Acute Myeloid Leukemia Clinical Trial
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
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.
Eligibility Criteria
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:
0 to 2 for Participants >= 75 years of age or
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:
aspartate aminotransferase (AST) <= 3.0 x ULN*
alanine aminotransferase (ALT) <= 3.0 x ULN*
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:
Age > 55 years with no menses for 12 or more months without an alternative medical cause.
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
Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); or
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:
At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and
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:
A hypomethylating agent, venetoclax and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS).
Chimeric Antigen Receptor (CAR)-T cell therapy.
Experimental therapies for MDS or Acute Myeloid Leukemia (AML).
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:
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; 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.)
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There are 164 Locations for this study
Duarte California, 91010, United States
Los Angeles California, 90095, United States
Sacramento California, 95817, United States
Atlanta Georgia, 30322, United States
Chicago Illinois, 60611, United States
Chicago Illinois, 60637, United States
Fort Wayne Indiana, 46804, United States
Topeka Kansas, 66606, United States
Louisville Kentucky, 40202, United States
Brewer Maine, 04412, United States
Baltimore Maryland, 21287, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02215, United States
Boston Massachusetts, 02215, United States
Grand Rapids Michigan, 49503, United States
New York New York, 10032, United States
New York New York, 10065, United States
Durham North Carolina, 27710, United States
Pittsburgh Pennsylvania, 15260, United States
Nashville Tennessee, 37203, United States
Houston Texas, 77030, United States
Temple Texas, 76508, United States
Salt Lake City Utah, 84112, United States
Burlington Vermont, 05405, United States
Woolloongabba Queensland, 4102, Australia
Adelaide South Australia, 5000, Australia
Melbourne Victoria, 3004, Australia
Melbourne Victoria, 3065, Australia
Parkville Victoria, 3050, Australia
Nedlands Western Australia, 6009, Australia
Perth Western Australia, 6000, Australia
Sankt Poelten Niederoesterreich, 3100, Austria
Linz Oberoesterreich, 4010, Austria
Linz Oberoesterreich, 4010, Austria
Graz Steiermark, 8036, Austria
Salzburg , 5020, Austria
Wien , 1140, Austria
Jette Bruxelles-Capitale, 1090, Belgium
Woluwe-Saint-Lambert Bruxelles-Capitale, 1200, Belgium
Gent Oost-Vlaanderen, 9000, Belgium
Brugge , 8000, Belgium
Porto Alegre Rio Grande Do Sul, 90035, Brazil
Ribeirão Preto Sao Paulo, 14051, Brazil
São Paulo Sao Paulo, 01236, Brazil
São Paulo Sao Paulo, 01246, Brazil
Calgary Alberta, T2N 4, Canada
Vancouver British Columbia, V6Z 1, Canada
Hamilton Ontario, L8V 1, Canada
Ottawa Ontario, K1H 8, Canada
Toronto Ontario, M5G 2, Canada
Fuzhou Fujian, 35000, China
Guangzhou Guangdong, 51051, China
Shijiazhuang Hebei, 05000, China
Zhengzhou Henan, 45000, China
Wuhan Hubei, 43002, China
Wuhan Hubei, 43002, China
Nanjing Jiangsu, 21002, China
Changchun Jilin, 13002, China
Shanghai Shanghai, 20006, China
Chengdu Sichuan, 61004, China
Tianjin Tianjin, 30002, China
