Acute Myeloid Leukemia (AML)Phase 1NCT02492737
Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation
A Phase 1 study testing AG881 in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome, run by Agios Pharmaceuticals, Inc. at 6 sites in 2 countries.
Trial summary
The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in advanced hematologic malignancies that harbor an IDH1 and/or IDH2 mutation Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome, Hematologic Malignancies
- What is being tested?
- AG881
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 7 Aug 2015to 21 Mar 2018
- 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
- Patients must be ≥18 years of age
- Patients must have documented IDH1 and/or IDH2 gene-mutated disease
- Patients must have an advanced hematologic malignancy with an IDH1 and/or IDH2 mutation
- Patient must be able to understand and willing to sign an informed consent
- Patients must have ECOG PS of 0 to 2
- Patients must have adequate hepatic function as evidenced by serum total bilirubin ≤1.5 upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic involvement
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- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to involvement by the neoplasm under consideration for treatment
- Patients must have adequate renal function as evidenced by a serum creatinine ≤2.0 × ULN or Creatinine clearance 40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation
- Patients must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer
- Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. Patients with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Who cannot join
- Patients who have undergone HSCT within 60 days
- Patients who received systemic anticancer therapy or radiotherapy <14 days prior to their first day of study drug administration
- Patients who received an investigational agent <14 days prior
- Patients who are pregnant or breast feeding
- Patients with an active severe infection who require anti-infective therapy or with an unexplained fever >38.5°C during Screening visits or on their first day of study drug administration (at the discretion of the Investigator, patients with tumor fever may be enrolled)
- Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of C1D1
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- Patients with a history of myocardial infarction within the last 6 months
- Patients with known unstable or uncontrolled angina pectoris
- Patients with a known history of severe and/or uncontrolled ventricular arrhythmias
- Patients with QTc interval ≥450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events
- Patients taking medications that are known to prolong the QT interval
- Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
- Patients with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during Screening
- Patients with immediately life-threatening, severe complications of hematologic malignancies such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
Study site
Aurora, Colorado, 80045
Study site
Boston, Massachusetts, 02215
Study site
Chicago, Illinois, 60611
Study site
Houston, Texas, 77030
Study site
New York, New York, 10065
About this study
Official title: A Phase I, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation
The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in advanced hematologic malignancies that harbor an IDH1 and/or IDH2 mutation
Read the detailed description
The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-881 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where patients will receive AG-881 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs or the patient is removed at the discretion of the investigator.
- Being tested
- AG881
- Keywords
- acute myeloid leukemia, AML, myelodysplastic syndrome, MDS, dual mutation, MPN, AITL, hematologic malignancies, IDH1, IDH2, AG-881
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG881Drug
AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression or development of other unacceptable toxicity
| Study group | Role | What they receive |
|---|---|---|
| AG881 | Experimental | AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression, development of other unacceptable toxicity or Investigator discretion Receives: Drug: AG881 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety/tolerability; incidence of adverse events
Measured: Up to 26 weeks, on average
Maximum Tolerated Dose and/or the recommended Phase II dose of AG-881 in patients with advanced hematologic malignancies
Measured: Up to 26 weeks, on average
Secondary outcomes (4)
Pharmacokinetics of AG-881 in patients with advanced hematologic malignancies
Measured: Up to 26 weeks, on average
Pharmacodynamic levels of AG-881
Measured: Up to 26 weeks, on average
Pharmacodynamic levels of 2-HG
Measured: Up to 26 weeks, on average
Clinical Activity according to the 2003 revised IWG criteria for AML, the 2006 modified IWG criteria for MDS, disease-specific response criteria for other hematologic malignancies
Measured: Up to 26 weeks, on average
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2015 (estimated)
- Study start7 Aug 2015
- Primary completion21 Mar 2018
- Study completion21 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by Agios Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02492737
- Sponsor's protocol ID
- AG881-C-001
- Status last verified
- Mar 2019
- First submitted
- 6 Jul 2015
- Last updated
- 8 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
DiNardo CD, De Botton S, Pollyea DA, Stone RM, Altman JK, Fathi AT, Limsakun T, Liang M, Choe S, Hossain M, Tron AE, Meng Q, Kapsalis SM, Pandya SS, Stein EM. Safety, efficacy, and PK/PD of vorasidenib in previously treated patients with mIDH1/2 hematologic malignancies: A phase 1 study. Am J Hematol. 2023 Sep;98(9):E233-E236. doi: 10.1002/ajh.27005. Epub 2023 Jun 24. No abstract available.
