Clinical trial NCT05144243: Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
Official title: A Phase 4 Study of Venetoclax in Combination With Azacitidine in Newly Diagnosed Subjects With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy in China
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Acute Myeloid Leukemia (AML)
Keywords: Acute Myeloid Leukemia
AML
Venetoclax
Venclexta
Azacitidine
Treatment Naïve AML
Untreated AML
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2021-12-03
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Acute myeloid leukemia (AML) is one of the most aggressive blood cancers, with a very low survival rate and few options for participants who are unable to undergo intensive chemotherapy, the current standard of care. This study is to evaluate how safe the combination of azacitidine and venetoclax is and how effective the combination of azacitidine and venetoclax is in adult participants with acute myeloid leukemia (AML), in China. Adverse events and change in disease state will be assessed.

The combination of azacitidine and venetoclax is being evaluated in the treatment of acute myeloid leukemia (AML). Participants will receive azacitidine with increasing doses of venetoclax. Adult participants with a diagnosis of AML will be enrolled. Around 40 participants will be enrolled in the study in approximately 30 sites in China.

At cycle 1 during ramp-up period, participants will receive venetoclax oral tablets once daily in increasing doses until the study dose is achieved on day 3. Then ventoclax oral tablets will continue once daily thereafter. Azacitidine will be given by subcutaneous injection (SC) for 7 days beginning on Day 1 of each 28-day cycle.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects.


Eligibility criteria: Inclusion Criteria:

* Confirmation of Acute myeloid leukemia (AML) diagnosis by World Health Organization (WHO) criteria, have a projected life expectancy of at least 12 weeks, previously untreated, and ineligible for treatment with intensive chemotherapy.
* Participant must be considered ineligible for induction therapy defined by the following:

  * \>= 75 years of age
  * \>=18 to 74 years of age with at least one of the following comorbidities:

    * Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3.
    * Cardiac history of congestive heart failure requiring treatment or ejection fraction \<= 50% or chronic stable angina.
    * Diffusing capacity of the lung for carbon monoxide (DLCO) \<= 65% or forced expiratory volume during the first second (FEV1) \<= 65%.
    * Creatinine clearance \>= 30 mL/min to \< 45 mL/min.
    * Moderate hepatic impairment with total bilirubin \> 1.5 to \<= 3.0 × upper limit of normal (ULN).
    * Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy.
* Must meet the laboratory requirements per the protocol.
* Must have an ECOG performance status of:

  * 0 to 2 for subject ≥ 75 year of age; or
  * 0 to 3 for subject ≥ 18 to 74 years of age.
* Female participant must not be pregnant or breastfeeding and is not considering becoming pregnant or donating eggs during the study or for approximately six months after the last dose of study drug.
* Female participants of childbearing potential must agree to use at least 1 protocol-specified method of birth control and male participants, if sexually active with female partner(s) of childbearing potential, must agree to practice the protocol-specified contraception.

Exclusion Criteria:

* History of any malignancies within 2 years prior to study entry with exception noted in the protocol.
* Have received any investigational drug 30 days prior to the first dose of study drug.
* Have received strong and/or moderate CYP3A inducers within 7 days prior to initiation of study treatment.
* Must not have received treatment with the following:

  * An hypomethylating agent (HMA), venetoclax, and/or any chemotherapeutic agent for myelodysplastic syndrome (MDS).
  * Prior therapy or experimental therapies for MDS or Acute myeloid leukemia (AML).
* Current participation in another research or observational study.
* Myeloproliferative neoplasm including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation, and AML with BCR-ABL1 translocation.
* Participant has acute promyelocytic leukemia.
* Participant has known active central nervous system (CNS) involvement with AML.
* Participant has a history of malabsorption syndrome or other condition that precludes enteral route of administration.
* Participant has known 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.
* Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) with high viral titers. Participants with HBV inactive carrier status and/or HCV with low viral titers on antivirals (non-exclusionary medications) are eligible.
* 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 chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or 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 exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to Approximately 19 Months
measure: Number of Laboratory Abnormalities from Clinical Laboratory Values (Hematology and Chemistry)
timeFrame: Up to Approximately 19 Months
Secondary outcomes:
measure: Percentage of Participants with Composite Complete Remission (CR [Complete Remission] + CRi [Complete Remission with Incomplete Blood Count Recovery]) Based on the Modified International Working Group (IWG) Criteria for Acute Myeloid Leukemia (AML)
timeFrame: Up to Approximately 19 Months
measure: Percentage of Participants with CR based on the modified IWG criteria for AML
timeFrame: Up to Approximately 19 Months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital (East) - Dongdan Campus /ID# 233179
state: Beijing
city: Beijing
country: China
facility: Peking University International Hospital /ID# 232254
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center /ID# 231793
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University /ID# 231792
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Second Provincial General Hospital /ID# 232059
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University /ID# 231938
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital /ID# 231444
state: Guangdong
city: Zhengzhou
country: China
facility: People's Hospital of Henan Province /ID# 232568
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital /ID# 231940
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 233178
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital /ID# 232452
state: Hubei
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University /ID# 232418
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University /ID# 231442
state: Jiangxi
city: Xining
country: China
facility: Qinghai University Affiliated Hospital /ID# 232419
state: Qinghai
city: Yibin
country: China
facility: The Second People's Hospital of Yibin /ID# 233180
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 232253
state: Tianjin
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University /ID# 233704
state: Zhejiang
city: Guiyang
country: China
facility: Duplicate_The Affiliated Hospital of Guizhou Medical University /ID# 232465
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: