A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Participants With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy

Acute Myeloid Leukemia (AML) Clinical Trial

— Viale-a  

Official title:

A Randomized, Double-Blind, Placebo Controlled Phase 3 Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02993523
• Other study ID #: M15-656
• Secondary ID: 2016-001466-28
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 2, 2017
• Est. completion date: September 25, 2024

Study information

• Verified date: June 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acute Myeloid Leukaemia (AML) is an aggressive and rare cancer of myeloid cells (a white blood cell responsible for fighting infections). Successful treatment of AML is dependent on what subtype of AML the participant has, and the age of the participant when diagnosed. Venetoclax is an experimental drug that kills cancer cells by blocking a protein (part of a cell) that allows cancer cells to stay alive. This study is designed to see if adding venetoclax to azacitidine works better than azacitidine on its own. This is a Phase 3, randomized, double-blind (treatment is unknown to participants and doctors), placebo controlled study in patients with AML who are >= 18 or more years old and have not been treated before. Participants who take part in this study should not be suitable for standard induction therapy (usual starting treatment). AbbVie is funding this study which will take place at approximately 180 hospitals globally and enroll approximately 400 participants. In this study, 2/3 of participants will receive venetoclax every day with azacitidine and the remaining 1/3 will receive placebo (dummy) tablets with azacitidine. Participants will continue to have study visits and receive treatment for as long as they are having a clinical benefit. The effect of the treatment on AML will be checked by taking blood, bone marrow, scans, measuring side effects and by completing health questionnaires. Blood and bone marrow tests will be completed to see why some people respond better than others. Additional blood tests will be completed for genetic factors and to see how long the drug remains in the body.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 443
• Est. completion date: September 25, 2024
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant must have confirmation of Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria, previously untreated and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due age or comorbidities.
• Participant must be >= 18 years of age.
• Participant must have a projected life expectancy of at least 12 weeks.
• Participant must be considered ineligible for induction therapy defined by the following: a. >= 75 years of age; or b. >= 18 to 74 years of age with at least one of the following comorbidities: i. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3; ii. Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction <= 50% or chronic stable angina; iii. Diffusing capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in 1 second (FEV1) <= 65%; iv. Creatinine clearance >= 30 mL/min to < 45 ml/min; v. Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of Normal (ULN); vi. Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the AbbVie Therapeutic Medical Director during screening and before study enrollment.
• Participant must have an ECOG Performance status:

1. 0 to 2 for Participants >= 75 years of age or

2. 0 to 3 for Participants >= 18 to 74 years of age.

• Participant must have adequate renal function as demonstrated by a creatinine >= 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection.
• Participant must have adequate liver function as demonstrated by:

1. aspartate aminotransferase (AST) <= 3.0 x ULN*

2. alanine aminotransferase (ALT) <= 3.0 x ULN*

3. bilirubin <= 1.5 x ULN* * Unless considered to be due to leukemic organ involvement i. Participants who are < 75 years of age may have a bilirubin of <= 3.0 x ULN

• Female participants must be either postmenopausal defined as:

1. Age > 55 years with no menses for 12 or more months without an alternative medical cause.

2. Age = 55 years with no menses for 12 or more months without an alternative medical cause AND an follicle stimulating hormone (FSH) level >40 international units per liter (IU/L); or

3. Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); or

4. Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control, starting at Study Day 1 through at least 90 days after the last dose of study drug.

• Male participants who are sexually active, must agree, from Study Day 1 through at least 90 days after the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 90 days after the last dose of study drug.
• Female participants of childbearing potential must have negative results for pregnancy

test performed:

1. At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and

2. Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7 days since obtaining the serum pregnancy test results.

• Participant must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

• Participant has received treatment with the following:

1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS).

2. Chimeric Antigen Receptor (CAR)-T cell therapy.

3. Experimental therapies for MDS or Acute Myeloid Leukemia (AML).

4. Current participation in another research or observational study.

• Participant has history of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
• Participant has the following:

a. Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2016 for Acute Myeloid Leukemia.

