We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. 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/NCT02966782




Registration number
NCT02966782
Ethics application status
Date submitted
15/11/2016
Date registered
17/11/2016
Date last updated
6/05/2021

Titles & IDs
Public title
A Study Evaluating Venetoclax Alone and in Combination With Azacitidine in Subjects With Relapsed/Refractory Myelodysplastic Syndromes (MDS)
Scientific title
A Phase 1b Study Evaluating the Safety and Pharmacokinetics of Venetoclax as a Single-Agent and in Combination With Azacitidine in Subjects With Relapsed/Refractory Myelodysplastic Syndromes
Secondary ID [1] 0 0
2016-001904-46
Secondary ID [2] 0 0
M15-522
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes (MDS) 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - venetoclax
Treatment: Drugs - azacitidine

Experimental: Venetoclax monotherapy (Cohort 1) -

Experimental: Venetoclax + azacitidine (Cohort 2) -

Experimental: Safety Expansion (Cohort 3) -


Treatment: Drugs: venetoclax
Tablet

Treatment: Drugs: azacitidine
Powder for injection, subcutaneously or intravenous

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

Outcomes
Primary outcome [1] 0 0
AUCt for azacitidine - Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for azacitidine
Timepoint [1] 0 0
Up to 32 days
Primary outcome [2] 0 0
Clearance (CL) for azacitidine
Timepoint [2] 0 0
Up to 32 days
Primary outcome [3] 0 0
Cmax for azacitidine - Maximum plasma concentration (Cmax) of azacitidine
Timepoint [3] 0 0
Up to 32 days
Primary outcome [4] 0 0
Tmax for venetoclax - Time to Cmax (peak time, Tmax) for venetoclax
Timepoint [4] 0 0
Up to 32 days
Primary outcome [5] 0 0
Recommended Phase 2 Dose (RPTD) and dosing schedules of venetoclax as monotherapy and in combination with azacitidine
Timepoint [5] 0 0
Measured from Day 1 until day 28 per dose level.
Primary outcome [6] 0 0
AUC[0 to infinity] for azacitidine - Area under the plasma concentration-time curve from Time 0 to infinite time.
Timepoint [6] 0 0
Up to 32 days
Primary outcome [7] 0 0
Tmax for azacitidine - Time to Cmax (peak time, Tmax) for azacitidine
Timepoint [7] 0 0
Up to 32 days
Primary outcome [8] 0 0
AUC [0-24] for venetoclax - AUC over a 24-hour dose interval (AUC[0-24]) for venetoclax
Timepoint [8] 0 0
Up to 32 days
Primary outcome [9] 0 0
AUCt for venetoclax - Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for venetoclax
Timepoint [9] 0 0
Up to 32 days
Primary outcome [10] 0 0
Cmax of venetoclax - Maximum plasma concentration (Cmax) of venetoclax
Timepoint [10] 0 0
Up to 32 days
Primary outcome [11] 0 0
Half-life (t[1/2]) for azacitidine - Terminal elimination half-life (t[1/2]) for azacitidine
Timepoint [11] 0 0
Up to 32 days
Secondary outcome [1] 0 0
Event-Free Survival (EFS)
Timepoint [1] 0 0
Measured from the date of the first dose of study drug to date of earliest disease progression, death, or initiation of new non-protocol-specified anti-MDS therapy without documented progression, and for up to 5 years after the last subject is enrolled.
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Measured from the date of first dose of study drug to the date of death, and for up to 5 years after the last subject is enrolled.
Secondary outcome [3] 0 0
Rate of bone marrow blast response - Proportion of participants with a bone marrow blast response
Timepoint [3] 0 0
Measured from Cycle 1 Day 1 (C1D1) as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
Secondary outcome [4] 0 0
Time to next treatment (TTNT)
Timepoint [4] 0 0
Measured from first dose of study drug to start of new non-protocol specified MDS therapy, and for up to 5 years after the last subject is enrolled.
Secondary outcome [5] 0 0
Duration of Response (DOR) - Defined as the number of days from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease.
Timepoint [5] 0 0
Measured from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease (PD), and for an anticipated maximum duration of 24 months.
Secondary outcome [6] 0 0
Rate of platelet (PLT) transfusion independence - Proportion of participants who become platelet transfusion-independent
Timepoint [6] 0 0
Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
Secondary outcome [7] 0 0
Time to Transformation acute myeloid leukemia (AML) - Defined as blast count greater than or equal to 20% in either peripheral blood or bone marrow.
Timepoint [7] 0 0
Measured from the date of first dose of study drug to the date of documented AML transformation for an anticipated maximum duration of 24 months.
Secondary outcome [8] 0 0
Progression-Free Survival (PFS)
Timepoint [8] 0 0
Measured from the date of the first dose of study drug to the date of earliest disease progression or death, and for an anticipated maximum duration of 24 months.
Secondary outcome [9] 0 0
Overall Response Rate (ORR) - ORR (equals the sum of rates of complete remission [CR] + marrow complete remission (mCR) + partial remission [PR]) of venetoclax as a single-agent and in combination with azacitidine.
Timepoint [9] 0 0
Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
Secondary outcome [10] 0 0
Complete Remission (CR) Rate - Proportion of subjects who achieved a complete remission.
Timepoint [10] 0 0
Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
Secondary outcome [11] 0 0
Rate of red blood cell (RBC) transfusion independence - Proportion of red blood cell (RBC) transfusion independence.
Timepoint [11] 0 0
Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
Secondary outcome [12] 0 0
Rate of complete cytogenetic response - Proportion of participants with complete cytogenetic response
Timepoint [12] 0 0
Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
Secondary outcome [13] 0 0
Rate of Hematologic Improvement (HI) - Proportion of participants with HI (erythroid/platelet/neutrophil responses)
Timepoint [13] 0 0
Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
Secondary outcome [14] 0 0
Rate of marrow complete remission (mCR) - Proportion of participants with marrow complete remission with or without hematological improvement.
Timepoint [14] 0 0
Measured from Cycle 1 Day 1 (C1D1) as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.