Hangzhou Zhejiang, 31000, China
Jinan , 25001, China
Zagreb Grad Zagreb, 10000, Croatia
Zagreb Grad Zagreb, 10000, Croatia
Osijek Osjecko-baranjska Zupanija, 31000, Croatia
Brno , 625 0, Czechia
Hradec Kralove , 500 0, Czechia
Ostrava , 708 5, Czechia
Plzen , 305 9, Czechia
Aalborg Nordjylland, 9000, Denmark
Tampere Pirkanmaa, 33520, Finland
Helsinki Uusimaa, 00290, Finland
Turku , 20520, Finland
Pessac Gironde, 33604, France
Angers , 49933, France
Paris , 75010, France
Toulouse Cedex 9 , 31059, France
Ulm Baden-Wuerttemberg, 89081, Germany
Frankfurt am Main Hessen, 60590, Germany
Muenster Nordrhein-Westfalen, 48149, Germany
Halle (Saale) , 06120, Germany
Hamburg , 20246, Germany
Hannover , 30625, Germany
Szeged Csongrad, 6725, Hungary
Debrecen Hajdu-Bihar, 4032, Hungary
Nyíregyháza Nyiregyhaza, 4400, Hungary
Kaposvár Somogy, 7400, Hungary
Budapest , 1085, Hungary
Budapest , 1088, Hungary
Budapest , 1097, Hungary
Ramat Gan Tel-Aviv, 52656, Israel
Tel Aviv-Yafo Tel-Aviv, 64239, Israel
Be'er Ya'aqov , 70300, Israel
Haifa , 31096, Israel
Jerusalem , 91120, Israel
Petach Tikva , 49414, Israel
Lecce Puglia, 73100, Italy
Rome Roma, 00133, Italy
Ancona , 60126, Italy
Bergamo , 24127, Italy
Bologna , 40138, Italy
Genova , 16132, Italy
Milan , 20122, Italy
Napoli , 80131, Italy
Reggio Calabria , 89124, Italy
Rome , 00189, Italy
Nagoya-shi Aichi, 464-8, Japan
Yoshida-gun Fukui, 910-1, Japan
Fukuoka-shi Fukuoka, 811-1, Japan
Fukuoka-shi Fukuoka, 812-8, Japan
Maebashi-shi Gunma, 371-0, Japan
Higashi Ibaraki, 311-3, Japan
Hitachi-shi Ibaraki, 317-0, Japan
Kyoto-shi Kyoto, 602-8, Japan
Sendai-shi Miyagi, 98085, Japan
Nagasaki-shi Nagasaki, 852-8, Japan
Okayama-shi Okayama, 700-8, Japan
Osaka-sayama-shi Osaka, 589-8, Japan
Osaka-shi Osaka, 545-8, Japan
Hidaka-shi Saitama, 350-1, Japan
Bunkyo-ku Tokyo, 113-8, Japan
Bunkyo-ku Tokyo, 113-8, Japan
Komae-shi Tokyo, 201-8, Japan
Shinagawa-ku Tokyo, 141-8, Japan
Yamagata-shi Yamagata, 990-9, Japan
Seoul Seoul Teugbyeolsi, 05030, Korea, Republic of
Seoul , 03080, Korea, Republic of
Seoul , 06351, Korea, Republic of
Nordlenangen Akershus, 1474, Norway
Drammen Buskerud, 3004, Norway
Bergen Hordaland, 5021, Norway
Gralum , 1714, Norway
Wroclaw Dolnoslaskie, 50-55, Poland
Krakow Malopolskie, 31-82, Poland
Chorzow Slaskie, 41-50, Poland
Braga , 4710-, Portugal
Porto , 4200-, Portugal
San Juan , 00921, Puerto Rico
Kemerovo Kemerovskaya Oblast, 65009, Russian Federation
Moscow Moskva, 12528, Russian Federation
Nizhniy Novgorod Nizhegorodskaya Oblast, 60312, Russian Federation
Penza Penzenskaya Oblast, 44007, Russian Federation
Ryazan Ryazanskaya Oblast, 39003, Russian Federation
Saratov Saratovskaya Oblast, 41001, Russian Federation
Moscow , 12516, Russian Federation
Samara , 44309, Russian Federation
Pretoria Gauteng, 0001, South Africa
Pretoria Gauteng, 0044, South Africa
Pamplona Navarra, 31008, Spain
Barcelona , 08036, Spain
Barcelona , 08041, Spain
Madrid , 28006, Spain
Madrid , 28007, Spain
Madrid , 28041, Spain
Malaga , 29010, Spain
Valencia , 46026, Spain
Uppsala Uppsala Lan, 751 8, Sweden
Uddevalla Vastra Gotalands Lan, 451 8, Sweden
Lund , 221 8, Sweden
Stockholm , 171 7, Sweden
Changhua city Changhua County, 50006, Taiwan
Kaohsiung , 807, Taiwan
Taichung City , 40447, Taiwan
Taipei City , 100, Taiwan
Ankara , 06100, Turkey
Ankara , 06620, Turkey
Samsun , 55139, Turkey
Kiev Vinnytska Oblast, 04112, Ukraine
Dnipro , 49102, Ukraine
Kyiv , 04107, Ukraine
Poltava , 36011, Ukraine
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