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

Acute Myelogenous Leukemia Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT02203773
• Other study ID #: M14-358
• Secondary ID: 2014-000687-18
• Status: Terminated
• Phase: Phase 1
• 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
• 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.

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelogenous Leukemia
• Treatment Naive AML

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

External Links

•   clinical study report synopsis