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)

Cancer Clinical Trial

— VIALE-T  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04161885
• Other study ID #: M19-063
• Secondary ID: 2019-002621-30
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 26, 2020
• Est. completion date: November 30, 2026

Study information

• Verified date: February 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 465
• Est. completion date: November 30, 2026
• Est. primary completion date: November 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Cancer
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Venetoclax
Tablet; Oral
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital /ID# 215678	Adelaide	South Australia
Australia	The Kinghorn Cancer Centre /ID# 214660	Darlinghurst	New South Wales
Australia	Alfred Health /ID# 240931	Melbourne	Victoria
Australia	Peter MacCallum Cancer Ctr /ID# 214653	Melbourne	Victoria
Brazil	Hospital Amaral Carvalho - Fundacao Doutor Amaral Carvalho /ID# 215145	Jaú	Sao Paulo
Brazil	Hospital de Clinicas de Porto Alegre /ID# 215042	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo /ID# 239516	Sao Paulo
Brazil	Hospital Nove de Julho /ID# 242359	São Paulo	Sao Paulo
Canada	CIUSSS de l'est de l'Ile-de-Montreal - Hopital Maisonneuve-Rosemont /ID# 214591	Montreal	Quebec
Canada	Royal Victoria Hospital / McGill University Health Centre /ID# 215253	Montreal	Quebec
Canada	Saskatoon Cancer Centre /ID# 238821	Saskatoon	Saskatchewan
Canada	Princess Margaret Cancer Centre /ID# 215344	Toronto	Ontario
Canada	Vancouver Coastal Health Research Institute (VCHRI) /ID# 215363	Vancouver	British Columbia
China	Aerospace Center Hospital /ID# 217018	Beijing	Beijing
China	Chinese PLA General Hospital /ID# 216287	Beijing	Beijing
China	Peking University People's Hospital /ID# 215551	Beijing	Beijing
China	Xiangya Hospital Central South University /ID# 219025	Changsha	Hunan
China	Fujian Medical University Union Hospital /ID# 215555	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital /ID# 218666	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University /ID# 215553	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University /ID# 216333	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 215550	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Nanchang University /ID# 239168	Nanchang	Jiangxi
China	Zhongda Hospital Southeast University /ID# 218926	Nanjing	Jiangsu
China	Shanghai Changhai Hospital /ID# 216334	Shanghai	Shanghai
China	Shenzhen Second People's Hospital /ID# 239401	Shenzhen	Guangdong
China	The First Affiliated Hospital of Soochow University /ID# 216605	Suzhou	Jiangsu
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 215546	Tianjin	Tianjin
China	Tongji Hospital Tongji Medical College Huazhong University of Science and Techno /ID# 215552	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 238373	Wuhan	Hubei
China	Tangdu Hospital of The Fourth Military Medical University, PLA /ID# 216282	Xi'an	Shanxi
China	The Affiliated Hospital of Xuzhou Medical University /ID# 239098	Xuzhou	Jiangsu
China	Henan Cancer Hospital /ID# 215554	Zhengzhou	Henan
Czechia	Fakultni Nemocnice Brno /ID# 214811	Brno
Czechia	Fakultni nemocnice Hradec Kralove /ID# 214814	Hradec Kralove
Czechia	Fakultni Nemocnice Ostrava /ID# 239922	Ostrava
Czechia	Ustav hematologie a krevni transfuze /ID# 215133	Praha
France	CHU de Besancon - Jean Minjoz /ID# 241171	Besancon	Doubs
France	CHRU Lille - Hopital Claude Huriez /ID# 217916	Lille	Nord
France	CHU de Nantes, Hotel Dieu -HME /ID# 214060	Nantes	Pays-de-la-Loire
France	CHU de Nice - Hôpital Archet 1 /ID# 214056	Nice	Alpes-Maritimes
France	AP-HP - Hopital Saint-Antoine /ID# 216957	Paris
