Combination Salvage Therapy With Venetoclax and Decitabine in Relapsed/Refractory AML

Who may be able to join

• 1. Diagnosis of AML according to WHO criteria regardless of subtype, including de novo and transformed MPN and transformed MDS 2. A. Refractory to induction chemotherapy consisting of Daunorubicin+Cytarabin ("3+7") based chemotherapy, including CPX351, including combinations with GemtuzumabOzogamicin or with the FLT3-inhibitors Midostaurin or Quizartinib. This trial defines refractory disease as one of the following: i. ≥20% bone marrow blasts at day 15 first cycle of intensive induction chemotherapy ii. ≥5-20% bone marrow blasts at day 15 of first cycle of intensive induction chemotherapy in patients, in whom relative blast count reduction as compared to initial diagnosis is ≤50% iii. c) ≥5% bone marrow blasts at day 28 of first cycle of induction chemotherapy, or at any point during a second cycle of induction chemotherapy OR 2. B. Relapse of AML/MDS IB2 after chemotherapy (≥5% medullary blasts in bone marrow assessment) 3. Must be ≥ 18 years at the time of signing the informed consent. 4. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures. 5. Able to adhere to the study visit schedule and other protocol requirements. 6. Patient is fit for aggressive induction chemotherapy and transplantation by assessment of an experienced hematologist 7. No known history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide (DLCO) >40% (adjusted for hemoglobin, if available) and FEV1/FVC >50% 8. Subject (male or female (FCBP))1 is willing to use highly effective birth control methods during treatment and for 3 months (male) and 6 months (female) after the end of treatment (adequate: combined hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition ofvulation, intrauterine device, intrauterine hormone-releasing system bilateral tubal occlusion, vasectomized partner2 sexual abstinence3). Female subjects who use hormonal contraceptives should also use a barrier method.
• A FCBP is defined as any female who does not meet the criteria of non-childbearing potential. These are as follows:
• documented hysterectomy, bilateral oophorectomy (ovarectomy), or bilateral tubal ligation
• post-menopausal (a practical definition accepts menopause ≥ 1 year without menses with an appropriate clinical profile, e.g. age > 45 years in the absence of hormone replacement therapy (HRT). In questionable cases, the subject must have a follicle stimulating hormone (FSH) value > 40 mIU/ml and an estradiol value < 40pg/ml.
• Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success
• In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. 9. All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment. 10. All subjects must agree not to share medication.
• in bone marrow aspiration cytomorphology, or bone marrow pathology, if aspiration morphology not available or not representative * time frame of tolerance from day 13 to day 20 **time frame of tolerance from day 21 to day 42