ABT-199 (Venetoclax) and Purine analogues as Novel Oral Drug Combination for Treatment of Relapsed/Refractory Acute Myeloid Leukemia (ApoAML)
- Conditions
- Acute myeloid leukemiaMedDRA version: 21.0Level: LLTClassification code: 10000886Term: Acute myeloid leukemia Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2024-510717-15-00
- Lead Sponsor
- Antwerp University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
Relapsed or refractory (r/r) AML • Diagnosis of acute myeloid leukemia (AML) according to the 2008 criteria of the World Health Organization (WHO). • All French-American-British (FAB) subtypes, except: M3 (acute promyelocytic leukemia) • Relapsed after or refractory to at least one cycle of intensive chemotherapy (combination of ara-c/anthracyclin) or four cycles of HMA (hypomethylating agents). Relapse and refractory disease will be defined according to the Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia 20 . Relapse is defined as >5% blasts in the bone marrow not attributed by another cause and occurring after initial remission. Refractory disease is defined as persistent AML in peripheral blood or bone marrow (>5%) at least =7 days after completion of the initial induction treatment. • Adult AML aged >/= 18 years • WHO performance status: 0-3 at the time of enrollment. Inclusion of a patient with WHO performance status 3 is only allowed if functional impairment is believed to be mainly attributed to the underlying disease (in this case AML). • ABT-199 (venetoclax) and PA-naïve. Patient may be prior exposed but not refractory to venetoclax. In case of previous therapy with venetoclax inclusion is only possible after discussion with the PI. • Prior to initiation of venetoclax, all patients should have a white blood cell count <25x10 9 /µl. Prior cytoreductive treatment might be required (e.g. hydroxyurea) and is permitted in order to lower the WBC count. The WBC should be determined =24 hours after the last dose of hydroxyurea. • Patients with severe renal impairment (CrCl = 15 ml/min and < 30 ml/min) can only be included if benefits outweigh risks (after discussion with PI) and will be closely monitored for TLS.
Participation in any other interventional clinical trial during the study period • Isolated central nervous system invasion of AML (in the absence of systemic relapse or refractory AML) will be excluded from the study. However, patients with both systemic relapse or refractory disease and central nervous system invasion of AML can be included in the study. Nevertheless, patients who are not able to adhere to the study requirement because of their neurological 11 condition will be excluded from the study. In patients with central nervous system invasion of AML the concomitant use of intrathecal chemotherapy is allowed in addition to the study drugs. • History or concomitant presence of any other malignancy, except for: o non-melanoma skin cancer o carcinoma in situ of the cervix o any other effectively treated malignancy that has been in remission for >5 years or that is highly likely to be cured at the time of enrollment. • Active HIV, hepatitis B or hepatitis C infection • Use of any antitumoral agent within less than 5 times the half-life of the agent prior to the screening bone marrow examination. As described in the inclusion criteria, after the screening bone marrow examination, the use of cytoreductive treatment prior to the initiation of venetoclax is permitted in order to lower the WBC-count to <25 000/µl (e.g. hydroxyurea). An exception is made in case of central nervous system invasion of acute myeloid leukemia in which the use of intrathecal chemotherapy is allowed before and during the study. • Use of G-CSF within less than 4 days prior to the screening bone marrow examination • Medical conditions requiring chronic therapy of moderate or strong CYP3A4 inducers without alternative • Patients with known hypersensitivity to the active substance or to any of the excipients should be excluded. • Pregnant or breastfeeding woman • Active uncontrolled systemic infection
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