Register a trial

Please note that the ANZCTR website will be unavailable from 1:00pm until 2:00pm (AEST) on Thursday 10th of April for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.


The ANZCTR website is back online for trial registration and updates. We apologise for any inconvenience caused while the site was inactive.


With activity expected to increase on the ANZCTR again, there may be extended wait times while we process pending studies, with priority being given to those trials submitted in February. Thank you for your patience.


Reset your password and enable multi-factor authentication (MFA)


For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.


  1. Go to the Login page, click ‘reset password’ and follow the instructions.
  2. Check your email for the link to set a new password.
  3. Create a new password that meets requirements.
  4. Return to the Login page and enter your new password. A verification code will be sent to your email.
  5. Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

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/study/NCT02942290




Registration number
NCT02942290
Ethics application status
Date submitted
18/10/2016
Date registered
24/10/2016

Titles & IDs
Public title
A Study Evaluating Venetoclax in Combination With Azacitidine in Participants With Treatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)
Scientific title
A Phase 1b Dose Escalation Study Evaluating the Safety and Pharmacokinetics of Venetoclax in Combination With Azacitidine in Subjects With Treatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)
Secondary ID [1] 0 0
2016-001657-41
Secondary ID [2] 0 0
M15-531
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 - Azacitidine
Treatment: Drugs - Venetoclax

Experimental: Venetoclax + Azacitidine -


Treatment: Drugs: Azacitidine
Powder for injection; taken subcutaneously (SC) or intravenous (IV); Administered on Days 1-7 of 28 days cycle or Days 1-5 of Week 1 \& Days 1-2 of Week 2 of 28 day cycle.

