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

Primary Purpose

Acute Myeloid Leukemia

Status

Recruiting

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Venetoclax+Decitabine

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
Patients unfit for intensive treatment modalities at the discretion of the investigator.
ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care.
Signed written informed consent according to ICH/EU/GCP and national local laws.
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:

Diagnosis of de novo AML
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.
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.
Uncontrolled bacterial or fungal infections
QTc >470 msec on screening ECG (Fridericia's formula)
A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 6 months.

Sites / Locations

Az. Ospedaliero - Universitaria CareggiRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

VenDec

Arm 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)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT04763928

First Posted

February 17, 2021

Last Updated

January 3, 2022

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto

1. Study Identification

Unique Protocol Identification Number

NCT04763928

Brief Title

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

Acronym

ENABLE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 3, 2021 (Actual)

Primary Completion Date

May 2024 (Anticipated)

Study Completion Date

May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

101 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

VenDec

Arm Type

Experimental

Arm 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)

Intervention Type

Drug

Intervention Name(s)

Venetoclax+Decitabine

Intervention Description

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.

Primary Outcome Measure Information:

Title

Efficacy of VEN-DEC regimen (event free survival)

Description

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

Time Frame

at 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Patients unfit for intensive treatment modalities at the discretion of the investigator. ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care. Signed written informed consent according to ICH/EU/GCP and national local laws. 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: Diagnosis of de novo AML 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. 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. Uncontrolled bacterial or fungal infections QTc >470 msec on screening ECG (Fridericia's formula) A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 6 months.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Paola Fazi

Phone

0670390528

p.fazi@gimema.it

First Name & Middle Initial & Last Name or Official Title & Degree

Enrico Crea

Phone

0670390514

e.crea@gimema.it

Facility Information:

Facility Name

Az. Ospedaliero - Universitaria Careggi

City

Firenze

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alessandro Vannucchi

12. IPD Sharing Statement

Learn more about this trial

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

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