Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Authorised, recruitment pending
Participants planned
75
Countries
1
Sites
1
Patients undergoing Fludarabine based lymphodepletion prior to CAR-T cell therapy, for hematological malignancy
The primary objective is to study the pharmacokinetics of F-Ara-A in patients undergoing lymphodepletion therapy prior to CAR-T therapy.
Key facts
- Sponsor
- Universitair Ziekenhuis Gent
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hemic and Lymphatic Diseases [C15], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]
- Decision date (initial)
- 2026-03-23
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Department of Hematology Ghent University Hospital · BHS study grant
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Dose response
The primary objective is to study the pharmacokinetics of F-Ara-A in patients undergoing lymphodepletion therapy prior to CAR-T therapy.
Secondary objectives 1
- The secondary objective is to determine the influence of covariates on F-Ara-A exposure.
Conditions and MedDRA coding
Patients undergoing Fludarabine based lymphodepletion prior to CAR-T cell therapy, for hematological malignancy
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Open label, single arm, single centre, non-randomised, prospective phase IV, pharmacological trial Post-marketing study of Fludarabine use in lymphodepletion prior to CAR-T therapy in real world setting to provide critical insights into Fludarabine exposure in routine clinical practice, in patients undergoing CAR-T therapy. This can reveal how different levels of exposure to the active metabolite might influence response to treatment and the occurrence of toxicity/morbidity.
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Age ≥ 18 years
- Be able to understand and sign an informed consent
- Women of childbearing potential (WOCBP) must use a reliable contraception method such as licensed hormonal or barrier methods during chemotherapy/conditioning and up 6 months after chemotherapy for female patients; For male patients use of barrier method should be used during chemotherapy/conditioning and up 6 months after chemotherapy
- Patients undergoing CAR T-cell therapy for hematological malignancies
- Planned lymphodepletion chemotherapy regimen containing Fludarabine prior to CAR-T cell therapy.
Exclusion criteria 7
- Pregnancy or lactation
- Known allergic reactions to components of the lymphodepletion regimen
- No other line available for blood sampling than the infusion line through which Fludarabine was administered (patients with a double or triple lumen central catheter will not be excluded as a second lumen is available for sampling) and patient unable or unwilling to undergo peripheral blood sampling
- Patients on dialysis
- Renal insufficiency with creatinine clearance < 30 ml/min
- Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with program participation, program drug administration, or would impair the ability of the patient to receive program therapy
- Patients with known hemolysis due to Fludarabine use or patients with active decompensated hemolytic anemia.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- Area under concentration time curve (AUC) of F-Ara-A from time 0 to infinity
- Coefficient of variation (CV) for plasma concentrations of F-Ara-A
- Maximum observed concentration (Cmax)
Secondary endpoints 1
- Patient covariates: - Sex - Creatinine - Creatinine clearance - Cystatine C - Cystatine C clearance - Actual body weight (ABW) - Ideal body weight (IBW) - Body mass index (BMI) - Body surface aera (BSA); To be assessed after the last included patient has finished LDC.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
Fludarabine Teva 25 mg/ml solution à diluer pour injection ou perfusion
PRD3852415 · Product
- Active substance
- Fludarabine Phosphate
- Substance synonyms
- FLUDARABINE 5'-MONOPHOSPHATE, FLUDARABINE MONOPHOSPHATE
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 30 mg/m2 milligram(s)/square meter
- Max total dose
- 120 mg/m2 milligram(s)/square meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- BE303721
- MA holder
- TEVA PHARMA BELGIUM N.V./S.A
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fludarabine Teva 25 Mg/Ml Konzentrat Zur Herstellung Einer Injektions- Oder Infusionsloesung
PRD4171638 · Product
- Active substance
- Fludarabine Phosphate
- Substance synonyms
- FLUDARABINE 5'-MONOPHOSPHATE, FLUDARABINE MONOPHOSPHATE
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 30 mg/m2 milligram(s)/square meter
- Max total dose
- 120 mg/m2 milligram(s)/square meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- BE303721
- MA holder
- TEVA PHARMA BELGIUM N.V./S.A
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fludarabine Teva 25 mg/ml concentraat voor oplossing voor injectie of infusie
PRD745724 · Product
- Active substance
- Fludarabine Phosphate
- Substance synonyms
- FLUDARABINE 5'-MONOPHOSPHATE, FLUDARABINE MONOPHOSPHATE
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 30 mg/m2 milligram(s)/square meter
- Max total dose
- 120 mg/m2 milligram(s)/square meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- BE303721
- MA holder
- TEVA PHARMA BELGIUM N.V./S.A