France	AP-HP - Hopital Saint-Louis /ID# 214054	Paris
France	Hopital Pitie Salpetriere /ID# 241072	Paris
France	CHU Bordeaux - Hopital Haut Leveque /ID# 214055	Pessac	Gironde
Germany	Klinikum Augsburg /ID# 239583	Augsburg
Germany	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 214244	Dresden
Germany	Universitaetsklinikum Halle (Saale) /ID# 239585	Halle (Saale)
Germany	Medizinische Hochschule Hannover /ID# 214243	Hannover
Germany	Universitaetsklinik Heidelberg /ID# 216623	Heidelberg	Baden-Wuerttemberg
Germany	Universitaetsklinikum Leipzig /ID# 245892	Leipzig	Sachsen
Germany	Universitaetsklinikum Muenster /ID# 215213	Muenster	Nordrhein-Westfalen
Germany	Universitaetsklinikum Wuerzburg /ID# 215212	Wuerzburg
Greece	General Hospital of Athens Evangelismos /ID# 238810	Athens	Attiki
Greece	University General Hospital Attikon /ID# 238812	Athens	Attiki
Greece	University General Hospital of Patras /ID# 238811	RION Patras Achaia
Hungary	Debreceni Egyetem Klinikai Kozpont /ID# 241123	Debrecen	Hajdu-Bihar
Israel	Rabin Medical Center /ID# 214509	Haifa	H_efa
Israel	Rambam Health Care Campus /ID# 214507	Haifa	H_efa
Israel	Hadassah Medical Center-Hebrew University /ID# 218697	Jerusalem	Yerushalayim
Israel	Schneider Children's Medical Center /ID# 224326	Petah Tikva	HaMerkaz
Israel	Sheba Medical Center /ID# 239571	Ramat Gan	Tel-Aviv
Israel	The Chaim Sheba Medical Center /ID# 214305	Ramat Gan	Tel-Aviv
Israel	Tel Aviv Sourasky Medical Center /ID# 214508	Tel Aviv	Tel-Aviv
Italy	ASST Spedali civili di Brescia /ID# 215997	Brescia
Italy	IEO -Istituto Europeo di Oncologia /ID# 242579	Milan	Milano
Italy	Ospedale San Raffaele IRCCS /ID# 214311	Milan	Milano
Italy	Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 254964	Rome	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 214910	Rome	Lazio
Italy	A.O.U. Citta della Salute e della Scienza di Torino /ID# 216148	Turin	Torino
Japan	Anjou Kousei Hospital /ID# 215857	Anjo-shi	Aichi
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 215939	Bunkyo-ku	Tokyo
Japan	National Cancer Center Hospital /ID# 242639	Chuo-ku	Tokyo
Japan	Kyushu University Hospital /ID# 215285	Fukuoka-shi	Fukuoka
Japan	Fukushima Medical University Hospital /ID# 252293	Fukushima-shi	Fukushima
Japan	Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital /ID# 217522	Hiroshima-shi	Hiroshima
Japan	Tokai University Hospital /ID# 250086	Isehara-shi	Kanagawa
Japan	Imamura General Hospital /ID# 215688	Kagoshima-shi	Kagoshima
Japan	Kanazawa University Hospital /ID# 242955	Kanazawa-shi	Ishikawa
Japan	Kobe City Medical Center General Hospital /ID# 215388	Kobe-shi	Hyogo
Japan	Kyoto University Hospital /ID# 243209	Kyoto-shi	Kyoto
Japan	Toranomon Hospital /ID# 215311	Minato-ku	Tokyo
Japan	Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital /ID# 215679	Nagoya-shi	Aichi
Japan	Hyogo Medical University Hospital /ID# 215389	Nishinomiya-shi	Hyogo
Japan	Okayama University Hospital /ID# 214842	Okayama-shi	Okayama
Japan	Osaka Metropolitan University Hospital /ID# 215227	Osaka-shi	Osaka
Japan	Kindai University Hospital /ID# 214917	Osakasayama-shi	Osaka
Japan	Jichi Medical University Saitama Medical Center /ID# 216092	Saitama-shi	Saitama
Japan	Hokkaido University Hospital /ID# 215937	Sapporo-shi	Hokkaido
Japan	Tohoku University Hospital /ID# 214670	Sendai-shi	Miyagi
Japan	National Center for Child Health and Development /ID# 242479	Setagaya-ku	Tokyo
Japan	Jichi Medical University Hospital /ID# 216091	Shimotsuke-shi	Tochigi
Japan	Keio University Hospital /ID# 243549	Shinjuku-ku	Tokyo
Japan	Yamagata University Hospital /ID# 253304	Yamagata-shi	Yamagata
Japan	Kanagawa Cancer Center /ID# 215029	Yokohama-shi	Kanagawa
Japan	University of Fukui Hospital /ID# 253383	Yoshida-gun	Fukui
