Acute myeloid leukemia in patients who are non-fit for standard induction therapy (except acute promyelocytic leukemia) and present with de novo, secondary, released or refractory AML MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Venclyxto
Pharmaceutical Form: Tablet
Sponsors
HUS Helsinki University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Patients who present with one of the following (except acute promyelocytic leukemia) a. De novo or secondary AML patients who are non-fit for standard induction therapy (see below) b. Relapsed or refractory AML patients following at least 1 line of prior therapies (see below) 3. Ex vivo sensitivity testing performed to assess venetoclax sensitivity a. Validation cohort: All participants are treated with venetoclax+azacitidine irrespective of the ex vivo screening results. b. Study cohort: Only the participants exhibiting ex vivo sensitivity to venetoclax are included to study therapy. 4. Participant must have ECOG Performance status = 2 for participants = 75 years of age OR = 3 for participants = 18 to 74 years of age 5. Leukocyte count =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Participant has acute promyelocytic leukemia (APL) 2. The leukemic cell content (blast percentage) in bone marrow/peripheral blood (depending which is used for drug sensitivity testing) is = 10 % 3. ECOG >3 (see also inclusion criteria 4) 4. Participant has known CNS involvement with AML (note: CSF or radiological investigations are not required without clinical suspicion) 5. Participant with known HIV infection or active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection that is not controlled with anti-viral medication. 6. Participant has cardiovascular disability status of New York Heart Association Class = 2. Class 2 is defined as cardiac disease in which participants are comfortable at rest but ordinary physical activity results in palpitations, fatigue, dyspnea, or anginal pain. 7. Evidence of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participation in this study (including but not limited to): a. Participant has a chronic respiratory disease that requires continuous oxygen use b. Systemic uncontrolled infection requiring therapy (viral, bacterial or fungal) c. Malabsorption syndrome or other condition that precludes enteral route of administration. d. Uncontrolled GVHD. 8. Participant has a history of other malignancies prior to study entry, with the exception of previous malignancy treated with curative intent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate usability of ex vivo drug sensitivity testing for patient selection and to validate the ex vivo/in vivo drug sensitivity correlation. ;Secondary Objective: -To evaluate resistance mechanisms of venetoclax in primary patient samples -To evaluate venetoclax based combinations in resistant samples to overcome resistance -To unravel biomarkers (i.e. gene expression, protein levels and phosphorylation status of specific proteins, etc.) for sensitivity/resistance -To evaluate the correlation of venetoclax blood concentrations on treatment responses;Primary end point(s): CR/CRi rate before Cycle 4;Timepoint(s) of evaluation of this end point: Bone marrow examinations before C4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The correlation of ex vivo sensitivity and specific responses (OS, DOR, EFS, MRD status) The correlation of venetoclax blood concentrations specific responses (OS, DOR, EFS, MRD status) ;Timepoint(s) of evaluation of this end point: Entire study | — |
Countries
Finland
Contacts
Public ContactMika Kontro
HUS Helsinki University Hospital
Outcome results
None listed