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

NCT ID: NCT02203773

Last Updated: 2023-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

212 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-06

Study Completion Date

2022-06-16

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Myelogenous Leukemia Myelogenous Leukemia Treatment Naive AML

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ABT-199 + Azacitidine

Treatment Naive Acute Myelogenous Leukemia

Group Type EXPERIMENTAL

ABT-199

Intervention Type 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.

Azacitidine

Intervention Type 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 + Decitabine

Treatment Naive Acute Myelogenous Leukemia

Group Type EXPERIMENTAL

ABT-199

Intervention Type 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

Intervention Type 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+Posaconazole

Treatment Naive Acute Myelogenous Leukemia

Group Type EXPERIMENTAL

Posaconazole

Intervention Type 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

Intervention Type 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

Intervention Type 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

Interventions

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Posaconazole

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.

Intervention Type DRUG

ABT-199

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.

Intervention Type DRUG

Decitabine

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

Intervention Type DRUG

Azacitidine

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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

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City of Hope /ID# 129718

Duarte, California, United States

Site Status

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

Sacramento, California, United States

Site Status

Univ of Colorado Cancer Center /ID# 127859

Aurora, Colorado, United States

Site Status

Emory Midtown Infectious Disease Clinic /ID# 129715

Atlanta, Georgia, United States

Site Status

Northwestern University Feinberg School of Medicine /ID# 128741

Chicago, Illinois, United States

Site Status

The University of Chicago Medical Center /ID# 128742

Chicago, Illinois, United States

Site Status

Johns Hopkins University /ID# 129699

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute /ID# 127857

Boston, Massachusetts, United States

Site Status

Columbia University Medical Center /ID# 130289

New York, New York, United States

Site Status

Duke Cancer Center /ID# 129720

Durham, North Carolina, United States

Site Status

University of Texas MD Anderson Cancer Center /ID# 127860

Houston, Texas, United States

Site Status

University of Texas MD Anderson Cancer Center /ID# 141581

Houston, Texas, United States

Site Status

University of Washington /ID# 129717

Seattle, Washington, United States

Site Status

St George Hospital /ID# 130356

Kogarah, New South Wales, Australia

Site Status

Peter MacCallum Cancer Ctr /ID# 130352

Melbourne, Victoria, Australia

Site Status

Alfred Health /ID# 130353

Melbourne, Victoria, Australia

Site Status

Hopital Haut-Lévêque /ID# 134388

Pessac, Gironde, France

Site Status

Duplicate_Hopital Universitaire Purpan /ID# 134389

Toulouse, Haute-Garonne, France

Site Status

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

Paris, , France

Site Status

Universitaetsklinikum Ulm /ID# 130341

Ulm, Baden-Wurttemberg, Germany

Site Status

Universitaetsklinikum Leipzig /ID# 130346

Leipzig, Saxony, Germany

Site Status

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

Dresden, , Germany

Site Status

Duplicate_Klinikum Rechts der Isar /ID# 130347

Munich, , Germany

Site Status

Countries

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United States Australia France Germany

References

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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 Sep 5. doi: 10.1038/s41375-025-02730-3. Online ahead of print.

Reference Type DERIVED
PMID: 40913104 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39133921 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36007102 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35829925 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35063965 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35046058 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30361262 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29339097 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28161120 (View on PubMed)

Related Links

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Other Identifiers

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2014-000687-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M14-358

Identifier Type: -

Identifier Source: org_study_id

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