MIGHTY: CAR T cells targeting B7-H3 for pediatric, teen, and young adult sarcoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

MIGHTY is a multicenter, open-label Phase 1 study evaluating autologous hBRCA84D CAR T cells directed against B7-H3 in patients aged 1–24 with relapsed or refractory RMS, ES, or DSRCT. Participants undergo leukapheresis to collect T cells, followed by a 15-day cell manufacturing period and a lymphodepleting chemotherapy regimen. Patients receive the CAR T cells at one of three dose levels and are closely monitored for safety, feasibility of manufacturing, engraftment, expansion, and persistence, with inpatient observation for 2–4 weeks and 1 year of follow-up. The trial aims to determine feasibility, safety, and tolerability of the ATIMP, along with CAR T cell behavior after infusion.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Age ≥ 1 and ≤ 24 years.
2. Tissue diagnosis of RMS, ES or DSRCT
3. Expression of B7-H3 in the tumour
4. Relapsed or refractory disease after one or multiple lines of previous treatment.
5. Measurable disease by cross sectional imaging. Patients with only bone marrow detectable disease (bone marrow aspirate or trephine) are NOT eligible for the study.
6. At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on other early phase clinical trial.
7. Performance status: Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≥ 50%.
8. Creatinine ≤1.5 x Upper Limit of Normal (ULN) for age, if higher, an estimated (calculated) creatinine clearance must be ≥ 60 ml/min/1.73 m2.
9. Left ventricular ejection fraction (LVEF) ≥ 50%
10. Absolute lymphocyte count ≥ 0.25 x 109/L.
11. Women of childbearing potential (WOCBP) must have a negative pregnancy test and agree to comply with the pregnancy reporting requirements of the protocol (if applicable).
12. Written informed consent.

Exclusion Criteria:

1. Patients with only bone marrow detectable disease in the absence of measurable disease by cross sectional imaging.
2. Patients with active, inoperative central nervous system (CNS) disease including leptomeningeal disease.
3. Active hepatitis B, C or HIV infection.
4. Inability to tolerate leukapheresis.
5. Clinically significant systemic illness or medical condition (e.g., significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.
6. Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine as per the local SmPC.
7. Any contraindication to the use of Anticoagulant Citrate Dextrose Solution.
8. Known allergy to albumin, EDTA or DMSO.
9. Primary immunodeficiency or history of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression /systemic disease modifying agents within the last 2 years.
10. Prior treatment with investigational or approved gene therapy or cell therapy products.
11. Life expectancy \<3 months.
12. Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of hBRCA84D CAR T cells infusion.
13. Women who are pregnant or breastfeeding.
14. Patients who have received any live vaccine in the six weeks prior to planned lymphodepletion

Exclusion criteria for the ATIMP infusion:

1. Uncontrolled fungal, bacterial, viral, or other infection. Previously diagnosed infection for which the patient continues to receive antimicrobial therapy is permitted if responding to treatment and clinically stable at the time of scheduled hBRCA84D CAR T cell infusion.
2. Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of hBRCA84D CAR T cell infusion.

Where it's running

• Great Ormond Street Hospital
  London, United Kingdom Recruiting
• University College London Hospital
  London, United Kingdom Recruiting

Study contacts

• Study coordinator: MIGHTY Trial Coordinator
• Email: ctc.mighty@ucl.ac.uk
• Phone: +4420 7679 9852

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.