• Participant has acute promyelocytic leukemia
• Participant has known active central nervous system (CNS) involvement with AML.
• Participant has known human immunodeficiency virus (HIV) infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax) HIV testing will be performed at Screening, only if required per local guidelines or institutional standards.
• Participant is known to be positive for hepatitis B or C infection [HCV Ab indicative of a previous or current infection; and/or positive HBs Ag or detected sensitivity on hepatitis B virus (HBV) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) test for HBc Ab and/or HBs Ab positivity] with the exception of those with an undetectable viral load within 3 months screening. Hepatitis B or C testing is not required.
• Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment; additional details as described in the protocol.
• Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
• Participant has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
• Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications including excipients of azacitidine that in the opinion of the investigator would adversely affect his/her participating in this study.
• Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.
• Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
• Participant has a history of other malignancies within 2 years prior to study entry,

with the exception of:

1. Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;

2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;

3. Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; requires discussion with TA MD.

• Participant has a white blood cell count > 25 × 10^9/L. (Hydroxyurea or leukapheresis are permitted to meet this criterion.)

Related Conditions & MeSH terms

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

Intervention

Drug:
• Azacitidine
Solution for subcutaneous or intravenous administration.
• Venetoclax
Tablet
• Placebo
Matching placebo tablet

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital /ID# 154271	Adelaide	South Australia
Australia	Alfred Health /ID# 154275	Melbourne	Victoria
Australia	St Vincent's Hospital Melbourne /ID# 155094	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital /ID# 163924	Nedlands	Western Australia
Australia	The Royal Melbourne Hospital /ID# 155095	Parkville	Victoria
Australia	Royal Perth Hospital /ID# 154274	Perth	Western Australia
Australia	Princess Alexandra Hospital /ID# 154272	Woolloongabba	Queensland
Austria	Medizinische Universitaet Graz /ID# 157882	Graz	Steiermark
Austria	Ordensklinikum Linz GmbH Barmherzige Schwestern /ID# 154888	Linz	Oberoesterreich
Austria	Ordensklinikum Linz GmbH Elisabethinen /ID# 154885	Linz	Oberoesterreich
Austria	Duplicate_Landeskrankenhaus Salzburg /ID# 169719	Salzburg
Austria	Universitaetsklinikum St. Poelten /ID# 167436	Sankt Poelten	Niederoesterreich
Austria	Hanusch Krankenhaus /ID# 155676	Wien
Belgium	AZ Sint-Jan Brugge /ID# 154041	Brugge
Belgium	UZ Gent /ID# 153392	Gent	Oost-Vlaanderen
Belgium	UZ Brussel /ID# 153393	Jette	Bruxelles-Capitale
Belgium	UCL Saint-Luc /ID# 153391	Woluwe-Saint-Lambert	Bruxelles-Capitale
Brazil	Hospital de Clinicas de Porto Alegre /ID# 157779	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP /ID# 153099	Ribeirão Preto	Sao Paulo
Brazil	Instituto de Ensino e Pesquisa São Lucas /ID# 157778	São Paulo	Sao Paulo
Brazil	Instituto do Câncer do Estado de São Paulo - ICESP /ID# 153095	São Paulo	Sao Paulo
Canada	Tom Baker Cancer Centre /ID# 159645	Calgary	Alberta
Canada	Juravinski Cancer Centre /ID# 153650	Hamilton	Ontario
Canada	Ottawa Hospital Research Institute /ID# 153541	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre /ID# 153651	Toronto	Ontario
Canada	St. Paul's Hospital /ID# 159644	Vancouver	British Columbia
China	The First Hospital of Jilin University /ID# 167490	Changchun	Jilin
China	West China Hospital, Sichuan University /ID# 167492	Chengdu	Sichuan
China	Fujian Medical University Union Hospital /ID# 167314	Fuzhou	Fujian
China	Nanfang Hospital of Southern Medical University /ID# 170148	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 167317	Hangzhou	Zhejiang
China	Qilu Hospital of Shandong University /ID# 167485	Jinan
China	Jiangsu Province Hospital /ID# 167489	Nanjing	Jiangsu
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 167318	Shanghai	Shanghai
