Phase I/II study of anti-GD2 Chimeric Antigen Receptor-Expressing T cells in pediatric patients affected by High Risk and/or relapsed/refractory Neuroblastoma

Phase 1

• Conditions: High Risk and/or relapsed/refractory Neuroblastoma; MedDRA version: 20.0Level: LLTClassification code 10019260Term: Heart block AV third degreeSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-002475-26-IT
• Lead Sponsor: IRCCS Ospedale Pediatrico Bambino Gesù

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-01-03
• Last Update Posted: 12 February 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Procurement eligibility
All the patients must meet the following eligibility inclusion criteri a at the time of procurement. l, Diagnosis of NBL that have been treated with frontline therapy and is judged to be incurable, based upon the following criteria:
a, Relapse after first-line treatment, proved by a positive 123-I-mMIBG-scan b, Persistence/progression ofdisease after the initiation ofthe upfront treatment
Treatment eligibility
3.2.1 Phase I -Patient Inelusion Criteria
The patient must meet the following eligibility incJusion eriteria to be enrolled to receive treatment in the Phase I study.
1. Diagnosis ofNBL that have been treated with frontline therapy and is judged to be incurable, based upon the following criteria:
a.
Relapse after first-line treatment, proved by a positive 123-I-mMIBG-scan
b.
Persistenee/progression of disease after the initiation of the upfront treatment
2.
Patients must have measurable or evaluable disease at the time of treatment enrollment, as shown by bone marrow biopsy/aspirate, US or CT/MRI sean or by 123I-mMrBG scano
3.
Reeover from the toxic effeet of previous chemotherapies: grade 4 and or 3 nonhematologic toxicities must have resolved to grade :::2; if some effeets ofthe therapies have become chronic (Le. treatment associated thrombocytopenia), the patient must be clinical!y stable, according to the opinion of the treating physicians, and meet ali other eligibility criteria.
4.
Age: 12 months -18 years.
5.
Voluntary informed consent is given. For subjects < 18 years old their legaI guardian must give informed consento Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.
6.
Clinical performance status: Patients > 16 years of age: Karnofsky greater than or equa! to 60%; Patients less than or equal to 16 years ofage: Lansky scale greater than or equal to 60%.
7.
Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
8.
Females ofchild-bearing potential must havea negative pregnancy test because ofthe potentially dangetous effects on the fetus.
3.2.2 Phase II -Patients Inclusion criteria
The patient must meet the following eligibility inclusion criteria to be enrolled to receive treatmènt in the Phase n study.
l. Diagnosis of NBL that have been treated with frontline therapy and is judged to be incurable, based upon the following criteria:
a.
Relapse after first-line treatment, proved by a positive MlBG-scan
b.
Persistence/progression ofdisease after the initiation of the upfront treatment
OR
2.
Diagnosis of High Risk NBL at high risk of relapse, defined by stage IIIIIV and MycN amplification, at the end of the first-line treatmentaccording to the Standard of Care, even ifNED.
3.
Patients with relapsed/refractory disease must have measurable or evaluable disease at the time oftreatment enrollment, as shown by bone marrow biopsy/aspirate, US or CT/MRI scan or by MIBG-scan.
4.
Recover from the toxic effect of previous chemotherapies: grade 4 and or 3 nonhematologic toxicities must have resolved to grade :::;2; if some effects ofthe therapies have become chronic (i.e. treatment associated thrombocytopenia), the patient must be clinically stable, according to the opinion of the treating physicians, and meet

Exclusion Criteria

Procurement eligibility
Phase 1111 Exclusion Criteria
l. Severe, uncontrolled active intercurrent infections
2.
HIV or active HCV and/or HBV infection
3.
Concurrent or recent prior therapies, before apheresis:
a.
Systemic steroids (at a dose equivalent to or greater 2 mg/kg prednisone) in the 2 weeks before apheresis collection. Recent or current use of inhaled/topical/non-absorbable steroids is not exclusionary.
b.
Systemic chemotherapy in the 2 weeks preceding apberesis collection.
c.
Immunosuppressive agents in the 2 weekspreceding apheresis collection.
d.
Radiation therapy must have been completed at least 3 weeks prior to apheresis.
e.
Il3l MIBG therapy must have been completes at least 6 weeks prior to enrol1ment
f.
Anti-GD2 murinemonoclonal antibody (ch14.l8 antibody) in the 2 weeks preceding apheresis colleetion
g.
Other anti-neoplastic investigational agents currently or within 30 days prior to apheresis (Le. start of protoeol therapy);
h.
Exeeptions:
i. Subjects receiving steroid therapy at physiologic replaeement doses only are allowed provided there has been no ìncrease in dose for at least 2 weeks prior to starting apheresis.
Treatment eligibility
Phase I/I1 ~ Patient Exclusion criteria
l. Pregnant or lactating women
2.
Severe, uncontro Iled acti ve intercurrent infections
3.
Active hepatitis B or hepatitis C infection
4.
HIV infection
5.
Rapidly progressive disease with life-expectancy < 6 weeks
6.
History of grade 3 or 4 hypersensitivity to muri ne protein~containing products
7.
Hepatic function: Inadequate liver function defined as total bilirubin > 4x upper limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN based on age and laboratory specific normal ranges
8.
Renal function: serum creatinine > 3x ULN for age.
9.
Blood oxygen saturation < 90%.
lO. Cardiac function: Left ventricular ejection fraction )ower than 45% by ECHO.
Il. Marrow function: ANC lower than 500/mm3 and/or platelets lower than 20.000 (not
reached by transfusion).
12. Congestive heart failure, cardiac arrhythmia, psychiatric illness, or soci al situations that would limit compliance with study requirements or in the opinion ofthe PI would pose an unacceptable risk to the subject.
) 3. Untreated CNS metastasis; patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
14. Concurrent or recent prior therapies, before infusion:
a.
Systemic steroids (at a dose equivalent to or greater 2 mg/kg prednisone) in the 2 weeks before infusion. Recent or current use of inhaled/topicallnon~ absorbable steroids is not exclusionary.
b.
Systemic chemotherapy in the 2 weeks preceding infusion.
c.
Immunosuppressive agents less than or equal to 30 days.
d.
Radiation therapy must have been completed at least 3 weeks prior to enrollment.
e.
1131 ~MIBG therapy must have been completed at least 6 weeks prior to enrollment
f.
Anti~GD2 murine monoclonal antibody (eh) 4. 18 antibody) in the 2 weeks preceding infusion g. Other anti-neoplastic investigational agents currently or within 30 days prior
to start of protocol therapy;
. h. Exceptions:
i. Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis;

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified