Leukemia, Myeloid, AcutePhase 1/2NCT02632721
A Trial to Find and Investigate a Safe Dose of BI 836858 in Combination With Decitabine for Patients With Acute Myeloid Leukemia (AML)
A Phase 1/2 study testing Decitabine and BI 836858 in people with Leukemia, Myeloid, Acute, run by Boehringer Ingelheim at 14 sites in 4 countries.
Trial summary
Phase I Dose Escalation: Primary objective is to determine the Maximum Tolerated Dose (MTD) and the recommended dose for Phase I Extension. Secondary objective is to investigate the safety, pharmacokinetics and efficacy of BI 836858 in combination with decitabine Phase I Extension: Primary objective is to collect… 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?
- Decitabine and BI 836858
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 14 sitesin 4 countries
- Study dates
- 16 Jun 2016to 16 Jan 2023
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1)
- Phase I Dose Escalation:
- Male or female patients >/= 18 years of age with relapsed or refractory AML
- Male or female patients >/= 65 years of age with previously untreated AML ineligible for receiving standard intensive therapy
- Phase I Extension and Phase II:
- -- Male or female patients >/= 65 years of age with previously untreated AML ineligible for receiving standard intensive therapy
- 2) Histologically or cytologically confirmed AML according to the WHO classification 3) Patients must be eligible for treatment with decitabine 4) Eastern co-operative oncology group (ECOG) performance score </=2 at screening Further inclusion criteria apply.
Who cannot join
- Acute promyelocytic leukemia (APL, French-American-British (FAB) subtype M3), according to WHO classification.
- Patients who are candidates for allogeneic stem cell transplantation.
- Active chronic graft versus host disease requiring immunosuppressive treatment.
- Phase I extension and Phase II only:
- Prior treatment with a hypomethylating agent, such as prior treatment for Myelodysplastic Syndrome (MDS).
- Prior treatment with Cluster of differentiation 33 (CD33) antibody. Further exclusion criteria apply.
Trial locations and contacts
14 sites in 4 countries.
14 sites in 4 countries
Germany6 sites
Universitätsklinikum Augsburg
Augsburg, 86156
Vivantes Netzwerk für Gesundheit GmbH
Berlin, 10967
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, 01307
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Universitätsklinikum Jena
Jena, 07740
Universitätsklinikum Münster
Münster, 48149
United States4 sites
Northwestern University
Chicago, Illinois, 60611
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Mayo Clinic Cancer Center
Jacksonville, Florida, 32224
Northwell Health
Lake Success, New York, 11042
Spain3 sites
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Clínic de Barcelona
Barcelona, 08036
Hospital Politècnic La Fe
Valencia, 46026
About this study
Official title: An Open-label, Phase I/II Trial to Determine the Maximum Tolerated Dose and Investigate Safety, Pharmacokinetics and Efficacy of BI 836858 in Combination With Decitabine in Patients With Acute Myeloid Leukemia
Phase I Dose Escalation:
Primary objective is to determine the Maximum Tolerated Dose (MTD) and the recommended dose for Phase I Extension.
Secondary objective is to investigate the safety, pharmacokinetics and efficacy of BI 836858 in combination with decitabine
Phase I Extension:
Primary objective is to collect additional data on safety, pharmacokinetics and efficacy and to define the Recommended Phase II Dose (RP2D) of BI 836858 in combination with decitabine.
Phase II: Primary objective is to investigate efficacy, safety and pharmacokinetics of BI 836858 in combination with decitabine compared to decitabine monotherapy.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- Decitabine, BI 836858
- 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.
DecitabineDrug
BI 836858Drug
| Study group | Role | What they receive |
|---|---|---|
| Phase I dose escalation: BI 836858 20 mg + decitabine (intensive) | Experimental | Dose escalation. Receives: Drug: Decitabine; Drug: BI 836858 |
| Phase I dose escalation: BI 836858 40 mg + decitabine (intensive) | Experimental | Dose escalation. Receives: Drug: Decitabine; Drug: BI 836858 |
| Phase I dose escalation: BI 836858 80 mg + decitabine (intensive) | Experimental | Dose escalation. Receives: Drug: Decitabine; Drug: BI 836858 |
| Phase I Extension A: BI 836858 80 mg + decitabine (intensive) | Experimental | Extension phase. Receives: Drug: Decitabine; Drug: BI 836858 |
| Phase I Extension B: BI 836858 80 mg + decitabine (standard) | Experimental | Extension phase. Receives: Drug: Decitabine; Drug: BI 836858 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Number of Patients With Dose Limiting Toxicity (DLT(s)) During First Treatment Cycle
Number of patients with dose limiting toxicity (DLT(s)) for BI 836858 in combination with decitabine during first treatment cycle (Phase 1).