China	The Second Hospital of Hebei Medical University /ID# 167316	Shijiazhuang	Hebei
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 167487	Tianjin	Tianjin
China	Tongji Hospital Tongji Medical College Huazhong University of Science and Techno /ID# 167315	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 167493	Wuhan	Hubei
China	Henan Cancer Hospital /ID# 167320	Zhengzhou	Henan
Croatia	Duplicate_Klinicki bolnicki centar Osijek /ID# 153623	Osijek	Osjecko-baranjska Zupanija
Croatia	Clinical Hospital Dubrava /ID# 153515	Zagreb	Grad Zagreb
Croatia	Klinicki bolnicki centar Zagreb /ID# 153383	Zagreb	Grad Zagreb
Czechia	Fakultni Nemocnice Brno /ID# 154019	Brno
Czechia	Fakultni nemocnice Hradec Kralove /ID# 154021	Hradec Kralove
Czechia	Fakultni nemocnice Ostrava /ID# 154017	Ostrava
Czechia	Fakultni nemocnice Plzen /ID# 154018	Plzen
Denmark	Aalborg University Hospital /ID# 154047	Aalborg	Nordjylland
Finland	Helsinki University Hospital /ID# 155223	Helsinki	Uusimaa
Finland	Tampere University Hospital /ID# 154963	Tampere	Pirkanmaa
Finland	Turku University Hospital /ID# 154964	Turku
France	Chu Angers /Id# 153792	Angers
France	AP-HP - Hopital Saint-Louis /ID# 153787	Paris
France	CHU Bordeaux - Hopital Haut Leveque /ID# 153789	Pessac	Gironde
France	IUCT Oncopole /ID# 153788	Toulouse Cedex 9
Germany	Universitaetsklinikum Frankfurt /ID# 153060	Frankfurt am Main	Hessen
Germany	Universitaetsklinikum Halle (Saale) /ID# 153058	Halle (Saale)
Germany	Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 153056	Hamburg
Germany	Medizinische Hochschule Hannover /ID# 153055	Hannover
Germany	Universitaetsklinikum Muenster /ID# 153059	Muenster	Nordrhein-Westfalen
Germany	Universitaetsklinikum Ulm /ID# 153054	Ulm	Baden-Wuerttemberg
Hungary	Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 158990	Budapest
Hungary	Duplicate_Semmelweis Egyetem /ID# 153815	Budapest
Hungary	Semmelweis Egyetem /ID# 153816	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont /ID# 153814	Debrecen	Hajdu-Bihar
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 153813	Kaposvár	Somogy
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Josa Andras Okta /ID# 169854	Nyíregyháza	Nyiregyhaza
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont /ID# 153812	Szeged	Csongrad
Israel	Assaf Harofeh Medical Center /ID# 158063	Be'er Ya'aqov
Israel	Rambam Health Care Campus /ID# 154174	Haifa
Israel	Hadassah /ID# 154172	Jerusalem
Israel	Rabin Medical Center /ID# 154176	Petach Tikva
Israel	The Chaim Sheba Medical Center /ID# 154173	Ramat Gan	Tel-Aviv
Israel	Tel Aviv Sourasky Medical Center /ID# 154175	Tel Aviv-Yafo	Tel-Aviv
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 171220	Ancona
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 152875	Bergamo
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 152883	Bologna
Italy	Ospedale Policlinico San Martino /ID# 158104	Genova
Italy	Presidio Ospedaliero Vito Fazzi /ID# 170837	Lecce	Puglia
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 152882	Milan
Italy	Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli /ID# 152879	Napoli
Italy	Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 152877	Reggio Calabria
Italy	Azienda Ospedaliero-Universitaria Sant'Andrea /ID# 152876	Rome
Italy	Fondazione PTV Policlinico Tor Vergata /ID# 152881	Rome	Roma
Japan	Juntendo University Hospital /ID# 168309	Bunkyo-ku	Tokyo
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 168639	Bunkyo-ku	Tokyo
Japan	Kyushu University Hospital /ID# 169095	Fukuoka-shi	Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center /ID# 201111	Fukuoka-shi	Fukuoka
Japan	Saitama Medical University International Medical Center /ID# 167814	Hidaka-shi	Saitama
Japan	National Hospital Organization Mito Medical Center /ID# 168219	Higashi	Ibaraki
Japan	Hitachi General Hospital /ID# 201109	Hitachi-shi	Ibaraki
Japan	The Jikei University Daisan Hospital /ID# 168745	Komae-shi	Tokyo
Japan	Duplicate_Kyoto Prefectural University of Medicine /ID# 167661	Kyoto-shi	Kyoto
Japan	Gunmaken Saiseikai Maebashi Hospital /ID# 168316	Maebashi-shi	Gunma
Japan	Nagasaki University Hospital /ID# 168632	Nagasaki-shi	Nagasaki
Japan	Aichi Cancer Center Hospital /ID# 200824	Nagoya-shi	Aichi
Japan	Okayama University Hospital /ID# 204124	Okayama-shi	Okayama
