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Acute Myelogenous LeukemiaPhase 1NCT02203773

Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)

A Phase 1 study testing Posaconazole, ABT-199 and Decitabine in people with Acute Myelogenous Leukemia and Myelogenous Leukemia, run by AbbVie at 23 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered venetoclax (ABT-199) combined with decitabine or azacitidine and the preliminary efficacy of these combinations. Read more about this study

Who is it for?
Ages 60 years and older
What is being tested?
Posaconazole, ABT-199 and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
212 participants
Where
23 sitesin 4 countries
Study dates
6 Oct 2014to 16 Jun 2022
Phase
Phase 1
Are there results?
None posted in the registry

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

Who may be able to join

  • Subjects must have confirmation of Acute Myeloid Leukemia (AML) by WHO criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
  • Subject must have received no prior treatment for AML with the exception of hydroxyurea
  • Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for subjects greater than or equal to 75 years of age, or 0 to 3 for subjects greater than or equal to 60 to 74 years of age
  • Subject must have adequate kidney and liver function as described in the protocol

Who cannot join

  • Subject has received treatment with the following hypomethylating agent and/or chemo therapeutic agent for for an antecedent hematologic disorder (AHD) (Subjects may have been treated with other agents for AHD i.e., Myelodysplastic syndrome [MDS])
  • Subject has history of Myeloproliferative Neoplasm (MPN).
  • Subject has favorable risk cytogenetics as categorized by the National Comprehensive Cancer Network Guidelines Version 2, 2014 for AML.
  • Subject has t(8;21), inv(16), t(16;16) or t(15;17) karyotype abnormalities.
  • Subject has acute promyelocytic leukemia.
  • Subject has known active central nervous system involvement with AML.
Show all 12Show fewer
  • Subject has received a strong and/or moderate CYP3A inducer within 7 days prior to the initiation of study treatment.
  • Subject has a history of other malignancies prior to study entry, with the exception of:
  • Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
  • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
  • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Subject has a white blood cell count > 25 × 10^9/L. Note: Hydroxyurea is permitted to meet this criterion.

Trial locations and contacts

23 sites in 4 countries.

23 sites in 4 countries

United States13 sites

  • Emory Midtown Infectious Disease Clinic /ID# 129715

    Atlanta, Georgia, 30322

  • Univ of Colorado Cancer Center /ID# 127859

    Aurora, Colorado, 80045

  • Johns Hopkins University /ID# 129699

    Baltimore, Maryland, 21287

  • Dana-Farber Cancer Institute /ID# 127857

    Boston, Massachusetts, 02215

  • Northwestern University Feinberg School of Medicine /ID# 128741

    Chicago, Illinois, 60611-2927

  • The University of Chicago Medical Center /ID# 128742

    Chicago, Illinois, 60637-1443

  • City of Hope /ID# 129718

    Duarte, California, 91010

  • Duke Cancer Center /ID# 129720

    Durham, North Carolina, 27710-3000

  • University of Texas MD Anderson Cancer Center /ID# 127860

    Houston, Texas, 77030

  • University of Texas MD Anderson Cancer Center /ID# 141581

    Houston, Texas, 77030

  • Columbia University Medical Center /ID# 130289

    New York, New York, 10032-3729

  • University of California, Davis Comprehensive Cancer Center /ID# 129719

    Sacramento, California, 95817

  • University of Washington /ID# 129717

    Seattle, Washington, 98109

Other trials in United States

Germany4 sites

  • Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 130342

    Dresden, 01307

  • Universitaetsklinikum Leipzig /ID# 130346

    Leipzig, Saxony, 04103

  • Duplicate_Klinikum Rechts der Isar /ID# 130347

    Munich, 81675

  • Universitaetsklinikum Ulm /ID# 130341

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

Australia3 sites

  • St George Hospital /ID# 130356

    Kogarah, New South Wales, 2217

  • Peter MacCallum Cancer Ctr /ID# 130352

    Melbourne, Victoria, 3000

  • Alfred Health /ID# 130353

    Melbourne, Victoria, 3004

Other trials in Australia

France3 sites

  • AP-HP - Hopital Saint-Louis /ID# 130349

    Paris, 75010

  • Hopital Haut-Lévêque /ID# 134388

    Pessac, Gironde, 33604

  • Duplicate_Hopital Universitaire Purpan /ID# 134389

    Toulouse, Haute-Garonne, 31059

Other trials in France

About this study

Official title: A Phase 1b Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine in Treatment-Naive Subjects With Acute Myelogenous Leukemia Who Are Greater Than or Equal to 60 Years of Age and Who Are Not Eligible for Standard Induction Therapy

This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered venetoclax (ABT-199) combined with decitabine or azacitidine and the preliminary efficacy of these combinations. In addition, there is a drug-drug interaction (DDI) sub-study only at a single site, to assess the pharmacokinetics and safety of venetoclax (ABT-199) in combination with posaconazole.

