Clinical trial NCT02203773: Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2014-07-30
Enrollment: 212
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Measured up to 1 year after the last subject last dose
measure: Maximum observed plasma concentration (Cmax)
timeFrame: For approximately 5 days following a single dose of ABT-199.
measure: Time to Cmax (peak time, Tmax),
timeFrame: For approximately 5 days following a single dose of ABT-199.
measure: The area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC0-24)
timeFrame: For approximately 5 days following a single dose of ABT-199.
measure: Half-Life (t1/2)
timeFrame: For approximately 5 days following a single dose of ABT-199.
measure: Clearance (CL)
timeFrame: For approximately 5 days following a single dose of ABT-199.
measure: Complete Remission Rate
timeFrame: Measured up to 1 year after the last subject last dose
measure: Complete Remission with incomplete blood count recovery rate
timeFrame: Measured up to 1 year after the last subject last dose
measure: Overall Response Rate
timeFrame: Measured up to 1 year after the last subject last dose
measure: Overall Survival
timeFrame: Measured up to 1 year after the last subject last dose
Secondary outcomes:
measure: Event Free Survival
timeFrame: Measured up to 1 year after the last subject last dose
measure: Duration of Response
timeFrame: Measured up to 1 year after the last subject last dose
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope /ID# 129718
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center /ID# 129719
state: California
city: Aurora
country: United States
facility: Univ of Colorado Cancer Center /ID# 127859
state: Colorado
city: Atlanta
country: United States
facility: Emory Midtown Infectious Disease Clinic /ID# 129715
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 128741
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center /ID# 128742
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University /ID# 129699
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 127857
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center /ID# 130289
state: New York
city: Durham
country: United States
facility: Duke Cancer Center /ID# 129720
state: North Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 127860
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 141581
state: Texas
city: Seattle
country: United States
facility: University of Washington /ID# 129717
state: Washington
city: Kogarah
country: Australia
facility: St George Hospital /ID# 130356
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Ctr /ID# 130352
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health /ID# 130353
state: Victoria
city: Pessac CEDEX
country: France
facility: Hopital Haut-Lévêque /ID# 134388
state: Gironde
city: Toulouse
country: France
facility: Duplicate_Hopital Universitaire Purpan /ID# 134389
state: Haute-Garonne
city: Paris
country: France
facility: AP-HP - Hopital Saint-Louis /ID# 130349
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm /ID# 130341
state: Baden-Wuerttemberg
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig /ID# 130346
state: Sachsen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 130342
city: Munich
country: Germany
facility: Duplicate_Klinikum Rechts der Isar /ID# 130347
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.