COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02203773




Registration number
NCT02203773
Ethics application status
Date submitted
10/07/2014
Date registered
30/07/2014
Date last updated
24/03/2020

Titles & IDs
Public title
Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
Scientific 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
Secondary ID [1] 0 0
2014-000687-18
Secondary ID [2] 0 0
M14-358
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myelogenous Leukemia 0 0
Myelogenous Leukemia 0 0
Treatment Naive AML 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Posaconazole
Treatment: Drugs - ABT-199
Treatment: Drugs - Decitabine
Treatment: Drugs - Azacitidine

Experimental: ABT-199 + Azacitidine - Treatment Naive Acute Myelogenous Leukemia

Experimental: ABT-199 + Decitabine - Treatment Naive Acute Myelogenous Leukemia

Experimental: ABT-199+Decitabine+Posaconazole - Treatment Naive Acute Myelogenous Leukemia


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Complete Remission Rate - Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.
Timepoint [1] 0 0
Measured up to 1 year after the last subject last dose
Primary outcome [2] 0 0
The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) - The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration.
Timepoint [2] 0 0
For approximately 5 days following a single dose of ABT-199.
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
Measured up to 1 year after the last subject last dose
Primary outcome [4] 0 0
half-life (t1/2) - The time required for the concentration of the drug to reach half of its original value.
Timepoint [4] 0 0
For approximately 5 days following a single dose of ABT-199.
Primary outcome [5] 0 0
Maximum observed plasma concentration (Cmax) - Maximum observed concentration, occurring at Tmax.
Timepoint [5] 0 0
For approximately 5 days following a single dose of ABT-199.
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
Measured up to 1 year after the last subject last dose
Primary outcome [7] 0 0
Clearance (CL) - Clearance is defined as the rate at which drug is cleared from the blood.
Timepoint [7] 0 0
For approximately 5 days following a single dose of ABT-199.
Primary outcome [8] 0 0
AUC from 0-24 (AUC0-24) - The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.
Timepoint [8] 0 0
For approximately 5 days following a single dose of ABT-199.
Primary outcome [9] 0 0
Time to Cmax (peak time, Tmax), - The time at which maximum plasma concentration (Cmax) is observed.
Timepoint [9] 0 0
For approximately 5 days following a single dose of ABT-199.
Primary outcome [10] 0 0
AUC from 0 to infinity (AUC8) - Area under the plasma concentration-versus-time curve from time zero to infinity.
Timepoint [10] 0 0
For approximately 5 days following a single dose of ABT-199.
Primary outcome [11] 0 0
Overall Survival - Overall survival will be defined as the number of days from the date of enrollment to the date of death.
Timepoint [11] 0 0
Measured up to 1 year after the last subject last dose
Secondary outcome [1] 0 0
Percent of subjects who move on to stem cell transplant - The percent of subjects who move on to stem cell transplant will be summarized.
Timepoint [1] 0 0
Measured up to 1 year after the last subject last dose
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
Measured up to 1 year after the last subject last dose
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Measured up to 1 year after the last subject last dose

Eligibility
Key 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
Minimum age
60 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St George Hospital /ID# 130356 - Kogarah
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Ctr /ID# 130352 - Melbourne
Recruitment hospital [3] 0 0
Alfred Health /ID# 130353 - Melbourne
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
France
State/province [11] 0 0
Gironde
Country [12] 0 0
France
State/province [12] 0 0
Haute-Garonne
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
Germany
State/province [14] 0 0
Sachsen
Country [15] 0 0
Germany
State/province [15] 0 0
Thueringen
Country [16] 0 0
Germany
State/province [16] 0 0
Dresden
Country [17] 0 0
Germany
State/province [17] 0 0
Munich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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 website
https://clinicaltrials.gov/show/NCT02203773
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications