Medical condition: Rhabdomyosarcoma (RMS), Ewing sarcoma (ES) and Desmoplastic small round cell tumour (DSRCT). Medical condition in lay language: Sarcoma Therapeutic areas: Diseases [C] - Cancer [C04] Cancer
Conditions
Interventions
All trial patients undergo the following:
1. Leukapheresis: following registration, patients will undergo an unstimulated leukapheresis which will be sent to The ‘Centre for Cell, Gene & Tissue Ther
Sponsors
Cancer Research UK & UCL Cancer Trials Centre
Eligibility
Sex/Gender
All
Age
1 Years to 24 Years
Inclusion criteria
Inclusion criteria: 1. Age = 1 and = 24 years 2. Tissue diagnosis of Rhabdomyosarcoma, Ewing sarcoma or Desmoplastic small round cell tumour 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 phases clinical trial 7. Performance status: Karnofsky (age = 10 years) or Lansky (age < 10) score = 50%. Patients who are unable to walk because of paralysis, but who can sit upright unassisted in a wheelchair, will be considered ambulatory to assess performance score 8. Creatinine =1.5 ULN for age, if higher, an estimated (calculated) creatinine clearance must be = 60 ml/min/1.73 m2 9. Left ventricular ejection fraction =50% 10. Absolute lymphocyte count = 0.25 x 109/L 11. Women of childbearing potential 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
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 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 the assessment of safety or efficacy of the investigational regimen and its requirements 6. Any contraindication to lymphodepletion or 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 the time of hBRCA84D CAR T cell infusion 13. Women who are pregnant or breastfeeding Exclusion criteria for hBRCA84D CAR T cell 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 the time of hBRCA84D CAR T cell infusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety: toxicity of hBRCA84D CAR T cells as assessed by the incidence of grade 3-5 toxicity causally related to the ATIMP (particularly severe cytokine release syndrome and severe neurotoxicity) occurring within 28 days of hBRCA84D CAR T cell infusion 2. Feasibility of generation of the ATIMP as evaluated by the number of therapeutic products generated and the number of ATIMPs infused after successful manufacture | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Objective response rate based on cross-sectional imaging after intravenous (iv) administration of hBRCA84D CAR T cells from any time point following CAR T infusion 2. Clinical outcomes including Progression Free Survival (PFS) and Time to Progression (TTP) after iv administration of hBRCA84D CAR T cells (PFS – time from CAR T infusion to progression or death, TTP – time from first response (=MR) until progression) 3. Overall survival after iv administration of hBRCA84D CAR T cells (time from CAR T infusion to death by any cause) | — |
Countries
England, United Kingdom
Outcome results
None listed