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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02966782




Registration number
NCT02966782
Ethics application status
Date submitted
15/11/2016
Date registered
17/11/2016

Titles & IDs
Public title
A Study Evaluating Venetoclax Alone and in Combination With Azacitidine in Participants 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
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
Timepoint [3] 0 0
Up to 32 days
Primary outcome [4] 0 0
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
Timepoint [6] 0 0
Up to 32 days
Primary outcome [7] 0 0
Tmax for azacitidine
Timepoint [7] 0 0
Up to 32 days
Primary outcome [8] 0 0
AUC [0-24] for venetoclax
Timepoint [8] 0 0
Up to 32 days
Primary outcome [9] 0 0
AUCt for venetoclax
Timepoint [9] 0 0
Up to 32 days
Primary outcome [10] 0 0
Cmax of venetoclax
Timepoint [10] 0 0
Up to 32 days
Primary outcome [11] 0 0
Half-life (t[1/2]) for azacitidine
Timepoint [11] 0 0
Up to 32 days
Primary outcome [12] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [12] 0 0
Up to Maximum of 24 months
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 Modified Overall Response (mORR)
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 mORR
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
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)
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)
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
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
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
Duration of Complete Response (CR)
Timepoint [12] 0 0
Measured from date of first response (CR) to the to the earliest documentation of progressive disease or death of any cause, and for an anticipated maximum duration of 24 months.
Secondary outcome [13] 0 0
Rate of Hematologic Improvement (HI)
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)
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.
Secondary outcome [15] 0 0
Duration of ORR
Timepoint [15] 0 0
Measured from the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, 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
Sex
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/03/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/04/2023
Sample size
Target
Accrual to date
Final
70
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 Vincent's Hospital Melbourne /ID# 155950 - Fitzroy Melbourne
Recruitment hospital [4] 0 0
The Royal Melbourne Hospital /ID# 155949 - Parkville
Recruitment hospital [5] 0 0
Royal Perth Hospital /ID# 155951 - Perth
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
6000 - Perth
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
Dresden
Country [13] 0 0
Germany
State/province [13] 0 0
Halle (Saale)
Country [14] 0 0
Germany
State/province [14] 0 0
Munich

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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/NCT02966782