CAR T cells to fight acute myeloid leukaemia

Phase 1

• Conditions: Haematological Disorders; Paediatric relapsed CAR33+ acute myeloid leukaemia

• Registration Number: ISRCTN14430213
• Lead Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-12-01
• Last Update Posted: 22 January 2024
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Demographic characteristics:
1. Male or female patients
2. Age ranging between 6 months and <16 years old

Medical and therapeutic criteria:
1. Relapsed AML ahead of planned allogeneic haematopoietic stem cell transplantation (allo-SCT). Morphologically confirmed with leukemic blasts in the bone marrow (>5%) or a quantifiable minimal residual disease (MRD) load (by multiparameter flow cytometry and/or quantitative polymerase chain reaction)
2. CD33+ (>95%) blast leukaemia associated immunophenotype (LAIP)
3. Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available
4. Estimated life expectancy = 12 weeks
5. Lansky (age < 16 years at the time of assent/consent) and Eastern Cooperative Oncology Group ECOG performance status < 2

Exclusion Criteria

1. Patients/parents unwilling to undergo a follow-up for 15 years
2. Foreseeable poor compliance to the study procedures
3. Evidence of disease progression after cytoreduction
4. Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer Network guidelines
5. Absence of suitable HLA matched or mismatched donor
6. Weight <6 kgs
7. Presence of donor-specific anti-HLA antibodies directed against BE-CAR33
8. GvHD requiring systemic therapy
9. Systemic steroid therapy prednisolone >0.5mg/kg/day
10. Known hypersensitivity to any of the test materials or related compounds
11. Active bacterial, fungal or viral infection 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.
12. 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.
13. Lactating female participants unwilling to stop breastfeeding
14. Prior CAR T cell therapy known to be associated with =Grade 3 cytokine release syndrome (CRS) or =Grade 3 drug-related CNS toxicity

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Safety monitored at baseline, lymphodepletion, D0 (investigational medicinal product infusion day), D7, D17, D21, D28 post-infusion, at GD-1 (one day before bone marrow transplant (BMT) and additional points in following months: M1, M2, M3, M6 and M12 post-BMT will include:<br>1. Clinical examination and vital signs <br>2. Standard blood parameters<br>3. Oxygen saturation & cardiac assessment<br>4. Cytokines <br>5. Infections<br>National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) will be used to grade events. Specialized grading scales for cytokine release syndrome and graft versus host disease will be applied

Secondary Outcome Measures

Name	Time	Method
Ability of BE-CAR33 to achieve myeloablation and disease remission ahead of allogeneic stem cell transplantation (Allo-SCT). Disease response assessed between D21-D28 will include:<br>Bone marrow examination for disease levels measured using flow cytometry and/or molecular minimal residual disease tests