DLT was defined as any non-disease-related non-haematological adverse event (AE) of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher. Expected non-haematological disease-related AEs were not to be regarded as a DLT.
These included complications resulting from haematological AEs such as:
- Bleeding and complications from bleeding due to thrombocytopenia as defined by the Investigator,
- Infection and complications from infections due to neutropenia as defined by the Investigator,
- Constitutional symptoms due to anaemia as defined by the Investigator
Measured: Up to 28 days (first treatment cycle).
Phase I: Maximum Tolerated Dose (MTD) of BI 836858 in Combination With Decitabine
The Maximum tolerated dose (MTD) of BI 836858 in combination with decitabine was estimated after the dose escalation part of the trial obtaining on the basis of dose limiting toxicities (DLT(s)) observed during the first treatment cycle. However, for those patients who receive more than one cycle of the combination treatment, all adverse events that constitute a DLT will be considered for re-estimation of the MTD based on the Bayesian logistic regression model (BLRM). The MTD is defined as the highest dose of BI 836858 (in combination with decitabine) with less than 25% risk of the true DLT rate being above 33% during the MTD evaluation period.
Measured: From first drug administration until end of treatment, up to 941 days.
Secondary outcomes (1)
Phase 1: Number of Patients With Objective Response (CR + CRi)
Number of patients with objective response (Complete remission (CR) + complete remission with incomplete remission (CRi)).
CR was defined as bone marrow (BM) blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0 x 109/L [1,000/μL]; platelet count > 100 x 109/L [100,000/μL]; independence of red blood cells transfusions (no transfusion for 1 week prior to the assessment). No minimum duration of response is required.
CRi was defined as all CR criteria except for residual neutropenia (< 1.0 x 109/L [1,000/μL]) or thrombocytopenia (< 100 x 109/L [100,000/μL]).
Measured: From start of treatment until the earliest of progression, death or end of trial, up to 971 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2015 (estimated)
- Study start16 Jun 2016
- Primary completion16 Jan 2023
- Study completion16 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Phase I Dose Escalation: Open-label, single-arm, dose escalation \- To determine the maximum tolerated dose (MTD) and the recommended dose for Phase I Extension (RExP1D) Phase I Extension: Open-label, two consecutive groups (cohort A and B) - To collect additional data on safety, pharmacokinetics and efficacy and to decide if the RExP1D will become the Recommended Phase II Dose (RP2D) Phase II: Open-label, two-arm randomized \- To investigate efficacy, safety and pharmacokinetics of BI 836858 in combination with decitabine compared to decitabine monotherapy
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02632721
- Sponsor's protocol ID
- 1315.2
- Other IDs
- 2015-002892-30, 2015
- Status last verified
- Feb 2024
- First submitted
- 15 Dec 2015
- Last updated
- 19 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase I/II Trial to Determine the Maximum Tolerated Dose and Investigate Safety, Pharmacokinetics and Efficacy of BI 836858 in Combination With Decitabine in Patients With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT02632721
- Acronym / sponsor ID
- 1315.2
- Conditions
- Leukemia, Myeloid, Acute
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 16 Jun 2016 (actual)
- Primary completion
- 16 Jan 2023 (actual)
- Study completion
- 16 Jan 2023 (actual)
- First posted
- 17 Dec 2015 (estimated)
- Results
- Posted 19 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase I Dose Escalation:
Primary objective is to determine the Maximum Tolerated Dose (MTD) and the recommended dose for Phase I Extension.
Secondary objective is to investigate the safety, pharmacokinetics and efficacy of BI 836858 in combination with decitabine
Phase I Extension:
Primary objective is to collect additional data on safety, pharmacokinetics and efficacy and to define the Recommended Phase II Dose (RP2D) of BI 836858 in combination with decitabine.
