VIALE-T: 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 (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04161885
Collaborator
(none)
424
Enrollment
130
Locations
3
Arms
70.2
Anticipated Duration (Months)
3.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main objective of this study is to evaluate the efficacy of venetoclax in combination with azacitidine to improve Relapse Free Survival (RFS) in AML patients 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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
424 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open Label Phase 3 Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine After Allogeneic Stem Cell Transplantation in Subjects With Acute Myeloid Leukemia (AML) (VIALE-T)
Actual Study Start Date :
Feb 26, 2020
Anticipated Primary Completion Date :
Jun 29, 2024
Anticipated Study Completion Date :
Jan 3, 2026

Arms and Interventions

ArmIntervention/Treatment
Experimental: Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care

Participants will be administered various doses and dose regiments of venetoclax and AZA. Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days)

Drug: Venetoclax
Tablet; Oral
Other Names:
  • ABT-199
  • GDC-0199
  • VENCLEXTA
  • Drug: Azacitidine
    Subcutaneous (SC) or intravenous (IV) injection

    Other: Best Supportive Care (BSC)
    BSC is the best supportive care, without AML directed therapy, determined per the investigator and institutional guidelines.

    Experimental: Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSC

    Participants will be administered with venetoclax and AZA at a dose level determined in Part 1 in addition to best supportive care (when required). Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days).

    Drug: Venetoclax
    Tablet; Oral
    Other Names:
  • ABT-199
  • GDC-0199
  • VENCLEXTA
  • Drug: Azacitidine
    Subcutaneous (SC) or intravenous (IV) injection

    Other: Best Supportive Care (BSC)
    BSC is the best supportive care, without AML directed therapy, determined per the investigator and institutional guidelines.

    Experimental: Part 2: Arm B - Best Supportive Care (BSC)

    Participants will receive treatment as prescribed by their physician according to the BSC for up to 24 cycles (1 cycle = 28 days)

    Other: Best Supportive Care (BSC)
    BSC is the best supportive care, without AML directed therapy, determined per the investigator and institutional guidelines.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1) [Upto the first treatment cycle (28 days)]

      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.

    2. Relapse-Free Survival (RFS) (Part 2) [Up to 39 months after the first participant is randomized]

      RFS is defined as the number of days from randomization to the date of relapse or the date of death from any cause, whichever comes first.

    Secondary Outcome Measures

    1. Overall Survival (OS) (Part 2) [Up to 45 months after the first participant is randomized]

      OS is defined as the number of days from the date of randomization to the date of death from any cause.

    2. Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) (Part 2) [Up to 39 months after the first participant is randomized]

      GRFS is defined as number of days from the date of randomization to occurrence of disease relapse OR occurrence or worsening of GvHD OR death from any cause.

    3. Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants (Part 2) [Up to 39 months after the first participant is randomized]

      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.

    4. Graft-versus-Host Disease (GvHD) rate (Part 2) [Up to 39 months after the first participant is randomized]

      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

    5. Change From Randomization in Fatigue in Adult Participants (Part 2) [Up to 39 months after the first participant is randomized]

      Fatigue is measured as Patient Reported Outcome (PRO) using Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue SF 7a.

    6. Minimal Residual Disease (MRD) Response Rate in Participants With MRD >= 10^-3 at Randomization (Part 2) [Up to 39 months after the first participant is randomized]

      MRD conversion rate is defined as percentage of participants who convert to MRD < 10^-3 after initiation of treatment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 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 14 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.

