SarcomaPhase 1MIGHTYNCT07751380
Multi-modular Chimeric Antigen Receptor T Cells tarGeting B7-H3 in Children, Teenage & Young Adult Sarcoma
A Phase 1 study testing Biological/Vaccine: hBRCA84D CAR T cells in people with Sarcoma, run by University College, London at 2 sites in United Kingdom.
Trial summary
MIGHTY is a multicentre, open label, phase 1 clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children, teenagers and young adults aged 1-24 with relapsed or refractory (r/r) rhabdomyosarcoma (RMS), Ewing sarcoma (ES) or desmoplastic small round cell tumour (DSRCT). Read more about this study
- Who is it for?
- Ages 1 year to 24 years
- Conditions the study is for
- Sarcoma
- What is being tested?
- Biological/Vaccine: hBRCA84D CAR T cells
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 23 Jul 2025to Jul 2042
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥ 1 and ≤ 24 years.
- Tissue diagnosis of RMS, ES or DSRCT
- Expression of B7-H3 in the tumour
- Relapsed or refractory disease after one or multiple lines of previous treatment.
- Measurable disease by cross sectional imaging. Patients with only bone marrow detectable disease (bone marrow aspirate or trephine) are NOT eligible for the study.
- At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on other early phase clinical trial.
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- Performance status: Karnofsky (age ≥ 10 years) or Lansky (age < 10) score ≥ 50%.
- 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.
- Left ventricular ejection fraction (LVEF) ≥ 50%
- Absolute lymphocyte count ≥ 0.25 x 109/L.
- 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).
- Written informed consent.
Who cannot join
- Patients with only bone marrow detectable disease in the absence of measurable disease by cross sectional imaging.
- Patients with active, inoperative central nervous system (CNS) disease including leptomeningeal disease.
- Active hepatitis B, C or HIV infection.
- Inability to tolerate leukapheresis.
- 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.
- Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine as per the local SmPC.
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- Any contraindication to the use of Anticoagulant Citrate Dextrose Solution.
- Known allergy to albumin, EDTA or DMSO.
- 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.
- Prior treatment with investigational or approved gene therapy or cell therapy products.
- Life expectancy <3 months.
- Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of hBRCA84D CAR T cells infusion.
- Women who are pregnant or breastfeeding.
- Patients who have received any live vaccine in the six weeks prior to planned lymphodepletion
- 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.
- Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of hBRCA84D CAR T cell infusion.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Karin Straathof contact
United Kingdom2 sites, 2 recruiting
- Recruiting
Great Ormond Street Hospital
London
Olga Slater
- Recruiting
University College London Hospital
London
Sandra Strauss
About this study
MIGHTY is a multicentre, open label, phase 1 clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children, teenagers and young adults aged 1-24 with relapsed or refractory (r/r) rhabdomyosarcoma (RMS), Ewing sarcoma (ES) or desmoplastic small round cell tumour (DSRCT).
The study will assess the feasibility of generating the ATIMP and administering hBRCA84D CAR T cells to patients with r/r RMS, ES or DSRCT.
Read the detailed description
MIGHTY is a multicentre, open label, phase 1 clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children, teenagers and young adults aged 1-24 with relapsed or refractory (r/r) rhabdomyosarcoma (RMS), Ewing sarcoma (ES) or desmoplastic small round cell tumour (DSRCT).
The ATIMP for this study (hBRCA84D CAR T cells) are autologous T cells targeting B7-H3 in patients with r/r RMS, ES, or DSRCT.
Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which will take approximately 15 days to generate.
Patients will receive lymphodepleting (LD) chemotherapy with fludarabine administered over 4 days (Day -6 to Day -3) and cyclophosphamide administered over 2 days (Day -4 and Day-3).
Patients will be treated at one of three dose levels following LD chemotherapy as described above.
The study will evaluate the feasibility of generating the ATIMP, the safety of administering ATIMP, the tolerability of the ATIMP and how effectively the CAR T cells engraft, expand and persist following administration in patients with r/r RMS, ES or DSRCT.
Following infusion of the CAR T cells, patients will be monitored for between 2-4 weeks as an inpatient. Following discharge, patients will enter the interventional follow up phase and be followed up for 1 year. Patients will be seen at 6 weeks post infusion then 3 monthly until 1 year post CAR T cells infusion.
If patients relapse within the first-year post CAR T cell infusion, they will come off the interventional follow up and will be followed up annually until 15 years after the CAR T infusion.
After completing the 1-year interventional phase of the study, all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until 15 years post CAR T infusion.
- Conditions
- Sarcoma
- Being tested
- Biological/Vaccine: hBRCA84D CAR T cells
- Keywords
- sarcoma, CAR T cells
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological/Vaccine: hBRCA84D CAR T cellsDrug
The hBRCA84D CAR T cells target B7-H3 positive cells.
| Study group | Role | What they receive |
|---|---|---|
| hBRCA84D CAR T cells | Experimental | Treatment with hBRCA84D CAR T cells Receives: Drug: Biological/Vaccine: hBRCA84D CAR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of administering the ATIMP
Incidence of grade 3-5 toxicity causally related to the ATIMP, particularly severe cytokine release syndrome and severe neurotoxicity.
Measured: 28 days
Number of therapeutic products generated and the number of ATIMPs infused after successful manufacture
Feasibility of generation of the ATIMP as evaluated by the number of therapeutic products generated and the number of ATIMPs infused after successful manufacture.
Measured: 28 days
Secondary outcomes (4)
Objective response rate
Based on cross-sectional imaging after the ATIMP intravenous administration
Measured: 1 year
Progression Free Survival (PFS)
Progression Free Survival (PFS) after the ATIMP intravenous administration
Measured: 1 year
Time to Progression (TTP)
Time to Progression (TTP) after the ATIMP intravenous administration
Measured: 1 year
Overall survival
Overall Survival after the ATIMP intravenous administration
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2026
- Study start23 Jul 2025
- Primary completionJul 2028 (estimated)
- Study completionJul 2042 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SarcomaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single Group Assignment
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07751380
- Sponsor's protocol ID
- UCL/150859
- Acronym
- MIGHTY
- Status last verified
- Aug 2026
- First submitted
- 3 Aug 2026
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No