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

NCT02203773 | Terminated Phase 1 FDA Drug

• 2 other identifiers: M14-3582014-000687-18
• Study Type: interventional
• Target: 212
• Locations: 4 countries
• Sites: 23

Brief 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. 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.

Conditions

Acute Myelogenous Leukemia; Myelogenous Leukemia; Treatment Naive AML

Keywords

Acute Myelogenous Leukemia; AML; Myelogenous Leukemia; ABT-199; GDC-0199; Treatment Naive AML; Untreated AML; Venetoclax; Venclexta

Outcome Measures

Primary Outcomes (10)

• 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 up to 1 year after the last subject last dose

• Maximum observed plasma concentration (Cmax)

  Maximum observed concentration, occurring at Tmax.

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

• Time to Cmax (peak time, Tmax),

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

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

• 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.

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

• Half-Life (t1/2)

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

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

• Clearance (CL)

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

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

• Complete Remission Rate

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

  Measured up to 1 year after the last subject last dose

• 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 up to 1 year after the last subject last dose

• 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 up to 1 year after the last subject last dose

• Overall Survival

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

  Measured up to 1 year after the last subject last dose

Secondary Outcomes (2)

• Event Free Survival

  Measured up to 1 year after the last subject last dose

• Duration of Response

  Measured up to 1 year after the last subject last dose

Study Arms (3)

ABT-199 + Azacitidine

EXPERIMENTAL

Treatment Naive Acute Myelogenous Leukemia

Drug: ABT-199; Drug: Azacitidine

ABT-199 + Decitabine

EXPERIMENTAL

Treatment Naive Acute Myelogenous Leukemia

Drug: ABT-199; Drug: Decitabine

ABT-199+Decitabine+Posaconazole

EXPERIMENTAL

Treatment Naive Acute Myelogenous Leukemia

Drug: Posaconazole; Drug: ABT-199; Drug: Decitabine

Interventions

Posaconazole DRUG

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-199+Decitabine+Posaconazole

ABT-199 DRUG

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.

ABT-199 + Azacitidine; ABT-199 + Decitabine; ABT-199+Decitabine+Posaconazole

Decitabine DRUG

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

ABT-199 + Decitabine; ABT-199+Decitabine+Posaconazole

Azacitidine DRUG

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.

ABT-199 + Azacitidine

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc.: collaborator

Study Sites (23)

City of Hope /ID# 129718

Duarte, California, 91010, United States

Location

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

Sacramento, California, 95817, United States

Location

Univ of Colorado Cancer Center /ID# 127859

Aurora, Colorado, 80045, United States

Location

Emory Midtown Infectious Disease Clinic /ID# 129715

Atlanta, Georgia, 30322, United States

Location

Northwestern University Feinberg School of Medicine /ID# 128741

Chicago, Illinois, 60611-2927, United States

Location

The University of Chicago Medical Center /ID# 128742

Chicago, Illinois, 60637-1443, United States

Location

Johns Hopkins University /ID# 129699

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute /ID# 127857

Boston, Massachusetts, 02215, United States

Location

Columbia University Medical Center /ID# 130289

New York, New York, 10032-3729, United States

Location

Duke Cancer Center /ID# 129720

Durham, North Carolina, 27710-3000, United States

Location

University of Texas MD Anderson Cancer Center /ID# 127860

Houston, Texas, 77030, United States

Location

University of Texas MD Anderson Cancer Center /ID# 141581

Houston, Texas, 77030, United States

Location

University of Washington /ID# 129717

Seattle, Washington, 98109, United States

Location

St George Hospital /ID# 130356

Kogarah, New South Wales, 2217, Australia

Location

Peter MacCallum Cancer Ctr /ID# 130352

Melbourne, Victoria, 3000, Australia

Location

Alfred Health /ID# 130353

Melbourne, Victoria, 3004, Australia

Location

Hopital Haut-Lévêque /ID# 134388

Pessac, Gironde, 33604, France

Location

Duplicate_Hopital Universitaire Purpan /ID# 134389

Toulouse, Haute-Garonne, 31059, France

Location

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

Paris, 75010, France

Location

Universitaetsklinikum Ulm /ID# 130341

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Universitaetsklinikum Leipzig /ID# 130346

Leipzig, Saxony, 04103, Germany

Location

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

Dresden, 01307, Germany

Location

Duplicate_Klinikum Rechts der Isar /ID# 130347

Munich, 81675, Germany

Location

Related Publications (9)

• 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.

  PMID: 40913104 DERIVED

• 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.

  PMID: 39133921 DERIVED

• 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.

  PMID: 36007102 DERIVED

• 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.

  PMID: 35829925 DERIVED

• 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.

  PMID: 35063965 DERIVED

• 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.

  PMID: 35046058 DERIVED

• 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.

  PMID: 30361262 DERIVED

• 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.

  PMID: 29339097 DERIVED

• 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.

  PMID: 28161120 DERIVED

Related Links

• clinical study report synopsis

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myeloid

Interventions

posaconazole; venetoclax; Decitabine; Azacitidine

Condition Hierarchy (Ancestors)

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

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 10, 2014
• First Posted: July 30, 2014
• Study Start: October 6, 2014
• Primary Completion: June 16, 2022
• Study Completion: June 16, 2022
• Last Updated: May 16, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); DE (4); US (13); AU (3)