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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02203773
Other study ID # M14-358
Secondary ID 2014-000687-18
Status Terminated
Phase Phase 1
First received
Last updated
Start date October 6, 2014
Est. completion date June 16, 2022

Study information

Verified date May 2023
Source AbbVie
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 212
Est. completion date June 16, 2022
Est. primary completion date June 16, 2022
Accepts healthy volunteers No
Gender All
Age group 60 Years and older
Eligibility 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.

Study Design


Intervention

Drug:
Posaconazole
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.
ABT-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.
Decitabine
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
Azacitidine
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.

Locations

Country Name City State
Australia St George Hospital /ID# 130356 Kogarah New South Wales
Australia Alfred Health /ID# 130353 Melbourne Victoria
Australia Peter MacCallum Cancer Ctr /ID# 130352 Melbourne Victoria
France AP-HP - Hopital Saint-Louis /ID# 130349 Paris
France Hopital Haut-Lévêque /ID# 134388 Pessac CEDEX Gironde
France Duplicate_Hopital Universitaire Purpan /ID# 134389 Toulouse Haute-Garonne
Germany Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 130342 Dresden
Germany Universitaetsklinikum Leipzig /ID# 130346 Leipzig Sachsen
Germany Duplicate_Klinikum Rechts der Isar /ID# 130347 Munich
Germany Universitaetsklinikum Ulm /ID# 130341 Ulm Baden-Wuerttemberg
United States Emory Midtown Infectious Disease Clinic /ID# 129715 Atlanta Georgia
United States Univ of Colorado Cancer Center /ID# 127859 Aurora Colorado
United States Johns Hopkins University /ID# 129699 Baltimore Maryland
United States Dana-Farber Cancer Institute /ID# 127857 Boston Massachusetts
United States Northwestern University Feinberg School of Medicine /ID# 128741 Chicago Illinois
United States The University of Chicago Medical Center /ID# 128742 Chicago Illinois
United States City of Hope /ID# 129718 Duarte California
United States Duke Cancer Center /ID# 129720 Durham North Carolina
United States University of Texas MD Anderson Cancer Center /ID# 127860 Houston Texas
United States University of Texas MD Anderson Cancer Center /ID# 141581 Houston Texas
United States Columbia University Medical Center /ID# 130289 New York New York
United States University of California, Davis Comprehensive Cancer Center /ID# 129719 Sacramento California
United States University of Washington /ID# 129717 Seattle Washington

Sponsors (2)

Lead Sponsor Collaborator
AbbVie Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Measured up to 1 year after the last subject last dose
Primary Maximum observed plasma concentration (Cmax) Maximum observed concentration, occurring at Tmax. For approximately 5 days following a single dose of ABT-199.
Primary Time to Cmax (peak time, Tmax), The time at which maximum plasma concentration (Cmax) is observed. For approximately 5 days following a single dose of ABT-199.
Primary 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. For approximately 5 days following a single dose of ABT-199.
Primary Half-Life (t1/2) The time required for the concentration of the drug to reach half of its original value. For approximately 5 days following a single dose of ABT-199.
Primary Clearance (CL) Clearance is defined as the rate at which drug is cleared from the blood. For approximately 5 days following a single dose of ABT-199.
Primary Complete Remission Rate Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission. Measured up to 1 year after the last subject last dose
Primary 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. Measured up to 1 year after the last subject last dose
Primary 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. Measured up to 1 year after the last subject last dose
Primary Overall Survival Overall survival will be defined as the number of days from the date of first dose to the date of death. Measured up to 1 year after the last subject last dose
Secondary 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. Measured up to 1 year after the last subject last dose
Secondary 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). Measured up to 1 year after the last subject last dose
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