Treatment: Drugs: Venetoclax
Oral; Tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
AUCt for Azacitidine
Assessment method [1] 0 0
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
Cmax of venetoclax
Assessment method [2] 0 0
Maximum plasma concentration (Cmax) of venetoclax.
Timepoint [2] 0 0
Up to 32 days
Primary outcome [3] 0 0
AUCt for venetoclax
Assessment method [3] 0 0
Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for venetoclax.
Timepoint [3] 0 0
Up to 32 days
Primary outcome [4] 0 0
Tmax of venetoclax
Assessment method [4] 0 0
Time to Cmax (peak time, Tmax) of venetoclax.
Timepoint [4] 0 0
Up to 32 days
Primary outcome [5] 0 0
AUC[0 to infinity] for azacitidine
Assessment method [5] 0 0
Area under the plasma concentration-time curve from Time 0 to infinite time.
Timepoint [5] 0 0
Up to 32 days
Primary outcome [6] 0 0
Recommended Phase 2 dose (RPTD) and dosing schedule of venetoclax in combination with azacitidine
Assessment method [6] 0 0
The RPTD of venetoclax \[co-administered venetoclax and azacitidine\] will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data \[upon completion of the dose escalation phase\].
Timepoint [6] 0 0
Measured from Day 1 until Day 28 per dose level.
Primary outcome [7] 0 0
Half-life (t[1/2]) for azacitidine
Assessment method [7] 0 0
Terminal elimination half-life (t\[1/2\]) for azacitidine.
Timepoint [7] 0 0
Up to 32 days
Primary outcome [8] 0 0
Cmax for azacitidine
Assessment method [8] 0 0
Maximum plasma concentration (Cmax) of azacitidine.
Timepoint [8] 0 0
Up to 32 days
Primary outcome [9] 0 0
AUC[0-24] for venetoclax
Assessment method [9] 0 0
AUC over a 24-hour dose interval (AUC\[0-24\]) for venetoclax.
Timepoint [9] 0 0
Up to 32 days
Primary outcome [10] 0 0
Clearance (CL) for azacitidine
Assessment method [10] 0 0
Clearance is defined as the volume of plasma cleared of the drug per unit time.
Timepoint [10] 0 0
Up to 32 days
Primary outcome [11] 0 0
Tmax for azacitidine
Assessment method [11] 0 0
Time to Cmax (peak time, Tmax) of azacitidine.
Timepoint [11] 0 0
Up to 32 days
Primary outcome [12] 0 0
Complete Remission (CR) Rate
Assessment method [12] 0 0
Complete remission rate will be defined as the proportion of participants who achieved a complete response per the International Working Group (IWG) 2006 criteria for Myelodysplastic Syndromes (MDS).
Timepoint [12] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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 [1] 0 0
Rate of red blood cell (RBC) transfusion independence
Assessment method [1] 0 0
Percentages of participants who become RBC transfusion-independent.
Timepoint [1] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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 [2] 0 0
Progression-Free Survival (PFS)
Assessment method [2] 0 0
PFS is defined as the number of days from the date of the first dose of study drug to the date of earliest disease progression or death due to disease progression or febrile neutropenia.
Timepoint [2] 0 0
Measured from the date of first dose of study drug to the date of earliest disease progression or death due to disease progression or febrile neutropenia, and for an anticipated maximum duration of 24 months.
Secondary outcome [3] 0 0
Overall Survival (OS)
Assessment method [3] 0 0
OS is defined as number of days from the date of first dose of the study drug to the date of death of any cause.
Timepoint [3] 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 participant is enrolled.
Secondary outcome [4] 0 0
Hematologic Improvement (HI) rate
Assessment method [4] 0 0
Percentages of participants with HI (erythroid/platelet/neutrophil responses).
Timepoint [4] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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 [5] 0 0
Rate of platelet (PLT) transfusion independence
Assessment method [5] 0 0
Percentages of participants who become platelet transfusion-independent.
Timepoint [5] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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 [6] 0 0
Event-Free Survival (EFS)
Assessment method [6] 0 0
Event-free survival (EFS) will be defined as the number of days from the date of the first dose of study drug to the date of earliest disease progression or death of any cause.
Timepoint [6] 0 0
Measured from the date of the first dose of study drug to the date of earliest disease progression, death of any cause and for up to 5 yrs after the last participant is enrolled
Secondary outcome [7] 0 0
Time to transformation to acute myeloid leukemia (AML)
Assessment method [7] 0 0
Defined as the number of days from the date of the first dose of study drug to the date of documented AML transformation.
Timepoint [7] 0 0
Measured from the date of first dose of study drug to date of documented AML transformation, defined as the presence of blast count greater than or equal to 20% in either peripheral blood or bone marrow for an anticipated maximum duration of 24 months.
Secondary outcome [8] 0 0
Overall Response Rate (OR)
Assessment method [8] 0 0
OR (equals the rates of complete remission \[CR\] + partial remission \[PR\]) of venetoclax in combination with azacitidine.
Timepoint [8] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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 [9] 0 0
Time to next treatment (TTNT)
Assessment method [9] 0 0
Time to next treatment (TTNT) will be defined as the time from the first dose of study drug to start of new non-protocol specified MDS therapy or death from any cause.
Timepoint [9] 0 0
Measured from the first dose of study drug to start of new non-protocol specified MDS therapy, and for up to 5 years after the last participant is enrolled.
Secondary outcome [10] 0 0
Marrow Complete Remission (mCR) Rate
Assessment method [10] 0 0
Defined as the proportion of participants who achieved a marrow complete response with or without hematological improvement per the International Working Group (IWG) 2006 criteria for Myelodysplastic Syndromes.
Timepoint [10] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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
Modified Overall Response Rate (mOR)
Assessment method [11] 0 0
mOR (equals CR + PR + mCR) of venetoclax in combination with azacitidine.
Timepoint [11] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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
Duration of CR
Assessment method [12] 0 0
Duration of CR will be defined as the number of days from the date of first response CR to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.
Timepoint [12] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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
Duration of mOR
Assessment method [13] 0 0
Duration of response (mOR) will be defined as the number of days from the date of first response (CR, PR or mCR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.
Timepoint [13] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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
Duration of OR
Assessment method [14] 0 0
Duration of response (OR) will be defined as the number of days from the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.
Timepoint [14] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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 [15] 0 0
Rate of AML transformation
Assessment method [15] 0 0
The AML transformation rate is defined as the proportion of participants transformed to Acute Myelogenous Leukemia.
Timepoint [15] 0 0
Measured from the date of first dose of study drug to date of documented AML transformation, defined as the presence of blast count greater than or equal to 20% in either peripheral blood or bone marrow for an anticipated maximum duration of 24 months.
Secondary outcome [16] 0 0
Time to First Response (CR)
Assessment method [16] 0 0
Time to first response (CR) will be defined as the number of days from the date of first dose of the study drug to the date of the first response of CR.
Timepoint [16] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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 [17] 0 0
Time to First Response (mOR)
Assessment method [17] 0 0
Time to first response (mOR) will be defined as the number of days from the date of first dose of the study drug to the date of the first response of (CR, PR, or mCR).
Timepoint [17] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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 [18] 0 0
Time to First Response (OR)
Assessment method [18] 0 0
Time to first response (OR) will be defined as the number of days from the date of first dose of the study drug to the date of the first response of (CR or PR).
Timepoint [18] 0 0
Measured from Cycle 1 Day 1 as long as the participant 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
* Participant must have documented diagnosis of untreated de novo MDS with:

