Clinical Trials /

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

NCT02203773

Description:

This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered 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 ABT-199 in combination with posaconazole.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: M14-358
  • SECONDARY ID: 2014-000687-18
  • NCT ID: NCT02203773

Conditions

  • Acute Myelogenous Leukemia
  • Myelogenous Leukemia
  • Treatment Naive AML

Interventions

DrugSynonymsArms
PosaconazoleABT-199+Decitabine+Posaconazole
ABT-199ABT-199 + Decitabine
DecitabineABT-199 + Decitabine
AzacitidineABT-199 + Azacitidine

Purpose

This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered 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 ABT-199 in combination with posaconazole.

Trial Arms

NameTypeDescriptionInterventions
ABT-199 + AzacitidineExperimentalTreatment Naive Acute Myelogenous Leukemia
  • ABT-199
  • Azacitidine
ABT-199 + DecitabineExperimentalTreatment Naive Acute Myelogenous Leukemia
  • ABT-199
  • Decitabine
ABT-199+Decitabine+PosaconazoleExperimentalTreatment Naive Acute Myelogenous Leukemia
  • Posaconazole
  • ABT-199
  • Decitabine

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 )
             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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Remission Rate
Time Frame:Measured up to 2 years after the last subject enrolled has their last study visit.
Safety Issue:
Description:Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.

Secondary Outcome Measures

Measure:Percent of subjects who move on to stem cell transplant
Time Frame:Measure up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description:The percent of subjects who move on to stem cell transplant will be summarized.
Measure:Duration of Response
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
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:Event Free Survival
Time Frame:Measured up to 2 years after the last subject enrolled has their last study visit.
Safety Issue:
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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Acute Myelogenous Leukemia
  • AML
  • Myelogenous Leukemia
  • ABT-199
  • GDC-0199
  • Treatment Naive AML
  • Untreated AML

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