Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - Other
Status
Ongoing, recruiting
Participants planned
38
Countries
1
Sites
6
Patients with myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) or secondary acute myeloid leukemia (sAML) before stem cell transplantation
To find the MTD of Venetoclax when added to Fludarabin, Amsacrine and Ara-C + Treosulfan and evaluate , whether the addition of Venetoclax to sequential conditioning with Fludarabine + Amsacrine + Ara-C (FLAMSA) + Treosulfan for allogeneic blood stem cell transplantation in patients with high-risk MDS, CMML or sAML (FL…
Key facts
- Sponsor
- Heinrich-Heine-Universitaet Duesseldorf
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Trial duration
- 26 May 2023 → ongoing
- Decision date (initial)
- 2024-07-25
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- AbbVie Deutschland GmbH & Co. KG · Eurocept International B.V. · Medac GmbH
External identifiers
- EU CT number
- 2024-514688-24-00
- EudraCT number
- 2022-002435-66
- ClinicalTrials.gov
- NCT05807932
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
To find the MTD of Venetoclax when added to Fludarabin, Amsacrine and Ara-C + Treosulfan and evaluate , whether the addition of Venetoclax to sequential conditioning with Fludarabine + Amsacrine + Ara-C (FLAMSA) + Treosulfan for allogeneic blood stem cell transplantation in patients with high-risk MDS, CMML or sAML (FLAMSAClax) is safe
Secondary objectives 3
- To assess incidence, course und severity of aGvHD and cGvHD as well as incidence, course and severity of VOD and graft failure, time to hematopoietic reconstitution (ANC>500/μl, PLT>20000/μl and PLT>50000/μl) and time to transfusion independence
- To analyse best response within the first 100 days (± 7) after transplantation (according to IWG-criteria for MDS and ELN-criteria for AML) as well as response rates at day +30 (± 3) , +60 (± 7) and +100 (± 7) after transplantation. In detail, time to complete donor chimerism in blood and marrow and disappearance of molecular markers of disease
- To evaluate event-free survival, cumulative incidence of relapse and overall survival
Conditions and MedDRA coding
Patients with myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) or secondary acute myeloid leukemia (sAML) before stem cell transplantation
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | LLT | 10024329 | Leukemia | 10029104 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Treatment period Conditioning therapy before allogeneic blood stem cell transplantation (Standard of care with Fludarabine, Amsacrine, Ara-C followed by Treosulfan) including 6 or 8 days of Venetoclax treatment
|
Not Applicable | None | ||
| 2 | Follow-up period Patients will be followed up for 2 years after allogeneic blood stem cell transplantation to collect data on disease status and survival
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- MDS, CMML or sAML according to WHO classification (revised version 2016) with a marrow blast count >5% and/or high-risk genetic features (eg. bad risk karyotype according to the IPSS-R / ELN classification or presence of unfavorable somatic mutations (e.g. TP53, RUNX1, IDH1, IDH2, KMT2A, DEK-NUP214 or RAS pathway mutations including NRAS, KRAS, PTPN11, CBL, NF1, RIT1 or KIT), falling into the "high" or "very high" risk category of the IPSS-R or IPSS M) any time between diagnosis and inclusion.
Exclusion criteria 1
- previous cytotoxic therapy exceeding oral Hydroxyurea or >2 courses of treatment with Azacytidine, Decitabine or low dose Ara-C alone or in combination with Venetoclax
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- safety, defined as the maximal organ toxicity to each organ system according to CTC criteria as well as the number of AEs of grade III or greater until day +30 (± 3) after transplantation
Secondary endpoints 13
- safety, defined as the maximal organ toxicity to each organ system according to CTC criteria as well as the number of AEs of grade III or greater until day +100 (± 7) after transplantation
- graft failure defined as no donor chimerism at day +30 (± 3) after transplantation
- incidence, course und severity of aGvHD and cGvHD during the first 2 years after transplantation
- incidence, course and severity of VOD
- time (days from day 0) to hematopoietic reconstitution (ANC>500/µl, PLT>20000/µl and PLT>50000/µl)
- time (days from day 0) to transfusion independence
- best disease response within the first 100 days (± 7) after transplantation (according to IWG-criteria for MDS and ELN-criteria for AML)
- disease response and donor chimerism at day +30 (± 3), +60 (± 7) and +100 (± 7) after transplantation (according to IWG-criteria for MDS and ELN-criteria for AML)
- time (days from day 0) to complete donor chimerism in blood and marrow
- disappearance of molecular markers of disease (yes/no, time in days from day 0 )
- event-free survival (EFS, death, relapse and disease progression will be recorded as event)
- cumulative incidence of relapse (CIR, disease progression and relapse will be recorded as event)
- overall survival (OS, death will be recorded as event)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 5
SCP2015642 · ATC
- Active substance
- Amsacrine
- Route of administration
- INTRAVENOUS
- Authorisation status
- Authorised
- ATC code
- L01XX01 — AMSACRINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP139856 · ATC
- Active substance
- Mycophenolate Mofetil
- Route of administration
- ORAL
- Authorisation status
- Authorised
- ATC code
- L04AA06 — MYCOPHENOLIC ACID
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP133064 · ATC
- Active substance
- Tacrolimus
