Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
166
Countries
3
Sites
27
Chronic Lymphocytic Leukemia (CLL)
To evaluate the efficacy of venetoclax (Venclexa® or Venclyxto®) in combination with obinutuzumab (Gazyva® or Gazyvaro®) (VEN + G) compared with fludarabine, cyclophosphamide, and rituximab (FCR)/ bendamustine and rituximab (BR) on the basis of minimal residual disease (MRD) response rate
Key facts
- Sponsor
- F. Hoffmann-La Roche AG
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 7 May 2020 → 20 Mar 2025
- Decision date (initial)
- 2024-07-29
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- F. Hoffmann-La Roche Ltd
External identifiers
- EU CT number
- 2023-504036-17-00
- EudraCT number
- 2019-003327-37
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Others
To evaluate the efficacy of venetoclax (Venclexa® or Venclyxto®) in combination with obinutuzumab (Gazyva® or Gazyvaro®) (VEN + G) compared with fludarabine, cyclophosphamide, and rituximab (FCR)/ bendamustine and rituximab (BR) on the basis of minimal residual disease (MRD) response rate
Secondary objectives 3
- To evaluate the efficacy of VEN + G compared with FCR/BR on the basis of progression-free survival, MRD response rate in peripheral blood (PB) and bone marrow (BM), overall response rate, duration of objective response, best response achieved, event-free survival, overall survival, tumor lysis syndrome risk reduction rate and reduction in mandatory hospitalizations
- To evaluate safety of VEN + G compared with FCR/BR on the basis of nature, frequency, and severity of adverse events, changes in vital signs, physical findings, clinical laboratory test results, premature withdrawals
- To compare disease and treatment-related symptoms and to evaluate changes in physical functioning, role functioning, and global health status/quality of life following treatment with the combination of VEN + G compared with FCR/BR in patients with previously untreated CLL without del(17p) or TP53 mutation
Conditions and MedDRA coding
Chronic Lymphocytic Leukemia (CLL)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10008976 | Chronic lymphocytic leukemia | 10029104 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | PHASE III STUDY TO COMPARE VENETOCLAX/OBINUTUZIMAB VS FLUDARABINE CYCLOPHOSPHAMIDE + FCR/BENDAMUSTIN A Study to Compare the Efficacy and Safety of a Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/ Bendamustine and Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) without DEL (17P) or TP53 mutation
|
Randomised Controlled | None | ARM A: Patients randomized to Arm A (VEN G) will receive 12 cycles of treatment, each with a precise duration of 28 days. During the first cycle, obinutuzumab will be administered intravenously on Days 1 (and 2), 8, and 15 as well as on Day 1 of Cycles 26. Continuous daily administration, with a 5-week ramp-up period, of venetoclax starts on Cycle 1, Day 22. Venetoclax will be administered until the end of Cycle 12. ARM B: Patients randomized to Arm B (FCR/BR 50:50) will receive 6 cycles of FCR consisting of a single cycle of a single infusion of rituximab on Day 1 and fludarabine and cyclophosphamide infusions on Days 13 of each 28-day cycle or bendamustine as infusions on Days 1 and 2 and a single cycle of rituximab on Day 1 of each 28-day cycle. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Aged 18 years or older
- Have previously untreated documented CLL according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
- Cumulative illness rating scale score <=6 and creatinine clearance >=70 mL/min as calculated by the Standard Cockcroft and Gault Formula
- Hematology values within the following limits, unless cytopenia is caused by the underlying disease (i.e., no evidence of additional BM dysfunction; e.g., myelodysplastic syndrome, hypoplastic BM): o Absolute neutrophil count >=1.0 × 109/L, unless there is BM involvement o Platelet count >=75 × 109/L and more than 7 days since last transfusion, or >=30 × 109/L if there is BM involvement
- Adequate liver function as indicated by a total bilirubin, aspartate aminotransferase, and Alanine transaminase <=2 times the institutional upper limit of normal value, unless directly attributable to the patient’s CLL
- Life expectancy >6 months
Exclusion criteria 6
- Transformation of CLL to aggressive non-Hodgkin’s lymphoma
- Patients with small lymphocyclic lymphoma (SLL) only (a diagnosis of CLL/SLL is permitted)
- Known central nervous system involvement
- Patients with a history of confirmed progressive multifocal leukoencephalopathy
- Detected del (17p) or TP53 mutation (valid test within 6-months from screening is required for randomization)
- An individual organ/system impairment score of 4 as assessed by the cumulative illness rating scale (CIRS) definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 1. MRD response rate measured in PB using next‑generation sequencing (NGS) at Month 15
Secondary endpoints 18
- 1. Progression-free survival
- 2. MRD response rate, in PB at end of treatment response visit
- 3. MRD response rate in BM at end of treatment response visit
- 4. ORR which includes complete remission (CR), complete remission with incomplete blood count recovery (Cri), and partial response (PR) at the Month 15 assessment
- 5. Complete response rate at the Month 15 assessment