* International Prognostic Scoring System (IPSS) risk categories Int-2 or High (minimum IPSS overall score of 1.5) OR Revised IPSS (IPSS-R) categories intermediate, high or very high (score of > 3) and
* Presence of less than 20% bone marrow blasts per bone marrow biopsy/aspirate.
* Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has received prior therapy for MDS. (Prior supportive care in form of transfusions or growth factors, etc., is not considered prior therapy).
* Participant has received prior therapy with a BCL-2 Homology 3 (BH3) mimetic.
* Participant has a diagnosis other than previously untreated de novo MDS (as defined in the protocol) including:

* MDS with IPSS risk categories Low or Int-1 (overall IPSS score < 1.5)
* Therapy-related MDS (t-MDS).
* MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).
* MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN.
* Participant has received allogeneic Hematopoietic Stem Cell Transplantation (HSCT) or solid organ transplantation.
* Participant has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug.

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
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
12/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/01/2027
Actual
Sample size
Target
129
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital /ID# 154958 - Concord
Recruitment hospital [2] 0 0
Duplicate_St. Vincent's Hospital, Darlinghurst /ID# 222846 - Darlinghurst
Recruitment hospital [3] 0 0
St George Hospital /ID# 154954 - Kogarah
Recruitment hospital [4] 0 0
Liverpool Hospital /ID# 222410 - Liverpool
Recruitment hospital [5] 0 0
Calvary Mater Newcastle /ID# 154957 - Waratah
Recruitment hospital [6] 0 0
Princess Alexandra Hospital /ID# 154990 - Woolloongabba
Recruitment hospital [7] 0 0
Austin Health /ID# 154955 - Heidelberg
Recruitment hospital [8] 0 0
The Alfred Hospital /ID# 154956 - Melbourne
Recruitment hospital [9] 0 0
Fiona Stanley Hospital /ID# 222847 - Murdoch
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2298 - Waratah
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment postcode(s) [9] 0 0
6150 - Murdoch
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
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
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
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
France
State/province [12] 0 0
Pays-de-la-Loire
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
Germany
State/province [14] 0 0
Baden-Wuerttemberg
Country [15] 0 0
Germany
State/province [15] 0 0
Nordrhein-Westfalen
Country [16] 0 0
Germany
State/province [16] 0 0
Sachsen
Country [17] 0 0
Germany
State/province [17] 0 0
Halle (Saale)
Country [18] 0 0
Germany
State/province [18] 0 0
Munich
Country [19] 0 0
Italy
State/province [19] 0 0
Roma
Country [20] 0 0
Italy
State/province [20] 0 0
Bologna
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Norfolk
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Oxfordshire
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Birmingham
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

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

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02942290