Korea, Republic of	Asan Medical Center /ID# 214893	Seoul
Korea, Republic of	Samsung Medical Center /ID# 239087	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 214891	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 214892	Seoul
Spain	Hospital Clinic de Barcelona /ID# 215108	Barcelona
Spain	Hospital Santa Creu i Sant Pau /ID# 240397	Barcelona
Spain	Hospital General Universitario Gregorio Maranon /ID# 215107	Madrid
Spain	Hospital Universitario La Paz /ID# 218103	Madrid
Spain	Hospital Universitario Ramon y Cajal /ID# 218102	Madrid
Spain	Hospital Universitario Virgen del Rocio /ID# 215463	Sevilla
Spain	Hospital Clinico Universitario de Valencia /ID# 215106	Valencia
Switzerland	Universitätsspital Basel /ID# 215892	Basel	Basel-Stadt
Switzerland	Universitatsspital Zurich /ID# 215891	Zurich	Zuerich
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 215197	Kaohsiung
Taiwan	China Medical University Hospital /ID# 215198	Taichung
Taiwan	Taichung Veterans General Hospital /ID# 239288	Taichung
Taiwan	Taipei Veterans General Hosp /ID# 239289	Taipei
Taiwan	National Taiwan University Hospital /ID# 215245	Taipei City
Taiwan	Linkou Chang Gung Memorial Hospital /ID# 215319	Taoyuan City
United Kingdom	University Hospitals Birmingham NHS Foundation Trust /ID# 215120	Birmingham
United Kingdom	NHS Greater Glasgow and Clyde /ID# 215663	Glasgow	Scotland
United Kingdom	Imperial College Healthcare NHS Trust /ID# 215665	London
United Kingdom	King's College Hospital NHS Foundation Trust /ID# 215338	London
United Kingdom	The Royal Marsden NHS Foundation Trust /ID# 215124	London
United Kingdom	University College London Hospitals NHS Foundation Trust /ID# 215662	London
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 248359	Newcastle upon Tyne
United States	UCHSC Anschultz Cancer Pavilion /ID# 215618	Aurora	Colorado
United States	University of Maryland Med Ctr /ID# 213855	Baltimore	Maryland
United States	Massachusetts General Hospital /ID# 215765	Boston	Massachusetts
United States	Montefiore Medical Center - Moses Campus /ID# 241669	Bronx	New York
United States	Roswell Park Comprehensive Cancer Center /ID# 217857	Buffalo	New York
United States	University of North Carolina /ID# 215814	Chapel Hill	North Carolina
United States	Ann & Robert H Lurie Children's Hospital of Chicago /ID# 215840	Chicago	Illinois
United States	The University of Chicago Medical Center /ID# 215616	Chicago	Illinois
United States	UC Health - Cincinnati /ID# 239263	Cincinnati	Ohio
United States	University Hospitals - Seidman Cancer Center /ID# 239260	Cleveland	Ohio
United States	Texas Oncology - Medical City Dallas /ID# 216720	Dallas	Texas
United States	Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 213735	Dallas	Texas
United States	Colorado Blood Cancer Institute /ID# 215980	Denver	Colorado
United States	Karmanos Cancer Institute - Dresner Clinic /ID# 214581	Detroit	Michigan
United States	City of Hope /ID# 213681	Duarte	California
United States	The John Theurer Cancer /ID# 215251	Hackensack	New Jersey
United States	Penn State Hershey Medical Ctr /ID# 217120	Hershey	Pennsylvania
United States	Indiana Blood & Marrow Transpl /ID# 215842	Indianapolis	Indiana
United States	University of Mississippi Medical Center /ID# 239343	Jackson	Mississippi
United States	Mayo Clinic /ID# 239710	Jacksonville	Florida
United States	University of Arkansas for Medical Sciences /ID# 239804	Little Rock	Arkansas
United States	Univ of Wisconsin Hosp/Clinics /ID# 216096	Madison	Wisconsin
United States	Loyola University Medical Ctr /ID# 215617	Maywood	Illinois
United States	Masonic Cancer Center /ID# 239492	Minneapolis	Minnesota
United States	TriStar Centennial Medical Center /ID# 218750	Nashville	Tennessee