PubMed 37354069
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation
- ClinicalTrials.gov ID
- NCT02492737
- Acronym / sponsor ID
- AG881-C-001
- Keywords
- acute myeloid leukemia, AML, myelodysplastic syndrome, MDS, dual mutation, MPN, AITL, hematologic malignancies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Aug 2015 (actual)
- Primary completion
- 21 Mar 2018 (actual)
- Study completion
- 21 Mar 2018 (actual)
- First posted
- 9 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in advanced hematologic malignancies that harbor an IDH1 and/or IDH2 mutation
Detailed description
The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-881 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where patients will receive AG-881 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs or the patient is removed at the discretion of the investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AG881 | Experimental | Drug: AG881AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression, development of other unacceptable toxicity or Investigator discretion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must be ≥18 years of age
- Patients must have documented IDH1 and/or IDH2 gene-mutated disease
- Patients must have an advanced hematologic malignancy with an IDH1 and/or IDH2 mutation
- Patient must be able to understand and willing to sign an informed consent
- Patients must have ECOG PS of 0 to 2
Key exclusion criteria (14 listed)
- Patients who have undergone HSCT within 60 days
- Patients who received systemic anticancer therapy or radiotherapy <14 days prior to their first day of study drug administration
- Patients who received an investigational agent <14 days prior
- Patients who are pregnant or breast feeding
- Patients with an active severe infection who require anti-infective therapy or with an unexplained fever >38.5°C during Screening visits or on their first day of study drug administration (at the discretion of the Investigator, patients with tumor fever may be enrolled)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AG881AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression or development of other unacceptable toxicity | Drug | AG881 |
Primary outcome
Safety/tolerability; incidence of adverse events
Time frame: Up to 26 weeks, on average
Maximum Tolerated Dose and/or the recommended Phase II dose of AG-881 in patients with advanced hematologic malignancies
Time frame: Up to 26 weeks, on average
4 secondary outcomes
Pharmacokinetics of AG-881 in patients with advanced hematologic malignancies
Time frame: Up to 26 weeks, on average
Pharmacodynamic levels of AG-881
Time frame: Up to 26 weeks, on average
Pharmacodynamic levels of 2-HG
Time frame: Up to 26 weeks, on average
Clinical Activity according to the 2003 revised IWG criteria for AML, the 2006 modified IWG criteria for MDS, disease-specific response criteria for other hematologic malignancies
Time frame: Up to 26 weeks, on average
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2019.
- Derived from this study: PubMed 37354069DiNardo CD, De Botton S, Pollyea DA, Stone RM, Altman JK, Fathi AT, Limsakun T, Liang M, Choe S, Hossain M, Tron AE, Meng Q, Kapsalis SM, Pandya SS, Stein EM. Safety, efficacy, and PK/PD of vorasidenib in previously treated patients with mIDH1/2 hematologic malignancies: A phase 1 study. Am J Hematol. 2023 Sep;98(9):E233-E236. doi: 10.1002/ajh.27005. Epub 2023 Jun 24. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AG881 in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome, run by Agios Pharmaceuticals, Inc. at 6 sites in 2 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 10 inclusion and 14 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 8 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, France. 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?
Safety/tolerability; incidence of adverse events (time frame: Up to 26 weeks, on average). The study lists 2 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 NCT02492737, 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 8 Mar 2019.