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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004554-17 | EudraCT Number |
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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.
The purpose of this trial is to explore the safety and feasibility of deploying autologous anti-GD2 CAR T-cells for the immunotherapy of neuroblastoma. The CAR T-cell trials employing second generation receptors and lymphodepleting conditioning regimes have produced objective clinical responses in patients with relapsed leukaemias. The trial aims to evaluate similar CAR T-cells but directed against the antigen GD2. Neuroblastoma is well suited to this form of targeted therapy because of the homogeneous and almost universal expression of GD2 on the surface of neuroblastoma cells, and because of the poor prognosis of eligible patients.
1RG-CART will be administered intravenously. As the CAR T-cells are designed to survive and proliferate on encountering antigen, no direct relationship is anticipated between cell dose and either efficacy or toxicity. Rather, clinical benefit is more likely to be observed in those patients in whom in vivo expansion successfully occurs. A possible key determinant of expansion will be prior lymphodepletion of the patients. For this reason this trial is designed to evaluate a phased introduction of lymphodepletion in successive patient cohorts, rather than T-cell dose escalation. Only if there is insufficient expansion of T-cells following full lymphodepletion will the T-cell dose be escalated. Rituximab (MabThera®) will be used as a rescue medication only when necessary, and will be considered a non-investigational medicinal product (NIMP) in this trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Level 1 | Other | Patients in Dose Level 1 will receive 1x10^7 1RG-CART/m^2 intravenously (IV) on Day 0. |
|
| Dose Level 2 | Other | Patients 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 | Other | Patients 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 | Other | Patients 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 | Other |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Leukapheresis | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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]) |
| Measure | Description | Time Frame |
|---|---|---|
| 1RG-CART Counts in the Peripheral Blood | Number of patients with 1RG-CART levels in peripheral blood above the limit of quantification for the assay (10 cells/µL) by flow cytometry. | From Day 0 until end of trial (median 38.5 days, range 20 to 233 days) |
| Assessment of Tumour Response From Baseline (RECIST) |
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Eligibility Criteria for Leukapheresis/Venepuncture
Inclusion Criteria:
Written informed consent* for leukapheresis/venepuncture and transduction of T-cells.
Suitability for leukapheresis/venepuncture defined as:
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
Exclusion Criteria:
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
Inclusion Criteria:
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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Anderson, Prof | University College London Institute of Child Health & Great Ormond Street Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University College London Institute of Child Health & Great Ormond Street Hospital | London | WC1N 3JH | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33239386 | Background | 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. | |
| 37640679 |
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17 trial participants were enrolled at one trial site between 29 February 2016 and 19 November 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Level 1 | Patients in Dose Level 1 will receive 1x10^7 1RG-CART/m^2 IV on Day 0. Assigned Interventions: Leukapheresis 1RG-CART |
| FG001 | Dose Level 2 | Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide 1RG-CART/m^2 |
| FG002 | Dose Level 3 | Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide Fludarabine 1RG-CART/m^2 |
| FG003 | Dose Level 4 | Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide Fludarabine 1RG-CART/m^2 |
| FG004 | Dose Level 5 | If 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). Assigned Interventions: Leukapheresis Cyclophosphamide Fludarabine 1RG-CART/m^2 |
| FG005 | Patients Who Underwent Leukapheresis But Did Not Proceed to Receive Any IMP | Patients who were enrolled and underwent leukapheresis but who did not receive any IMP. Assigned Interventions: Leukapheresis |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Level 1 | Patients in Dose Level 1 will receive 1x10^7 1RG-CART/m^2 IV on Day 0. Assigned Interventions: Leukapheresis 1RG-CART |
