TriangleNCT02203773 · CITED IN SOURCE DOCUMENTS
Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1
- Status at capture
- TERMINATED
- Registry last update
- 2023-05-16
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- Inclusion Criteria: * 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 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: * 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.
- healthy Volunteers
- false
- minimum Age
- 60 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Treatment Naive Acute Myelogenous Leukemia
- intervention Names
- Drug: ABT-199
- Drug: Azacitidine
- label
- ABT-199 + Azacitidine
- type
- EXPERIMENTAL
- description
- Treatment Naive Acute Myelogenous Leukemia
- intervention Names
- Drug: ABT-199
- Drug: Decitabine
- label
- ABT-199 + Decitabine
- type
- EXPERIMENTAL
- description
- Treatment Naive Acute Myelogenous Leukemia
- intervention Names
- Drug: Posaconazole
- Drug: ABT-199
- Drug: Decitabine
- label
- ABT-199+Decitabine+Posaconazole
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- ABT-199+Decitabine+Posaconazole
- description
- 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.
- name
- Posaconazole
- type
- DRUG
- arm Group Labels
- ABT-199 + Azacitidine
- ABT-199 + Decitabine
- ABT-199+Decitabine+Posaconazole
- description
- 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.
- name
- ABT-199
- type
- DRUG
- arm Group Labels
- ABT-199 + Decitabine
- ABT-199+Decitabine+Posaconazole
- description
- 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
- name
- Decitabine
- type
- DRUG
- arm Group Labels
- ABT-199 + Azacitidine
- description
- 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.
- name
- Azacitidine
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 212
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Number of Participants Experiencing Adverse Events (AEs)
- time Frame
- Measured up to 1 year after the last subject last dose
- description
- Maximum observed concentration, occurring at Tmax.
- measure
- Maximum observed plasma concentration (Cmax)
- time Frame
- For approximately 5 days following a single dose of ABT-199.
- description
- The time at which maximum plasma concentration (Cmax) is observed.
- measure
- Time to Cmax (peak time, Tmax),
- time Frame
- For approximately 5 days following a single dose of ABT-199.
- description
- The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.
- measure
- The area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC0-24)
- time Frame
- For approximately 5 days following a single dose of ABT-199.
- description
- The time required for the concentration of the drug to reach half of its original value.
- measure
- Half-Life (t1/2)
- time Frame
- For approximately 5 days following a single dose of ABT-199.
- description
- Clearance is defined as the rate at which drug is cleared from the blood.
- measure
- Clearance (CL)
- time Frame
- For approximately 5 days following a single dose of ABT-199.
- description
- Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.
- measure
- Complete Remission Rate
- time Frame
- Measured up to 1 year after the last subject last dose
- description
- 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.
- measure
- Complete Remission with incomplete blood count recovery rate
- time Frame
- Measured up to 1 year after the last subject last dose
- description
- 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.
- measure
- Overall Response Rate
- time Frame
- Measured up to 1 year after the last subject last dose
- description
- Overall survival will be defined as the number of days from the date of first dose to the date of death.
- measure
- Overall Survival
- time Frame
- Measured up to 1 year after the last subject last dose
- secondary Outcomes
- description
- 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.
- measure
- Event Free Survival
- time Frame
- Measured up to 1 year after the last subject last dose
- description
- 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).
- measure
- Duration of Response
- time Frame
- Measured up to 1 year after the last subject last dose
Full study description
- 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.
Source references
- references
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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
- type
- DERIVED
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- 56-day post-baseline period. The median time to first response of CR or CRh was 1.0 months (range: 0.6 to 14.3 months) with VEN+AZA treatment. M14-358 M14-358 (NCT02203773) was a non-randomized, open-label trial that evaluated the efficacy of VENCLEXTA in combination with azacitidine (N=84) or decitabine (N=31) in patients with n
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- l was granted based on the results of two studies.<div class="pdq-content-list"><ol id="_621" class="lower-alpha"><li>The first study (<a href="/clinicaltrials/NCT02203773">NCT02203773</a>) was a nonrandomized, open-label, phase Ib clinical trial of venetoclax in combination with azacitidine or decitabine.[<a href="#cit/section_4
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- based on the results of two studies.<div class="pdq-content-list"><ol id="_621" class="lower-alpha"><li>The first study (<a href="/clinicaltrials/NCT02203773">NCT02203773</a>) was a nonrandomized, open-label, phase Ib clinical trial of venetoclax in combination with azacitidine or decitabine.[<a href="#cit/section_4.24">24</a>]
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- March 14, 2025
Preserved source evidence · Not medical advice