL

Patients will undergo careful screening to confirm that this treatment is appropriate for them. Patients will receive BE CAR-33 before their scheduled bone marrow transplant. Chemotherapy will be given prior to BE CAR-33 infusion to improve the ability of CAR T-cells to establish and grow. Patients will then receive a single infusion of the BE CAR-33 cells and will be closely monitored in hospital for the next 4 weeks. Patient will start chemotherapy for their scheduled bone marrow transplant 28 days after BE-CAR33 infusion unless their disease is progressing. Patients will be monitored on the study for 1 year after transplant and then long term in routine clinics.

Biological: Cryopreserved BE CAR33 T Cells (BE752TBTTBCAR33PBL)

Interventions

Cryopreserved BE CAR33 T Cells (BE752TBTTBCAR33PBL) BIOLOGICAL

Single-dose intravenous infusion (weight-based dosing) of a banded dose of CAR33+ T cells/kg. BECAR33 Total duration of treatment: 28 days follow up: 12 months

Also known as: BECAR33

Single dose intravenous infusion of a banded dose of CAR33+ T Cells/Kg BECAR33

Eligibility Criteria

• Age: 6 Months - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Wellcome Trust: collaborator
• Great Ormond Street Hospital for Children NHS Foundation Trust: lead

Study Sites (1)

Great Ormond Street Hospital for Children

London, WC1N3JH, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Waseem Qasim, Prof

  Great Ormond Street Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1, open label, non-randomised

Study Record Dates

• First Submitted: July 4, 2023
• First Posted: July 12, 2023
• Study Start: July 21, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)