Trial in AML Secondary to MPNs Patients, Unfit for Intensive Chemotherapy, Investigating a Treatment Combination Including Decitabine and Venetoclax (ENABLE)

Gruppo Italiano Malattie EMatologiche dell'Adulto

Status and phase: Active, not recruiting; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Venetoclax+Decitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT04763928

AML2420

Details and patient eligibility

About

Prospective, multi-center, intervention, open clinical trial for the treatment of AML secondary to MPN in patients unfit for intensive chemotherapy investigating a combination regimen including VEN and DEC.

Full description

Prospective, multi-center, intervention, open clinical trial for the treatment of AML secondary to MPN in patients unfit for intensive chemotherapy, investigating a combination regimen including VEN and DEC to improve the survival outcome.

Enrollment: 101 patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with AML secondary to myeloproliferative neoplasms (sAML), untreated, newly diagnosed, according to WHO 2016 criteria based on conventional cytological, cytogenetic, and immunophenotypic disease characterization
2. Patients unfit for intensive treatment modalities at the discretion of the investigator.
3. ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care.
4. Signed written informed consent according to ICH/EU/GCP and national local laws.
5. Males enrolled in the study with partners who are women of childbearing potential, must be willing to use an acceptable barrier contraceptive method during the trial

Exclusion criteria

1. Diagnosis of de novo AML
2. Pre-existing, uncontrolled pathology such as heart failure (congestive/ischaemic, acute myocardial infarction within the post 3 months, untreatable arrhythmias, NYHA classes III and IV), sever liver disease with total bilirubin ≥2,5 x ULN and/or ALT>3 ULN (unless attributable to AML), acute or chronic pancreatitis, kidney function impairment with Creatinine Clearance (CrCl) level <30ml/min (calculated by Cockcroft Gault formula) (unless attributable to AML) and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent or to cope with the intended treatment plan. For altered liver, pancreas and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following adequate supportive measures.
3. Pre-existing HIV positive serology (i.e. already known before enrolment). The participation to the study will require serology testing for HIV positivity at baseline: in case of HIV positivity or refusal to perform HIV testing, the patient will be considered not eligible.
4. Uncontrolled bacterial or fungal infections
5. QTc >470 msec on screening ECG (Fridericia's formula)
6. A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 6 months.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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101 participants in 1 patient group

VenDec

Experimental group

Description:

Patients will receive a combination of VENETOCLAX (400 mg per day orally on days 1 to 28 of 28-days courses) and DECITABINE (20 mg/sqm intravenously on days 1 to 5 of 28-days courses)

Treatment:

Drug: Venetoclax+Decitabine