    • 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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Alabama at Birmingham - Main /ID# 214524BirminghamAlabamaUnited States35233
    2City of Hope /ID# 213681DuarteCaliforniaUnited States91010
    3University of California, Los Angeles /ID# 218199Los AngelesCaliforniaUnited States90095
    4UCHSC Anschultz Cancer Pavilion /ID# 215618AuroraColoradoUnited States80045-2517
    5Colorado Blood Cancer Institute /ID# 215980DenverColoradoUnited States80218
    6Mayo Clinic /ID# 239710JacksonvilleFloridaUnited States32224
    7AdventHealth Medical Group Blood & Marrow Transplant at Orlando /ID# 213985OrlandoFloridaUnited States32804-5505
    8Ann & Robert H Lurie Children's Hospital of Chicago /ID# 215840ChicagoIllinoisUnited States60611
    9The University of Chicago Medical Center /ID# 215616ChicagoIllinoisUnited States60637-1443
    10Loyola University Medical Ctr /ID# 215617MaywoodIllinoisUnited States60153
    11Indiana Blood & Marrow Transpl /ID# 215842IndianapolisIndianaUnited States46237
    12Ochsner Clinic Foundation-New Orleans /ID# 213834New OrleansLouisianaUnited States70121
    13Greenebaum Comprehensive Cancer Center - UM /ID# 213855BaltimoreMarylandUnited States21201-1544
    14Massachusetts General Hospital /ID# 215765BostonMassachusettsUnited States02114
    15Beth Israel Deaconess Medical Center /ID# 221181BostonMassachusettsUnited States02215-5400
    16Karmanos Cancer Institute - Dresner Clinic /ID# 214581DetroitMichiganUnited States48201-2013
    17Mayo Clinic - Rochester /ID# 214685RochesterMinnesotaUnited States55905-0001
    18University of Mississippi Medical Center /ID# 239343JacksonMississippiUnited States39216-4500
    19The John Theurer Cancer /ID# 215251HackensackNew JerseyUnited States07601
    20Roswell Park Comprehensive Cancer Center /ID# 217857BuffaloNew YorkUnited States14263
    21Weill Cornell Medical College /ID# 214887New YorkNew YorkUnited States10065
    22Univ Rochester Med Ctr /ID# 215877RochesterNew YorkUnited States14642
    23University of North Carolina /ID# 215814Chapel HillNorth CarolinaUnited States27514
    24University of Oklahoma, Stephenson Cancer Center /ID# 215611Oklahoma CityOklahomaUnited States73104-5418
    25Oregon Health & Science University /ID# 215874PortlandOregonUnited States97239-3011
    26Penn State Hershey Medical Ctr /ID# 217120HersheyPennsylvaniaUnited States17033
    27Children's Hospital of Philadelphia - Main /ID# 215410PhiladelphiaPennsylvaniaUnited States19104-4319
    28Perelman Center for Advanced Medicine - /ID# 214518PhiladelphiaPennsylvaniaUnited States19104-5127
    29Allegheny General Hospital /ID# 216756PittsburghPennsylvaniaUnited States15212
    30UPMC Hillman Cancer Ctr /ID# 213715PittsburghPennsylvaniaUnited States15232
    31St Jude Children's Research Hospital /ID# 214074MemphisTennesseeUnited States38105
    32TriStar Centennial Medical Center /ID# 218750NashvilleTennesseeUnited States37203-1551
    33Texas Oncology - Medical City Dallas /ID# 216720DallasTexasUnited States75230
    34Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 213735DallasTexasUnited States75246-2003
    35Texas Transplant Institute /ID# 214691San AntonioTexasUnited States78229
    36University of Utah /ID# 238860Salt Lake CityUtahUnited States84112-5500
    37Fred Hutchinson Cancer Research Center /ID# 214436SeattleWashingtonUnited States98109-1024
    38Univ of Wisconsin Hosp/Clinics /ID# 216096MadisonWisconsinUnited States53792-0001
    39The Kinghorn Cancer Centre /ID# 214660DarlinghurstNew South WalesAustralia2010
    40Royal Adelaide Hospital /ID# 215678AdelaideSouth AustraliaAustralia5000
    41Peter MacCallum Cancer Ctr /ID# 214653MelbourneVictoriaAustralia3000
    42Hospital de Clinicas de Porto Alegre /ID# 215042Porto AlegreRio Grande Do SulBrazil90035-903
