Leukemia, Myeloid, AcutePhase 1NCT03127735
BAY1436032 in Patients With Mutant IDH1(mIDH1) Advanced Acute Myeloid Leukemia (AML)
A Phase 1 study testing BAY1436032 in people with Leukemia, Myeloid, Acute, run by Bayer at 13 sites in 2 countries.
Trial summary
To determine the maximum tolerated and / or recommended Phase II dose of oral mutant IDH1 (mIDH1) inhibitor BAY1436032 and to characterize its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy in patients with mIDH1-R132X advanced acute myeloid leukemia (AML) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- BAY1436032
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 14 Jun 2017to 15 Mar 2019
- 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 with advanced AML that harbors IDH1 mutation
- Patients are relapsed from or refractory to at least 1 previous line of therapy
- Good kidney and liver function
- Male or female patients
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Women must have a negative serum pregnancy test within 7 days prior to the first dose of study drug or be surgically or biologically sterile or postmenopausal
Who cannot join
- Previously treated with any prior mIDH1 targeted therapy
- Extramedullary disease only
- History of clinically significant or active cardiac disease
- Active clinically significant infection
- Unresolved chronic toxicity of previous AML treatment
- Taking known strong cytochrome P450 (CYP) 2C8 inducers or inhibitors
- Pregnancy or breast-feeding
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States8 sites
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263-0001
Ohio State University
Columbus, Ohio, 43210
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Mount Sinai Medical Center
New York, New York, 10029
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Montefiore Medical Center
The Bronx, New York, 10467-2490
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
Germany5 sites
Universitätsklinikum Charite zu Berlin
Berlin, 12200
Universitätsklinikum Hamburg Eppendorf (UKE)
Hamburg, 20246
Medizinische Hochschule Hannover (MHH)
Hanover, Lower Saxony, 30625
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Universitätsklinikum Leipzig AöR
Leipzig, Saxony
About this study
Official title: An Open-label, Non-randomized, Multicenter Phase I Study to Determine the Maximum Tolerated and / or Recommended Phase II Dose of Oral Mutant IDH1 (mIDH1) Inhibitor BAY1436032 and to Characterize Its Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Efficacy in Patients With mIDH1-R132X Advanced Acute Myeloid Leukemia (AML)
To determine the maximum tolerated and / or recommended Phase II dose of oral mutant IDH1 (mIDH1) inhibitor BAY1436032 and to characterize its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy in patients with mIDH1-R132X advanced acute myeloid leukemia (AML)
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- BAY1436032
- Keywords
- Phase 1, mIDH1, IDH1 mutation, mIDH1 inhibitor
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY1436032Drug
BAY1436032 administered continuously as a single agent dosed twice a day orally on Days 1 to 28 of a 28-day cycle.
Patients may continue treatment with BAY1436032 until disease progression, development of other unacceptable toxicity or Investigator discretion.
| Study group | Role | What they receive |
|---|---|---|
| BAY1436032 | Experimental | Dose escalation:
Various doses of study drug will be tested on a small number of patients/dose with the goal of identifying the most appropriate dose(s) for further evaluation in dose expansion. The MTD of the study drug may or may not be identified. It is anticipated that 3-4 patients will be treated at each dose of study drug to be tested and that 15-20 total patients will be treated in this part of the trial.
Dose expansion:
Up to 2 different doses of study drug will be tested on up to 30 patients/dose with the goal of identifying the most appropriate RP2D for further clinical development. The doses to be evaluated in this part of the trial will be selected based on information obtained during dose escalation. Receives: Drug: BAY1436032 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) or RP2D of BAY1436032
If the MTD is not reached during dose escalation, the primary variable will be the recommended phase 2 dose (RP2D) of BAY1436032
Measured: Within first 4 weeks of first dose
Number of participants with Adverse Events as a Measure of
As a measure of safety and tolerability
Measured: Up to 12 weeks
Secondary outcomes (10)
Objective efficacy response
Response assessment for AML in this study will be based on the modified Cheson criteria. The following categories are used to capture the investigator's AML response evaluation:
- Complete remission (CR)
- Morphologic CR with CRh (morphologic CR with incomplete hematological recovery) and the response category CRp (morphologic CR with incomplete platelet recovery)
- Partial remission (PR)
- Response categories for morphologic leukemia-free state (MLFS), stable disease and progressive disease
- Progressive disease
Measured: Up to 12 weeks
Duration of response
Efficacy data
Measured: Up to 12 weeks
Event-free survival (EFS)
EFS defined as time from start of treatment to treatment failure, relapse, or death due to any cause.
Measured: Up to 12 weeks
Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline
Assess pharmacodynamic (PD) effects and evidence of clinical efficacy associated with BAY 1436032 administration in patients. Change from baseline and percent change from baseline will be calculated.
Measured: Up to 12 weeks
Cmax (maximum observed drug concentration in plasma after a single dose)
As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients.
PK parameters normalized for dose and / or dose and body weight will be calculated.
Measured: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hour post-dose (each cycle is 28 days)
AUC(0-8) (AUC from time 0 to 8 h after a single dose)
As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients.
