Study of Venetoclax in Combination With Azacytidine in AML Patients Selected Using Ex Vivo Drug Sensitivity Screening

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Recruiting
participants needed

100
sponsor

Helsinki University Central Hospital

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Updated on 19 February 2024

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cancer

HIV Infection

remission

white blood cell count

heart disease

renal function

heart failure

ejection fraction

induction therapy

myeloid leukemia

cytarabine

graft versus host disease

azacitidine

hydroxyurea

clofarabine

mitoxantrone

induction chemotherapy

carbon monoxide

anthracyclines

forced expiratory volume

hepatitis

fatigue

leukemia

stable angina

venetoclax

acute promyelocytic leukemia

refractory acute myeloid leukemia (aml)

secondary acute myeloid leukemia

allogeneic transplantation

angina

blood cell count

malabsorption

neoadjuvant therapy

cardiac disorder

acute myeloid leukemia

refractory aml

chronic stable angina

Summary

This is a multi center two-stage, two-arm, open label phase II study of venetoclax in combination with azacytidine in acute myeloid leukemia patients selected for therapy with ex vivo venetoclax sensitivity screening. This study will characterize the usability of ex vivo drug sensitivity testing for patient selection for selecting the responsive patients for venetoclax therapy. The exploratory study will aim to find novel combinations for overcoming resistance as well as finding/validating biomarkers for both sensitivity and resistance.

Details

Condition	Acute myeloid leukemia, Acute myeloid leukemia
Age	18-100 years
Treatment	Venetoclax
Clinical Study Identifier	NCT04267081
Sponsor	Helsinki University Central Hospital
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Written informed consent
	Patients who present with one of the following (except acute promyelocytic leukemia)
	De novo or secondary AML patients who are non-fit for standard induction therapy (see below)
	Relapsed or refractory AML patients following at least 1 line of prior therapies (see below)
	Ex vivo sensitivity testing performed to assess venetoclax sensitivity
	Validation cohort: All participants are treated with venetoclax+azacitidine irrespective of the ex vivo screening results
	Study cohort: Only the participants exhibiting ex vivo sensitivity to venetoclax are included to study therapy
	Participant must have ECOG Performance status 2 for participants 75 years of age OR 3 for participants 18 to 74 years of age
	Leukocyte count < 25 x10E9/l. Hydroxyurea use is permitted to meet this criterion
	Participant must have adequate renal function as demonstrated by a calculated creatinine clearance 30 mL/min; determined by the Cockcroft Gault formula
	Participant must have adequate liver function as demonstrated by
	alanine aminotransferase (ALT) 4.0 ULN
	bilirubin 1.5 ULN
	Specific inclusion criteria for participants non-fit for standard chemotherapy
	Participant must be
	years of age OR 18 to 69 years of age and ineligible for intensive
	chemotherapy meeting at least one of the criteria following
	Clinically significant comorbidities, reflected at least 1 of
	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 karyotype associated with poor outcome with standard chemotherapy
	Patient's refusal from intensive chemotherapy 9\. Specific inclusion criteria for relapsed patients
	Participant must be 55 years of age with non-CBF AML relapse OR 18 of age and
	meeting at least one of the criteria following
	Not candidate for intensive chemotherapy (see the criteria 8.)
	The duration of remission < 12 months
	Relapse after allogeneic transplantation
	nd (or higher) relapse. 10\. Specific inclusion criteria for refractory patients The patients who fail to achieve a complete or partial remission after induction chemotherapy (two cycles of chemotherapy containing cytarabine or clofarabine, in compilation with topoisomerase II inhibitor (e.g. anthracycline or mitoxantrone)
Exclusion Criteria
	Participant has acute promyelocytic leukemia (APL)
	The leukemic cell content (blast percentage) in bone marrow/peripheral blood (depending which is used for drug sensitivity testing) is 10 %
	ECOG >3 (see also inclusion criteria 4)
	Participant has known CNS involvement with AML (note: CSF or radiological investigations are not required without clinical suspicion)
	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
	Participant has cardiovascular disability status of New York Heart Association Class
	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
	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)
	Participant has a 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
	Participant has a history of other malignancies prior to study entry, with the exception of previous malignancy treated with curative intent

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forced expiratory volume

acute promyelocytic leukemia

refractory acute myeloid leukemia (aml)

secondary acute myeloid leukemia

allogeneic transplantation

acute myeloid leukemia

refractory aml

chronic stable angina

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Study of Venetoclax in Combination With Azacytidine in AML Patients Selected Using Ex Vivo Drug Sensitivity Screening