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 6
CARVYKTI 3.2 × 10^6 – 1 × 10^8 cells dispersion for infusion
PRD9718535 · Product
- Active substance
- Ciltacabtagene Autoleucel
- Substance synonyms
- LCAR-B38M CAR-T cells, AUTOLOGOUS BI-EPITOPE BCMA-TARGETED CAR T-CELLS JNJ-68284528, LCAR-B38M-TRANSDUCED CAR-T CELLS JNJ-68284528, AUTOLOGOUS HUMAN T CELLS GENETICALLY MODIFIED EX-VIVO WITH A LENTIVIRAL VECTOR ENCODING A CHIMERIC ANTIGEN RECEPTOR FOR B-CELL MATURATION ANTIGEN, Autologous human T cells genetically modified ex-vivo with a lentiviral vector encoding a CAR for BCMA, JNJ-68284528, LCAR-B38M
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 0000 Other
- Max total dose
- 0000 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01XL05 — -
- Marketing authorisation
- EU/1/22/1648/001
- MA holder
- JANSSEN-CILAG INTERNATIONAL NV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/1/22/1648
- Modified vs. Marketing Authorisation
- No
Endoxan 500 mg, poeder voor oplossing voor injectie
PRD350463 · Product
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 900 mg/m2 milligram(s)/square meter
- Max total dose
- 1500 mg/m2 milligram(s)/square meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01AA01 — CYCLOPHOSPHAMIDE
- Marketing authorisation
- BE 000682
- MA holder
- BAXTER SA
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Endoxan 1000 mg, poeder voor oplossing voor injectie
PRD350464 · Product
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 900 mg/m2 milligram(s)/square meter
- Max total dose
- 1500 mg/m2 milligram(s)/square meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01AA01 — CYCLOPHOSPHAMIDE
- Marketing authorisation
- BE 151207
- MA holder
- BAXTER SA
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
YESCARTA 0.4 – 2 x 10e8 cells dispersion for infusion
PRD6563420 · Product
- Active substance
- Axicabtagene Ciloleucel
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 0000 Other
- Max total dose
- 0000 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01XX70 — -
- Marketing authorisation
- EU/1/18/1299/001
- MA holder
- KITE PHARMA EU B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/15/1579
- Modified vs. Marketing Authorisation
- No
Tecartus 0.4 - 2 x 10e8 cells dispersion for infusion
PRD8604659 · Product
- Active substance
- Brexucabtagene Autoleucel
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 0000 Other
- Max total dose
- 0000 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01XL06 — -
- Marketing authorisation
- EU/1/20/1492/001
- MA holder
- KITE PHARMA EU B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/19/2220
- Modified vs. Marketing Authorisation
- No
Kymriah 1.2 x 10^6 – 6 x 10^8 cells dispersion for infusion
PRD6577962 · Product
- Active substance
- Tisagenlecleucel
- Substance synonyms
- TISAGENLECLEUCEL-T, CTL019
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 0000 Other
- Max total dose
- 0000 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01XL04 — -
- Marketing authorisation
- EU/1/18/1297/001
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/14/1266
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitair Ziekenhuis Gent
- Sponsor organisation
- Universitair Ziekenhuis Gent
- Address
- Corneel Heymanslaan 10
- City
- Gent
- Postcode
- 9000
- Country
- Belgium
Scientific contact point
- Organisation
- Universitair Ziekenhuis Gent
- Contact name
- Anke Delie
Public contact point
- Organisation
- Universitair Ziekenhuis Gent
- Contact name
- HIRUZ CTU
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Authorised, recruitment pending | 75 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
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) | D1_Protocol 2025-524278-40-00_public | 3.0 |
| Protocol (for publication) | D2_Risk Analysis Matrix 2025-524278-40-00_public | 1.0 |
| Protocol (for publication) | D2_Risk Assessment Plan 2025-524278-40-00_public | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Dutch_public | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF English_public | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF French_public | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnant partner Dutch_public | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnant partner English_public | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF pregnant partner French_public | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF sponsor statement_public | 1 |
| Subject information and informed consent form (for publication) | L3_Informed consent procedure | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Smpc-Fludarabine-FR | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Smpc-Fludarabine-NL | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis ENG 2025-524278-40-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis FR 2025-524278-40-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis GER 2025-524278-40-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis NDL 2025-524278-40-00 | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2026-01-22 | Belgium | Acceptable with conditions 2026-03-23
|
2026-03-23 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2026-04-07 | Belgium | Acceptable 2026-05-18
|
2026-05-18 |