- Substance synonyms
- TACROLIMUS ANHYDROUS
- Route of administration
- ORAL
- Authorisation status
- Authorised
- ATC code
- L04AD02 — TACROLIMUS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD2186236 · Product
- Active substance
- Venetoclax
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Authorisation status
- Not Authorised
- MA holder
- ABBVIE DEUTSCHLAND GMBH & CO. KG
- Paediatric formulation
- No
- Orphan designation
- No
SCP142361 · ATC
- Active substance
- Cytarabine
- Substance synonyms
- ARA-C, CYTOSINE ARABINOSIDE
- Route of administration
- INTRAVENOUS
- Authorisation status
- Authorised
- ATC code
- L01BC01 — CYTARABINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 8
SCP172157 · ATC
- Active substance
- Mycophenolic Acid
- Substance synonyms
- MYCOPHENOLATE
- Route of administration
- INFUSION
- Authorisation status
- Authorised
- ATC code
- L04AA04 — ANTITHYMOCYTE IMMUNOGLOBULIN (RABBIT)
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP180112 · ATC
- Active substance
- Glatiramer Acetate
- Substance synonyms
- COPOLYMER-1
- Route of administration
- INJECTION
- Authorisation status
- Authorised
- ATC code
- L03AA13 — PEGFILGRASTIM
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP130703 · ATC
- Active substance
- Allopurinol
- Route of administration
- ORAL
- Authorisation status
- Authorised
- ATC code
- M04AA01 — ALLOPURINOL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP107125968 · ATC
- Active substance
- Fludarabine Phosphate
- Substance synonyms
- FLUDARABINE 5'-MONOPHOSPHATE, FLUDARABINE MONOPHOSPHATE
- Route of administration
- INFUSION
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP8268998 · ATC
- Active substance
- Rasburicase
- Route of administration
- INFUSION
- Authorisation status
- Authorised
- ATC code
- V03AF07 — RASBURICASE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP104873455 · ATC
- Active substance
- Febuxostat Hemihydrate
- Route of administration
- ORAL
- Authorisation status
- Authorised
- ATC code
- M04AA03 — FEBUXOSTAT
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP2062450 · ATC
- Active substance
- Treosulfan
- Route of administration
- INFUSION
- Authorisation status
- Authorised
- ATC code
- L01AB02 — TREOSULFAN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP118777783 · ATC
- Active substance
- Filgrastim
- Substance synonyms
- NT100H, FILGRASTIM (GENETICAL RECOMBINATION)
- Route of administration
- INJECTION
- Authorisation status
- Authorised
- ATC code
- L03AA02 — FILGRASTIM
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Heinrich-Heine-Universitaet Duesseldorf
- Sponsor organisation
- Heinrich-Heine-Universitaet Duesseldorf
- Address
- Universitaetsstrasse 1, Bilk Bilk
- City
- Duesseldorf
- Postcode
- 40225
- Country
- Germany
Scientific contact point
- Organisation
- Heinrich-Heine-Universitaet Duesseldorf
- Contact name
- Prof. Guido Kobbe
Public contact point
- Organisation
- Heinrich-Heine-Universitaet Duesseldorf
- Contact name
- Prof. Guido Kobbe
Locations
1 EU/EEA country · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ongoing, recruiting | 38 | 6 |
| Rest of world | — | 0 | — |
Investigational sites
University Hospital Cologne AöR
Klinik I für Innere Medizin, Kerpener Strasse 62, Lindenthal, Cologne
Universitaetsklinikum Duesseldorf AöR
Klinik für Hämatologie, Onkologie und Klinische Immunologie, Moorenstrasse 5, Bilk, Duesseldorf
Universitaetsklinikum Jena KöR
Klinik für Innere Medizin II, Am Klinikum 1, Lobeda, Jena
Klinikum rechts der Isar der TU Muenchen AöR
Klinik und Poliklinik für Innere Medizin III, Ismaninger Strasse 22, Au-Haidhausen, Munich
Universitaetsklinikum Aachen AöR
Klinik für Hämatologie, Onkologie, Hämastaseologie und Stammzelltransplantation, Pauwelsstrasse 30, 52074, Aachen
Universitaetsklinikum Frankfurt AöR
Medizinische Klinik II, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
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 |
|---|---|---|---|---|---|
| Germany | 2023-05-26 | 2023-09-13 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 12 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-514688-24 V04F 20250415 redacted | 4 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements Placeholder | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF FLAMSAClax | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Schwangerschaft Partner FLAMSAClax | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Schwangerschaft Partnerin FLAMSAClax | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Schwangerschaft Studienteilnehmerin FLAMSAClax | 2 |
| Subject information and informed consent form (for publication) | L2_Other subject information material Infoschreiben Anderungen | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material Patiententagebuch 400mg | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material Patiententagebuch 400mg Vortherapie | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material Patiententagebuch 800mg | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material Patiententagebuch 800mg Vortherapie | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2024-514688-24_redacted | 4 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-09 | Germany | Acceptable 2024-07-24
|
2024-07-25 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-04-30 | Germany | Acceptable 2025-06-02
|
2025-06-25 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-08-07 | Germany | Acceptable 2025-08-27
|
2025-08-29 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-10-09 | Germany | Acceptable 2025-08-27
|
2025-10-09 |
| 5 | SUBSTANTIAL MODIFICATION | SM-3 | 2026-04-01 | Germany | Acceptable 2026-04-27
|
2026-05-06 |