Venetoclax and Decitabine Assessment in Patients (≥60 - <75 Years) with Newly Diagnosed AML Eligible for Allo-SCT

NCT04476199 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: GITMO-VEN-DEC
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 25

Brief Summary

This trial is a no profit, prospective, phase II, multicentre, non-randomised, uncontrolled, single group assignment, open label study to evaluate the safety and efficacy of the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) as "bridge" to allo-SCT in elderly (≥ 60 - \< 75 years) AML patients. The primary objective is to evaluate the proportion of elderly (≥60 - \<75 years) patients with newly diagnosed AML, eligible for allo-SCT, treated with the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/Cri/MLFS.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Allogenic Stem Cell Transplant

Outcome Measures

Primary Outcomes (7)

• Response to VEN-DEC chemo-free combination (ELN Guidelines)

  response to VEN-DEC induction will be assessed on bone marrow according to the ELN Guidelines (13), as following: - CR without minimal residual disease (CR-MRD neg); (Complete Remission ) bone marrow blasts 5%) - CR remission with incomplete hematologic recovery (CRi): Morphologic Leukemia-free State (MLFS) Partial Remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%; - Primary refractory disease/Non response (NR): No CR or CRi after 2 courses of VEN-DEC; excluding patients with death in aplasia or death due to indeterminate cause;

  At the end of cycle 2 (each cycle is 28 days)

• Allo-SCT

  Proportion of patients who undergo to allo-SCT in first CR/CRi/MLFS

  18 months from 1st enrolled patient

• Allo-SCT Engraftment

  Percentage of patients with Neutrophil engraftment and percentage of patients with platelet engraftment

  up to 24 weeks

• Overall Survival (OS)

  at 2 year post transplant. OS is defined as the time from transplant to the date of death due to any cause or to the last date the patient was known to be alive (censored observation) or to the date of the data cut-off for final analysis

  at 2 year post transplant

• Cumulative incidence of Non-Relapse Mortality

  NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 100 days

  at 100 days

• Cumulative incidence of Non-Relapse Mortality

  NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 180 days

  at 180 days

• Cumulative incidence of Non-Relapse Mortality

  NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 365 days

  at 365 days

Study Arms (1)

Treatment with VEN-DEC

EXPERIMENTAL

Venetoclax will be given with a 3-day ramp up beginning with 100 mg dose on Day 1, with 200mg on Day 2, to reach the final dose of 400 mg on Day 3 of Cycle 1. Venetoclax will be continued at 400 mg daily. Tumor lysis prophylaxis will be administered from day -4, cycle 1 (oral uric acid reducing agent and hydration with at least 1.5 L/day).Decitabine will be administered at the dose of 20 mg/sqm intravenously from day 1 to day 5 every 28 days (VEN-DEC) for 2 cycles.

Combination Product: Venetoclax and Decitabine

Interventions

Venetoclax and Decitabine COMBINATION_PRODUCT

The prognosis of acute myeloid leukemia (AML) patients aged over 60 years is poor and allogeneic stem cell transplantation (allo-SCT) is the only curative option.The association VEN-DEC is a promising combination therapy for AML elderly patients who are fit and eligible for allo-SCT.

Treatment with VEN-DEC

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \>60 \<75 years of age
• Diagnosis of AML eligible for allo-SCT from any donor
• High- and Intermediate-Risk ELN
• WBC \<25x109/L (Hydroxyurea is permitted to meet this criterion)
• adequate hepatic function (bilirubin ≤2 UNL; ALT/AST ≤2,5 UNL)
• adequate renal function (creatinine clearance ≥50 ml/min)
• ECOG Performance Status \< 2
• 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.
• Women of childbearing potential must use highly effective contraception for at least 1 month after the last dose of VEN and for however long the EU SmPC says for DEC
• Willing and able to comply with all of the requirements and visits in the protocol.
• Written and signed informed consent.

