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Myelodysplastic Syndromes (MDS)Phase 1NCT02966782

A Study Evaluating Venetoclax Alone and in Combination With Azacitidine in Participants With Relapsed/Refractory Myelodysplastic Syndromes (MDS)

A Phase 1 study testing venetoclax and azacitidine in people with Myelodysplastic Syndromes (MDS), run by AbbVie at 23 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes (MDS)
What is being tested?
venetoclax and azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
23 sitesin 3 countries
Study dates
7 Mar 2017to 5 Apr 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

23 sites in 3 countries.

23 sites in 3 countries

United States10 sites

  • University of Colorado Hospital /ID# 155365

    Aurora, Colorado, 80045

  • Pediatric Endocrine Associates /ID# 171227

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute /ID# 155361

    Boston, Massachusetts, 02215

  • Duplicate_University of Chicago /ID# 155364

    Chicago, Illinois, 60637

  • University of Texas MD Anderson Cancer Center /ID# 155362

    Houston, Texas, 77030

  • Yale University /ID# 162544

    New Haven, Connecticut, 06510

  • Columbia Univ Medical Center /ID# 156388

    New York, New York, 10032-3725

  • Oregon Health and Science University /ID# 155360

    Portland, Oregon, 97239

  • University of Arizona Cancer Center - North Campus /ID# 157503

    Tucson, Arizona, 85719-1478

  • University of Massachusetts - Worcester /ID# 155366

    Worcester, Massachusetts, 01655

Other trials in United States

Germany8 sites

  • Universitaetsklinikum Koeln /ID# 155519

    Cologne, North Rhine-Westphalia, 50937

  • Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 154898

    Dresden, 01307

  • Universitaetsklinikum Duesseldorf /ID# 154899

    Düsseldorf, North Rhine-Westphalia, 40225

  • Marien Hospital Duesseldorf /ID# 155518

    Düsseldorf, North Rhine-Westphalia, 40479

  • Universitaetsklinikum Halle (Saale) /ID# 158643

    Halle, 06120

  • Universitaetsklinikum Leipzig /ID# 154897

    Leipzig, Saxony, 04103

  • Universitatsklinikum Mannheim /ID# 156038

    Mannheim, Baden-Wurttemberg, 68167

  • Klinikum rechts der Isar - Technische Universitaet Muenchen /ID# 154896

    Munich, 81675

Other trials in Germany

Australia5 sites

  • St Vincent's Hospital Melbourne /ID# 155950

    Fitzroy Melbourne, Victoria, 3065

  • St George Hospital /ID# 156037

    Kogarah, New South Wales, 2217

  • Liverpool Hospital /ID# 155952

    Liverpool, New South Wales, 2170

  • The Royal Melbourne Hospital /ID# 155949

    Parkville, Victoria, 3050

  • Royal Perth Hospital /ID# 155951

    Perth, Western Australia, 6000

Other trials in Australia

About this study

Official 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

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).

Being tested
venetoclax, azacitidine
Keywords
Relapsed/refractory, Venetoclax, Azacitidine
Medical subject headings
Myelodysplastic Syndromes, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • venetoclaxDrug

    Also called ABT-199, GDC-0199

    Tablet

  • azacitidineDrug

    Also called Vidaza

    Powder for injection, subcutaneously or intravenous

Study groups in NCT02966782
Study groupRoleWhat they receive
Venetoclax monotherapy (Cohort 1)ExperimentalNot described
Receives: Drug: venetoclax
Venetoclax + azacitidine (Cohort 2)ExperimentalNot described
Receives: Drug: venetoclax; Drug: azacitidine
Safety Expansion (Cohort 3)ExperimentalNot described
Receives: Drug: venetoclax; Drug: azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. AUCt for azacitidine

    Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for azacitidine

    Measured: Up to 32 days

  2. Clearance (CL) for azacitidine

    Measured: Up to 32 days

  3. Cmax for azacitidine

    Maximum plasma concentration (Cmax) of azacitidine

    Measured: Up to 32 days

  4. Tmax for venetoclax

    Time to Cmax (peak time, Tmax) for venetoclax

    Measured: Up to 32 days

  5. Recommended Phase 2 Dose (RPTD) and dosing schedules of venetoclax as monotherapy and in combination with azacitidine

    Measured: Measured from Day 1 until day 28 per dose level.

