Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2014-000687-18 | EudraCT Number |
Not provided
Not provided
Not provided
Strategic considerations
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ABT-199 + Azacitidine | Experimental | Treatment Naive Acute Myelogenous Leukemia |
|
| ABT-199 + Decitabine | Experimental | Treatment Naive Acute Myelogenous Leukemia |
|
| ABT-199+Decitabine+Posaconazole | Experimental | Treatment Naive Acute Myelogenous Leukemia |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 up to 1 year after the last subject last dose |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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:
Subject has a white blood cell count > 25 × 10^9/L. Note: Hydroxyurea is permitted to meet this criterion.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| ABBVIE INC. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope /ID# 129718 | Duarte | California | 91010 | United States | ||
| University of California, Davis Comprehensive Cancer Center /ID# 129719 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40913104 | Derived | 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. | |
| 39133921 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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. |
|
| 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 |
|
| 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. |
|
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 |
| 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 up to 1 year after the last subject last dose |
| Sacramento |
| California |
| 95817 |
| United States |
| Univ of Colorado Cancer Center /ID# 127859 | Aurora | Colorado | 80045 | United States |
| Emory Midtown Infectious Disease Clinic /ID# 129715 | Atlanta | Georgia | 30322 | United States |
| Northwestern University Feinberg School of Medicine /ID# 128741 | Chicago | Illinois | 60611-2927 | United States |
| The University of Chicago Medical Center /ID# 128742 | Chicago | Illinois | 60637-1443 | United States |
| Johns Hopkins University /ID# 129699 | Baltimore | Maryland | 21287 | United States |
| Dana-Farber Cancer Institute /ID# 127857 | Boston | Massachusetts | 02215 | United States |
| Columbia University Medical Center /ID# 130289 | New York | New York | 10032-3729 | United States |
| Duke Cancer Center /ID# 129720 | Durham | North Carolina | 27710-3000 | United States |
| University of Texas MD Anderson Cancer Center /ID# 127860 | Houston | Texas | 77030 | United States |
| University of Texas MD Anderson Cancer Center /ID# 141581 | Houston | Texas | 77030 | United States |
| University of Washington /ID# 129717 | Seattle | Washington | 98109 | United States |
| St George Hospital /ID# 130356 | Kogarah | New South Wales | 2217 | Australia |
| Peter MacCallum Cancer Ctr /ID# 130352 | Melbourne | Victoria | 3000 | Australia |
| Alfred Health /ID# 130353 | Melbourne | Victoria | 3004 | Australia |
| Hopital Haut-Lévêque /ID# 134388 | Pessac | Gironde | 33604 | France |
| Duplicate_Hopital Universitaire Purpan /ID# 134389 | Toulouse | Haute-Garonne | 31059 | France |
| AP-HP - Hopital Saint-Louis /ID# 130349 | Paris | 75010 | France |
| Universitaetsklinikum Ulm /ID# 130341 | Ulm | Baden-Wurttemberg | 89081 | Germany |
| Universitaetsklinikum Leipzig /ID# 130346 | Leipzig | Saxony | 04103 | Germany |
| Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 130342 | Dresden | 01307 | Germany |
| Duplicate_Klinikum Rechts der Isar /ID# 130347 | Munich | 81675 | Germany |
| 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. |
| 36007102 | 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. |
| 35829925 | 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. |
| 35063965 | 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. |
| 35046058 | 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. |
| 30361262 | 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. |
| 29339097 | 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. |
| 28161120 | 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. |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D007951 | Leukemia, Myeloid |
| ID | Term |
|---|---|
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C101425 | posaconazole |
| C579720 | venetoclax |
| D000077209 | Decitabine |
| D001374 | Azacitidine |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
Not provided
Not provided