Being tested
Posaconazole, ABT-199, Decitabine, Azacitidine
Keywords
Acute Myelogenous Leukemia, AML, Myelogenous Leukemia, ABT-199, GDC-0199, Treatment Naive AML, Untreated AML, Venetoclax, Venclexta
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myeloid

What participants receive

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

  • PosaconazoleDrug

    Posaconazole will be administered orally twice a day on Cycle 1 Day 21 and once daily from Cycle 1 Day 22 to Cycle 1 Day 28.

  • ABT-199Drug

    ABT-199 is taken orally once daily starting on Day 2 of cycle 1 and begin on day 1 of every other cycle thereafter. This is a dose escalation study, therefore the dose of ABT-199 will change.

  • DecitabineDrug

    Decitabine will be administered by IV infusion over 1 hour beginning on Day 1 thru Day 5 of each Cycle for a minimum of 4 Cycles

  • AzacitidineDrug

    Azacitidine will be administered by IV infusion over 10 to 40 minutes or subcutaneously based on the institutional guidelines, beginning on Day 1 through Day 7 of each Cycle, for a minimum of 4 Cycles.

Study groups in NCT02203773
Study groupRoleWhat they receive
ABT-199 + AzacitidineExperimentalTreatment Naive Acute Myelogenous Leukemia
Receives: Drug: ABT-199; Drug: Azacitidine
ABT-199 + DecitabineExperimentalTreatment Naive Acute Myelogenous Leukemia
Receives: Drug: ABT-199; Drug: Decitabine
ABT-199+Decitabine+PosaconazoleExperimentalTreatment Naive Acute Myelogenous Leukemia
Receives: Drug: Posaconazole; Drug: ABT-199; Drug: Decitabine

What is being measured

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

  1. Number of Participants Experiencing Adverse Events (AEs)

    An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug.

    Measured: Measured up to 1 year after the last subject last dose

  2. Maximum observed plasma concentration (Cmax)

    Maximum observed concentration, occurring at Tmax.

    Measured: For approximately 5 days following a single dose of ABT-199.

  3. Time to Cmax (peak time, Tmax),

    The time at which maximum plasma concentration (Cmax) is observed.

    Measured: For approximately 5 days following a single dose of ABT-199.

  4. The area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC0-24)

    The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.

    Measured: For approximately 5 days following a single dose of ABT-199.

  5. Half-Life (t1/2)

    The time required for the concentration of the drug to reach half of its original value.

    Measured: For approximately 5 days following a single dose of ABT-199.

  6. Clearance (CL)

    Clearance is defined as the rate at which drug is cleared from the blood.

    Measured: For approximately 5 days following a single dose of ABT-199.

  7. Complete Remission Rate

    Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.

    Measured: Measured up to 1 year after the last subject last dose

  8. Complete Remission with incomplete blood count recovery rate

    Complete Remission with incomplete blood count recovery rate will be determined by the number of subjects who achieve a Complete Remission with incomplete blood count recovery.

    Measured: Measured up to 1 year after the last subject last dose

  9. Overall Response Rate

    Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), or partial remission (PR) per the International Working Group criteria for AML.

    Measured: Measured up to 1 year after the last subject last dose

  10. Overall Survival

    Overall survival will be defined as the number of days from the date of first dose to the date of death.

    Measured: Measured up to 1 year after the last subject last dose

Secondary outcomes (2)

  1. Event Free Survival

    Event-free survival (EFS) will be defined as the number of days from the date of first dose to the date of earliest evidence of relapse, subsequent treatment other than stem cell transplant while in composite complete response (CR + CRi), or death.

    Measured: Measured up to 1 year after the last subject last dose

  2. Duration of Response

    Duration of response will be defined as the number of days from the date of first response per the IWG criteria for AML to the earliest recurrence or progressive disease (PD).

