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High Risk Myelodysplastic SyndromePhase 1/2NCT03214562

Venetoclax With Combination Chemotherapy in Treating Patients With Newly Diagnosed or Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1/2 study testing Cytarabine, Filgrastim and Fludarabine in people with High Risk Myelodysplastic Syndrome and Recurrent 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 Ib/II trial studies the best dose and side effects of venetoclax and how well it works when given with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or acute myeloid leukemia that has come back or does not respond to treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cytarabine, Filgrastim and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
116 participants
Where
1 siteUnited States
Study dates
26 Sep 2017to 30 Sep 2027
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of AML by World Health Organization (WHO) criteria. Patients with high risk myelodysplastic syndrome (MDS) as defined by the presence of >= 10% blasts are also eligible at the discretion of the principal investigator
  • Patients older than 65 who are deemed fit to receive intensive chemotherapy by the treating physician will be eligible after discussion with the principal investigator (PI).
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Creatinine clearance >= 30 mL/min based on the Cockcroft-Gault equation
  • Total bilirubin < 1.5 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x ULN unless considered due to leukemic involvement
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  • Ability to understand and provide signed informed consent
  • Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug
  • Only patients who are relapsed, refractory, or intolerant of standard AML therapy will be eligible for Part 1 (minimum of 1 prior line of AML-directed therapy)

Who cannot join

  • Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML)
  • Patients having received any prior BCL2 inhibitor therapy
  • Subject has known active central nervous system (CNS) involvement with AML
  • Patients with New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 40% by echocardiogram or multi-gated acquisition (MUGA) scan
  • Patients with a history of myocardial infarction within the last 6 months or unstable / uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias
  • Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
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  • Patients with known dysphagia, short-gut syndrome, or other conditions that would affect the ingestion or gastrointestinal absorption of drugs administered orally
  • Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study
  • Subject has a white blood cell count > 25 x 10{9}/L. (Note: hydroxyurea is permitted to meet this criterion)
  • Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (a) appropriate method(s) of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide)

Trial locations and contacts

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

DiNardo, MD contact

(713) 794-1141

cdinardo@mdanderson.org

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Courtney DiNardo, 713-794-1141, cdinardo@mdanderson.org

    Courtney DiNardo

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1b/2 Study of the BCL-2 Inhibitor Venetoclax in Combination With Standard Intensive AML Induction/Consolidation Therapy With FLAG-IDA in Patients With Newly Diagnosed or Relapsed/Refractory AML

This phase Ib/II trial studies the best dose and side effects of venetoclax and how well it works when given with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or acute myeloid leukemia that has come back or does not respond to treatment. Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine, cytarabine, filgrastim and idarubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax together with combination chemotherapy may work better in treating patients with acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and tolerability and to determine the dose-limiting toxicity and the maximum tolerated dose MTD of the combination of fludarabine, cytarabine, filgrastim (GCSF), idarubicin (FLAG-IDA) + venetoclax for patients with acute myeloid leukemia (AML) (Phase 1b).

II. To determine the overall activity of this combination in patients newly diagnosed or relapsed/refractory (AML) (Phase 2).

SECONDARY OBJECTIVES:

  1. Determine the preliminary assessment of efficacy by response to revised International Working Group (IWG) criteria and time to response variables including overall survival (OS), event-free survival (EFS) and duration of response (DOR).

II. Determine biomarkers that may be predictive of venetoclax activity.

OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.

INDUCTION THERAPY: Patients receive venetoclax orally (PO) on days 1-14, fludarabine intravenously (IV) over 30 minutes on days 2-6, cytarabine IV over 4 hours on days 2-6, idarubicin IV over 15-30 minutes on days 4 and 5, filgrastim subcutaneously (SC) on days 1-7, or pegfilgrastim SC after day 5. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: Patients receive venetoclax PO on days 1-7, fludarabine IV over 30 minutes on days 2-4, cytarabine IV over 4 hours on days 2-4, filgrastim SC on days 1-7, or pegfilgrastim SC after days 3. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive idarubicin as in Induction Therapy during 1 cycle of Consolidation Therapy per the treating physician.

MAINTENANCE THERAPY: Patients receive venetoclax PO on days 1-28. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 30 days.

