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

NCT ID: NCT04763928

Last Updated: 2024-11-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-03
• Study Completion Date: 2026-04-30

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Venetoclax+Decitabine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ematologia A.O. SS. Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Ematologia AOU delle Marche

Ancona, , Italy

Ematologia AOU Policlinico Bari

Bari, , Italy

Ematologia ASST Papa Giovanni XXIII

Bergamo, , Italy

Ematologia IRCCS AOU di Bologna

Bologna, , Italy

Ematologia ASST Spedali Civili di Brescia

Brescia, , Italy

Ematologia Businco

Cagliari, , Italy

Ematologia Istituto Oncologico Veneto IRCCS

Castelfranco Veneto, , Italy

Ematologia AOU Policlinico Rodolico-San Marco

Catania, , Italy

Ematologia A.O.U Arcispedale S.Anna

Cona, , Italy

Ematologia Ospedale A.Carle

Cuneo, , Italy

Az. Ospedaliero - Universitaria Careggi

Florence, , Italy

Ematologia IRCCS Ospedale Policlinico San Martino

Genova, , Italy

Ematologia AOU di Modena

Modena, , Italy

Ematologia AORN Cardarelli

Napoli, , Italy

Ematologia Federico II

Napoli, , Italy

Ematologia P.O. A.Tortora

Pagani, , Italy

Ematologia AOU Policlinico Giaccone

Palermo, , Italy

Ematologia Santa Maria della Misericordia

Perugia, , Italy

Ematologia PO Santo Spirito ASL Pescara

Pescara, , Italy

Ematologia Ospedale S.M.delle Croci

Ravenna, , Italy

Ematologia AOU S.Andrea

Roma, , Italy

Ematologia Fondazione PTV

Roma, , Italy

Ematologia Ospedale Sant'Eugenio

Roma, , Italy

Ematologia Policlinico Gemelli

Roma, , Italy

Ematologia Policlinico Umberto I

Roma, , Italy

Ematologia Policlinico Santa Maria alle Scotte

Siena, , Italy

Ematologia A.O.S. Maria Di Terni

Terni, , Italy

Ematologia Città della Salute e della Scienza

Torino, , Italy

Ematologia ORDINE MAURIZIANO DI TORINO

Torino, , Italy

Ematologia Santa Maria della Misericordia

Udine, , Italy

Ematologia ASST SETTE LAGHI

Varese, , Italy

Ematologia Ospedale Belcolle

Viterbo, , Italy

Countries

Italy

Other Identifiers

AML2420

Identifier Type: -

Identifier Source: org_study_id