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AzTrials

Acute Myeloid LeukemiaPhase 2NCT03586609

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

A Phase 2 study testing Azacitidine, Cladribine and Cytarabine in people with Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Azacitidine, Cladribine and Cytarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
1 siteUnited States
Study dates
25 Oct 2018to 30 Apr 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting
  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Tapan M. Kadia, 713-792-7305, kadia@mdanderson.org

    Tapan M. Kadia

    Recruiting

Other trials in United States

About this study

Official title: Phase II Study of Venetoclax Added to Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed by Consolidation With Cladribine Plus LDAC Alternating With 5-Azacitidine With Venetoclax in Patients With Untreated AML

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the complete response (CR/complete response with incomplete recovery [CRi]) rate of patients with acute myeloid leukemia (AML) treated with venetoclax combined with cladribine (2-CDA) plus low-dose cytarabine (LDAC) alternating with 5-azacytidine.

SECONDARY OBJECTIVES:

  1. To assess overall survival (OS) of patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine.

II. To assess the disease free survival (DFS) patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine and achieved a complete response (CR/CRi).

III. To assess the overall response rate of patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine.

IV. To assess toxicity and induction mortality of patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine.

EXPLORATORY OBJECTIVES:

  1. Evaluate and determine venetoclax pharmacokinetics (pK) in presence or absence of concomitantly administered drugs such as posaconazole, voriconazole, isafuconazole, and fluconazole.

II. Investigate the correlation between venetoclax pK with toxicities and efficacy.

III. Investigate the correlation of baseline cytogenetic and mutational data with likelihood of response and resistance to the regimen.

IV. Evaluate the depth of response with minimal residual disease (MRD) testing and correlate with long term outcome.

OUTLINE:

INDUCTION: Patients receive cladribine intravenously (IV) daily over 1-2 hours on days 1-5, cytarabine subcutaneously (SC) twice daily (BID) on days 1-10, and venetoclax orally (PO) daily on days 1-21. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR or CRi after cycle 1 may receive a second induction cycle. Patients who do not achieve CR or CRi after second induction cycle may proceed to cycle 3 of consolidation per investigator.

CONSOLIDATION/MAINTENANCE:

Patients who achieve CR or CRi after cycle 1 of induction receive cladribine IV over 1-2 hours daily on days 1-3, cytarabine SC BID on days 1-10, and venetoclax PO once daily (QD) on days 1-21 of cycle 2. All patients receive cladribine IV daily over 1-2 hours of cycles 5-6, 9-10, 13-14, and 17-18, cytarabine SC BID on days 1-3 of cycles 5-6, 9-10, 13-14, and 17-18, venetoclax PO QD on days 1-21 of cycle 3-18, and azacitidine SC daily or IV over 30-60 minutes on days 1-7 of cycles 3-4, 7-8, 1-12, and 15-18. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months for 5 years.

Being tested
Azacitidine, Cladribine, Cytarabine, Venetoclax
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC

    Given SC or IV

  • CladribineDrug

    Also called 2-CdA, 2CDA, CdA, Cladribina

    Given IV

  • CytarabineDrug

    Also called .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

    Given SC

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

Study groups in NCT03586609
Study groupRoleWhat they receive
Treatment (cladribine, cytarabine, venetoclax, azacitidine)ExperimentalSee Detailed Description.
Receives: Drug: Azacitidine; Drug: Cladribine; Drug: Cytarabine; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)
  1. Overall response rate

    Will be estimated along with the 95% confidence intervals.

    Measured: Up to 5 years

  2. Overall survival (OS)

    Kaplan-Meier method will be used to assess the OS probabilities. The median OS will be reported, along with the 95% confidence intervals.

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

  3. Disease-free survival (DFS)

    Kaplan-Meier method will be used to assess the DFS probabilities. The median DFS will be reported, along with the 95% confidence intervals.

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

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

    The Bayesian approach will be implemented for toxicity monitoring, where toxicity is defined as any grade 3 or higher non-hematological toxicity which is at least possibly related to the treatment that occurs during the first 2 cycles of treatment. Safety data will be summarized by category, severity and frequency.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2018
  2. Study start25 Oct 2018
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
145 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03586609
Sponsor's protocol ID
2018-0020
Other IDs
NCI-2018-01318, 2018-0020
Status last verified
Sep 2026
First submitted
2 Jul 2018
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 42035228
  • 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.

    PubMed 35704787

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacitidine, Cladribine and Cytarabine in people with Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tapan Kadia (713-563-3534, kadia@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of complete response (CR/complete response with incomplete recovery [CRi]) (time frame: Up to completion of cycle 2 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03586609, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.

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