A Phase I Trial of Anti-GD2 T-cells (1RG-CART)
A Cancer Research UK Phase I Trial of Anti-GD2 Chimeric Antigen Receptor (CAR) Transduced T-cells (1RG-CART) in Patients With Relapsed or Refractory Neuroblastoma
2 other identifiers
interventional
17
1 country
1
Brief Summary
The purpose of this first in human study is to determine the safety and feasibility of 1RG-CART therapy in patients with relapsed or refractory neuroblastoma. 1RG-CART therapy is a novel immunotherapy under investigation in which patients have their T-cells (a type of white blood cell) collected and modified in the laboratory, before they are given back to the patient. The T-cells are modified to express a chimeric antigen receptor (CAR) which targets disialoganglioside (GD2), a marker expressed on the surface of neuroblastoma cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Feb 2016
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 24, 2016
CompletedStudy Start
First participant enrolled
February 29, 2016
CompletedFirst Posted
Study publicly available on registry
May 4, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 16, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 16, 2020
CompletedResults Posted
Study results publicly available
August 17, 2021
CompletedAugust 17, 2021
July 1, 2021
4.8 years
February 24, 2016
June 15, 2021
July 23, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma
Feasibility of 1RG-CART therapy assessed as the number of patients who commence T-cell processing and are subsequently evaluable for 1RG-CART engraftment at Day 14.
Day 14
Safety and Tolerability of 1RG-CART Therapy
Number of serious adverse events, non-serious adverse events and adverse events that are related to fludarabine, cyclophosphamide or 1RG-CART.
From the time of informed consent to leukapheresis until withdrawal from the trial or start of other anti-cancer therapy (a median time period of 132 days [range 68 to 301 days])
To Determine Recommended Phase II Regimen by Assessing the Number of DLTs at Each Dose Level
Number of dose limiting toxicities (DLTs) at each dose level.
From the time of informed consent to leukapheresis until withdrawal from the trial or start of other anti-cancer therapy (a median time period of 132 days [range 68 to 301 days])
Secondary Outcomes (6)
1RG-CART Counts in the Peripheral Blood
From Day 0 until end of trial (median 38.5 days, range 20 to 233 days)
Assessment of Tumour Response From Baseline (RECIST)
Day 28, 2 months and 4 months
Assessment of Tumour Response From Baseline (irRC)
Day 28, 2 months and 4 months
Assessment of Tumour Response From Baseline (INRC)
Day 28, 2 months and 4 months
To Evaluate Anti-tumour Activity (Progression Free Survival)
Up to 2 years
- +1 more secondary outcomes
Study Arms (6)
Dose Level 1
OTHERPatients in Dose Level 1 will receive 1x10\^7 1RG-CART/m\^2 intravenously (IV) on Day 0.
Dose Level 2
OTHERPatients in Dose Level 2 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -4 to -1) followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.
Dose Level 3
OTHERPatients in Dose Level 3 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.
Dose Level 4
OTHERPatients in Dose Level 4 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^8 1RG-CART/m\^2 IV on Day 0.
Dose Level 5
OTHERIf the required level of 1RG-CART survival is not reached, a further cohort of patients (Dose Level 5) will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 5-10x10\^8 1RG-CART/m\^2 IV which could be be split over two days (Day 0 and Day 1).
Patients who underwent leukapheresis but did not proceed to receive any IMP
OTHERPatients who were enrolled and underwent leukapheresis but who did not receive any IMP.
Interventions
Eligibility Criteria
You may qualify if:
- Written informed consent\* for leukapheresis/venepuncture and transduction of T-cells.
- 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.
- Relapsed or refractory neuroblastoma (the patient must have evidence of active disease even if they do not currently require active treatment).
- Patients must have at least one lesion that can be evaluated for response by imaging and/or diffuse bone marrow infiltration.
- Adequate renal function, defined as a glomerular filtration rate (GFR) ≥ 30 mL/min/1.73m\^2 (corrected).
- Karnofsky score ≥60% if ≥16 years old or Lansky performance score of ≥60% if \<16 years old
- \*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.
You may not qualify if:
- Eligibility Criteria for the Main Trial
- Histologically proven neuroblastoma, which is relapsed or refractory to conventional treatment.
- Patients must have at least one lesion that can be evaluated for response by imaging and/or diffuse bone marrow infiltration.
- 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 the trial.
- Life expectancy of at least two months.
- Karnofsky score ≥60% if ≥16 years old or Lansky performance score of ≥60% if \<16 years old
- Adequate renal function, defined as a GFR of ≥30 mL/min/1.73m\^2 (corrected).
- Written (signed and dated) informed consent to the main trial\* and be capable of co-operating with treatment and follow-up.
- \*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 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 washout period.
- Patients for whom rituximab is contraindicated due to severe previous hypersensitivity or any other reason.
- Patients must have recovered from the acute reversible effects of any previous therapy before infusion of the 1RG-CART.
- 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.
- Co-existing chronic progressive neurological disease.
- Airway compromise by direct tumoural invasion or compression.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University College London Institute of Child Health & Great Ormond Street Hospital
London, WC1N 3JH, United Kingdom
Related Publications (2)
Straathof K, Flutter B, Wallace R, Jain N, Loka T, Depani S, Wright G, Thomas S, Cheung GW, Gileadi T, Stafford S, Kokalaki E, Barton J, Marriott C, Rampling D, Ogunbiyi O, Akarca AU, Marafioti T, Inglott S, Gilmour K, Al-Hajj M, Day W, McHugh K, Biassoni L, Sizer N, Barton C, Edwards D, Dragoni I, Silvester J, Dyer K, Traub S, Elson L, Brook S, Westwood N, Robson L, Bedi A, Howe K, Barry A, Duncan C, Barone G, Pule M, Anderson J. Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma. Sci Transl Med. 2020 Nov 25;12(571):eabd6169. doi: 10.1126/scitranslmed.abd6169.
PMID: 33239386BACKGROUNDLi X, Li W, Xu L, Song Y. Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments. Chin Med J (Engl). 2024 Jun 5;137(11):1285-1302. doi: 10.1097/CM9.0000000000002818. Epub 2023 Aug 28.
PMID: 37640679DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
For the secondary outcome measure of Overall Survival, one patient from Dose Level 1 withdrew consent to continue with the trial, therefore the time to death (if applicable) for this patient was not collected.
Results Point of Contact
- Title
- Regulatory Affairs Manager
- Organization
- Cancer Research UK Centre for Drug Development
Study Officials
- PRINCIPAL INVESTIGATOR
John Anderson, Prof
University College London Institute of Child Health & Great Ormond Street Hospital
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 24, 2016
First Posted
May 4, 2016
Study Start
February 29, 2016
Primary Completion
December 16, 2020
Study Completion
December 16, 2020
Last Updated
August 17, 2021
Results First Posted
August 17, 2021
Record last verified: 2021-07
Data Sharing
- IPD Sharing
- Will not share