Eligibility
Key inclusion criteria
- Subjects who have relapsed or refractory MDS.

- Subject enrolled in venetoclax monotherapy must have documented failure of prior
therapy with a hypomethylating agent (HMA). HMA-failure is defined as:

1. Relapse after initial complete or partial response or hematological improvement
after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within
the last 5 years, OR

2. Failure to achieve complete or partial response or hematological improvement
after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within
the last 5 years

- Subjects must have presence of < 20% bone marrow blasts per bone marrow
biopsy/aspirate at screening.

- Subject is not a candidate to undergo allogenic hematopoietic stem cell
transplantation (HSCT).

- Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of
=2.

- Subject must have adequate hematologic, renal, and hepatic function.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subject has received prior therapy with a BH3 mimetic.

- Subject has MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).

- Subject has MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic
myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable
MDS/MPN.

- Subject has received allogeneic HSCT or solid organ transplantation.

- Subject has received a live attenuated vaccine within 4 weeks prior to the first dose
of study drug.

- Subject is pregnant or breastfeeding.

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
Parallel
Other design features
Phase
Phase 1
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,WA
Recruitment hospital [1] 0 0
St George Hospital /ID# 156037 - Kogarah
Recruitment hospital [2] 0 0
Liverpool Hospital /ID# 155952 - Liverpool
Recruitment hospital [3] 0 0
St. Vincents Hosp Melbourne /ID# 155950 - Fitzroy
Recruitment hospital [4] 0 0
Royal Perth Hospital /ID# 155951 - Shenton Park
Recruitment hospital [5] 0 0
Royal Melbourne Hospital /ID# 155949 - Melbourne
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
6008 - Shenton Park
Recruitment postcode(s) [5] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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
Connecticut
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
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Germany
State/province [9] 0 0
Baden-Wuerttemberg
Country [10] 0 0
Germany
State/province [10] 0 0
Nordrhein-Westfalen
Country [11] 0 0
Germany
State/province [11] 0 0
Sachsen
Country [12] 0 0
Germany
State/province [12] 0 0
Halle
Country [13] 0 0
Germany
State/province [13] 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
Celgene
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Genentech, Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1b, open-label, multicenter study designed to evaluate the safety and
pharmacokinetics of venetoclax as a single-agent and in combination with azacitidine in
participants with relapsed/refractory Myelodysplastic Syndromes (MDS).
Trial website
https://clinicaltrials.gov/show/NCT02966782
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