A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML)



Sponsor:   AbbVie


Sommario: The main objective of this study is to evaluate the efficacy of venetoclax in combination
with azacitidine to improve Overall Survival (OS) in Acute Myeloid Leukemia (AML)
participants compared to Best Supportive Care (BSC) when given as maintenance therapy
following allogeneic stem cell transplantation (SCT).

This study will have 2 parts: Part 1 (Dose Confirmation), which may include participants
who are greater than or equal to 18 years old; Part 2 (Randomization) which may include
participants who are greater than or equal to 12 years old. During Part 1, recommended
Phase 3 dose of venetoclax in combination with azacitidine will be determined and during
Part 2, the efficacy and safety of venetoclax with azacitidine (Part 2 Arm A) will be
compared with BSC (Part 2 Arm B).




TIPOLOGIA STUDIO

 
Interventistico



FASE

 
Fase 3




TRATTAMENTO

  
    
  
  • Venetoclax
  • Azacitidine
  • Best Supportive Care (BSC)
    • 






OBIETTIVO PRIMARIO


  
  • Misura: Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1)
  • Tempo: Up to the first treatment cycle (28 days)
  • Descrizione: DLTs are any of the hematologic, nonhematologic toxicities, adverse events (AEs)
occurring following administration of venetoclax and AZA as described in the protocol and
evaluated by the Investigator and the sponsor.
  • Misura: Overall Survival (OS) (Part 2)
  • Tempo: Up to 45 months after the first participant is randomized
  • Descrizione: OS is defined as the number of days from the date of randomization to the date of death
from any cause.




OBIETTIVO SECONDARIO


  
  • Misura: Morphologic Relapse-Free Survival (RFS) (Part 2)
  • Tempo: Up to 39 months after the first participant is randomized
  • Descrizione: Morphologic relapse from AML defined as bone marrow blasts of >= 5% or reappearance of
blasts in the peripheral blood not attributable to any other cause (e.g., bone marrow
regeneration) in at least 2 peripheral blood samples at least one week apart or
development of extramedullary disease after achieving a complete remission (CR) or
complete remission with incomplete count recovery (CRi); or the date of death from any
cause, whichever comes first as determined by Independent Review Committee (IRC).
  • Misura: Composite Relapse-Free Survival (RFS) (Part 2)
  • Tempo: Up to 39 months after the first participant is randomized
  • Descrizione: Morphologic relapse from AML, non-morphologic relapse from AML, which is defined as
increase in disease burden determined by standard methods with reappearance or
acquisition of new findings with or without change in anti-leukemic treatment per
investigator decision due to cytogenetic abnormalities or change in molecular marker or
measurable residual disease by multiparameter flow with sensitivity to at least 10^-3; or
the date of death from any cause, whichever comes first as determined by IRC.
  • Misura: Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) (Part 2)
  • Tempo: Up to 39 months after the first participant is randomized
  • Descrizione: GRFS is defined as number of days from the date of randomization to occurrence of disease
relapse OR incidence of GvHD OR death from any cause.
  • Misura: Graft-versus-Host Disease (GvHD) Rate (Part 2)
  • Tempo: Up to 39 months after the first participant is randomized
  • Descrizione: GvHD rate is defined as grade 2 or higher for acute graft-versus-host disease (aGvHD) and
moderate/severe for chronic graft-versus-host disease (cGvHD) assessed by investigator.
  • Misura: Change from Baseline in Physical Functioning as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) (Part 2)
  • Tempo: Up to 39 months after the first participant is randomized
  • Descrizione: The EORTC-QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item
and single scales including 5 functional scales (physical, role, emotional, social, and
cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health
status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation,
diarrhea, and financial difficulties). Participantts rate items on a 4-point scale
ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
  • Misura: Change From Randomization in Fatigue in Adult Participants (Part 2)
  • Tempo: Up to 39 months after the first participant is randomized
  • Descrizione: Fatigue is measured as Patient Reported Outcome (PRO) using Patient Reported Outcomes
Measurement Information System (PROMIS) Cancer Fatigue SF 7a.
  • Misura: Measurable Residual Disease (MRD) Response Rate in Participants With MRD >= 10^-3 at Randomization (Part 2)
  • Tempo: Up to 39 months after the first participant is randomized
  • Descrizione: MRD conversion rate is defined as percentage of participants who convert to MRD < 10^-3
after initiation of treatment.
  • Misura: Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants (Part 2)
  • Tempo: Up to 39 months after the first participant is randomized
  • Descrizione: Time to deterioration defined as number of days from randomization to either
deterioration of >= 5 points based on the European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3 or death due
to any cause.
  • Misura: Change in Patient Reported Signs, Symptoms and Impact of Acute Myeloid Leukemia (AML) as Measured by the European Quality-of-Life-5 Dimensional-5-Level (EQ-5D-5L)
  • Tempo: Up to 39 months after the first participant is randomized
  • Descrizione: The EQ-5D-5L is a generic preference instrument that has been validated in numerous
population and has 5 dimensions: mobility, self-care, usual activities, pain/discomfort
and anxiety/depression. These dimensions are measured on a 5-point scale: with higher
scores representing better functioning/quality of life and greater symptom burden.




CRITERI DI ELIGIBILITA'


    
             
  • 
        Criteri di inclusione e esclusione
        
    Inclusion Criteria:

  -  Participants must be at least 18 years old for Part 1 and, at least 12 years old for
     Part 2.

  -  Participant must be diagnosed with Acute Myeloid Leukemia (AML) by World Health
     Organization (WHO) criteria (2017) and either be planning for allogeneic stem cell
     transplantation or have received allogeneic stem cell transplantation within the
     past 60 days.

  -  Blast percentage in bone marrow before transplant must be < 10%.

  -  Blast count in peripheral blood must be "0" and Blast percentage in bone marrow must
     be < 5% after transplant.

  -  Participant meet adequate renal, hepatic and hematologic criteria as described in
     the protocol.

  -  Participants >= 17 years old must have a Karnofsky Performance Scale (KPS) score >
     50 and participants between 12 to 16 years old must have a Lansky Play Performance
     Scale score > 40.

Exclusion Criteria:

  -  History of disease progression during prior treatment with venetoclax.

  -  History of any other malignancy within 2 years prior to study entry, except for:
     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; Myelodysplastic Syndrome, Myeloproliferative
     neoplasm (only allowed if it transformed to AML and AML should be the indication for
     marrow transplantation).

  -  Participant has known infection with HIV or history of being positive for hepatitis
     B virus (HBV) or hepatitis C virus (HCV) infection.

  -  Presence of clinical or laboratory symptoms/signs of extramedullary myeloid
     malignancy.
    
        
    • 
    




SESSO

  
Tutti




  


ETA' MINIMA



Età Minima: 12 Years

Età Massima: N/A






LUOGO


  
IRCCS Ospedale San Raffaele /ID# 214311
Milan	3173435, 20132
Istituto Europeo Di Oncologia /ID# 242579
Milan	3173435, 20141
A.O.U. CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO - Ospedale Molinette /ID# 216148
Turin	3165524, 10126
Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 254964
Rome	3169070, 00161
Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 214910
Rome	3169070, 00168
ASST degli Spedali Civili di Brescia /ID# 215997
Brescia	3181554, 25123