Leukemia, Lymphocytic, Chronic, B-CellPhase 1NCT01296932
BI836826 Dose Escalation in Relapsed Chronic Lymphocytic Leukaemia (CLL)
A Phase 1 study testing BI 836826 in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Boehringer Ingelheim at 10 sites in 3 countries.
Trial summary
Adult patients with chronic lymphocytic leukaemia who experience a relapse after at least two prior treatment regimens may be enrolled in this trial. The trial will examine whether monotherapy with BI 836826 is safe and tolerable at escalating dose levels. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Lymphocytic, Chronic, B-Cell
- What is being tested?
- BI 836826
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 11 Feb 2011to 10 Jul 2017
- Phase
- Phase 1
- 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
- Diagnosis of relapsed or refractory chronic lymphocytic leukaemia.
- At least two prior treatment regimens for chronic lymphocytic leukaemia.
- At least one criterion for active disease as defined by the International Workshop on CLL.
- Absolute lymphocyte count lower than 200 x 10^9/l .
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2.
- Age 18 years or older.
- Written informed consent which is consistent with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines and local legislation.
Who cannot join
- Treatment with anti Cluster of Differentiation (CD) 20 therapy within 4 weeks, or alemtuzumab within 8 weeks, or any cytotoxic antileukemia therapy within 2 weeks, Ibrutinib or Idelalisib within 1 week prior to the first administration of the trial drug.
- Prior allogeneic stem cell transplantation.
- Active autoimmune haemolytic anemia.
- Active autoimmune thrombocytopenia.
- Known transformation to an aggressive B-cell malignancy.
- Concurrent treatment with relevant doses of systemic glucocorticosteroids.
Show all 24Show fewer
- Prior history of malignancy other than chronic lymphocytic leukaemia (exceptions to this rule are defined in the clinical trial protocol).
- Aspartate aminotransferase or alanine aminotransferase > 2.5 x upper limit of normal.
- Total bilirubin > 1.5 x upper limit of normal.
- Absolute Neutrophil Count < 1.000/µl.
- Platelets < 25.000/µL.
- Estimated Glomerular Filtration Rate <45 mL/min.
- Proteinuria Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher.
- Significant concurrent disease.
- Any infectious disease requiring treatment at the time of enrolment or within the previous 2 weeks.
- Hepatitis B or C.
- Human Immunodeficiency Virus (HIV) infection.
- Cytomegalovirus (CMV) viremia.
- Women of childbearing potential not using a highly effective method of birth control during the trial until one year after the last dose.
- Pregnancy or breast feeding.
- Known or suspected active alcohol or drug abuse.
- Treatment with another investigational drug within the past four weeks before start of therapy or concomitantly with this trial.
- Prior treatment with BI 836826.
- Patients unable to comply with the protocol
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
Germany4 sites
Universitätsklinikum Köln (AöR)
Cologne, 50937
Universitätsklinikum Frankfurt
Frankfurt am Main, 60590
Universitätsklinikum Heidelberg
Heidelberg, 69120
Universitätsklinikum Ulm
Ulm, 89081
Belgium3 sites
Brussels - UNIV Saint-Luc
Brussels, 1200
Edegem - UNIV UZ Antwerpen
Edegem, 2650
UNIV UZ Gent
Ghent, 9000
France3 sites
INS Paoli-Calmettes
Marseille, 13273
CTR Investigation Clinique, onco, Montpellier
Montpellier, 34295
INS Universitaire du Cancer
Toulouse, 31059
About this study
Official title: A Phase I, Open, Dose Escalation Trial With BI 836826 in Patients With Advanced Chronic Lymphocytic Leukaemia
Adult patients with chronic lymphocytic leukaemia who experience a relapse after at least two prior treatment regimens may be enrolled in this trial. The trial will examine whether monotherapy with BI 836826 is safe and tolerable at escalating dose levels.
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Being tested
- BI 836826
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 836826Drug
Monotherapy with BI 836826 at escalating dose levels administered as an intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Patients with relapsed CLL | Experimental | Patients with relapsed CLL after at least two prior treatment regimens will receive BI 836826. Receives: Drug: BI 836826 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Dose-Limiting Toxicities Adverse Events (DLTs)
Dose-Limiting Toxicities (DLTs) were defined as any drug-related non-haematologic adverse event of Common Terminology Criteria for AE (CTCAE) Grade 3 or higher, except infusion related reactions associated with the administration of BI 836826. In addition complications due to haematologic AEs were considered as DLTs and were added in more detail in an amendment later on.
