Description:
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.
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
Drug | Synonyms | Arms |
---|
Posaconazole | | ABT-199+Decitabine+Posaconazole |
ABT-199 | | ABT-199 + Azacitidine |
Decitabine | | ABT-199 + Decitabine |
Azacitidine | | ABT-199 + Azacitidine |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
ABT-199 + Azacitidine | Experimental | Treatment Naive Acute Myelogenous Leukemia | |
ABT-199 + Decitabine | Experimental | Treatment Naive Acute Myelogenous Leukemia | |
ABT-199+Decitabine+Posaconazole | Experimental | Treatment 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 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 60 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants Experiencing Adverse Events (AEs) |
Time Frame: | Measured up to 1 year after the last subject last dose |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | Event Free Survival |
Time Frame: | Measured up to 1 year after the last subject last dose |
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. |
Measure: | Duration of Response |
Time Frame: | Measured up to 1 year after the last subject last dose |
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). |
Details
Phase: | Phase 1 |
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
- Venetoclax
- Venclexta
Last Updated
August 20, 2021