PK parameters normalized for dose and / or dose and body weight will be calculated.
Measured: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose (each cycle is 28 days)
AUC(0-12) (AUC from time 0 to 12 h after a single dose)
if feasible
Measured: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hour post-dose (each cycle is 28 days)
Cmax,md (Cmax after multiple doses)
As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients.
PK parameters normalized for dose and / or dose and body weight will be calculated.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hour post-dose on Day 15; (each cycle is 28 days)
AUC(0-8)md (AUC from time 0 to 8 h after multiple doses)
As a secondary objective of this study evaluate the pharmacokinetics (PK) of BAY 1436032 in patients.
PK parameters normalized for dose and / or dose and body weight will be calculated.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)
if feasible
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2017
- Study start14 Jun 2017
- Primary completion6 Dec 2018
- Study completion15 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by BayerThe 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
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03127735
- Sponsor's protocol ID
- 19036
- Other IDs
- 2016-004095-22, 2016
- Status last verified
- May 2019
- First submitted
- 6 Apr 2017
- Last updated
- 14 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-randomized, Multicenter Phase I Study to Determine the Maximum Tolerated and / or Recommended Phase II Dose of Oral Mutant IDH1 (mIDH1) Inhibitor BAY1436032 and to Characterize Its Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Efficacy in Patients With mIDH1-R132X Advanced Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT03127735
- Acronym / sponsor ID
- 19036
- Conditions
- Leukemia, Myeloid, Acute
- Keywords
- Phase 1, mIDH1, IDH1 mutation, mIDH1 inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 14 Jun 2017 (actual)
- Primary completion
- 6 Dec 2018 (actual)
- Study completion
- 15 Mar 2019 (actual)
- First posted
- 25 Apr 2017 (actual)
- 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.
To determine the maximum tolerated and / or recommended Phase II dose of oral mutant IDH1 (mIDH1) inhibitor BAY1436032 and to characterize its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy in patients with mIDH1-R132X advanced acute myeloid leukemia (AML)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BAY1436032 | Experimental | Drug: BAY1436032Dose escalation: Various doses of study drug will be tested on a small number of patients/dose with the goal of identifying the most appropriate dose(s) for further evaluation in dose expansion. The MTD of the study drug may or may not be identified. It is anticipated that 3-4 patients will be treated at each dose of study drug to be tested and that 15-20 total patients will be treated in this part of the trial. Dose expansion: Up to 2 different doses of study drug will be tested on up to 30 patients/dose with the goal of identifying the most appropriate RP2D for further clinical development. The doses to be evaluated in this part of the trial will be selected based on information obtained during dose escalation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with advanced AML that harbors IDH1 mutation
- Patients are relapsed from or refractory to at least 1 previous line of therapy
- Good kidney and liver function
- Male or female patients
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Key exclusion criteria (7 listed)
- Previously treated with any prior mIDH1 targeted therapy
- Extramedullary disease only
- History of clinically significant or active cardiac disease
- Active clinically significant infection
- Unresolved chronic toxicity of previous AML treatment
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 |
|---|---|---|
| BAY1436032BAY1436032 administered continuously as a single agent dosed twice a day orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with BAY1436032 until disease progression, development of other unacceptable toxicity or Investigator discretion. | Drug | BAY1436032 |
Primary outcome
Maximum tolerated dose (MTD) or RP2D of BAY1436032
Time frame: Within first 4 weeks of first dose
If the MTD is not reached during dose escalation, the primary variable will be the recommended phase 2 dose (RP2D) of BAY1436032
Number of participants with Adverse Events as a Measure of
Time frame: Up to 12 weeks
As a measure of safety and tolerability
10 secondary outcomes
Objective efficacy response
Time frame: Up to 12 weeks
Duration of response
Time frame: Up to 12 weeks
Event-free survival (EFS)
Time frame: Up to 12 weeks
Change of 2 hydroxyglutarate (2-HG) level obtained at baseline and post-baseline
Time frame: Up to 12 weeks
Cmax (maximum observed drug concentration in plasma after a single dose)
Time frame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hour post-dose (each cycle is 28 days)
AUC(0-8) (AUC from time 0 to 8 h after a single dose)
Time frame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose (each cycle is 28 days)
AUC(0-12) (AUC from time 0 to 12 h after a single dose)
Time frame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hour post-dose (each cycle is 28 days)
Cmax,md (Cmax after multiple doses)
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hour post-dose on Day 15; (each cycle is 28 days)
AUC(0-8)md (AUC from time 0 to 8 h after multiple doses)
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
AUC(0-12)md (AUC from time 0 to 12 h after multiple doses)
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hour post-dose on Day 15; (each cycle is 28 days)
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 14 May 2019.
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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.
13 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 BAY1436032 in people with Leukemia, Myeloid, Acute, run by Bayer at 13 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 6 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 14 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Germany. 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?
Maximum tolerated dose (MTD) or RP2D of BAY1436032 (time frame: Within first 4 weeks of first dose). 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?
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 14 May 2019.