Back to resultsBI836826 Dose Escalation in Relapsed Chronic Lymphocytic Leukaemia (CLL)
Primary Purpose
Leukemia, Lymphocytic, Chronic, B-Cell
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BI 836826
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell
Eligibility Criteria
Inclusion criteria:
- 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.
Exclusion criteria:
- 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.
- 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
Sites / Locations
- Brussels - UNIV Saint-Luc
- Edegem - UNIV UZ Antwerpen
- UNIV UZ Gent
- INS Paoli-Calmettes
- CTR Investigation Clinique, onco, Montpellier
- INS Universitaire du Cancer
- Universitätsklinikum Frankfurt
- Universitätsklinikum Heidelberg
- Universitätsklinikum Köln (AöR)
- Universitätsklinikum Ulm
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Patients with relapsed CLL
Arm Description
Patients with relapsed CLL after at least two prior treatment regimens will receive BI 836826.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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).
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01296932
First Posted
February 15, 2011
Last Updated
August 10, 2020
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT01296932
Brief Title
BI836826 Dose Escalation in Relapsed Chronic Lymphocytic Leukaemia (CLL)
Official Title
A Phase I, Open, Dose Escalation Trial With BI 836826 in Patients With Advanced Chronic Lymphocytic Leukaemia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
February 11, 2011 (Actual)
Primary Completion Date
May 30, 2017 (Actual)
Study Completion Date
July 10, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphocytic, Chronic, B-Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Patients with relapsed CLL
Arm Type
Experimental
Arm Description
Patients with relapsed CLL after at least two prior treatment regimens will receive BI 836826.
Intervention Type
Drug
Intervention Name(s)
BI 836826
Intervention Description
Monotherapy with BI 836826 at escalating dose levels administered as an intravenous infusion.
Primary Outcome Measure Information:
Title
Number of Patients With Dose-Limiting Toxicities Adverse Events (DLTs)
Description
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.
Time Frame
14 days after first administration of BI836826 (MTD evaluation period)
Title
Maximum Tolerated Dose (MTD)
Description
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.
Time Frame
14 days after first administration of BI836826 (MTD evaluation period)
Secondary Outcome Measure Information:
Title
Best Percentage Change From Baseline in Number of Lymphocytes in the Peripheral Blood
Description
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).
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
Title
Number of Patients With Improved Haemoglobin Count for at Least Two Subsequent Response Assessments
Description
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.
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
Title
Number of Patients With Improved Platelet Count for at Least Two Subsequent Response Assessments
Description
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.
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
Title
Number of Patients With Improved Neutrophil Count for at Least Two Subsequent Response Assessments
Description
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.
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
Title
Best Overall Response According to 'International Workshop on Chronic Lymphocytic Leukemia' (IWCLL) Criteria
Description
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.
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.
Title
Progression-free Survival
Description
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.
Time Frame
Data collected up to cut-off date 26Oct2016, Up to 1809 days.
Title
Failure-free Survival
Description
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.
Time Frame
Data collected up to cut-off date 26Oct2016, Up to 1809 days.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
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.
Exclusion criteria:
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.
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
Brussels - UNIV Saint-Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Edegem - UNIV UZ Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
UNIV UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
INS Paoli-Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
CTR Investigation Clinique, onco, Montpellier
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
INS Universitaire du Cancer
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Universitätsklinikum Frankfurt
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Universitätsklinikum Köln (AöR)
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Universitätsklinikum Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/
Description
Related Info
Learn more about this trial
BI836826 Dose Escalation in Relapsed Chronic Lymphocytic Leukaemia (CLL)
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