You may not qualify if:

• Previous treatment for AML (Hydroxyurea is allowed) or for an antecedent Myelodysplastic Syndrome (MDS).
• Absence of informed consent
• AML patients with t(15;17); t(8;21); inv(16)
• Subject has known active CNS involvement with AML.
• Low Risk ELN
• grade \>2 NCI-CTCAE (v. 5) adverse events at the time of enrollment
• Serious organ dysfunction: left ventricular ejection fraction \< 40%, FEV1, FVC, DLCO (diffusion capacity) \<40% of predicted, LFT \> 5 times the upper limit of normal, or creatinine clearance \< 40 ml/min.
• The evidence of HBV or HCV active infection (HBV DNA HCV RNA positive test).
• Patients with HIV infection
• Current uncontrolled infections
• Patients with other life-threatening concurrent disease
• Subjects with known hypersensitivity to any of the component medication
• Subject has a history of other malignancies within 2 years prior to study entry, with the exception of:
• Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;

Sponsors & Collaborators

• Gruppo Italiano Trapianto di Midollo Osseo: lead

Study Sites (25)

USD, Trapianti di Midollo osseo, Azienda Spedali Civili di Brescia

Brescia, Brescia, 25100, Italy

Location

Unità Terapia Intensiva Ematologica e terapia cellulari - casa della sofferenza

San Giovanni Rotondo, Foggia, 71100, Italy

Location

UO Ematologia e TMO - Ospedale C. Panico

Tricase, Lecce, Italy

Location

Ospedale San Gerardo

Monza, Monza, 20900, Italy

Location

Clinica di Ematologia. AOU Ospedali Riuniti di Ancona

Ancona, Italy

Location

UOC di Ematologia, Ospedale C e G Mazzoni

Ascoli Piceno, Italy

Location

U.O. Ematologia con Trapianto, Policlinico di Bari

Bari, Italy

Location

Ospedale Seragnoli Malpighi

Bologna, Italy

Location

Ospedale Policlinico di Catania, TMO

Catania, Italy

Location

Struttura Complessa di Ematologia, Azienda Ospedaliera Santa Croce e Carle

Cuneo, Italy

Location

Terapie Cellulari e Medicina Trasfusionale, Ospedale Careggi

Florence, Italy

Location

UO Ematologia, Programma Trapianti IRCCS Ospedale Policlinico San Martino, Genova

Genova, Italy

Location

Centro Trapianto Fondazione IRCCS Cà Granda - Osp. Maggiore

Milan, Italy

Location

Div. di Ematologia e TMO, Istituto Nazionale Tumori

Milan, Italy

Location

Div. di Ematologia, Talamona, Osp. Niguarda, Ca-Granda

Milan, Italy

Location

Istituto Clinico Humanitas, Oncologia ed Ematologia

Milan, Italy

Location

Unità Operativa di Ematologia e Trapianto Midollo Osseo (UTMO), Ospedale San Raffaele di Milano

Milan, Italy

Location

UOSC Ematologia con Trapianto CSE, AORN A. Cardarelli, AORN Cardarelli

Napoli, Italy

Location

CTMO Osp. V. Cervello Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello

Palermo, Italy

Location

Dip.di Ematologia, Osp. Civile di Pescara, Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico

Pescara, Italy

Location

CTMO Centro Unico, Regionale Trapianti di Cellule Staminali e Terapie Cellulari, "A. Neri", Grande Osp. Bianchi, Melacrino Morelli

Reggio Calabria, Italy

Location

Policlinico Tor Vergata

Roma, Italy

Location

A.O.U. Citta della Salute e della Scienza

Torino, Italy

Location

UOC di Ematologia, Osp. dell'Angelo

Venezia, Italy

Location

Div. di Ematologia - Unità di TMO e Oncoematologia Pediatrica Policlinico GB Rossi

Verona, Italy

Location

Related Publications (1)

• Russo D, Polverelli N, Bernardi S, Santarone S, Farina M, Borlenghi E, Onida F, Castagna L, Bramanti S, Carella AM, Sorasio R, Martino M, Alati C, Olivieri A, Beltrami G, Curti A, Vetro C, Leotta S, Mancini V, Terruzzi E, Bernardi M, Galieni P, Musto P, Cerretti R, Giaccone L, Skert C, Radici V, Vezzoli M, Calza S, Leoni A, Garuffo L, Bonvicini C, Pellizzeri S, Malagola M, Ciceri F. Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2024 Nov;11(11):e830-e838. doi: 10.1016/S2352-3026(24)00241-2. Epub 2024 Sep 20.

  PMID: 39312920 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Domenico Russo, MD

  Spedali Civili Brescia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: These patients may undergo allo-SCT after 2 - 4 cycles of VEN-DEC

Study Record Dates

• First Submitted: July 2, 2020
• First Posted: July 20, 2020
• Study Start: December 9, 2019
• Primary Completion: February 3, 2023
• Study Completion: June 30, 2025
• Last Updated: January 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (25)