Venetoclax for Acute myeloid leukemia | Myelodysplastic syndrome (higher-risk)

Inclusion criteria

• {"criterion_text":"- Age between 18 and 75 years at the time of signing the Informed Consent"}
• {"criterion_text":"- Availability of a suitable donor"}
• {"criterion_text":"- Documented diffusion lung capacity for carbon monoxide (DLCO) >40% (adjusted for hemoglobin, if available) and FEV1/FVC >50%"}
• {"criterion_text":"- Left ventricular ejection fraction (LVEF) ≥40%"}
• {"criterion_text":"- GFR (CKD-EPI) ≥ 30 ml/min/1,73 m2"}
• {"criterion_text":"- Bilirubin≤ 3x ULN and AST ≤ 5x ULN"}
• {"criterion_text":"- Thoracic imaging (either X-ray or computed tomography (CT)) without evidence of active infection or second malignancy"}
• {"criterion_text":"- Absence of an active, clinically uncontrolled infection"}
• {"criterion_text":"- Subject (male or female) is willing to use highly effective methods during treatment and for 6 months (male or female) after the end of treatment (adequate: combined hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner1, sexual abstinence2). Female participants using homonal contraceptives should use a barrier method as well"}
• {"criterion_text":"- Absence of pregnancy confirmed by a highly sensitive pregnancy test not older than 3 days at time of screening (only FCBP)."}
• {"criterion_text":"- Subject agrees not to share medication"}
• {"criterion_text":"- Patient is fluent in German"}
• {"criterion_text":"- Signed written Informed Consent with the cognitive ability to understand all consequences of trial participation and to comply with all trial relatred procedures"}
• {"criterion_text":"- Diagnosis of AML,MDS/AML (according to ICC 20226) or HR- MDS (IPSS-R7 >3.5 or IPSS-M8 >0; according to ICC 20226 and IWG 20232)"}
• {"criterion_text":"- Myeloid neoplasm (AML, MDS/AML or higher-risk MDS according to ICC 20226 and IWG 20232) under control* at time of screening"}
• {"criterion_text":"- Eligiblity for alloHCT according to a board of experienced haematologist"}
• {"criterion_text":"- Karnofsky Performance Index ≥60%"}
• {"criterion_text":"- Planned alloHCT with Peripheral Blood Stem Cells (PBS"}
• {"criterion_text":"- nfusion of allogeneic stem cells schedulded between day 14 and day 28 after Screening"}

Exclusion criteria

• {"criterion_text":"- APL (AML with t(15;17))"}
• {"criterion_text":"- MDS/MPN (ICC 20226)"}
• {"criterion_text":"- Karnofsky Performance Index <60%"}
• {"criterion_text":"- Patient scheduled for haploidentical allogeneic hematopoetic stem cell transplantation or bone marrow stem cell transplantation"}
• {"criterion_text":"- Presence of extramedullary myelosarcoma"}
• {"criterion_text":"- Disease Relapse after prior CRc (see Appendix for Definition"}
• {"criterion_text":"- History of allogeneic hematopoietic stem cell transplantation"}
• {"criterion_text":"- Significant active cardiac disease within 6 months prior to the start of study treatmen"}
• {"criterion_text":"- Documented diffusion lung capacity for carbon monoxide (DLCO) ≤40% (adjusted for hemoglobin, if available) and FEV1/FVC ≤50%"}
• {"criterion_text":"- GFR (CKD-EPI) < 30 ml/min/1,73 m2"}
• {"criterion_text":"- Bilirubin> 3x ULN or AST > 5x ULN"}
• {"criterion_text":"- Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia."}
• {"criterion_text":"- Active viral infection, including hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection, that is uncontrolled prior to first dose of study treatment and may interfere with the study objectives or which could expose the patient to undue risk through the participation in the clinical trial. An infection controlled with an approved antiviral treatment is allowed"}
• {"criterion_text":"- Presence of Proven, Probable or Possible Invasive Fungal Disease (IFD) as defined by EORTC/MSG 20209 Definitions (please consult Appendix)."}
• {"criterion_text":"- Serologies suggestive of recent (<6 months) infection or reactivation with/of Toxoplasma gondii (based on IgG, IgM and Avidity) or of infection with Treponema pallidum (based on TPPA)."}
• {"criterion_text":"- Any clinically uncontrolled infection (bacterial or unknown pathogen), defined as persisting or recurring fever or rising levels of CRP (≥10 mg/dl) despite intravenous antibacterial or antifungal therapy (initiated or escalated at least 72h hours ago)."}
• {"criterion_text":"- mmediate life‐threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminated intravascular coagulation"}
• {"criterion_text":"- Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs."}
• {"criterion_text":"- Patients with a currently active second malignancy. Patients are not considered to have a currently active malignancy, if they have completed therapy and are considered by their physician to be at <30% risk of relapse within one year. However, patients with the following history/concurrent conditions are allowed: • Basal or squamous cell carcinoma of the skin; • Carcinoma in situ of the cervix; • Carcinoma in situ of the breast; • Incidental histologic finding of prostate cancer"}
• {"criterion_text":"- Receipt of live, attenuated vaccine within 30 days prior to the study inclusion (NOTE: patients, if enrolled, should not receive live vaccine during the study and until 6 months after the therapy)"}
• {"criterion_text":"- Severe neurological or psychiatric disorder interfering with ability to give an informed consent"}
• {"criterion_text":"- Women during pregnancy and lactation"}
• {"criterion_text":"- History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product"}
• {"criterion_text":"- Participation in other trials interfering with the endpoint of this study. Prior trial participation is permitted, provided that treatment with the investigational medicinal product has been completed at least 4 days prior to screening for this trial (at least 10 days before study treatment)"}