Measured: 14 days after first administration of BI836826 (MTD evaluation period)
Maximum Tolerated Dose (MTD)
The maximum tolerated dose (MTD) was defined as the highest dose of BI 836826 studied for which the incidence of DLT was no more than 17% (i.e. 1 out of 6 patients) during the first treatment cycle. For those patients who received more than 1 cycle of BI 836826, all AEs corresponding to the DLT were considered for the purpose of confirming the MTD and for the selection of the recommended dose for treatment of the expansion cohort and for further development. All DLTs, occurring during the first or repeated treatment cycle were reported as significant AEs. As it was not possible to recruit a sufficient number of patients whilst the first part of the trial was still in progress, the recruitment was ended by the sponsor before the MTD or optimal biological dose (OBD) was reached.
Measured: 14 days after first administration of BI836826 (MTD evaluation period)
Secondary outcomes (7)
Best Percentage Change From Baseline in Number of Lymphocytes in the Peripheral Blood
In most patients with relapsed or refractory chronic lymphocytic leukaemia (CLL), malignant B-cells represent the majority of lymphocytes in the peripheral blood. Reduction of CLL-cells was assessed in the peripheral blood by absolute lymphocyte count, and flow cytometry. The number of lymphocytes in the peripheral blood was analysed in terms of the best percentage change from baseline until start of subsequent CLL therapy or progressive disease (PD).
Measured: baseline and ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days
Number of Patients With Improved Haemoglobin Count for at Least Two Subsequent Response Assessments
In patients with haemoglobin counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved haemoglobin count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.
Measured: ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days
Number of Patients With Improved Platelet Count for at Least Two Subsequent Response Assessments
In patients with platelet counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved platelet count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.
Measured: ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days
Number of Patients With Improved Neutrophil Count for at Least Two Subsequent Response Assessments
In patients with neutrophil count below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved neutrophil count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.
Measured: ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days
Best Overall Response According to 'International Workshop on Chronic Lymphocytic Leukemia' (IWCLL) Criteria
Response was assessed according to the IWCLL (International Workshop on Chronic Lymphocytic Leukemia) guidelines based on laboratory data from the peripheral blood and clinical examination by the investigator after each cycle prior to administration of the next dose of BI 836826, at the end of the treatment (EOT) visit, and at all Follow-up Visits. Best overall response will be analysed descriptively. Frequency distributions will be used to examine this endpoint.
Measured: Data collected up to cut-off date 26Oct2016 until Progressive disease (PD) to start of next Chronic Lymphocytic Leukaemia (CLL) therapy, Up to 1809 days.
Progression-free Survival
Progression-free survival (PFS) was defined as the time from the first administration of BI 836826 until disease progression or death, whichever occurred first. Disease progression= At least one of the following:
- 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L
- Progression of lymphadenopathy
- 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly
- 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly
- 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia
- Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.
Measured: Data collected up to cut-off date 26Oct2016, Up to 1809 days.
Failure-free Survival
Failure-free survival (FFS) was defined as the time from the first administration of BI 836826 until disease progression or death, or start of next Chronic Lymphocytic Leukemia (CLL) therapy, whichever occurred first. Disease progression= At least one of the following:
- 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L
- Progression of lymphadenopathy
- 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly
- 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly
- 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia
- Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.
Measured: Data collected up to cut-off date 26Oct2016, Up to 1809 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2011 (estimated)
- Study start11 Feb 2011
- Primary completion30 May 2017
- Study completion10 Jul 2017
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, Lymphocytic, Chronic, B-CellStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 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
- NCT01296932
- Sponsor's protocol ID
- 1270.1
- Other IDs
- 2010-021488-34
- Status last verified
- Aug 2020
- First submitted
- 15 Feb 2011
- Last updated
- 20 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open, Dose Escalation Trial With BI 836826 in Patients With Advanced Chronic Lymphocytic Leukaemia
- ClinicalTrials.gov ID
- NCT01296932
- Acronym / sponsor ID
- 1270.1
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 11 Feb 2011 (actual)
- Primary completion
- 30 May 2017 (actual)
- Study completion
- 10 Jul 2017 (actual)
- First posted
- 16 Feb 2011 (estimated)
- Results
- Posted 20 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adult patients with chronic lymphocytic leukaemia who experience a relapse after at least two prior treatment regimens may be enrolled in this trial. The trial will examine whether monotherapy with BI 836826 is safe and tolerable at escalating dose levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with relapsed CLL | Experimental | Drug: BI 836826Patients with relapsed CLL after at least two prior treatment regimens will receive BI 836826. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of relapsed or refractory chronic lymphocytic leukaemia.