- 6. MRD response rate in PB in patients with a complete remission /complete remission with incomplete blood count recovery (CR/Cri) at Month 15
- 7. MRD response rate in BM in patients with a CR/CRi at end of treatment visit
- 8. Best response up to and including the Month 15 assessment
- 9. Duration of objective response
- 10. Event-free survival
- 11. Overall survival
- 12. Tumor lysis syndrome risk reduction rate in Arm A
- 13. Reduction in mandatory hospitalizations during venetoclax ramp-up in Arm A
- 14. Changes in vital signs, physical findings, and clinical laboratory test results during and following study treatment
- 15. Premature withdrawals
- 16. Change in disease and treatment-related symptoms following treatment with the combination of VEN + G compared with FCR/BR in patients with previously untreated CLL without del (17p) or TP53 mutation as measured by MDASI-CLL
- 17. Change in physical functioning, role functioning and health-related quality of life following treatment with the combination of VEN + G compared with FCR/BR in patients with previously with previously untreated CLL without del(17p) or TP53 mutation as measured by EORTC QLQ-C30
- 18. Nature, frequency, and severity of adverse events and serious adverse event
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 4
Gazyvaro 1,000 mg concentrate for solution for infusion.
PRD1753415 · Product
- Active substance
- Obinutuzumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 1000 mg milligram(s)
- Max total dose
- 9 g gram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC15 — -
- Marketing authorisation
- EU/1/14/937/001
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/15/1504
- Modified vs. Marketing Authorisation
- No
PRD9859716 · Product
- Active substance
- Venetoclax
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 117.39 g gram(s)
- Max treatment duration
- 48 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- ABBVIE, INC.
- Paediatric formulation
- No
- Orphan designation
- No
PRD9859717 · Product
- Active substance
- Venetoclax
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 117.39 g gram(s)
- Max treatment duration
- 48 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- ABBVIE, INC.
- Paediatric formulation
- No
- Orphan designation
- No
PRD9859718 · Product
- Active substance
- Venetoclax
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 117.39 g gram(s)
- Max treatment duration
- 48 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- ABBVIE, INC.
- Paediatric formulation
- No
- Orphan designation
- No
Comparator 10
MabThera 500 mg concentrate for solution for infusion
PRD2154043 · Product
- Active substance
- Rituximab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 500 mg/m2 milligram(s)/sq. meter
- Max total dose
- 2875 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XC02 — RITUXIMAB
- Marketing authorisation
- EU/1/98/067/002
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD351417 · Product
- Active substance
- Cyclophosphamide Monohydrate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- IV INFUSION
- Max daily dose
- 250 mg/m2 milligram(s)/sq. meter
- Max total dose
- 4500 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01AA01 — CYCLOPHOSPHAMIDE
- Marketing authorisation
- 6035903.00.00
- MA holder
- BAXTER ONCOLOGY GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fludarabinphosphat "Ebewe", koncentrat til injektions-/infusionsvæske, opløsning
PRD727156 · Product
- Active substance
- Fludarabine Phosphate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 25 mg/m2 milligram(s)/sq. meter
- Max total dose
- 450 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- 41940
- MA holder
- EBEWE PHARMA
- MA country
- Denmark
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fludarabin Ebewe 25 mg/ml injektio-/infuusiokonsentraatti, liuosta varten
PRD745995 · Product
- Active substance
- Fludarabine Phosphate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 25 mg/m2 milligram(s)/sq. meter
- Max total dose
- 450 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- 22932
- MA holder
- EBEWE PHARMA
- MA country
- Finland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fludarabin Sandoz 25 mg/ml injekčný alebo infúzny koncentrát
PRD6079647 · Product
- Active substance
- Fludarabine Phosphate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 25 mg/m2 milligram(s)/sq. meter
- Max total dose
- 450 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- 44/0418/08-S
- MA holder
- SANDOZ PHARMACEUTICALS D.D.
- MA country
- Slovakia
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Neoflubin 25 mg/ml Konzentrat zur Herstellung einer Injektions- oder Infusionslösung
PRD719854 · Product
- Active substance
- Fludarabine Phosphate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 25 mg/m2 milligram(s)/sq. meter
- Max total dose
- 450 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- 1-27630
- MA holder
- EBEWE PHARMA
- MA country
- Austria
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fludarabine „Ebewe” 25 mg/ml, süste-/infusioonilahuse kontsentraat
PRD762371 · Product
- Active substance
- Fludarabine Phosphate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 25 mg/m2 milligram(s)/sq. meter
- Max total dose
- 400 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- 592808
- MA holder
- SANDOZ PHARMACEUTICALS D.D.
