A Randomized, Placebo-Controlled Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2
- Conditions
- Acute myeloid leukemia, Myelodysplastic Syndrome With Excess Blasts-2Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Registration Number
- CTIS2023-507518-28-00
- Lead Sponsor
- niversitaetsklinikum Ulm AöR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 250
Patients with newly diagnosed acute myeloid leukemia (AML), or myelodysplastic syndrome with excess blasts-2 (MDS-EB2) according to World Health Organization (WHO) classification, Female patient must either: o Be of nonchildbearing potential: •Postmenopausal (defined as at least 1 year without any menses) •Documented surgically sterile (e.g. documented hysterectomy, bilateral oophorectomy, bilateral salpingectomy or congenital sterile) or status posthysterectomy (at least 1 month prior to screening) o Or, if of childbearing potential (not surgically sterile and not postmenopausal) •Not planning to become pregnant during the study and for 27 weeks after the final study drug administration •And have a negative urine or serum pregnancy test at screening •And, if heterosexually active, agree to consistently apply one highly effective* method of birth control in combination to a barrier method for the duration of the study and for 27 weeks after the final study drug administration. *Highly effective forms of birth control include ?Consistent and correct usage of established hormonal contraceptives that inhibit ovulation, for at least 1 month prior to taking study drug. (Hormonal contraception is only a highly effective method of birth control, if a combined (estrogen and progestogen containing) hormonal contraception or a progestogen-only hormonal contraception – both associated with inhibition of ovulation - is used.) ?Established intrauterine device (IUD) or intrauterine system (IUS), ?Bilateral tubal occlusion, ?Vasectomy - a vasectomy is a highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used. ?Male is sterile due to a bilateral orchiectomy. ?Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual activity during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. *List is not all inclusive. Prior to enrolment, the investigator is responsible for confirming patient will utilize highly effective forms of birth control in combination with a barrier method according to locally accepted standards during the protocol defined period. •Female patient must agree not to breastfeed starting at screening and throughout the study period, and for 2 months and 1 week after the final study drug administration. •Female patient must not donate ova starting at screening and throughout the study period, and for 27 weeks after the final study drug administration., Men must use a latex condom during any sexual contact with WOCBP, even if they have undergone a successful vasectomy and must agree to avoid to father a child (while on therapy and for 27 weeks after the final study drug administration). In addition, their female partners of childbearing potential have to use a highly effective method of birth control., Male patient must not donate sperm starting at screening and throughout the study period and for 6 months after the final study drug administration., Able to understand and willing to sign an informed consent form (ICF)., Age = 18 years, no upper age limit, Patients considered eligible for intensive chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status = 2., Molecular analysis centrally p
Acute promyelocytic leukemia (APL) with t(15;17)(q24.1;q21.1); PML-RARA; or one of the other pathognomonic variant chromosomal translocations/ fusion genes., Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs., 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: oBasal or squamous cell carcinoma of the skin; oCarcinoma in situ of the cervix; oCarcinoma in situ of the breast; oIncidental histologic finding of prostate cancer., 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)., Severe neurological or psychiatric disorder interfering with ability to give an informed consent., Known or suspected hypersensitivity to any of the chemotherapeutic agents used., No consent for registration, storage and processing of the individual disease characteristics and course as well as information of the family physician about study participation., No consent for biobanking of patient’s biological specimens., Participation in other prospective studies with anti-leukemic and/or investigational agents., The patient is a pregnant or lactating woman, or plans to become pregnant during the study., AML with t(9;22)(q34.1;q11.2)/BCR::ABL1; or myeloid blast crisis of CML., Patients with AML and activating FLT3 mutations who have access (including reimbursement) to treatment with a FLT3 inhibitor approved for first-line therapy of AML., Prior treatment of MDS with intensive chemotherapy or allogeneic hematopoietic cell transplantation (HCT) with a curative intent, Significant active cardiac disease within 6 months prior to the start of study treatment, including: oNew York Heart Association (NYHA) class III or IV congestive heart failure; oMyocardial infarction; oUnstable angina and/or stroke; oSevere cardiac arrhythmias oLeft ventricular ejection fraction (LVEF) <40% by ultrasound obtained within 28 days prior to the start of study treatment., Severe obstructive or restrictive ventilation disorder., Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening is only required, if there is a clinical suspicion of CNS involvement by leukemia during screening., Active infection, including hepatitis B or hepatitis C antibody 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 antibiotic/ antiviral/ antifungal treatment that is not a strong or moderate CYP3A inducer is allowed., Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminated intravascular coagulation.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method