Venetoclax, Cladribine, Low Dose Cytarabine, and Azacitidine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age50 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Participants with previously untreated acute myeloid leukemia (AML). Prior therapy with hydroxyurea, hematopoietic growth factors, HMA, ATRA, or a total dose of cytarabine up to 2g (for emergency use for stabilization) is allowed.
• Age >/= 50 years. Participants aged < 50 years who are unsuitable for standard induction therapy may be eligible after discussion with primary investigator
• Adequate organ function as defined below:
• liver function (bilirubin < 2mg/dL, AST and/or ALT <3 x ULN). Unless liver enzyme abnormalities are determined by the treating MD and PI to be due to leukemic infiltration.
• kidney function (creatinine < 1.5 x ULN ).
• ECOG performance status of ≤ 2.
• A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
• Participants must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the participants is required prior to their enrollment on the protocol.

You cannot join if

• Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Participants with documented hypersensitivity to any of the components of the chemotherapy program.
• Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
• Prior therapy with venetoclax
• Participants with a diagnosis of acute promyelocytic leukemia (AML-M3) will be excluded from this study.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

venetoclax. An orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia. NCI Drug Dictionary

cladribine. A purine nucleoside antimetabolite analogue. Cladribine triphosphate, a phosphorylated metabolite of cladribine, incorporates into DNA, resulting in single-strand breaks in DNA, depletion of nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP), and apoptosis. Because this agent is resistant to adenosine deaminase, an enzyme that inactivates some antineoplastic agents, it is selectively toxic to lymphocytes and monocytes which exhibit little deoxynucleotide deaminase activity. NCI Drug Dictionary

ADE regimen. A regimen consisting of high-dose cytarabine (Ara-C), daunorubicin and etoposide, that is used for the treatment of pediatric and adult acute myeloid leukemia (AML). NCI Drug Dictionary

azacitidine. A pyrimidine nucleoside analogue of cytidine with antineoplastic activity. Azacitidine is incorporated into DNA, where it reversibly inhibits DNA methyltransferase, thereby blocking DNA methylation. Hypomethylation of DNA by azacitidine may activate tumor suppressor genes silenced by hypermethylation, resulting in an antitumor effect. This agent is also incorporated into RNA, thereby disrupting normal RNA function and impairing tRNA cytosine-5-methyltransferase activity. NCI Drug Dictionary

Treatments listed in the registry

• Azacitidine (Drug): Given SC or IV
• Cladribine (Drug): Given IV
• Cytarabine (Drug): Given SC
• Venetoclax (Drug): Given PO

Na · Single Group · masking: None

Main goals

• Rate of complete response (CR/complete response with incomplete recovery [CRi]) (Up to completion of cycle 2 (each cycle is 28 days))

Other goals

• Overall response rate
• Overall survival (OS)
• Disease-free survival (DFS)
• Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Planned enrollment: 145 (estimated).

• M D Anderson Cancer Center, Houston, Texas

Site status as of Oct 30, 2026. Check the live record before contacting a site.

These papers are listed in the registry record. Unless a paper is marked as about this trial, it is background research on the treatment or disease, not results from this study.

• Publication about this trial (to be verified before citing)Kadia TM, Bataller A, Bazinet A, Borthakur G, Daver N, Short NJ, DiNardo C, Jabbour E, Rausch CR, Issa GC, Pemmaraju N, Ohanian M, Maiti A, Montalban-Bravo G, Sasaki K, Bouligny IM, Yilmaz M, Haddad FG, Masarova L, Chien K, Alvarado Y, Jain N, Popat U, Shpall E, Loghavi S, Qiao W, Wang X, Garcia-Manero G, Ravandi F, Kantarjian HM. Cladribine With Low-Dose Cytarabine and Venetoclax Alternating With Azacitidine and Venetoclax for Newly Diagnosed Acute Myeloid Leukemia. Am J Hematol. 2026 Jul;101(7):1737-1747. doi: 10.1002/ajh.70328. Epub 2026 Apr 25.
• Linked by the registry; not confirmed as results from this trialKadia TM, Reville PK, Wang X, Rausch CR, Borthakur G, Pemmaraju N, Daver NG, DiNardo CD, Sasaki K, Issa GC, Ohanian M, Montalban-Bravo G, Short NJ, Jain N, Ferrajoli A, Bhalla KN, Jabbour E, Takahashi K, Malla R, Quagliato K, Kanagal-Shamanna R, Popat UR, Andreeff M, Garcia-Manero G, Konopleva MY, Ravandi F, Kantarjian HM. Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. J Clin Oncol. 2022 Nov 20;40(33):3848-3857. doi: 10.1200/JCO.21.02823. Epub 2022 Jun 15.

• ClinicalTrials.gov NCT03586609
• NCI Drug Dictionary: C103147
• NCI Drug Dictionary: C1336
• NCI Drug Dictionary: C408
• NCI Drug Dictionary: C288

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 4, 2026. Public record; not medical advice.