- MA country
- Estonia
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Levact 2,5 mg/ml Pulver für ein Konzentrat zur Herstellung einer Infusionslösung
PRD9513082 · Product
- Active substance
- Bendamustine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 90 mg/m2 milligram(s)/sq. meter
- Max total dose
- 1080 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01AA09 — -
- Marketing authorisation
- 70972.00.00
- MA holder
- PHARMAAND GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Levact 2,5 mg/ml poudre pour solution à diluer pour perfusion
PRD10144504 · Product
- Active substance
- Bendamustine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 90 mg/m2 milligram(s)/sq. meter
- Max total dose
- 1080 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01AA09 — -
- Marketing authorisation
- BE376022
- MA holder
- PHARMAAND GMBH
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Bendamustin cell pharm® 2,5 mg/ml Pulver für ein Konzentrat zur Herstellung einer Infusionslösung
PRD3489660 · Product
- Active substance
- Bendamustine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 90 mg/m2 milligram(s)/sq. meter
- Max total dose
- 1080 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01AA09 — -
- Marketing authorisation
- 95676.00.00
- MA holder
- STADAPHARM GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
F. Hoffmann-La Roche AG
- Sponsor organisation
- F. Hoffmann-La Roche AG
- Address
- Grenzacherstrasse 124
- City
- Basel
- Postcode
- 4058
- Country
- Switzerland
Scientific contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Public contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Third parties 6
| Organisation | City, country | Duties |
|---|---|---|
| Perceptive Informatics Inc. ORG-100013171
|
Billerica, United States | Interactive response technologies (IRT) |
| Yprime LLC ORG-100042888
|
Malvern, United States | Other |
| Q Squared Solutions LLC ORG-100043195
|
Durham, United States | Laboratory analysis |
| Adaptive Biotechnologies Corp. ORG-100044428
|
Seattle, United States | Laboratory analysis |
| CellCarta ORG-100039881
|
Antwerp, Belgium | Laboratory analysis |
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Laboratory analysis |
Locations
3 EU/EEA countries · 27 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 54 | 11 |
| Italy | Ended | 50 | 10 |
| Spain | Ended | 17 | 6 |
| Rest of world
United States, Australia
|
— | 45 | — |
Investigational sites
Centre Hospitalier Universitaire Reims
Hématologie clinique, Rue Du General Koenig, 51092, Reims Cedex
Hospices Civils De Lyon
Service Hématologie, 165 Chemin Du Grand Revoyet, 69310, Pierre Benite
Centre Hospitalier Universitaire De Bordeaux
Service d'Hématologie, Avenue De Magellan, 33600, Pessac
Centre Hospitalier Universitaire De Caen Normandie
Service d’Hématologie, Avenue De La Cote De Nacre, 14000, Caen
Centre Hospitalier Universitaire De Poitiers
Hématologie, 2 Rue De La Miletrie, 86000, Poitiers
Centre Hospitalier De Perpignan
Hématologie, 20 Avenue Du Languedoc, Cs 49954, Perpignan Cedex
Centre Hospitalier Intercommunal Toulon / La Seine-Sur-Mer
Hématologie, 54 Rue Henri Sainte Claire Deville, Cs 91400, Toulon Cedex
Centre Hospitalier Universitaire De Lille
Service des Maladies du Sang, Rue Michel Polonowski, 59000, Lille
Clinique Victor Hugo
Hématologie, Centre De Cancerologie De La Sarthe, 64 Rue De Degre, Le Mans
Assistance Publique Hopitaux De Paris
Service d'Hématologie Lymphoïde, 51 Avenue Du Mal De Lattre De Tassigny, 94010, Creteil Cedex
Centre Hospitalier Regional Universitaire De Tours
Hématologie, 2 Boulevard Tonnelle, 37044, Tours Cedex 9
Azienda Sanitaria Locale Della Provincia Di Lecce
U.O.C. Ematologia, Via Antonio Miglietta 5, 73100, Lecce
Azienda Ospedaliero Universitaria Di Modena
Struttura Complessa di Ematologia, Largo Del Pozzo 71, 41124, Modena
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Dip. Ematologia, Viale Del Policlinico 155, 00161, Rome
Hospital Santa Maria Della Misericordia
Dipartimento di Medicina, Piazzale Giorgio Menghini 1, 06129, Perugia
Istituto Tumori Bari Giovanni Paolo II
Unità S.C. di Ematologia, Viale Orazio Flacco 65, 70124, Bari
IRCCS Ospedale Policlinico San Martino
U.O. Ematologia, Largo Rosanna Benzi 10, 16132, Genoa
ASST Grande Ospedale Metropolitano Niguarda
Struttura Complessa di Ematologia, Piazza Dell'ospedale Maggiore 3, 20162, Milan
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Unità Operativa Semplice di Area (“U.O.S.A.”) di Leucemia Linfatica Cronica, Largo Francesco Vito 1, 00168, Rome
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
U.O.C. di Ematologia, Via Francesco Sforza 35, 20122, Milan
Azienda Ospedaliero-Universitaria Maggiore Della Carita
S.C.D.U. Ematologia, Corso Giuseppe Mazzini 18, 28100, Novara
Hospital Universitario De Toledo
Servicio de Hematología, Avenue Del Rio Guadiana Sn, 45007, Toledo
Hospital Universitario La Paz
Servicio de Hematología, Paseo De La Castellana 261, 28046, Madrid
University Hospital Virgen Del Rocio S.L.
