Acute Myelogenous Leukemia, Myelogenous Leukemia, Treatment Naive AML
Conditions
Keywords
Acute Myelogenous Leukemia, AML, Myelogenous Leukemia, ABT-199, GDC-0199, Treatment Naive AML, Untreated AML, Venetoclax, Venclexta
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.
Interventions
DRUGPosaconazole
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.
DRUGABT-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.
DRUGDecitabine
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
DRUGAzacitidine
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.
Sponsors
Genentech, Inc.
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Measured up to 1 year after the last subject last dose | Overall survival will be defined as the number of days from the date of first dose to the date of death. |
| Complete Remission with incomplete blood count recovery rate | Measured up to 1 year after the last subject last dose | 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 | Measured up to 1 year after the last subject last dose | 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. |
| Number of Participants Experiencing Adverse Events (AEs) | Measured up to 1 year after the last subject last dose | 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) | For approximately 5 days following a single dose of ABT-199. | Maximum observed concentration, occurring at Tmax. |
| Time to Cmax (peak time, Tmax), | For approximately 5 days following a single dose of ABT-199. | 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) | For approximately 5 days following a single dose of ABT-199. | The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval. |
| Half-Life (t1/2) | For approximately 5 days following a single dose of ABT-199. | The time required for the concentration of the drug to reach half of its original value. |
| Clearance (CL) | For approximately 5 days following a single dose of ABT-199. | Clearance is defined as the rate at which drug is cleared from the blood. |
| Complete Remission Rate | Measured up to 1 year after the last subject last dose | Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | Measured up to 1 year after the last subject last dose | 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). |
| Event Free Survival | Measured up to 1 year after the last subject last dose | 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. |
Countries
Australia, France, Germany, United States
Outcome results
None listed