Primary endpoints

• {"endpoint_text":"- Overall Survival (OS) at day 28 after alloHCT","definition_or_measurement_approach":"Overall Survival (OS) at day 28 after alloHCT (as stated in primaryEndPoints/mainObjective); no further definition provided in the record."}

Secondary endpoints

• {"endpoint_text":"- Adverse Events ≥ CTCAE grade 4","definition_or_measurement_approach":"Adverse events graded by CTCAE (grade 4 or higher) from first day of conditioning until day 28 after alloHCT (as stated in secondary objectives)."}
• {"endpoint_text":"- Non-relapse Mortality (NRM) at day 100 after alloHCT","definition_or_measurement_approach":"Non-relapse mortality assessed at day 100 after alloHCT (no additional measurement detail provided)."}
• {"endpoint_text":"- Overall survival (OS) day 100 after alloHCT","definition_or_measurement_approach":"Overall survival assessed at day 100 after alloHCT."}
• {"endpoint_text":"- Cumulative Incidence of Relapse (CIR) day 100 after alloHCT","definition_or_measurement_approach":"Cumulative incidence of relapse at day 100 after alloHCT (no additional detail provided)."}
• {"endpoint_text":"- Adverse Events ≥ CTCAE grade 3","definition_or_measurement_approach":"Adverse events graded by CTCAE (grade 3 or higher)."}
• {"endpoint_text":"- Rate of delayed Engraftment at day 28 after alloHCT","definition_or_measurement_approach":"Rate of delayed engraftment assessed at day 28 after alloHCT."}
• {"endpoint_text":"- Stage and Grade of acute GVHD at day 100 after alloHCT","definition_or_measurement_approach":"Assessment of acute graft-versus-host disease stage and grade at day 100 after alloHCT."}
• {"endpoint_text":"- Composite Complete Remission (cCR) Rate at day 100 after alloHCT by pathological assessement of bone marrow biopsy** and peripheral blood count","definition_or_measurement_approach":"Composite complete remission rate at day 100 assessed by bone marrow biopsy pathology and peripheral blood counts."}
• {"endpoint_text":"- Rate of MRD-negativity at day 100 after alloHCT by flow cytometric assessment","definition_or_measurement_approach":"MRD-negativity rate at day 100 assessed by flow cytometry."}
• {"endpoint_text":"- Rate of MRD-negativity at day 100 after alloHCT by qPCR","definition_or_measurement_approach":"MRD-negativity rate at day 100 assessed by qPCR."}
• {"endpoint_text":"- Rate of complete Donor Chimersim","definition_or_measurement_approach":"Rate of complete donor chimerism (based on STR using PCR) in peripheral blood and bone marrow at day 100 after alloHCT (as stated in objectives)."}
• {"endpoint_text":"- Rate of patients with >50/µl T-helper cells at day 100 after alloHCT by flow cytometric assessment","definition_or_measurement_approach":"Rate of patients with >50/µl T-helper cells at day 100 assessed by flow cytometry."}
• {"endpoint_text":"- Health-related Quality of Life at day 100 after alloHCT assessed with FACT-BMT4 and EQ-5D- 5L-VAS5","definition_or_measurement_approach":"HRQoL at day 100 measured by FACT-BMT and EQ-5D-5L VAS instruments."}
• {"endpoint_text":"- Cumulative number of hospitalized days at day 100","definition_or_measurement_approach":"Total number of hospitalized days up to day 100 after alloHCT."}

Germany

Earliest CTIS Part Ii Submission Date

05-08-2025

Latest Decision Or Authorization Date

23-09-2025

Processing Time Days

49

Number Of Sites

1

Number Of Participants

27

Primary sponsor

Full Name

Universitaetsklinikum Tuebingen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany