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Acute Myelogenous LeukemiaPhase 2NCT01994837

A Phase 2 Study of ABT-199 in Subjects With Acute Myelogenous Leukemia (AML)

A Phase 2 study testing ABT-199 in people with Acute Myelogenous Leukemia and AML, run by AbbVie.

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 was a Phase 2, open-label, multicenter study evaluating the preliminary efficacy and safety of venetoclax (ABT-199) administered orally in participants with acute myelogenous leukemia (AML). Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
ABT-199
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
No sites listed yet
Study dates
Nov 2013to Dec 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological or cytological confirmation of relapsed or refractory acute myelogenous leukemia (AML) (by World Health Organization [WHO] classification) or untreated AML in participants who are unfit for intensive therapy.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.
  • Participant must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 50 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula using ideal body mass (IBM) instead of mass.
  • Participant must have adequate liver function as demonstrated by:
  • aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN)*
  • alanine aminotransferase (ALT) ≤ 3.0 × ULN*
  • bilirubin ≤ 1.5 × ULN* *unless considered due to leukemic organ involvement. (Participants with Gilbert's Syndrome may have had a bilirubin > 1.5 × ULN per discussion between the investigator and AbbVie medical monitor)

Who cannot join

  • Participant has received acute anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy within 14 days or 5 half-lives (whichever is shorter) prior to first dose of ABT-199.
  • Participant has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.
  • Participant has received potent Cytochrome P450, family 3, subfamily A (CYP3A) inducers (such as rifampin, carbamazepine, phenytoin and St. John's wort) and warfarin or requires the use of warfarin (due to potential drug-drug interactions that may potentially increase the exposure of warfarin and complications of this effect) within 7 days prior to the first dose of study drug.
  • Participant has received CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 5 days prior to the first dose of study drug.
  • Participant has a white blood cell count > 25 x 10^9/L.
  • Participant has acute promyelocytic leukemia (French-American-British Class M3 AML).
  • Participants with known active central nervous system (CNS) disease.

About this study

This was a Phase 2, open-label, multicenter study evaluating the preliminary efficacy and safety of venetoclax (ABT-199) administered orally in participants with acute myelogenous leukemia (AML).

Read the detailed description

The primary objective was to evaluate the preliminary efficacy of venetoclax administered orally in participants with relapsed and/or refractory (R/R) acute myelogenous leukemia (AML) or frontline therapy in patients with AML who were unfit for intensive therapy. The secondary objective was to evaluate the preliminary safety of venetoclax administered orally in patients with AML. The first portion of the study was to consist of 19 participants with the objective of evaluating anti-tumor effects and confirming the safety of the regimen. The second portion (expansion) was to consist of 35 additional subjects to evaluate anti-tumor effects and safety and was to commence if an adequate efficacy signal (i.e., ≥ 5/19 achieved complete remission [CR], CR with incomplete bone marrow recovery [CRi] or partial remission [PR]) had been observed in the first portion of the study. The criterion for success would have been met if ≥ 16 of 54 participants achieved remission. The efficacy signal from first portion of the study was deemed insufficient for enrollment into the second portion of the study, as 4 of the 19 subjects achieved CR/CRi. During the trial, a number of participants were in screening at the point of the interim analysis. Given the early signs of clinical activity of venetoclax, disease severity, and prognosis of these participants without available options for therapy, they were allowed to initiate treatment ahead of completion of the interim analysis. Therefore, 32 participants were enrolled. No additional participants were screened or treated after the interim analysis was completed.

Being tested
ABT-199
Keywords
GDC-0199, Acute Myelogenous Leukemia, AML, ABT-199, Acute Myeloid Leukemia, Myeloid Leukemia
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myeloid

What participants receive

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

  • ABT-199Drug

    Also called ABT-199 also known as venetoclax

    Tablet

Study groups in NCT01994837
Study groupRoleWhat they receive
ABT-199ExperimentalContinuous dosing of venetoclax (ABT-199) QD (once daily) beginning with dose-escalation on Week 1 Day 1. Participants received a dose of 20 mg of ABT-199 on Week 1 Day 1, 50 mg on Day 2, 100 mg on Day 3, 200 mg on Day 4, 400 mg on Day 5, 800 mg on Day 6 and QD thereafter.
Receives: Drug: ABT-199

What is being measured

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

  1. Objective Remission Rate

    The objective remission rate (ORR) was defined as the percentage of participants who achieved complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), or partial remission (PR) per the International Working Group criteria for AML. Complete remission (CR) was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts. Complete remission with incomplete bone marrow recovery (CRi) was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL. Partial remission (PR) was defined as normalization in peripheral blood neutrophil and platelet counts with at least a 50% decrease in blasts persisting in bone marrow versus baseline.

