Phase I study of anti-GD2 Chimeric Antigen Receptor-Expressing T cells in pediatric and young adult patients affected by relapsed/refractory central nervous system tumors

Phase 1

• Conditions: Relapsed/refractory malignant central nervous system tumors; MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-004729-55-IT
• Lead Sponsor: IRCCS, OSPEDALE PEDIATRICO BAMBINO GESÙ DI ROMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-11-04
• Last Update Posted: 28 August 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

Procurement eligibility
1. Histological diagnosis of relapsed/refractory CNS tumors, including:
a. Medulloblastoma (MB)/other embryonal tumor (ARM A)
b. Hemispheric high-grade glioma (HGG) (ARM B)
c. Thalamic HGG, diffuse midline glioma (DMG) or diffuse intrinsic pontine glioma (DIPG) and other rare CNS tumors not included in Arm A and B (ARM C)
2. Eligibility according to GD2 expression:
- GD2-positivity: the patient will be considered eligible and will be enrolled in the present protocol since there is not any other effective treatment to be explored
- GD2-negativity: the patient will be considered NOT eligible for the treatment: an alternative treatment of rescue, whenever possible, or palliation will be proposed to the patient in this case
- Impossibility of obtaining tumor samples: the patient will be considered eligible and will be enrolled in the present protocol since there is not any other effective treatment to be explored
3. Age: 6 months – 30 years
4. Adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis
5. Written and signed informed consent from patients, parents or legal guardians. For subjects < 18 year-old their legal guardian must give informed consent. In addition, pediatric subjects will be included in age-appropriate discussion and written informed assent will be obtained for those greater than or equal to 7 years of age, when appropriate
6. Karnofsky/Lansky = 60

Treatment eligibility
1. Imaging assessments performed within 14 days of start of treatment
2. Age: 6 months – 30 years
3. Measurable or evaluable disease on at least 2 dimensions on MRI at the time of treatment enrollment
4. Karnofsky/Lansky = 60
5. Recover from the toxic effects of previous radiation and chemotherapies: grade 4 and or 3 non-hematologic toxicities must have resolved to grade = 2; in presence of chronic complications (i.e. treatment-associated thrombocytopenia), patient must be clinically stable, according to the opinion of the treating physicians, and meet all other eligibility criteria
6. Positioning of an implantable intraventricular access device (Codman Holter Rickham reservoir, Integra LifeSciences, NJ, U.S.A) and a microdialysis probe (71 high cutoff microdialysis bolt catheter, M Dialysis AB, Stockholm Sweden)
7. Written and signed informed consent from patients, parents or legal guardians. For subjects < 18 year-old their legal guardian must give informed consent. In addition, pediatric subjects will be included in age-appropriate discussion and written informed assent will be obtained for those greater than or equal to 7 years of age, when appropriate”
8. Patients of childbearing 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
9. Females of childbearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Severe, uncontrolled active infections
2. HIV or active HCV and/or HBV infection
3. Concurrent or recent prior therapies, before apheresis:
a. If receiving glucocorticoids, patient must be on a stable or weaning dose for at least 7 days prior to apheresis. Recent or current use of inhaled/topical/nonabsorbable steroids is not exclusionary. 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
b. Systemic chemotherapy in the 3 weeks preceding apheresis collection
c. Immunosuppressive agents in the 2 weeks preceding apheresis collection
d. Radiation therapy must have been completed at least 6 weeks prior to apheresis

1. Pregnant or lactating women
2. Severe, uncontrolled active infections
3. HIV or active HCV and/or HBV infection
4. Rapidly progressive disease with life expectancy < 6 weeks
5. History of grade 3 or 4 hypersensitivity to murine protein-containing products
6. 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
7. Renal function: serum creatinine > 3x ULN for age
8. Blood oxygen saturation < 90%
9. Cardiac function: left ventricular ejection fraction lower than 45% by ECHO
10.Marrow function: absolute neutrophils count (ANC) lower than 500/mm3 and/or platelets lower than 20.000 (not reached by transfusion)
11.Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the principal investigator (PI) would pose an unacceptable risk to the subject.
12.Concurrent or recent prior therapies, before infusion:
a. If receiving glucocorticoids, patient must be on a stable or weaning dose for at least 7 days prior to infusion. Recent or current use of inhaled/topical/nonabsorbable steroids is not exclusionary. 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
b. Systemic chemotherapy in the 3 weeks preceding infusion
c. Immunosuppressive agents less than or equal to 30 days
d. Radiation therapy must have been completed at least 6 weeks prior to enrollment
e. Other anti-neoplastic investigational agents currently or within 30 days prior to start of protocol therapy
13.Patient-derived GD2-CART01 production failure: vitality 20%, RCR positivity, Vector Copy Number >10, non-sterility, endotoxin contamination (> 1 EU/ml)

Study & Design

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