Phase II: Primary objective is to investigate efficacy, safety and pharmacokinetics of BI 836858 in combination with decitabine compared to decitabine monotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Phase I Dose Escalation: Open-label, single-arm, dose escalation - To determine the maximum tolerated dose (MTD) and the recommended dose for Phase I Extension (RExP1D) Phase I Extension: Open-label, two consecutive groups (cohort A and B) - To collect additional data on safety, pharmacokinetics and efficacy and to decide if the RExP1D will become the Recommended Phase II Dose (RP2D) Phase II: Open-label, two-arm randomized - To investigate efficacy, safety and pharmacokinetics of BI 836858 in combination with decitabine compared to decitabine monotherapy
| Arm | Type | Receives |
|---|---|---|
| Phase I dose escalation: BI 836858 20 mg + decitabine (intensive) | Experimental | Drug: Decitabine, Drug: BI 836858Dose escalation. |
| Phase I dose escalation: BI 836858 40 mg + decitabine (intensive) | Experimental | Drug: Decitabine, Drug: BI 836858Dose escalation. |
| Phase I dose escalation: BI 836858 80 mg + decitabine (intensive) | Experimental | Drug: Decitabine, Drug: BI 836858Dose escalation. |
| Phase I Extension A: BI 836858 80 mg + decitabine (intensive) | Experimental | Drug: Decitabine, Drug: BI 836858Extension phase. |
| Phase I Extension B: BI 836858 80 mg + decitabine (standard) | Experimental | Drug: Decitabine, Drug: BI 836858Extension phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1)
- Male or female patients >/= 18 years of age with relapsed or refractory AML
- Male or female patients >/= 65 years of age with previously untreated AML ineligible for receiving standard intensive therapy
- -- Male or female patients >/= 65 years of age with previously untreated AML ineligible for receiving standard intensive therapy
- 2) Histologically or cytologically confirmed AML according to the WHO classification 3) Patients must be eligible for treatment with decitabine 4) Eastern co-operative oncology group (ECOG) performance score </=2 at screening Further inclusion criteria apply.
Key exclusion criteria (6 listed)
- Acute promyelocytic leukemia (APL, French-American-British (FAB) subtype M3), according to WHO classification.
- Patients who are candidates for allogeneic stem cell transplantation.
- Active chronic graft versus host disease requiring immunosuppressive treatment.
- Phase I extension and Phase II only:
- Prior treatment with a hypomethylating agent, such as prior treatment for Myelodysplastic Syndrome (MDS).
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 |
|---|---|---|
| Decitabine | Drug | Phase I Extension A: BI 836858 80 mg + decitabine (intensive), Phase I Extension B: BI 836858 80 mg + decitabine (standard), Phase I dose escalation: BI 836858 20 mg + decitabine (intensive), Phase I dose escalation: BI 836858 40 mg + decitabine (intensive), Phase I dose escalation: BI 836858 80 mg + decitabine (intensive) |
| BI 836858 | Drug | Phase I Extension A: BI 836858 80 mg + decitabine (intensive), Phase I Extension B: BI 836858 80 mg + decitabine (standard), Phase I dose escalation: BI 836858 20 mg + decitabine (intensive), Phase I dose escalation: BI 836858 40 mg + decitabine (intensive), Phase I dose escalation: BI 836858 80 mg + decitabine (intensive) |
Primary outcome
Phase I: Number of Patients With Dose Limiting Toxicity (DLT(s)) During First Treatment Cycle
Time frame: Up to 28 days (first treatment cycle).
Number of patients with dose limiting toxicity (DLT(s)) for BI 836858 in combination with decitabine during first treatment cycle (Phase 1). DLT was defined as any non-disease-related non-haematological adverse event (AE) of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher. Expected non-haematological disease-related AEs were not to be regarded as a DLT. These included complications resulting from haematological AEs such as: * Bleeding and complications from bleeding due to thrombocytopenia as defined by the Investigator, * Infection and complications from infections due to neutropenia as defined by the Investigator, * Constitutional symptoms due to anaemia as defined by the Investigator
Phase I: Maximum Tolerated Dose (MTD) of BI 836858 in Combination With Decitabine
Time frame: From first drug administration until end of treatment, up to 941 days.
The Maximum tolerated dose (MTD) of BI 836858 in combination with decitabine was estimated after the dose escalation part of the trial obtaining on the basis of dose limiting toxicities (DLT(s)) observed during the first treatment cycle. However, for those patients who receive more than one cycle of the combination treatment, all adverse events that constitute a DLT will be considered for re-estimation of the MTD based on the Bayesian logistic regression model (BLRM). The MTD is defined as the highest dose of BI 836858 (in combination with decitabine) with less than 25% risk of the true DLT rate being above 33% during the MTD evaluation period.
1 secondary outcome
Phase 1: Number of Patients With Objective Response (CR + CRi)
Time frame: From start of treatment until the earliest of progression, death or end of trial, up to 971 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing
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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.
Boehringer Ingelheim study chair
Boehringer Ingelheim
14 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Decitabine and BI 836858 in people with Leukemia, Myeloid, Acute, run by Boehringer Ingelheim at 14 sites in 4 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 7 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 19 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Germany, United States, Spain, Italy. 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 combined 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.
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 19 Mar 2024). 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?
Phase I: Number of Patients With Dose Limiting Toxicity (DLT(s)) During First Treatment Cycle (time frame: Up to 28 days (first treatment cycle).). 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 19 Mar 2024.