| BG001 | Dose Level 2 | Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide 1RG-CART |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All eligible patients enrolled for leukapheresis/venepuncture. Patients who were enrolled for leukapheresis/venepuncture in error (due to ineligibility or administrative error) were excluded. | Posted | Count of Participants | Participants | Day 14 |
|
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])
Adverse events are reported for those patients who received IMP (fludarabine, cyclophosphamide or 1RG-CART) on the trial. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.02 or trial-specific (protocol defined) grading scheme for cytokine release syndrome (CRS) was used to grade AE severity.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Level 1 | Patients in Dose Level 1 will receive 1x10^7 1RG-CART/m^2 IV on Day 0. Assigned Interventions: Leukapheresis 1RG-CART |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (23.0). | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.0). | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Regulatory Affairs Manager | Cancer Research UK Centre for Drug Development | +44 203 4696878 | regulatory@cancer.org.uk |
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 18, 2019 | Jun 15, 2021 | Prot_000.pdf |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| D009447 | Neuroblastoma |
| D000080424 | Cytokine Release Syndrome |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
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| ID | Term |
|---|---|
| D007937 | Leukapheresis |
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| ID | Term |
|---|---|
| D016238 | Cytapheresis |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D001781 | Blood Component Removal |
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If 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 | Other | Patients who were enrolled and underwent leukapheresis but who did not receive any IMP. |
|
| Cyclophosphamide | Drug |
|
| Fludarabine | Drug |
|
| 1RG-CART | Genetic |
|
Assessment of best tumour response from baseline according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. |
| Day 28, 2 months and 4 months |
| Assessment of Tumour Response From Baseline (irRC) | Assessment of best tumour response from baseline according to Immune Related Response Criteria (irRC). | Day 28, 2 months and 4 months |
| Assessment of Tumour Response From Baseline (INRC) | Assessment of best tumour response from baseline according to International Neuroblastoma Response Criteria (INRC). | Day 28, 2 months and 4 months |
| To Evaluate Anti-tumour Activity (Progression Free Survival) | Progression free survival (progression by RECIST criteria). | Up to 2 years |
| To Evaluate Anti-tumour Activity (Overall Survival) | Overall survival. | Up to 2 years |
| Derived |
| Li 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. |
| Withdrawal by Subject |
|
| Disease Progression |
|
| BG002 | Dose Level 3 | Patients 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. Assigned Interventions: Cyclophosphamide Fludarabine Leukapheresis 1RG-CART |
| BG003 | Dose Level 4 | Patients 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. Assigned Interventions: Cyclophosphamide Fludarabine Leukapheresis 1RG-CART |
| BG004 | Dose Level 5 | If 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). Assigned Interventions: Cyclophosphamide Fludarabine Leukapheresis 1RG-CART |
| BG005 | Patients Who Underwent Leukapheresis But Did Not Proceed to Receive Any IMP | Patients who were enrolled and underwent leukapheresis but who did not receive any IMP. Assigned Interventions: Leukapheresis |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide 1RG-CART/m^2 |
| OG002 | Dose Level 3 | Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide Fludarabine 1RG-CART/m^2 |
| OG003 | Dose Level 4 | Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide Fludarabine 1RG-CART/m^2 |
| OG004 | Dose Level 5 | If 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). Assigned Interventions: Leukapheresis Cyclophosphamide Fludarabine 1RG-CART/m^2 |
| OG005 | Patients Who Underwent Leukapheresis But Did Not Proceed to Receive Any IMP | Patients who were enrolled and underwent leukapheresis but who did not receive any IMP. Assigned Interventions: Leukapheresis |
|
|
| Primary | 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. | All eligible patients who received at least one dose of 1RG-CART, cyclophosphamide or fludarabine. | Posted | Number | Events | 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]) |
|
|
|
| Primary | 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. | All eligible patients who received at least one dose of 1RG-CART, cyclophosphamide or fludarabine. | Posted | Number | DLT events | 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 | 1RG-CART Counts in the Peripheral Blood | Number of patients with 1RG-CART levels in peripheral blood above the limit of quantification for the assay (10 cells/µL) by flow cytometry. | All eligible patients who received 1RG-CART and provided at least one post-treatment blood sample taken on or after Day 14 for 1RG-CART analysis. | Posted | Count of Participants | Participants | From Day 0 until end of trial (median 38.5 days, range 20 to 233 days) |