    Measured: Measured up to 1 year after the last subject last dose

Timeline

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

  1. First posted30 Jul 2014 (estimated)
  2. Study start6 Oct 2014
  3. Primary completion16 Jun 2022
  4. Study completion16 Jun 2022

Why it stopped: Strategic considerations

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
212 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02203773
Sponsor's protocol ID
M14-358
Other IDs
2014-000687-18, 2014
Status last verified
May 2023
First submitted
10 Jul 2014
Last updated
16 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Venditti A, Hou JZ, Fenaux P, Jonas BA, Vrhovac R, Montesinos P, Garcia JS, Rizzieri D, Thirman MJ, Zhang M, Potluri J, Miller C, Dhalla M, Pullarkat V. Outcomes of patients treated with venetoclax plus azacitidine versus azacitidine alone stratified by advanced age and acute myeloid leukemia composite model. Leukemia. 2025 Nov;39(11):2697-2707. doi: 10.1038/s41375-025-02730-3. Epub 2025 Sep 5.

    PubMed 40913104

  • Dohner H, Pratz KW, DiNardo CD, Wei AH, Jonas BA, Pullarkat VA, Thirman MJ, Recher C, Schuh AC, Babu S, Li X, Ku G, Liu Z, Sun Y, Potluri J, Dail M, Chyla B, Pollyea DA. Genetic risk stratification and outcomes among treatment-naive patients with AML treated with venetoclax and azacitidine. Blood. 2024 Nov 21;144(21):2211-2222. doi: 10.1182/blood.2024024944.

    PubMed 39133921

  • Pollyea DA, Pratz KW, Wei AH, Pullarkat V, Jonas BA, Recher C, Babu S, Schuh AC, Dail M, Sun Y, Potluri J, Chyla B, DiNardo CD. Outcomes in Patients with Poor-Risk Cytogenetics with or without TP53 Mutations Treated with Venetoclax and Azacitidine. Clin Cancer Res. 2022 Dec 15;28(24):5272-5279. doi: 10.1158/1078-0432.CCR-22-1183.

    PubMed 36007102

  • Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13.

    PubMed 35829925

  • Konopleva M, Thirman MJ, Pratz KW, Garcia JS, Recher C, Pullarkat V, Kantarjian HM, DiNardo CD, Dail M, Duan Y, Chyla B, Potluri J, Miller CL, Wei AH. Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naive Acute Myeloid Leukemia. Clin Cancer Res. 2022 Jul 1;28(13):2744-2752. doi: 10.1158/1078-0432.CCR-21-3405.

    PubMed 35063965

  • Pollyea DA, DiNardo CD, Arellano ML, Pigneux A, Fiedler W, Konopleva M, Rizzieri DA, Smith BD, Shinagawa A, Lemoli RM, Dail M, Duan Y, Chyla B, Potluri J, Miller CL, Kantarjian HM. Impact of Venetoclax and Azacitidine in Treatment-Naive Patients with Acute Myeloid Leukemia and IDH1/2 Mutations. Clin Cancer Res. 2022 Jul 1;28(13):2753-2761. doi: 10.1158/1078-0432.CCR-21-3467.

    PubMed 35046058

  • DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752. Epub 2018 Oct 25.

    PubMed 30361262

  • DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. doi: 10.1016/S1470-2045(18)30010-X. Epub 2018 Jan 12.

    PubMed 29339097

  • Agarwal SK, DiNardo CD, Potluri J, Dunbar M, Kantarjian HM, Humerickhouse RA, Wong SL, Menon RM, Konopleva MY, Salem AH. Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments. Clin Ther. 2017 Feb;39(2):359-367. doi: 10.1016/j.clinthera.2017.01.003. Epub 2017 Feb 1.

    PubMed 28161120

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Posaconazole, ABT-199 and Decitabine in people with Acute Myelogenous Leukemia and Myelogenous Leukemia, run by AbbVie at 23 sites in 4 countries.

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 4 inclusion and 12 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: stopped early, as of the sponsor's last update on 16 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Germany, Australia, France. 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 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.

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

Are results available for this study?

The study was stopped early (reason given: Strategic considerations). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Adverse Events (AEs) (time frame: Measured up to 1 year after the last subject last dose). 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 NCT02203773, which also lists 9 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 16 May 2023.

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