Phase-I/II trial to assess the safety and efficacy of Venetoclax in addition to sequential conditioning with Fludarabine / Amsacrine / Ara-C (FLAMSA) + Treosulfan for allogeneic blood stem cell transplantation in patients with MDS, CMML or sAML

Heinrich-Heine-Universitaet Duesseldorf6 sites in 1 country38 target enrollmentJuly 25, 2024

Overview

Phase: Phase 1/2
Intervention: Not specified
Conditions: Not specified
Sponsor: Heinrich-Heine-Universitaet Duesseldorf
Enrollment: 38
Locations: 6
Primary Endpoint: 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
Status: Recruiting
Last Updated: 10 months ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

euclinicaltrials.eu

Start Date

July 25, 2024

End Date

TBD

Last Updated

10 months ago

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Heinrich-Heine-Universitaet Duesseldorf

Responsible Party

Principal Investigator

Prof. Guido Kobbe

Scientific

Heinrich-Heine-Universitaet Duesseldorf

Eligibility Criteria

Inclusion Criteria

•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

•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

Outcomes

Primary Outcomes

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 Outcomes

incidence, course und severity of aGvHD and cGvHD during the first 2 years after transplantation
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 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)