    43Hospital Amaral Carvalho /ID# 215145JaúSao PauloBrazil17210-070
    44Vancouver Coastal Health Research Institute (VCHRI) /ID# 215363VancouverBritish ColumbiaCanadaV5Z 1M9
    45Princess Margaret Cancer Centre /ID# 215344TorontoOntarioCanadaM5G 2M9
    46CIUSSS de l'est de l'Ile-de-Montreal - Hopital Maisonneuve-Rosemont /ID# 214591MontrealQuebecCanadaH1T 2M4
    47Royal Victoria Hospital / McGill University Health Centre /ID# 215253MontrealQuebecCanadaH4A 3J1
    48Anhui Provincial Hospital /ID# 216408HefeiAnhuiChina230001
    49Peking University People's Hospital /ID# 215551BeijingBeijingChina100044
    50Chinese PLA General Hospital /ID# 216287BeijingBeijingChina100853
    51Aerospace Center Hospital /ID# 217018BeijingBeijingChina861059
    52Fujian Medical University Union Hospital /ID# 215555FuzhouFujianChina350001
    53Guangdong Provincial People's Hospital /ID# 218666GuangzhouGuangdongChina510080
    54Henan Cancer Hospital /ID# 215554ZhengzhouHenanChina450008
    55Tongji Hospital Tongji Medical College Huazhong University of Science and Techno /ID# 215552WuhanHubeiChina430022
    56Zhongda Hospital Southeast University /ID# 218926NanjingJiangsuChina210009
    57Tangdu Hospital of The Fourth Military Medical University, PLA /ID# 216282Xi'anShaanxiChina710038
    58Shanghai Changhai Hospital /ID# 216334ShanghaiShanghaiChina200433
    59Shanghai General Hospital /ID# 216410ShanghaiShanghaiChina201600
    60Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 215546TianjinTianjinChina300020
    61The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 215550HangzhouZhejiangChina310006
    62Xiangya Hospital Central South University /ID# 219025ChangshaChina410008
    63Nanfang Hospital of Southern Medical University /ID# 215553GuangzhouChina510080
    64The First Affiliated Hospital of Soochow University /ID# 216605SoochowChina215006
    65Fakultni Nemocnice Brno /ID# 214811BrnoCzechia625 00
    66Fakultni nemocnice Hradec Kralove /ID# 214814Hradec KraloveCzechia500 05
    67Ustav hematologie a krevni transfuze /ID# 215133PrahaCzechia128 00
    68Chu de Nice-Hopital L'Archet Ii /Id# 214056NiceAlpes-MaritimesFrance06200
    69CHU Bordeaux - Hopital Haut Lévêque /ID# 214055Pessac CEDEXGirondeFrance33604
    70CHRU Lille - Hopital Claude Huriez /ID# 217916LilleHauts-de-FranceFrance59037
    71CHU de Nantes, Hotel Dieu -HME /ID# 214060NantesPays-de-la-LoireFrance44000
    72AP-HP - Hopital Saint-Louis /ID# 214054ParisFrance75010
    73AP-HP - Hopital Saint-Antoine /ID# 216957ParisFrance75012
    74Universitaetsklinik Heidelberg /ID# 216623HeidelbergBaden-WuerttembergGermany69120
    75Universitaetsklinikum Muenster /ID# 215213MuensterNordrhein-WestfalenGermany48149
    76Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 214244DresdenGermany01307
    77Universitaetsklinikum Halle (Saale) /ID# 239585Halle (Saale)Germany06120
    78Medizinische Hochschule Hannover /ID# 214243HannoverGermany30625
    79Universitaetsklinikum Wuerzburg /ID# 215212WuerzburgGermany97080
    80The Chaim Sheba Medical Center /ID# 214305Ramat GanTel-AvivIsrael5265601
    81Tel Aviv Sourasky Medical Center /ID# 214508Tel Aviv-YafoTel-AvivIsrael6423906
    82Rambam Health Care Campus /ID# 214507HaifaIsrael3109601
    83Hadassah Medical Center-Hebrew University /ID# 218697JerusalemIsrael91120
    84Schneider Children's Medical Center /ID# 224326Petah TikvaIsrael4920235
    85Rabin Medical Center /ID# 214509Petakh TikvaIsrael4941492
    86Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 214910RomeLazioItaly00168
    87Ospedale San Raffaele IRCCS /ID# 214311MilanLombardiaItaly20132
    88ASST Spedali civili di Brescia /ID# 215997BresciaItaly25123
    89A.O.U. Citta della Salute e della Scienza di Torino /ID# 216148TurinItaly10126
    90Anjou Kousei Hospital /ID# 215857Anjo-shiAichiJapan446-8602
