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

A Phase 2, Prospective, Multi-center Intervention Trial in Patients With Acute Myeloid Leukemia Secondary to Myeloproliferative Neoplasms Unfit for Intensive Chemotherapy Investigating a Treatment Combination Including Decitabine and Venetoclax

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax+Decitabine

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 101
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Firenze, Italy
    • Recruiting
    • Az. Ospedaliero - Universitaria Careggi
    • Contact: Alessandro Vannucchi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VenDec; 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)

Drug: Venetoclax+Decitabine; Patients will receive treatment with a combination of decitabine and venetoclax as follows: Decitabine 20 mg/sqm intravenously on days 1 to 5 of 28-days courses; Venetoclax 400 mg per day orally on days 1 to 28 of 28-days courses; a dose escalation period is provided at first cycle (ramp-up) in which VEN is administered as follows: 100 mg on day -2, 200 mg on day -1, and 400 mg on day 1, a dose that is continued subsequently, daily, for 28-day cycles. In case of achievement of response, the treatment will be continued until disease progression or death by other causes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of VEN-DEC regimen (event free survival)	Evaluation of the event free survival at 1 year of an experimental VEN-DEC combination arm in patients with AML secondary to MPN and unfit for intensive therapeutic strategy	at 1 year

Collaborators and Investigators

• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2021
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: February 17, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): January 4, 2022
• Last Update Submitted That Met QC Criteria: January 3, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine; Venetoclax
• Other Study ID Numbers: AML2420

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No