Status:
RECRUITING
Azacitidine in Combination With Low Dose Intensity Venetoclax in Patients With AML Incl. Explorative AML Profiling
Lead Sponsor:
Rigshospitalet, Denmark
Collaborating Sponsors:
Helse Stavanger HF
University Hospital of North Norway
Conditions:
Acute Myeloid Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
Multi-center phase II study of standard azacytidine treatment (AZA; D1-D7, 75mg/m2 qd) in combination with a short duration of "low-dose" venetoclax treatment (LD-VEN; D1-D14 before CR and D1-D7 after...
Detailed Description
Multi-center phase II study of standard azacytidine treatment (AZA; D1-D7, 75mg/m2 qd) in combination with a short duration of "low-dose" venetoclax treatment (LD-VEN; D1-D14 before CR and D1-D7 after...
Eligibility Criteria
Inclusion
- Written informed consent.
- Patients who present with one of the following (except acute promyelocytic leukemia).
- De novo or secondary AML unfit for standard induction therapy
- Relapsed/refractory AML after at least 1 line of prior therapies
- Written informed consent to participate in an exploratory research protocol including bio-banking, 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.
- ECOG Performance status ≤ 2 for patients ≥ 75 years of age OR ≤ 3 for patients ≥ 18 to 74 years of age.
- Leukocyte count \< 25 x10E9/l. Hydroxyurea use is permitted to meet this criterion
- Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined by the Cockcroft Gault formula.
- Adequate liver function as demonstrated by
- alanine aminotransferase (ALT) ≤ 4.0 × ULN.
- bilirubin ≤ 1.5 × ULN.
- Specific inclusion criteria for elderly/unfit AML patients:
- ≥ 70 years of age OR
- ≥ 18 to 69 years of age and ineligible for intensive chemotherapy meeting at least one of the following criteria:
- Clinically significant comorbidities, as reflected by at least 1 of the following criteria:
- Left ventricular ejection fraction (LVEF) \< 50%.
- Lung diffusion capacity for carbon monoxide (DLCO) ≤ 65% of expected.
- Forced expiratory volume in 1 second (FEV1) ≤ 65% of expected.
- Chronic stable angina or congestive heart failure controlled with medication.
- Alanine aminotransferase (ALT) 3.0-4.0 × ULN.
- Other contraindication(s) to anthracycline therapy (must be documented).
- Adverse risk genetics (ELN criteria) associated with poor outcome with standard chemotherapy.
- Patient declines intensive chemotherapy.
- Secondary AML after previous disease modifying treatment (i.e. HMA/induction chemotherapy and/or allogeneic stem cell transplantation) of clonal myeloid diseases such as MDS, MDS/MPN, or MPN.
- Specific inclusion criteria for relapsed AML patients:
- ≥ 55 years of age with non-CBF AML relapse OR
- ≥ 18 of age and meeting at least one of the following criteria:
- Not candidate for intensive chemotherapy (see criterion 8).
- Relapse after chemotherapy, or monotherapy with HMA, or allogeneic stem cell transplantation. (note: patients with 4th or higher relapse are excluded).
- Patient declines intensive chemotherapy.
- Specific inclusion criteria for refractory AML patients:
- Patients who fail to achieve a complete or partial remission after previous monotherapy with HMA or induction chemotherapy (at least 1 cycle of chemotherapy containing cytarabine or clofarabine, in combination with a topoisomerase II inhibitor (e.g. anthracycline or mitoxantrone).
Exclusion
- Acute promyelocytic leukemia (APL).
- Patients with 4th or higher AML relapse.
- Leukemic cell content (blast percentage) in bone marrow/peripheral blood \< 10 %.
- ECOG \>3.
- Prior venetoclax treatment for myeloid malignancy.
- AML patients with CNS involvement (note: cerebrospinal fluid or radiological investigations are not required without clinical suspicion).
- 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.
- 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.
- 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):
- Chronic respiratory disease that requires continuous oxygen use.
- Systemic uncontrolled infection requiring therapy (viral, bacterial or fungal).
- Malabsorption syndrome or other condition that precludes enteral route of administration.
- Uncontrolled GVHD.
- Previous malignancies with the exception of previous malignancy treated successfully with curative intent and indolent/smoldering malignancies (defined at the investigator's discretion).
- Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment).
- Fertile men or women of childbearing potential unless:
- Surgically sterile or ≥ 2 years after the onset of menopause.
- 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.
- Known hypersensitivity to venetoclax or azacitidine or excipients of any of the drugs.
Key Trial Info
Start Date :
May 24 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 1 2031
Estimated Enrollment :
117 Patients enrolled
Trial Details
Trial ID
NCT05431257
Start Date
May 24 2022
End Date
September 1 2031
Last Update
June 24 2022
Active Locations (1)
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1
Department of Hematology, Rigshospitalet
Copenhagen, Denmark, 2100