Eligibility Criteria for Leukapheresis/Venepuncture
1. Written informed consent* for leukapheresis/venepuncture and transduction of T-cells.
2. Suitability for leukapheresis/venepuncture defined as:
Negative for human immunodeficiency virus (HIV), human T-cell lymphotropic virus
(HTLV) 1, HTLV 2, syphilis and hepatitis B
Minimum T-lymphocyte count of 0.25x10^9/L
3. Relapsed or refractory neuroblastoma (the patient must have evidence of active disease
even if they do not currently require active treatment).
4. Patients must have at least one lesion that can be evaluated for response by imaging
and/or diffuse bone marrow infiltration.
5. Adequate renal function, defined as a glomerular filtration rate (GFR) ≥ 30
6. Karnofsky score ≥60% if ≥16 years old or Lansky performance score of ≥60% if <16 years
- - Informed consent from the patient"s parent or legal guardian is required for all
patients under 16 years of age.
Patients under 16 years of age may also provide
written assent to take part in the trial.
Patients should not meet (or be anticipated to meet) any of the exclusion criteria for the
main trial, see criteria below
Eligibility Criteria for the Main Trial
1. Histologically proven neuroblastoma, which is relapsed or refractory to conventional
2. Patients must have at least one lesion that can be evaluated for response by imaging
and/or diffuse bone marrow infiltration.
3. Aged ≥12 months at the time written consent is given for the dose escalation phase or
aged ≥6 months at the time written consent is given for the dose expansion phase of
4. Life expectancy of at least two months.
5. Karnofsky score ≥60% if ≥16 years old or Lansky performance score of ≥60% if <16 years
6. Adequate renal function, defined as a GFR of ≥30 mL/min/1.73m^2 (corrected).
7. Written (signed and dated) informed consent to the main trial* and be capable of
co-operating with treatment and follow-up.
1. Patients who have received anti-GD2 antibody treatment within the previous 2 weeks
(based on the half life of ch14.18 antibody being 1-3 days in children); patients who
have received dinutuximab or other anti-GD2-directed antibody may need a longer
2. Patients for whom rituximab is contraindicated due to severe previous hypersensitivity
or any other reason.
3. Patients must have recovered from the acute reversible effects of any previous therapy
before infusion of the 1RG-CART.
4. Current CNS involvement (including intradural meningeal involvement). Patients who
previously had CNS involvement but have been surgically treated and disease free for
≥2 months are eligible.
5. Co-existing chronic progressive neurological disease.
6. Airway compromise by direct tumoural invasion or compression.
7. Patients with active autoimmune disease requiring systemic treatment.
8. Patients who are taking or likely to require high dose systemic corticosteroids or
other immunosuppressive therapy (patients on steroid replacement therapy are
9. Patients at high medical risk because of non-malignant systemic disease including
active uncontrolled infection.
10. Major surgery from which the patient has not yet recovered.
11. Female patients who are able to become pregnant (or already pregnant or lactating).
However, those patients who have a negative serum or urine pregnancy test before
enrolment and agree to use two highly effective forms of contraception (oral; injected
or implanted hormonal contraception and condom; have an intra-uterine device and
condom; diaphragm with spermicidal gel and condom) effective at the first
administration of the lymphodepleting regimen or at administration of the 1RG-CART
(whichever comes first), throughout the trial and for six months afterwards are
considered eligible. Note that for female patients who receive cyclophosphamide or
rituximab, the contraceptive period should be extended to 12 months after
12. Male patients with partners of child-bearing potential (unless they agree to take
measures not to father children by using one form of highly effective contraception
[condom plus spermicide] effective at the first administration of the lymphodepleting
regimen or at administration of the 1RG-CART [whichever comes first], throughout the
trial and for six months afterwards). Men with pregnant or lactating partners must be
advised to use barrier method contraception (for example: condom plus spermicidal gel)
to prevent exposure to the foetus or neonate.
13. Known to be serologically positive for hepatitis B, hepatitis C or HIV.
14. Any other condition which in the Investigator"s opinion would not make the patient a
good candidate for the clinical trial.
15. Is a participant in another clinical trial of an investigational medicinal product
(CTIMP). Participation in an observational trial or in the follow-up phase of a CTIMP
would be acceptable.