Using modified T cells to treat relapsed T-cell leukaemia in children

Phase 1 Study of Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7)

This study is testing a new cell therapy for children with relapsed T-cell leukaemia to see if it can safely help them fight the cancer before they get 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: NCT05397184 on ClinicalTrials.gov

What this trial studies

This phase I clinical trial aims to treat children aged 6 months to 16 years with relapsed or refractory T-cell acute lymphoid leukaemia using a novel cell therapy approach. The therapy involves the infusion of 'ready-made' CAR T cells, which are genetically modified using CRISPR base editing to enhance their ability to target and kill leukaemia cells while minimizing damage to normal cells. Prior to the infusion, patients will receive chemotherapy to improve the effectiveness of the CAR T cells. The primary goal is to assess the safety of this treatment and its potential to eradicate leukaemia before a planned bone marrow transplant.

Who should consider this trial

Good fit: Ideal candidates are children aged 6 months to 16 years with relapsed or refractory T-cell leukaemia who are eligible for a bone marrow transplant.

Not a fit: Patients who do not have a suitable donor for transplantation or those with other significant health issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve remission rates and outcomes for children with T-cell leukaemia prior to transplantation.

How similar studies have performed: Other studies using CAR T cell therapies have shown promising results, indicating potential for success with this novel approach.

Eligibility criteria

Demographic characteristics:

1. Male or female patients
2. Age ranging between 6 months and \<16 years

Medical and therapeutic criteria:

1. Relapsed/refractory T cell malignancy ahead of planned allogeneic haematopoietic stem cell transplantation (allo-SCT). Morphologically confirmed with leukemic blasts in the bone marrow (\>5%) or a quantifiable MRD load (by multiparameter flow cytometry and/or quantitative polymerase chain reaction)
2. CD7+ (\>99%) 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) or Karnofsky (age ≥16 years at the time of assent/consent) performance status ≥70; 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 kg
7. Presence of donor-specific anti-HLA antibodies directed against BE-CAR7
8. GvHD requiring systemic therapy
9. Systemic steroid therapy prednisolone \>0.5 mg/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 antifungal 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 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

• Ilyas Ali — London, United Kingdom (Recruiting)

Study contacts

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

Conditions Relapsed/Refractory T-cell Acute Lymphoid Leukaemia