United States	Ochsner Clinic Foundation-New Orleans /ID# 213834	New Orleans	Louisiana
United States	Columbia University Medical Center /ID# 240875	New York	New York
United States	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 240680	New York	New York
United States	Weill Cornell Medical College /ID# 214887	New York	New York
United States	University of Oklahoma, Stephenson Cancer Center /ID# 215611	Oklahoma City	Oklahoma
United States	AdventHealth Medical Group Blood & Marrow Transplant at Orlando /ID# 213985	Orlando	Florida
United States	Children's Hospital of Philadelphia - Main /ID# 215410	Philadelphia	Pennsylvania
United States	Perelman Center for Advanced Medicine - /ID# 214518	Philadelphia	Pennsylvania
United States	Allegheny General Hospital /ID# 216756	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Ctr /ID# 213715	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University /ID# 215874	Portland	Oregon
United States	Virginia Commonwealth University Medical Center Main Hospital /ID# 239203	Richmond	Virginia
United States	Mayo Clinic - Rochester /ID# 214685	Rochester	Minnesota
United States	Texas Transplant Institute /ID# 214691	San Antonio	Texas
United States	Arizona Oncology - Scottsdale - Cancer Transplant Institute /ID# 239711	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center /ID# 214436	Seattle	Washington
United States	University of Arizona Cancer Center - Tucson /ID# 242507	Tucson	Arizona
United States	Wake Forest Univ HS /ID# 239210	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1)	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.	Up to the first treatment cycle (28 days)
Primary	Overall Survival (OS) (Part 2)	OS is defined as the number of days from the date of randomization to the date of death from any cause.	Up to 45 months after the first participant is randomized
Secondary	Morphologic Relapse-Free Survival (RFS) (Part 2)	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).	Up to 39 months after the first participant is randomized
Secondary	Composite Relapse-Free Survival (RFS) (Part 2)	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.	Up to 39 months after the first participant is randomized
Secondary	Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) (Part 2)	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.	Up to 39 months after the first participant is randomized
Secondary	Graft-versus-Host Disease (GvHD) Rate (Part 2)	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.	Up to 39 months after the first participant is randomized
Secondary	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)	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).	Up to 39 months after the first participant is randomized
Secondary	Change From Randomization in Fatigue in Adult Participants (Part 2)	Fatigue is measured as Patient Reported Outcome (PRO) using Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue SF 7a.	Up to 39 months after the first participant is randomized
Secondary	Measurable Residual Disease (MRD) Response Rate in Participants With MRD >= 10^-3 at Randomization (Part 2)	MRD conversion rate is defined as percentage of participants who convert to MRD < 10^-3 after initiation of treatment.	Up to 39 months after the first participant is randomized
Secondary	Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants (Part 2)	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.	Up to 39 months after the first participant is randomized
Secondary	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)	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.	Up to 39 months after the first participant is randomized

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