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



Sponsor:   Gruppo Italiano Trapianto di Midollo Osseo


Sommario: 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.




TIPOLOGIA STUDIO

 
Interventistico



FASE

 
Fase 2




TRATTAMENTO

  
    
  






OBIETTIVO PRIMARIO


  
  • Misura: Response to VEN-DEC chemo-free combination (ELN Guidelines)
  • Tempo: At the end of cycle 2 (each cycle is 28 days)
  • Descrizione: 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;
  • Misura: Allo-SCT
  • Tempo: 18 months from 1st enrolled patient
  • Descrizione: Proportion of patients who undergo to allo-SCT in first CR/CRi/MLFS
  • Misura: Allo-SCT Engraftment
  • Tempo: up to 24 weeks
  • Descrizione: Percentage of patients with Neutrophil engraftment and percentage of patients with
platelet engraftment
  • Misura: Overall Survival (OS)
  • Tempo: at 2 year post transplant
  • Descrizione: 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
  • Misura: Cumulative incidence of Non-Relapse Mortality
  • Tempo: at 100 days
  • Descrizione: 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
  • Misura: Cumulative incidence of Non-Relapse Mortality
  • Tempo: at 180 days
  • Descrizione: 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
  • Misura: Cumulative incidence of Non-Relapse Mortality
  • Tempo: at 365 days
  • Descrizione: 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






CRITERI DI ELIGIBILITA'


    
             
  • 
        Criteri di inclusione e esclusione
        
    Inclusion Criteria:

  -  • 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.

Exclusion Criteria:

  -  • 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;

  -  Previous malignancy confined and surgically resected (or treated with other
     modalities) with curative intent. • Participation in another clinical trial within 1
     month before the start of this trial
    
        
    • 
    




SESSO

  
Tutti




  


ETA' MINIMA



Età Minima: 60 Years

Età Massima: 75 Years






LUOGO


  
Unità Terapia Intensiva Ematologica e terapia cellulari - casa della sofferenza
San Giovanni Rotondo	3168234, 71100
UO Ematologia e TMO - Ospedale C. Panico
Tricase	2522857, 
Ospedale San Gerardo
Monza	3172629, 20900
Clinica di Ematologia. AOU Ospedali Riuniti di Ancona
Ancona	3183089, 
UOC di Ematologia, Ospedale C e G Mazzoni
Ascoli Piceno	3182749, 
U.O. Ematologia con Trapianto, Policlinico di Bari
Bari	3182351, 
Ospedale Seragnoli Malpighi
Bologna	3181928, 
Ospedale Policlinico di Catania, TMO
Catania	2525068, 
Struttura Complessa di Ematologia, Azienda Ospedaliera Santa Croce e Carle
Cuneo	3177700, 
Terapie Cellulari e Medicina Trasfusionale, Ospedale Careggi
Florence	3176959, 
UO Ematologia, Programma Trapianti IRCCS Ospedale Policlinico San Martino, Genova
Genova	8969657, 
Centro Trapianto Fondazione IRCCS Cà Granda - Osp. Maggiore
Milan	6951411, 
Div. di Ematologia e TMO, Istituto Nazionale Tumori
Milan	6951411, 
Div. di Ematologia, Talamona, Osp. Niguarda, Ca-Granda
Milan	6951411, 
Istituto Clinico Humanitas, Oncologia ed Ematologia
Milan	6951411, 
Unità Operativa di Ematologia e Trapianto Midollo Osseo (UTMO), Ospedale San Raffaele di Milano
Milan	6951411, 
UOSC Ematologia con Trapianto CSE, AORN A. Cardarelli, AORN Cardarelli
Napoli	9031661, 
CTMO Osp. V. Cervello Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Palermo	2523920, 
Dip.di Ematologia, Osp. Civile di Pescara, Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico
Pescara	3171168, 
CTMO Centro Unico, Regionale Trapianti di Cellule Staminali e Terapie Cellulari, "A. Neri", Grande Osp. Bianchi, Melacrino Morelli
Reggio Calabria	2523630, 
Policlinico Tor Vergata
Roma	8957247, 
A.O.U. Citta della Salute e della Scienza
Torino	8980539, 
UOC di Ematologia, Osp. dell'Angelo
Venezia	3175005, 
Div. di Ematologia - Unità di TMO e Oncoematologia Pediatrica Policlinico GB Rossi
Verona	3164527,