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.

  • 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 IV

  • FilgrastimBiological

    Also called G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

    Given SC

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • IdarubicinDrug

    Also called 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDR

    Given IV

  • PegfilgrastimBiological

    Also called Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130

    Given SC

  • VenetoclaxDrug

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

    Given PO

Study groups in NCT03214562
Study groupRoleWhat they receive
Treatment (venetoclax, FLAG-IDA)ExperimentalSee detailed description.
Receives: Drug: Cytarabine; Biological: Filgrastim; Drug: Fludarabine; Drug: Idarubicin; Biological: Pegfilgrastim; Drug: Venetoclax

What is being measured

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

  1. Overall response rate (ORR)

    Defined as complete response (CR) + CR with incomplete blood count recovery (CRi) + partial response (PR). Will be estimated along with the 95% credible interval.

    Measured: Up to 6 years

  2. CR/CRi rate

    Will be estimated along with the 95% credible interval.

    Measured: Up to 6 years

  3. Hematologic response

    Will be estimated along with the 95% credible interval.

    Measured: Up to 6 years

  4. Duration of response

    Defined as the number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first. Will be calculated for all patients.

    Measured: From the date of initial response, assessed up to 6 years

  5. Event-free survival

    Defined as the number of days from the date of treatment initiation (i.e., course 1 day 1) to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first. Will be calculated for all patients. Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.

    Measured: From the date of treatment initiation, assessed up to 6 years

  6. Overall survival

    Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.

    Measured: Up to 6 years

  7. Anti-tumor activity

    Will be summarized graphically and with descriptive statistics.

    Measured: Up to 6 years

  8. Pharmacodynamic markers

    Two samples t-test /Wilcoxon rank sum tests will be used to compare pharmacodynamics/pharmacokinetics (PD/PK) parameters between responder and non-responders, and logistic regression analysis will also be used to evaluate the association of PD/PK parameters with response.

    Measured: Up to 6 years

  9. Drug exposure levels

    Will be summarized graphically and with descriptive statistics.

    Measured: Up to 6 years

  10. Overall incidence and severity of all adverse events

    Graded using Common Toxicity Criteria version 4.0. Safety data will be summarized using frequency and percentage, by category and severity.

    Measured: Up to 6 years

Secondary outcomes (1)

  1. Morphologic leukemia-free state

    Will be estimated along with the 95% credible interval.

    Measured: Up to 6 years

Timeline

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

  1. First posted11 Jul 2017
  2. Study start26 Sep 2017
  3. Primary completion30 Sep 2027 (estimated)
  4. Study completion30 Sep 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
116 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03214562
Sponsor's protocol ID
2016-0979
Other IDs
NCI-2018-01119, 2016-0979
Status last verified
Oct 2026
First submitted
10 Jul 2017
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • DiNardo CD, Jen WY, Takahashi K, Kadia TM, Loghavi S, Daver NG, Xiao L, Reville PK, Issa GC, Short NJ, Sasaki K, Wang SA, Mullin JK, Pierce S, Bradley C, Borthakur G, Maiti A, Alvarado Y, Pemmaraju N, Ferrajoli A, Swaminathan M, Ohanian M, Abbas HA, Hammond D, Burger J, Haddad F, Montalban-Bravo G, Chien K, Masarova L, Yilmaz M, Jain N, Andreeff M, Garcia-Manero G, Kornblau S, Ravandi F, Jabbour E, Konopleva MY, Kantarjian HM. Long term results of venetoclax combined with FLAG-IDA induction and consolidation for newly diagnosed and relapsed or refractory acute myeloid leukemia. Leukemia. 2025 Apr;39(4):854-863. doi: 10.1038/s41375-025-02531-8. Epub 2025 Feb 25.

    PubMed 40000842

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cytarabine, Filgrastim and Fludarabine in people with High Risk Myelodysplastic Syndrome and Recurrent 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 9 inclusion and 10 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 2 Nov 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 DiNardo, MD ((713) 794-1141, cdinardo@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (time frame: Up to 6 years). The study lists 10 primary outcomes in all. 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 NCT03214562, which also lists 1 linked publication.

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 2 Nov 2026.

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