    91Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital /ID# 215679Nagoya-shiAichiJapan453-8511
    92Kyushu University Hospital /ID# 215285Fukuoka-shiFukuokaJapan812-8582
    93Hokkaido University Hospital /ID# 215937Sapporo-shiHokkaidoJapan060-8648
    94Kobe City Medical Center General Hospital /ID# 215388Kobe-shiHyogoJapan650-0047
    95Hyogo College of Medicine College Hospital /Id# 215389Nishinomiya-shiHyogoJapan663-8501
    96Imamura General Hospital /ID# 215688Kagoshima-shiKagoshimaJapan890-0064
    97Kanagawa Cancer Center /ID# 215029Yokohama-shiKanagawaJapan241-8515
    98Tohoku University Hospital /ID# 214670Sendai-shiMiyagiJapan9808574
    99Okayama University Hospital /ID# 214842Okayama-shiOkayamaJapan700-8558
    100Osaka City University Hospital /ID# 215227Osaka-shiOsakaJapan545-8586
    101Kindai University Hospital /ID# 214917Osakasayama-shiOsakaJapan589-8511
    102Jichi Medical University Saitama Medical Center /ID# 216092Saitama-shiSaitamaJapan330-8503
    103Jichi Medical University Hospital /ID# 216091Shimotsuke-shiTochigiJapan329-0498
    104Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 215939Bunkyo-kuTokyoJapan113-8677
    105Seoul National University Hospital /ID# 214891SeoulKorea, Republic of03080
    106Asan Medical Center /ID# 214893SeoulKorea, Republic of05505
    107The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 214892SeoulKorea, Republic of06591
    108Rogachev Nat Med Research Ctr for Pediatric Hematology, Onc /ID# 216538MoscowMoskvaRussian Federation117198
    109Academician I.P. Pavlov First St. Petersburg State Medical University /ID# 214609St. PetersburgSankt-PeterburgRussian Federation197101
    110Kirov Research Institute of Hematology and Blood Transfusion of FMBA /ID# 216591KirovRussian Federation610027
    111Almazov National Medical Research Centre /ID# 214357Sankt-PeterburgRussian Federation197341
    112Hospital Clinic de Barcelona /ID# 215108BarcelonaSpain08036
    113Hospital General Universitario Gregorio Maranon /ID# 215107MadridSpain28007
    114Hospital Universitario Ramon y Cajal /ID# 218102MadridSpain28034
    115Hospital Universitario La Paz /ID# 218103MadridSpain28046
    116Hospital Universitario Virgen del Rocio /ID# 215463SevillaSpain41013
    117Hospital Clinico Universitario de Valencia /ID# 215106ValenciaSpain46010
    118Universitätsspital Basel /ID# 215892BaselBasel-StadtSwitzerland4031
    119Universitätsspital Zürich /ID# 215891ZürichZuerichSwitzerland8091
    120Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 215197KaohsiungTaiwan807
    121China Medical University Hospital /ID# 215198Taichung CityTaiwan40447
    122National Taiwan University Hospital /ID# 215245Taipei CityTaiwan100
    123Linkou Chang Gung Memorial Ho /ID# 215319Taoyuan CityTaiwan333
    124NHS Greater Glasgow and Clyde /ID# 215663GlasgowScotlandUnited KingdomG12 0XH
    125University Hospitals Birmingham NHS Foundation Trust /ID# 215120BirminghamUnited KingdomB15 2TH
    126University College London Hospitals NHS Foundation Trust /ID# 215662LondonUnited KingdomNW1 2PG
    127King's College Hospital NHS Foundation Trusts /ID# 215338LondonUnited KingdomSE5 9RS
    128The Royal Marsden NHS Foundation Trust /ID# 215124LondonUnited KingdomSW3 6JJ
    129Imperial College Healthcare NHS Trust /ID# 215665LondonUnited KingdomW2 1NY
    130Manchester University NHS Foundation Trust /ID# 215121ManchesterUnited KingdomM13 9WL

    Sponsors and Collaborators

    • AbbVie

    Investigators

    • Study Director: ABBVIE INC., AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT04161885
    Other Study ID Numbers:
    • M19-063
    • 2019-002621-30
    First Posted:
    Nov 13, 2019
    Last Update Posted:
    Oct 12, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by AbbVie
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 12, 2021