  6. AUC[0 to infinity] for azacitidine

    Area under the plasma concentration-time curve from Time 0 to infinite time.

    Measured: Up to 32 days

  7. Tmax for azacitidine

    Time to Cmax (peak time, Tmax) for azacitidine

    Measured: Up to 32 days

  8. AUC [0-24] for venetoclax

    AUC over a 24-hour dose interval (AUC[0-24]) for venetoclax

    Measured: Up to 32 days

  9. AUCt for venetoclax

    Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for venetoclax

    Measured: Up to 32 days

  10. Cmax of venetoclax

    Maximum plasma concentration (Cmax) of venetoclax

    Measured: Up to 32 days

  11. Half-life (t[1/2]) for azacitidine

    Terminal elimination half-life (t[1/2]) for azacitidine

    Measured: Up to 32 days

  12. Number of Participants With 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. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

    Measured: Up to Maximum of 24 months

Secondary outcomes (15)

  1. Event-Free Survival (EFS)

    Measured: 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.

  2. Overall Survival (OS)

    Measured: 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.

  3. Rate of Modified Overall Response (mORR)

    Proportion of participants with a mORR using best outcome will be calculated.

    Measured: 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.

  4. Time to next treatment (TTNT)

    Measured: 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.

  5. Duration of mORR

    Defined as the number of days from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier..

    Measured: 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.

  6. Rate of platelet (PLT) transfusion independence

    Proportion of participants who become platelet transfusion-independent

    Measured: 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.

  7. Time to Transformation acute myeloid leukemia (AML)

    Defined as blast count greater than or equal to 20% in either peripheral blood or bone marrow.

    Measured: 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.

  8. Progression-Free Survival (PFS)

    Measured: 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.

  9. 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.

    Measured: 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.

  10. Complete Remission (CR) Rate

    Proportion of subjects who achieved a complete remission.

    Measured: 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.

  11. Rate of red blood cell (RBC) transfusion independence

    Proportion of red blood cell (RBC) transfusion independence.

    Measured: 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.

  12. Duration of Complete Response (CR)

    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.

    Measured: 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.

  13. Rate of Hematologic Improvement (HI)

    Proportion of participants with HI (erythroid/platelet/neutrophil responses)

    Measured: 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.

  14. Rate of marrow complete remission (mCR)

    Proportion of participants with marrow complete remission with or without hematological improvement.

    Measured: 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.

  15. Duration of ORR

    Duration of response (ORR) 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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2016 (estimated)
  2. Study start7 Mar 2017
  3. Primary completion5 Apr 2023
  4. Study completion5 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02966782
Sponsor's protocol ID
M15-522
Other IDs
2016-001904-46, 2016
Status last verified
May 2023
First submitted
15 Nov 2016
Last updated
9 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, Filshie R, Odenike O, Watson AM, Krishnadasan R, Bajel A, Naqvi K, Zha J, Cheng WH, Zhou Y, Hoffman D, Harb JG, Potluri J, Garcia-Manero G. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. Am J Hematol. 2023 Feb;98(2):272-281. doi: 10.1002/ajh.26771. Epub 2022 Nov 10.

    PubMed 36309981

  • Franke GN, Luckemeier P, Platzbecker U. Allogeneic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes and Prevention of Relapse. Clin Lymphoma Myeloma Leuk. 2021 Jan;21(1):1-7. doi: 10.1016/j.clml.2020.10.008. Epub 2020 Oct 16.

    PubMed 33191169

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing venetoclax and azacitidine in people with Myelodysplastic Syndromes (MDS), run by AbbVie at 23 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Germany, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUCt for azacitidine (time frame: Up to 32 days). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02966782, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.

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