Acute Myelogenic Leukemia is aggressiv leukemia and treatment i challenging specialy in patients not eligible for intensiv chemotherapy or relapsed after intensiv chemotherapy.In this study we will use study medicine (low dose Venetoclax)in combination with standard treatment (Azacitidine) for better responce and survival and examine mechanism for drug sensitivity and resistence
Conditions
Interventions
Trade Name: Venclyxto
Product Name: VENETOCLAX
Pharmaceutical Form: Tablet
INN or Proposed INN: VENETOCLAX
Other descriptive name: Venetoclax
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
Righospitalet
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 unfit for standard induction therapy (see inclusion criterion 8). b. Relapsed/refractory AML after at least 1 line of prior therapies (see inclusion criterion 9). 3. Written informed consent to participate in an exploratory research protocol including biobanking, comprehensive AML profiling (genomics, transcriptomics, proteomics, etc.) and ex vivo drug sensitivity testing to assess venetoclax and other drug sensitivities. a. All patients are treated with azacitidine+venetoclax irrespective of the ex vivo screening results. 4. ECOG Performance status = 2 for patients = 75 years of age OR = 3 for patients = 18 to 74 years of age. 5. Leukocyte count =65 years) yes F.1.3.1 Number of subjects for this age range 53
Exclusion criteria
Exclusion criteria: 1. Acute promyelocytic leukemia (APL). 2. Patients with 4th or higher AML relapse. 3. Leukemic cell content (blast percentage) in bone marrow/peripheral blood 3 (see also inclusion criteria 4). 5. Prior venetoclax treatment for myeloid malignancy. 6. AML patients with CNS involvement (note: cerebrospinal fluid or radiological investigations are not required without clinical suspicion). 7. HIV infection or active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection that is not controlled with antiviral medication with the definition hereof at the discretion of the investigator. 8. Cardiovascular disability status of New York Heart Association Class = 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in palpitations, fatigue, dyspnea, or anginal pain. 9. Evidence of clinically significant condition(s), which at the investigator's discretion would adversely affect the patient's participation in this study (including but not limited to): 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. 10. Previous malignancies with the exception of previous malignancy treated successfully with curative intent and indolent/smoldering malignancies (defined at the investigator's discretion). 11. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment). 12. Fertile men or women of childbearing potential unless: a. Surgically sterile or = 2 years after the onset of menopause. b. Willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 3 months after the end of study treatment. 13. Known hypersensitivity to venetoclax or azacitidine or excipients of any of the drugs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of azacitidine in combination with low dose venetoclax in patients with AML (ORR=CR/CRi/MLFS rate, composite CR/CRh rate, PR rate). ;Secondary Objective: To assess overall survival (OS), duration of response (DOR), event free survival (EFS) in patients with AML. To assess the safety of azacitidine in combination with low dose venetoclax in patients with AML. ;Primary end point(s): Complete Remission CR Complete Remission with Incomplete Hematologic Recovery (CRi) Morphologic Leukemia-Free State MLFS ;Timepoint(s) of evaluation of this end point: When relevant data of all patients are available and validated | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival (OS), duration of response (DOR), event free survival (EFS) • The correlation of ex vivo sensitivity and specific clinical responses (OS, DOR, EFS, MRD status) • The correlation of venetoclax blood concentrations and specific responses (OS, DOR, EFS, MRD status) • Frequency and severity of adverse events (AEs) ;Timepoint(s) of evaluation of this end point: When relevant data of all patients are available and validated | — |
Countries
Denmark, Finland, Norway
Contacts
Public ContactPeter Brown
Rigshospitalet
Outcome results
None listed