Japan	Duplicate_Kindai University Hospital /ID# 167662	Osaka-sayama-shi	Osaka
Japan	Osaka Metropolitan University Hospital /ID# 169055	Osaka-shi	Osaka
Japan	Tohoku University Hospital /ID# 169259	Sendai-shi	Miyagi
Japan	NTT Medical Center Tokyo /ID# 167975	Shinagawa-ku	Tokyo
Japan	Yamagata University Hospital /ID# 167634	Yamagata-shi	Yamagata
Japan	University of Fukui Hospital /ID# 167432	Yoshida-gun	Fukui
Korea, Republic of	Duplicate_Konkuk University Medical Ctr /ID# 153973	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Samsung Medical Center /ID# 153674	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 153675	Seoul
Norway	Haukeland University Hospital /ID# 154281	Bergen	Hordaland
Norway	Drammen Sykehus /ID# 154280	Drammen	Buskerud
Norway	Sykehuset Ostfold Kalnes /ID# 157755	Gralum
Norway	Akershus universitetssykehus /ID# 154279	Nordlenangen	Akershus
Poland	SP ZOZ Zespol Szpitali Miejskich w Chorzowie /ID# 153385	Chorzow	Slaskie
Poland	Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym im. Ludwika Rydygiera w /ID# 169846	Krakow	Malopolskie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu /ID# 153389	Wroclaw	Dolnoslaskie
Portugal	Duplicate_Hospital de Braga /ID# 154797	Braga
Portugal	IPO Porto FG, EPE /ID# 154138	Porto
Puerto Rico	VA Caribbean Healthcare System /ID# 160507	San Juan
Russian Federation	Kuzbass Regional Clinical Hospital /ID# 157461	Kemerovo	Kemerovskaya Oblast
Russian Federation	Federal State Budgetary Ins NRC for Hematology of MoH of Russian Federation /ID# 155740	Moscow
Russian Federation	Moscow State budget healthcare /ID# 155738	Moscow	Moskva
Russian Federation	Nizhny Novgorod Regional Clinical Hospital named N.A. Semashko /ID# 153268	Nizhniy Novgorod	Nizhegorodskaya Oblast
Russian Federation	Duplicate_Regional Oncology Dispensary /ID# 153264	Penza	Penzenskaya Oblast
Russian Federation	State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 157460	Ryazan	Ryazanskaya Oblast
Russian Federation	Samara State Medical University /ID# 157462	Samara
Russian Federation	Saratov State Medical University n.a. V.I. Razumovskiy /ID# 153267	Saratov	Saratovskaya Oblast
South Africa	Albert Alberts Stem Cell Transplant Centre /ID# 153684	Pretoria	Gauteng
South Africa	University of Pretoria /ID# 153682	Pretoria	Gauteng
Spain	Hospital Clinic de Barcelona /ID# 153255	Barcelona
Spain	Hospital Santa Creu i Sant Pau /ID# 153193	Barcelona
Spain	Hospital General Universitario Gregorio Maranon /ID# 153260	Madrid
Spain	Hospital Universitario 12 de Octubre /ID# 153258	Madrid
Spain	Hospital Universitario de la Princesa /ID# 153256	Madrid
Spain	Hospital Universitario Virgen de la Victoria /ID# 153257	Malaga
Spain	Hospital Universitario de Navarra /ID# 153254	Pamplona	Navarra
Spain	Hospital Universitario y Politecnico La Fe /ID# 153259	Valencia
Sweden	Dup_VO Hematologi /ID# 153174	Lund
Sweden	Karolinska University Hospital /ID# 170003	Stockholm
Sweden	Uddevalla sjukhus /ID# 156875	Uddevalla	Vastra Gotalands Lan
Sweden	Akademiska Sjukhuset /ID# 153034	Uppsala	Uppsala Lan
Taiwan	Changhua Christian Hospital /ID# 153899	Changhua city	Changhua County
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 153902	Kaohsiung
Taiwan	China Medical University Hospital /ID# 153904	Taichung City
Taiwan	National Taiwan University Hospital /ID# 153900	Taipei City
Turkey	Ankara Universitesi Fakultesi /ID# 155200	Ankara
Turkey	Hacettepe University Faculty of Medicine /ID# 202073	Ankara
Turkey	Ondokuz Mayis Universitesi Tip /ID# 155201	Samsun
Ukraine	Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council /ID# 153511	Dnipro
Ukraine	Kyiv city clinical hospital #9 /ID# 153510	Kiev	Vinnytska Oblast
Ukraine	Kyiv Regional Onco Dispensary /ID# 153514	Kyiv
Ukraine	Poltava Reg Clin Hosp Sklifoso /ID# 153513	Poltava
United States	Emory Midtown Infectious Disease Clinic /ID# 162534	Atlanta	Georgia
United States	Johns Hopkins University /ID# 154104	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center /ID# 201155	Boston	Massachusetts
United States	Dana-Farber Cancer Institute /ID# 167009	Boston	Massachusetts
United States	Massachusetts General Hospital /ID# 200752	Boston	Massachusetts
United States	EMMC Cancer Care /ID# 154991	Brewer	Maine
United States	University Of Vermont Medical /ID# 157196	Burlington	Vermont
United States	Northwestern University Feinberg School of Medicine /ID# 201133	Chicago	Illinois