Servicio de Hematología, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Universitario De Navarra
Servicio de Hematología, Irunlarrea Kalea 3, 31008, Pamplona
Institut Catala D'oncologia
Servicio de Hematología, Carretera Canyet S/n, 08916, Badalona
Hospital General Universitario Morales Meseguer
Servicio de Hematología, Avenida Del Marques De Los Velez S/n, 30008, Murcia
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 |
|---|---|---|---|---|---|
| France | 2020-07-24 | 2025-03-19 | 2020-08-04 | 2023-01-23 | |
| Italy | 2020-05-13 | 2025-03-11 | 2020-05-20 | 2023-01-23 | |
| Spain | 2020-05-07 | 2025-03-18 | 2020-06-15 | 2023-01-23 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| CO41685_CTIS Final Results SUM-114248
|
2026-01-12T14:16:48 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| LPS_CO41685 | 2026-01-12T14:36:13 | Submitted | Laypersons Summary of Results |
Documents 27 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | LPS_CO41685_CRISTALLO_Final-results_04Nov_EN | NA |
| Laypersons summary of results (for publication) | LPS_CO41685_CRISTALLO_Final-results_04Nov_EN_ES-ES | NA |
| Laypersons summary of results (for publication) | LPS_CO41685_CRISTALLO_Final-results_04Nov_EN_FR-FR | NA |
| Laypersons summary of results (for publication) | LPS_CO41685_CRISTALLO_Final-results_04Nov_EN_IT-IT | NA |
| Protocol (for publication) | D1_Protocol 2023-504036-17-00 Redacted | 5 |
| Protocol (for publication) | d4_patient-facing-memo | 2 |
| Recruitment arrangements (for publication) | K Rcurit_arrenge_doc | 1 |
| Recruitment arrangements (for publication) | K_Rcurit_arrenge_doc | 1 |
| Recruitment arrangements (for publication) | K_Recruitment arrengement | N/A |
| Recruitment arrangements (for publication) | K0_Document additionnel CTR_2023-504036-17-00 redacted | 1 |
| Subject information and informed consent form (for publication) | L_ICF_Main | 6 |
| Subject information and informed consent form (for publication) | L_ICF_Main | 5 |
| Subject information and informed consent form (for publication) | L_ICF_PPA | 1 |
| Subject information and informed consent form (for publication) | L_ICF_PPA | 1 |
| Subject information and informed consent form (for publication) | L_ICF_RBR | 2 |
| Subject information and informed consent form (for publication) | L_ICF_RBR | 2 |
| Subject information and informed consent form (for publication) | L1_Privacy consent form other subject | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF main | 5.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF partner | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Endoxin | NA |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Fludarabin | NA |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Levact | NA |
| Summary of results (for publication) | CO41685_CTIS Final Results | NA |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_ENG-2023-504036-17-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_esES-2023-504036-17-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_FRFR-2023-504036-17-00 | 2 |
| Synopsis of the protocol (for publication) | d1_protocol-synopsis_ITIT-2023-504036-17-00 | 2 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-19 | Italy | Acceptable 2024-07-26
|
2024-07-29 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-10-11 | Italy | Acceptable 2025-01-27
|
2025-01-27 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-02-07 | Italy | Acceptable 2025-01-27
|
2025-02-07 |
| 4 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-02-13 | Italy | Acceptable | 2025-04-17 |
| 5 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-02-14 | Acceptable | 2025-04-11 |