Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
33
Countries
1
Sites
5
Acute lymphoblastic leukemia
To evaluate the efficacy (response rate) of ARI-0001 cells in paediatric patients with CD19+ acute lymphoblastic leukaemia that is resistant or refractory to therapy.
Key facts
- Sponsor
- Fundacio Sant Joan De Deu
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 22 Jul 2024 → ongoing
- Decision date (initial)
- 2024-07-22
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-515467-66-00
- EudraCT number
- 2022-001101-52
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To evaluate the efficacy (response rate) of ARI-0001 cells in paediatric patients with CD19+ acute lymphoblastic leukaemia that is resistant or refractory to therapy.
Secondary objectives 4
- To evaluate safety and tolerability of ARI-0001 therapy
- To further evaluate efficacy by evaluating duration of response and survival (event-free, relapse-free and overall survival) after ARI-0001 cell infusion
- To evaluate the kinetics of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid after its administration
- To evaluate functional CART-cell persistence by evaluating B-cell aplasia in peripheral blood
Conditions and MedDRA coding
Acute lymphoblastic leukemia
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10000844 | Acute lymphoblastic leukaemia | 10029104 |
Regulatory references
- EMA paediatric investigation plan (PIP)
- EMEA-003264-PIP01-22
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-513601-31-00 | Phase 2 study of the infusion of differentiated autologous T-cells from peripheral blood, expanded and transduced with a lentivirus to express a chimeric antigen receptor with anti-CD19 specificity (A3B1) conjugated with the co-stimulatory regions 4-1BB and CD3z (ARI-0001 cells) in patients with CD19+ acute lymphoid leukemia resistant or refractory to therapy | Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Age 0 to 18 years
- Diagnosis of relapsed /refractory CD19+ ALL defined as at least one of the following criteria: • First relapse if high-risk features. Definition of high risk 1st relapse will include at least one of the following: o any relapse before 6 months after completion of chemotherapy o high risk cytogenetics: t(4;11)(q21; q23) /AF4:: KMT2A or t (1;19) (q23; p13) / TCF3/PBX or t(17;19) (q22;p13)/ TCF3::HLF or hypodiploid (<44 chromosomes) or TP53 mutation and/ or TP53 deletion
- Disease burden defined as: • Morphologic relapse in bone marrow (≥5% blasts) or presence of leukemic blasts in an extramedullary site • MRD positivity (≥0.01%) by flow cytometry or PCR
- Subjects with the following features are NOT excluded: • Isolated extramedullary involvement • Down syndrome patients • CNS3 involvement if disease is stable and a thorough evaluation of risk/benefit assessment has been stablished by the principal investigator and the treating physician • Ph+ (BCR::ABL1) ALL if they are intolerant or have failed at least 1 TKI • Prior blinatumomab therapy provided blasts remain CD19+ >90% blasts at inclusion
- Performance status: Lansky (age <16 years) or Karnofsky (age ≥16 years) ≥ 50%
- Life expectancy >3 months
- Adequate venous access and no contraindications for lymphoapheresis
- Signature of informed consent (patient and/or legal guardian)
Exclusion criteria 11
- Any other concomitant neoplasia, unless it has been in complete remission for 3 years or longer
- Active immunosuppressive therapy with the exception of hydrocortisone 12 mg/m2/day (or equivalent);
- Active acute or chronic graft versus host disease (GVHD) >grade 1
- Prior therapies: • CAR-T cell therapy • Donor lymphocytes infusion <28 days before enrollment • Immunosuppressive therapy (cyclosporine, mophetil mycophenolate and others) must be stopped <14 days before enrollment • Alentuzumab, thymoglobulin (ATG) < 3 months before enrollment
- Active infection that is uncontrolled or requiring systemic intravenous medical therapy;
- Any experimental or non-commercialized therapy in the previous 4 weeks
- Active HIV, HBV or HCV infection
- Any concomitant and uncontrolled medical or psychiatric disease that, under investigator consideration, would prevent the subject from participating in the study
- Severe organic impairment defined by cardiac ejection fraction <50%, pulmonary reserve defined as > Grade 1 dyspnea and pulse oxygenation <91% on room air, creatinine >1.5 times greater than the upper limit of normality (ULN) for sex and age or conjugated bilirubin >2 x ULN
- Lactating or pregnant women
- Men or women of childbearing potential unable or unwilling to use highly efficient contraceptive measures during the study
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Complete response rate (complete remission [CR] rate plus CR rate with incomplete haematological recovery [CRi]), with undetectable measurable residual disease by multiparameter flow cytometry within day +100 after the infusion of ARI-0001 cells. In patients with isolated extramedullary disease, response evaluation will be done through morphology and flow cytometry of the cerebrospinal fluid (CSF) and/or imaging tests (PET-CT or MRI)
Secondary endpoints 8
- Key secondary endpoint: Event-free survival (EFS) at month 12
- Duration of remission: defined as the time from achievement of CR or CRi (whichever occurs first) to relapse or death due to ALL
- Relapse free survival (RFS) at 12 months
- Overall survival at 12 months
- Transplant and disease-free survival at 6 and 12 months
- In vivo survival of ARI-0001 cells in peripheral blood as determined by flow cytometry and by qPCR of the transgene weekly the first month, monthly in the first 6 months and then at 12 months.
