Back to resultsStudy of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
Primary Purpose
Acute Myelogenous Leukemia, Myelogenous Leukemia, Treatment Naive AML
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Posaconazole
ABT-199
Decitabine
Azacitidine
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring Acute Myelogenous Leukemia, AML, Myelogenous Leukemia, ABT-199, GDC-0199, Treatment Naive AML, Untreated AML, Venetoclax, Venclexta
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.
Sites / Locations
- City of Hope /ID# 129718
- University of California, Davis Comprehensive Cancer Center /ID# 129719
- Univ of Colorado Cancer Center /ID# 127859
- Emory Midtown Infectious Disease Clinic /ID# 129715
- Northwestern University Feinberg School of Medicine /ID# 128741
- The University of Chicago Medical Center /ID# 128742
- Johns Hopkins University /ID# 129699
- Dana-Farber Cancer Institute /ID# 127857
- Columbia University Medical Center /ID# 130289
- Duke Cancer Center /ID# 129720
- University of Texas MD Anderson Cancer Center /ID# 127860
- University of Texas MD Anderson Cancer Center /ID# 141581
- University of Washington /ID# 129717
- St George Hospital /ID# 130356
- Peter MacCallum Cancer Ctr /ID# 130352
- Alfred Health /ID# 130353
- Hopital Haut-Lévêque /ID# 134388
- Duplicate_Hopital Universitaire Purpan /ID# 134389
- AP-HP - Hopital Saint-Louis /ID# 130349
- Universitaetsklinikum Ulm /ID# 130341
- Universitaetsklinikum Leipzig /ID# 130346
- Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 130342
- Duplicate_Klinikum Rechts der Isar /ID# 130347
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
ABT-199 + Azacitidine
ABT-199 + Decitabine
ABT-199+Decitabine+Posaconazole
Arm Description
Treatment Naive Acute Myelogenous Leukemia
Treatment Naive Acute Myelogenous Leukemia
Treatment Naive Acute Myelogenous Leukemia
Outcomes
Primary Outcome Measures
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.
Maximum observed plasma concentration (Cmax)
Maximum observed concentration, occurring at Tmax.
Time to Cmax (peak time, Tmax),
The time at which maximum plasma concentration (Cmax) is observed.
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.
Half-Life (t1/2)
The time required for the concentration of the drug to reach half of its original value.
Clearance (CL)
Clearance is defined as the rate at which drug is cleared from the blood.
Complete Remission Rate
Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.
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.
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.
Overall Survival
Overall survival will be defined as the number of days from the date of first dose to the date of death.
Secondary Outcome Measures
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.
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).
Full Information
NCT ID
NCT02203773
First Posted
July 10, 2014
Last Updated
May 12, 2023
Sponsor
AbbVie
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02203773
Brief Title
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Strategic considerations
Study Start Date
October 6, 2014 (Actual)
Primary Completion Date
June 16, 2022 (Actual)
Study Completion Date
June 16, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
212 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABT-199 + Azacitidine
Arm Type
Experimental
Arm Description
Treatment Naive Acute Myelogenous Leukemia
Arm Title
ABT-199 + Decitabine
Arm Type
Experimental
Arm Description
Treatment Naive Acute Myelogenous Leukemia
Arm Title
ABT-199+Decitabine+Posaconazole
Arm Type
Experimental
Arm Description
Treatment Naive Acute Myelogenous Leukemia
Intervention Type
Drug
Intervention Name(s)
Posaconazole
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
ABT-199
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Decitabine
Intervention 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
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Intervention 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.
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Adverse Events (AEs)
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.
Time Frame
Measured up to 1 year after the last subject last dose
Title
Maximum observed plasma concentration (Cmax)
Description
Maximum observed concentration, occurring at Tmax.
Time Frame
For approximately 5 days following a single dose of ABT-199.
Title
Time to Cmax (peak time, Tmax),
Description
The time at which maximum plasma concentration (Cmax) is observed.
Time Frame
For approximately 5 days following a single dose of ABT-199.
Title
The area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC0-24)
Description
The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.
Time Frame
For approximately 5 days following a single dose of ABT-199.
Title
Half-Life (t1/2)
Description
The time required for the concentration of the drug to reach half of its original value.
Time Frame
For approximately 5 days following a single dose of ABT-199.
Title
Clearance (CL)
Description
Clearance is defined as the rate at which drug is cleared from the blood.
Time Frame
For approximately 5 days following a single dose of ABT-199.
Title
Complete Remission Rate
Description
Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.
Time Frame
Measured up to 1 year after the last subject last dose
Title
Complete Remission with incomplete blood count recovery rate
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.
Time Frame
Measured up to 1 year after the last subject last dose
Title
Overall Response Rate
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.
Time Frame
Measured up to 1 year after the last subject last dose
Title
Overall Survival
Description
Overall survival will be defined as the number of days from the date of first dose to the date of death.
Time Frame
Measured up to 1 year after the last subject last dose
Secondary Outcome Measure Information:
Title
Event Free Survival
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.
Time Frame
Measured up to 1 year after the last subject last dose
Title
Duration of Response
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).
Time Frame
Measured up to 1 year after the last subject last dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope /ID# 129718
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of California, Davis Comprehensive Cancer Center /ID# 129719
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Univ of Colorado Cancer Center /ID# 127859
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Emory Midtown Infectious Disease Clinic /ID# 129715
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine /ID# 128741
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2927
Country
United States
Facility Name
The University of Chicago Medical Center /ID# 128742
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1443
Country
United States
Facility Name
Johns Hopkins University /ID# 129699
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Dana-Farber Cancer Institute /ID# 127857
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Columbia University Medical Center /ID# 130289
City
New York
State/Province
New York
ZIP/Postal Code
10032-3729
Country
United States
Facility Name
Duke Cancer Center /ID# 129720
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710-3000
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center /ID# 127860
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center /ID# 141581
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Washington /ID# 129717
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
St George Hospital /ID# 130356
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Peter MacCallum Cancer Ctr /ID# 130352
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Alfred Health /ID# 130353
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Hopital Haut-Lévêque /ID# 134388
City
Pessac CEDEX
State/Province
Gironde
ZIP/Postal Code
33604
Country
France
Facility Name
Duplicate_Hopital Universitaire Purpan /ID# 134389
City
Toulouse
State/Province
Haute-Garonne
ZIP/Postal Code
31059
Country
France
Facility Name
AP-HP - Hopital Saint-Louis /ID# 130349
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Universitaetsklinikum Ulm /ID# 130341
City
Ulm
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
89081
Country
Germany
Facility Name
Universitaetsklinikum Leipzig /ID# 130346
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04103
Country
Germany
Facility Name
Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 130342
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Duplicate_Klinikum Rechts der Isar /ID# 130347
City
Munich
ZIP/Postal Code
81675
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35829925
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.
Results Reference
derived
PubMed Identifier
35063965
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.
Results Reference
derived
PubMed Identifier
35046058
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.
Results Reference
derived
PubMed Identifier
30361262
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.
Results Reference
derived
PubMed Identifier
29339097
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.
Results Reference
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PubMed Identifier
28161120
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.
Results Reference
derived
Links:
URL
https://www.abbvieclinicaltrials.com/study/?id=M14-358&Latitude=&Longitude=&LocationName=#additional-resources-section
Description
clinical study report synopsis
Learn more about this trial
Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
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