|
|
|
| Secondary | Assessment of Tumour Response From Baseline (RECIST) | Assessment of best tumour response from baseline according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. | All eligible patients who received at least one dose of 1RG-CART and had a baseline assessment of disease and at least one repeat disease assessment measured according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. | Posted | Count of Participants | Participants | Day 28, 2 months and 4 months |
|
|
|
| Secondary | Assessment of Tumour Response From Baseline (irRC) | Assessment of best tumour response from baseline according to Immune Related Response Criteria (irRC). | All eligible patients who received at least one dose of 1RG-CART and had a baseline assessment of disease and at least one repeat disease assessment measured according to Immune Related Response Criteria (irRC). | Posted | Count of Participants | Participants | Day 28, 2 months and 4 months |
|
|
|
| Secondary | Assessment of Tumour Response From Baseline (INRC) | Assessment of best tumour response from baseline according to International Neuroblastoma Response Criteria (INRC). | All eligible patients who received at least one dose of 1RG-CART and had a baseline assessment of disease and at least one repeat disease assessment measured according to International Neuroblastoma Response Criteria (INRC). | Posted | Count of Participants | Participants | Day 28, 2 months and 4 months |
|
|
|
| Secondary | To Evaluate Anti-tumour Activity (Progression Free Survival) | Progression free survival (progression by RECIST criteria). | All eligible patients who received 1RG-CART and completed a baseline assessment of disease and at least one repeat disease assessment. | Posted | Median | Full Range | Days | Up to 2 years |
|
|
|
| Secondary | To Evaluate Anti-tumour Activity (Overall Survival) | Overall survival. | Patients who received 1RG-CART. | Posted | Median | Full Range | Days | Up to 2 years |
|
|
|
| 3 |
| 4 |
| 0 |
| 4 |
| 4 |
| 4 |
| EG001 | Dose Level 2 | Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide 1RG-CART | 1 | 1 | 0 | 1 | 1 | 1 |
| EG002 | Dose Level 3 | Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide Fludarabine 1RG-CART | 1 | 1 | 0 | 1 | 1 | 1 |
| EG003 | Dose Level 4 | Patients 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. Assigned Interventions: Leukapheresis Cyclophosphamide Fludarabine 1RG-CART | 1 | 3 | 2 | 3 | 3 | 3 |
| EG004 | Dose Level 5 | If 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). Assigned Interventions: Leukapheresis Cyclophosphamide Fludarabine 1RG-CART | 0 | 3 | 3 | 3 | 3 | 3 |
| Pain | General disorders | MedDRA (23.0). | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (23.0). | Systematic Assessment | Two SAEs of pyrexia (one at Dose Level 4 and one at Dose Level 5) were also considered part of a protocol defined CRS event. |
|
| Post procedural cellulitis | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Pseudomonal bacteraemia | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Pseudomonal sepsis | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Laryngeal haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Coagulopathy | Blood and lymphatic system disorders | MedDRA (23.0). | Systematic Assessment | One AE of coagulopathy (Dose Level 4) was also considered part of a protocol defined CRS event. |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (23.0). | Systematic Assessment | One AE of febrile neutropenia (Dose Level 4) was also considered part of a protocol defined CRS event. |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (23.0). | Systematic Assessment |
|
| Neutrophilia | Blood and lymphatic system disorders | MedDRA (23.0). | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.0). | Systematic Assessment |
|
| Atrioventricular block second degree | Cardiac disorders | MedDRA (23.0). | Systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA (23.0). | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (23.0). | Systematic Assessment | One AE of tachycardia (Dose Level 5) was also considered part of a protocol defined CRS event. |
|
| Diplopia | Eye disorders | MedDRA (23.0). | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (23.0). | Systematic Assessment |
|
| Eye swelling | Eye disorders | MedDRA (23.0). | Systematic Assessment |
|
| Eyelid ptosis | Eye disorders | MedDRA (23.0). | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA (23.0). | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Localised oedema | General disorders | MedDRA (23.0). | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (23.0). | Systematic Assessment |