- B-cell aplasia, measured by flow cytometry, weekly the first month, monthly in the first 6 months, every 3 months from month 6 to month 12 and every 6 months until end of study
- Toxicity, defined as adverse events of grade ≥3 according to common toxicity criteria (version 5.0). Adverse events of significant interest will be CRS, ICANS and cerebral ooedema, which will be graded according to the ASTCT classification (1). Procedure-related mortality will also be measured.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD10699086 · Product
- Active substance
- Varnimcabtagene Autoleucel
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENOUS ADMINISTRATION
- Max daily dose
- 2 U unit(s)
- Max total dose
- 3 U unit(s)
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- FUNDACIÓ DE RECERCA CLINIC BARCELONA-INSTITUT D´INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER
- Paediatric formulation
- No
- Orphan designation
- No
Auxiliary 10
SUB07678MIG · Substance
- Active substance
- Fludarabine
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS ADMINISTRATION
- Max daily dose
- 30 mg/m2 milligram(s)/sq. meter
- Max total dose
- 90 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB01628MIG · Substance
- Active substance
- Dexchlorpheniramine Maleate
- Pharmaceutical form
- SYRUP
- Route of administration
- ORAL AND IV
- Max daily dose
- 0.15 mg/kg milligram(s)/kilogram
- Max total dose
- 0.45 mg/kg milligram(s)/kilogram
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08872MIG · Substance
- Active substance
- Methylprednisolone
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 2 mg/kg milligram(s)/kilogram
- Max total dose
- 6 mg/kg milligram(s)/kilogram
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06880MIG · Substance
- Active substance
- Cytarabine
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 500 mg/m2 milligram(s)/sq. meter
- Max total dose
- 1000 mg/m2 milligram(s)/square meter
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB20313 · Substance
- Active substance
- Tocilizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 2400 mg milligram(s)
- Max total dose
- 2400 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07337MIG · Substance
- Active substance
- Etoposide
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 150 mg/m2 milligram(s)/sq. meter
- Max total dose
- 450 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09611MIG · Substance
- Active substance
- Paracetamol
- Pharmaceutical form
- SYRUP
- Route of administration
- ORAL AND IV
- Max daily dose
- 1 g gram(s)
- Max total dose
- 3 g gram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB127300 · Substance
- Active substance
- Human Immunoglobulin G
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 500 mg/kg milligram(s)/kilogram
- Max total dose
- 500 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06859MIG · Substance
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 300 mg/m2 milligram(s)/sq. meter
- Max total dose
- 900 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05338MIG · Substance
- Active substance
- Allopurinol
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 300 mg/m2 milligram(s)/sq. meter
- Max total dose
- 2100 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 1 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fundacio Sant Joan De Deu
- Sponsor organisation
- Fundacio Sant Joan De Deu
- Address
- Calle Santa Rosa 39-57 3a Planta
- City
- Esplugues De Llobregat
- Postcode
- 08950
- Country
- Spain
Scientific contact point
- Organisation
- Fundacio Sant Joan De Deu
- Contact name
- Susana Rives
Public contact point
- Organisation
- Fundacio Sant Joan De Deu
- Contact name
- Clinical Trial Unit
Locations
1 EU/EEA country · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruitment ended | 33 | 5 |
| Rest of world | — | 0 | — |
Investigational sites
Hospital Universitari Vall D Hebron
Haematology, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
University Hospital Virgen Del Rocio S.L.
Haematology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Sant Joan De Deu Barcelona
Haematology, Passeig De Sant Joan De Deu 2, 08950, Esplugues De Llobregat
Hospital Universitario La Paz
Haematology, Paseo De La Castellana 261, 28046, Madrid
Hospital Infantil Universitario Nino Jesus
Haematology, Avenida Menendez Pelayo 65, 28009, Madrid
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2024-07-22 | 2024-07-22 | 2026-05-18 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 18 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Annexed_Protocol_ATMPs_Ped_V2_0_11MAR2024_for publication | 2 |
| Protocol (for publication) | D1_Protocol CART19BE03Ped_2024-515467-66-00 | 4 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | RECRUITMENT_ARRANGEMENTS | 1 |
| Recruitment arrangements (for publication) | RECRUITMENT_ARRANGEMENTS_ANONIM | 1 |
| Subject information and informed consent form (for publication) | AAS_CI_FUERA_ESPECIFICACION_CART19-BE-03Ped_ADULTO_08MAR2024_corregida | 1 |
| Subject information and informed consent form (for publication) | AAS_CI_FUERA_ESPECIFICACION_CART19-BE-03Ped_MENOR_MADURO_V1_29092023 | 1 |
| Subject information and informed consent form (for publication) | AAS_CI_FUERA_ESPECIFICACION_CART19-BE-03Ped_PADRES_V1_29092023 | 1 |
| Subject information and informed consent form (for publication) | Apendice 1_HIP_Proteccion datos_CART19-BE-03Ped_paciente | 2 |
| Subject information and informed consent form (for publication) | Apendice 1_HIP_Proteccion datos_CART19-BE-03Ped_PADRES | 2 |
| Subject information and informed consent form (for publication) | HIP_CI_CART19-BE-03Ped_ADULTOS | 3 |
| Subject information and informed consent form (for publication) | HIP_CI_CART19-BE-03Ped_ADULTOS_tc | 2 |
| Subject information and informed consent form (for publication) | HIP_CI_CART19-BE-03Ped_MENOR_MADURO | 3 |
| Subject information and informed consent form (for publication) | HIP_CI_CART19-BE-03Ped_MENOR_MADURO_tc | 2 |
| Subject information and informed consent form (for publication) | HIP_CI_CART19-BE-03Ped_PADRES | 4 |
| Subject information and informed consent form (for publication) | HIP_CI_CART19-BE-03Ped_PADRES_tc | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis EN 2024-515467-66-00 | 4 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ES 2024-515467-66-00 | 4 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-10 | Spain | Acceptable with conditions 2024-07-22
|
2024-07-22 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-11-21 | Spain | Acceptable 2025-01-08
|
2025-01-09 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-11-21 | Spain | Acceptable 2026-01-05
|
2026-01-16 |