This trial aims to find the MTD of Venetoclax when added to Fludarabin, Amsacrine and Ara-C + Treosulfan and to evaluate whether the addition of Venetoclax to sequential conditioning with FLAMSA + Treosulfan is safe for allogeneic blood stem cell transplantation in patients with high-risk MDS, CMML or sAML (FLAMSAClax)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Study treatment consists of the conditioning therapy including 6 or 8 days of Venetoclax treatment.
Amsacrine is part of the conditioning therapy and is administered on day -10 to -7 before allogeneic blood stem cell transplantation
Ara-C is part of the conditioning therapy and is administered on day -10 to -7 before allogeneic blood stem cell transplantation
Tacrolimus is used for prophylaxis of acute and chronic graft-versus-host-disease according to institutional standards.
Mycophenolate Mofetil is used for prophylaxis of acute and chronic graft-versus-host-disease according to institutional standards.
Universitätsklinikum Aachen - Med. Klinik IV
Aachen, North Rhine-Westphalia, Germany
RECRUITINGUniversitätsklinikum Düsseldorf - Klinik für Hämatologie, Onkologie und Klinische Immunologie
Düsseldorf, North Rhine-Westphalia, Germany
RECRUITINGUniversitätsklinikum Köln Klinik I für Innere Medizin
Cologne, Germany
RECRUITINGUniversitätsklinikum Frankfurt Medizinische Klinik II
Frankfurt, Germany
RECRUITINGUniversitätsklinikum Jena - Klinik für Innere Medizin II
Jena, Germany
RECRUITINGKlinikum rechts der Isar der TU München Klinik und Poliklinik für Innere Medizin III
München, Germany
RECRUITINGThe primary target variable is 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 within the first 30 days (± 3) after transplantation
maximal organ toxicity to each organ system according to CTC criteria as well as the number of AEs of grade III or greater within the first 30 days (± 3) after transplantation
Time frame: inclusion until day 30 (± 3) 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
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
Time frame: inclusion until day +100 (± 7) after transplantation
Graft failure at day +30 (± 3) after transplantation
Number of patients with graft failure (no donor chimerism at day +30 (± 3) after transplantation)
Time frame: transplantation until day +30 (± 3) after transplantation
Incidence of aGvHD during the first 2 years after transplantation
Incidence of aGvHD during the first 2 years after transplantation
Time frame: transplantation until 2 years after transplantation
Course of aGvHD during the first 2 years after transplantation
Course of aGvHD during the first 2 years after transplantation (response/no response to steroids)
Time frame: transplantation until 2 years after transplantation
Severity of aGvHD during the first 2 years after transplantation
Severity of aGvHD during the first 2 years after transplantation (according to Glucksberg criteria)
Time frame: transplantation until 2 years after transplantation
Incidence of cGvHD during the first 2 years after transplantation
Incidence of cGvHD during the first 2 years after transplantation
Time frame: transplantation until 2 years after transplantation
Course of cGvHD during the first 2 years after transplantation
Course of cGvHD during the first 2 years after transplantation (response/no response to steroids)
Time frame: transplantation until 2 years after transplantation
Severity of cGvHD during the first 2 years after transplantation
Severity of cGvHD during the first 2 years after transplantation (according to NIH criteria)
Time frame: transplantation until 2 years after transplantation
Incidence, course and severity of VOD
Incidence, course and severity of VOD (according to EBMT criteria)
Time frame: transplantation until 2 years after transplantation
Time to hematopoietic reconstitution
Time (days from day 0) to hematopoietic reconstitution (ANC\>500/µl, PLT\>20000/µl and PLT\>50000/µl)
Time frame: From date of transplantation (day 0) until the date of first documented hematopoietic reconstitution, assessed up to day 100
Time to transfusion independence
Time (days from day 0) to transfusion independence
Time frame: From date of transplantation (day 0) until the date of first documented transfusion independence, assessed up to day 100
Best disease response within the first 100 days (± 7) after transplantation
Best disease response within the first 100 days (± 7) after transplantation (according to IWG-criteria for MDS and ELN-criteria for AML)
Time frame: Transplantation to day 100 (± 7) after transplantation
Disease response and donor chimerism at day +30 (± 3), +60 (± 7) and +100 (± 7) after transplantation
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 frame: Transplantation until days +30 (± 3), +60 (± 7) and +100 (± 7) after transplantation
Time to complete donor chimerism in blood and marrow
Time (days from day 0) to complete donor chimerism in blood and marrow
Time frame: From date of transplantation (day 0) until the date of first documented donor chimerism in blood and marrow, assessed up to day 100
Disappearance of molecular markers of disease
Disappearance of individual molecular markers of disease (time in days from day 0)
Time frame: From date of transplantation (day 0) until the date of first documented disappearance of individual molecular marker, assessed through study completion, an average of 2 years
Event-free survival
Event-free survival (death,relapse and disease progression will be recorded as event)
Time frame: inclusion until 2 years after transplantation
Cumulative incidence of relapse
Cumulative incidence of relapse (disease progression and relapse will be recorded as event)
Time frame: inclusion until 2 years after transplantation
Overall survival
Overall survival (OS, death will be recorded as event)
Time frame: inclusion until 2 years after transplantation
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