|
| Pain | General disorders | MedDRA (23.0). | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (23.0). | Systematic Assessment | Three AEs of pyrexia (one at Dose Level 4 and two at Dose Level 5) were also considered part of a protocol defined CRS event. |
|
| Swelling | General disorders | MedDRA (23.0). | Systematic Assessment |
|
| Swelling face | General disorders | MedDRA (23.0). | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA (23.0). | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA (23.0). | Systematic Assessment |
|
| Anaphylactic reaction | Immune system disorders | MedDRA (23.0). | Systematic Assessment |
|
| Epstein-Barr viraemia | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Parainfluenzae virus infection | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Vascular device infection | Infections and infestations | MedDRA (23.0). | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (23.0). | Systematic Assessment |
|
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA (23.0). | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Blood fibrinogen increased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA (23.0). | Systematic Assessment | Five AEs of C-reactive protein increased (two at Dose Level 4 and three at Dose Level 5) were also considered part of a protocol defined CRS event. |
|
| Lymphocyte count decreased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Pseudomonas test positive | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Serum ferritin increased | Investigations | MedDRA (23.0). | Systematic Assessment | One AE of serum ferritin increased (Dose Level 4) was also considered part of a protocol defined CRS event. |
|
| Weight decreased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| White blood cells urine positive | Investigations | MedDRA (23.0). | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (23.0). | Systematic Assessment |
|
| Fluid overload | Metabolism and nutrition disorders | MedDRA (23.0). | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (23.0). | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (23.0). | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (23.0). | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (23.0). | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (23.0). | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (23.0). | Systematic Assessment | One AE of hyponatraemia (Dose Level 4) was also considered part of a protocol defined CRS event. |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (23.0). | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (23.0). | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (23.0). | Systematic Assessment | Two AEs of headache (one at Dose Level 4 and one at Dose Level 5) were also considered part of a protocol defined CRS event. |
|
| Neurological symptom | Nervous system disorders | MedDRA (23.0). | Systematic Assessment | One AE of neurological symptom (Dose Level 4) was also considered part of a protocol defined CRS event. |
|
| Presyncope | Nervous system disorders | MedDRA (23.0). | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA (23.0). | Systematic Assessment |
|
| Glycosuria | Renal and urinary disorders | MedDRA (23.0). | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (23.0). | Systematic Assessment |
|
| Nephropathy toxic | Renal and urinary disorders | MedDRA (23.0). | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA (23.0). | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0). | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (23.0). | Systematic Assessment |
|
| Oxygen therapy | Surgical and medical procedures | MedDRA (23.0). | Systematic Assessment | One AE of oxygen therapy (Dose Level 4) was also considered part of a protocol defined CRS event. |
|
| Capillary leak syndrome | Vascular disorders | MedDRA (23.0). | Systematic Assessment | One AE of capillary leak syndrome (Dose Level 4) was also considered part of a protocol defined CRS event. |
|
| Hypertension | Vascular disorders | MedDRA (23.0). | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (23.0). | Systematic Assessment | One AE of hypotension (Dose Level 4) was also considered part of a protocol defined CRS event. |
|
Not provided
Not provided
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D012769 | Shock |
| D047589 |
| Leukocyte Reduction Procedures |
| D002469 | Cell Separation |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D008919 | Investigative Techniques |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| NSAEs |
|
| Fludarabine Related AEs |
|
| Cyclophosphamide Related AEs |
|
| 1RG-CART Related AEs |
|
| Best Response (RECIST) progressive disease (PD) |
|
| Best Response (irRC) progressive disease (irPD) |
|
| Best Response (irRC) not evaluable (NE) |
|
| Best Response (INRC) No response |
|
| Best Response (INRC) Progressive disease |
|