- At least two prior treatment regimens for chronic lymphocytic leukaemia.
- At least one criterion for active disease as defined by the International Workshop on CLL.
- Absolute lymphocyte count lower than 200 x 10^9/l .
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2.
Key exclusion criteria (24 listed)
- Treatment with anti Cluster of Differentiation (CD) 20 therapy within 4 weeks, or alemtuzumab within 8 weeks, or any cytotoxic antileukemia therapy within 2 weeks, Ibrutinib or Idelalisib within 1 week prior to the first administration of the trial drug.
- Prior allogeneic stem cell transplantation.
- Active autoimmune haemolytic anemia.
- Active autoimmune thrombocytopenia.
- Known transformation to an aggressive B-cell malignancy.
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 |
|---|---|---|
| BI 836826Monotherapy with BI 836826 at escalating dose levels administered as an intravenous infusion. | Drug | Patients with relapsed CLL |
Primary outcome
Number of Patients With Dose-Limiting Toxicities Adverse Events (DLTs)
Time frame: 14 days after first administration of BI836826 (MTD evaluation period)
Dose-Limiting Toxicities (DLTs) were defined as any drug-related non-haematologic adverse event of Common Terminology Criteria for AE (CTCAE) Grade 3 or higher, except infusion related reactions associated with the administration of BI 836826. In addition complications due to haematologic AEs were considered as DLTs and were added in more detail in an amendment later on.
Maximum Tolerated Dose (MTD)
Time frame: 14 days after first administration of BI836826 (MTD evaluation period)
The maximum tolerated dose (MTD) was defined as the highest dose of BI 836826 studied for which the incidence of DLT was no more than 17% (i.e. 1 out of 6 patients) during the first treatment cycle. For those patients who received more than 1 cycle of BI 836826, all AEs corresponding to the DLT were considered for the purpose of confirming the MTD and for the selection of the recommended dose for treatment of the expansion cohort and for further development. All DLTs, occurring during the first or repeated treatment cycle were reported as significant AEs. As it was not possible to recruit a sufficient number of patients whilst the first part of the trial was still in progress, the recruitment was ended by the sponsor before the MTD or optimal biological dose (OBD) was reached.
7 secondary outcomes
Best Percentage Change From Baseline in Number of Lymphocytes in the Peripheral Blood
Time frame: baseline and ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days
Number of Patients With Improved Haemoglobin Count for at Least Two Subsequent Response Assessments
Time frame: ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days
Number of Patients With Improved Platelet Count for at Least Two Subsequent Response Assessments
Time frame: ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days
Number of Patients With Improved Neutrophil Count for at Least Two Subsequent Response Assessments
Time frame: ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days
Best Overall Response According to 'International Workshop on Chronic Lymphocytic Leukemia' (IWCLL) Criteria
Time frame: Data collected up to cut-off date 26Oct2016 until Progressive disease (PD) to start of next Chronic Lymphocytic Leukaemia (CLL) therapy, Up to 1809 days.
Progression-free Survival
Time frame: Data collected up to cut-off date 26Oct2016, Up to 1809 days.
Failure-free Survival
Time frame: Data collected up to cut-off date 26Oct2016, Up to 1809 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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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
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 836826 in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Boehringer Ingelheim at 10 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 7 inclusion and 24 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 20 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, Belgium, 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?
Yes. Results are posted in the registry (first posted 20 Aug 2020). 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?
Number of Patients With Dose-Limiting Toxicities Adverse Events (DLTs) (time frame: 14 days after first administration of BI836826 (MTD evaluation period)). 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 20 Aug 2020.