    Measured: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

Secondary outcomes (9)

  1. Complete Remission Rate

    The complete remission (CR) rate was defined as the percentage of participants who achieved CR per the International Working Group criteria for AML. Complete remission was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts.

    Measured: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

  2. Duration of Remission

    Duration of remission was defined as the number of days from the date of first remission (CR, CRi, or PR) per the International Working Group criteria for AML to the earliest recurrence or progressive disease (PD). In this study, the duration of remission analysis was not performed because of the low remission rate, per the Statistical Analysis Plan.

    Measured: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

  3. Time to Progression

    Time to progression was defined as the number of months from the date of enrollment to the date of earliest disease progression. If a participant did not experience disease progression, then the data for that participant was censored at the date of the last disease assessment.

    Measured: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

  4. Progression-free Survival

    Progression-free survival was defined as the number of months from the date of enrollment to the date of earliest progression or death. If a participant did not experience disease progression or death, then the data was censored at the date of the last disease assessment.

    Measured: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

  5. Overall Survival

    Overall survival was defined as the number of months from the date of enrollment to the date of death for all dosed participants. For participants who did not die, their data were censored at the date of last study visit or the last known date to be alive, whichever was later.

    Measured: Measured up to 2 years after the last subject had enrolled in the study.

  6. Percentage of Participants Who Received Subsequent Stem Cell Transplant

    The percentage of participants who received a subsequent allogenic (from a healthy donor) stem cell transplant was summarized.

    Measured: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

  7. Rate of Minimal Residual Disease (MRD) Negativity

    The rate of minimal residual disease (MRD) response was defined as the percentage of participants who had MRD negative status. Only participants with a reported MRD assessment (negative or positive) from the local laboratory at the investigator site were used in the calculation of MRD response rate.

    Measured: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

  8. Complete Remission With Incomplete Marrow Recovery (CRi) Rate

    The complete remission with incomplete bone marrow recovery (CRi) rate was defined as the percentage of participants who achieved CRi per the International Working Group criteria for AML. Complete remission with incomplete bone marrow recovery was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL.

    Measured: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

  9. Complete Remission Rate and Complete Remission With Incomplete Marrow Recovery (CRi) Rate

    The complete remission rate and the complete remission with incomplete marrow recovery rate (Cri) was defined as the percentage of participants who achieved complete remission (CR) or complete remission with incomplete bone marrow recovery (CRi), per the International Working Group criteria for AML. Complete remission (CR) was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts. Complete remission with incomplete bone marrow recovery (CRi) was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL.

    Measured: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

Timeline

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

  1. First posted26 Nov 2013 (estimated)
  2. Study startNov 2013
  3. Primary completionDec 2014
  4. Study completionDec 2014

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01994837
Sponsor's protocol ID
M14-212
Status last verified
Jan 2018
First submitted
20 Nov 2013
Last updated
6 Jun 2018
Data monitoring committee
No

Publications

  • Konopleva M, Pollyea DA, Potluri J, Chyla B, Hogdal L, Busman T, McKeegan E, Salem AH, Zhu M, Ricker JL, Blum W, DiNardo CD, Kadia T, Dunbar M, Kirby R, Falotico N, Leverson J, Humerickhouse R, Mabry M, Stone R, Kantarjian H, Letai A. Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia. Cancer Discov. 2016 Oct;6(10):1106-1117. doi: 10.1158/2159-8290.CD-16-0313. Epub 2016 Aug 12.

    PubMed 27520294

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ABT-199 in people with Acute Myelogenous Leukemia and AML, run by AbbVie.

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 7 inclusion and 7 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 6 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Remission Rate (time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier). 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 NCT01994837, which also lists 1 linked publication.

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 6 Jun 2018.

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