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

NCT03586609 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2018-0020NCI-2018-01318
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well venetoclax, cladribine, low dose cytarabine, and azacitidine work in treating patients with acute myeloid leukemia that has previously not been treated. Drugs used in chemotherapy, such as venetoclax, cladribine, and low dose cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax, cladribine, low dose cytarabine induction followed by cladribine, low dose cytarabine, and azacitidine consolidation may work better in treating patients with acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Rate of complete response (CR/complete response with incomplete recovery [CRi])

  The optimum two-stage design will be implemented. Will be estimated along with the 95% confidence intervals.

  Up to completion of cycle 2 (each cycle is 28 days)

Secondary Outcomes (4)

• Overall response rate

  Up to 5 years

• Overall survival (OS)

  Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years

• Disease-free survival (DFS)

  Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years

• Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 5 years

Study Arms (1)

Treatment (cladribine, cytarabine, venetoclax, azacitidine)

EXPERIMENTAL

See Detailed Description.

Drug: Azacitidine; Drug: Cladribine; Drug: Cytarabine; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given SC or IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, Onureg, U-18496, Vidaza

Treatment (cladribine, cytarabine, venetoclax, azacitidine)

Cladribine DRUG

Given IV

Also known as: 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Treatment (cladribine, cytarabine, venetoclax, azacitidine)

Cytarabine DRUG

Given SC

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (cladribine, cytarabine, venetoclax, azacitidine)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (cladribine, cytarabine, venetoclax, azacitidine)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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 may not qualify 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Kadia 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.

  PMID: 35704787 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; Cladribine; Cytarabine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyadenosines; Deoxyribonucleosides; Arabinonucleosides

Study Officials

• Tapan M Kadia

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tapan Kadia

CONTACT

713-563-3534; kadia@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2018
• First Posted: July 13, 2018
• Study Start: October 25, 2018
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)