United States	University of Chicago Medicine /ID# 154108	Chicago	Illinois
United States	City of Hope /ID# 154105	Duarte	California
United States	Duke Cancer Center /ID# 154106	Durham	North Carolina
United States	Fort Wayne Medical Oncology /ID# 157190	Fort Wayne	Indiana
United States	Sepctrum Health Medical Center /ID# 159522	Grand Rapids	Michigan
United States	University of Texas MD Anderson Cancer Center /ID# 154100	Houston	Texas
United States	University of California, Los Angeles /ID# 154107	Los Angeles	California
United States	Norton Cancer Institute /ID# 154992	Louisville	Kentucky
United States	Tennessee Oncology-Nashville Centennial /ID# 200854	Nashville	Tennessee
United States	Columbia Univ Medical Center /ID# 154101	New York	New York
United States	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 165077	New York	New York
United States	University of Pittsburgh MC /ID# 154102	Pittsburgh	Pennsylvania
United States	University of California, Davis Comprehensive Cancer Center /ID# 162725	Sacramento	California
United States	University of Utah /ID# 157192	Salt Lake City	Utah
United States	Baylor Scott & White Medical Center- Temple /ID# 157191	Temple	Texas
United States	Cotton-O'Neil Clinical Res Ctr /ID# 155136	Topeka	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Croatia,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Norway,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  South Africa,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is defined as the number of days from the date of randomization to the date of death. Log rank test was used to compare the OS distribution between two treatment arms. Cox regression was used to report the hazard ratio.	From the study start up to death or alive or lost to follow-up (up to approximately 4.8 years; data cut off date: 1 December 2021)
Primary	Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Marrow Recovery (CRi)	CR and CRi was calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count >10^3/ microliter (mcL), platelets >10^5/mcL, red cell transfusion independence, and bone marrow with <5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of =10^3/mcL or platelets =10^5/mcL. Percentages are rounded off to whole number at the nearest decimal.	From the study start up to death (up to approximately 4.8 years; data cut-off date: 1 December 2021)
Secondary	Event-free Survival (EFS)	EFS will be defined as the number of days from randomization to the date of progressive disease, relapse from CR or CRi, treatment failure or death from any cause.	Measured up to 2 years after the last participant is randomized
Secondary	Global Health Status/Quality of Life (GHS/QoL)	Improvement in GHS/QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30).	Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last subject last visit
Secondary	Percentage of Participants Achieving Composite Complete Remission (CR or CRi)	This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count > 10^3/mcL, platelets > 10^5/mcL, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of <= 10^3/mcL or platelets <= 10^5/mcL.	Up to 6 months after the first 225 participants are randomized
Secondary	Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR+CRh)	A response of CRh is defined as Bone marrow with <5% blasts, peripheral blood neutrophil count >0.5*10^3/mcL and peripheral blood platelet count >0.5*10^5/mcL.	Measured up to 2 years after the last participant is randomized
Secondary	Post Baseline Transfusion Independence Rate	Transfusion Independence is defined as a period of 56 days with no transfusion between first dose of study drug and the last dose of study drug + 30 days. The rate of conversion for red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependence.	Measured up to 2 years after the last participant is randomized
Secondary	Complete Remission (CR) Rate	The percentage of participants with complete remission (CR) will be calculated based on the modified IWG criteria for AML.	Measured up to 2 years after the last participant is randomized
Secondary	Fatigue/Quality of Life (QoL)	Fatigue QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form (SF) 7a global fatigue score	Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last participant last visit

External Links

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