- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01296932
BI836826 Dose Escalation in Relapsed Chronic Lymphocytic Leukaemia (CLL)
A Phase I, Open, Dose Escalation Trial With BI 836826 in Patients With Advanced Chronic Lymphocytic Leukaemia
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Bruxelles, Belgium, 1200
- Brussels - UNIV Saint-Luc
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Edegem, Belgium, 2650
- Edegem - UNIV UZ Antwerpen
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Gent, Belgium, 9000
- UNIV UZ Gent
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Marseille, France, 13273
- INS Paoli-Calmettes
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Montpellier Cedex 5, France, 34295
- CTR Investigation Clinique, onco, Montpellier
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Toulouse, France, 31059
- INS Universitaire du Cancer
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Frankfurt am Main, Germany, 60590
- Universitatsklinikum Frankfurt
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Heidelberg, Germany, 69120
- Universitätsklinikum Heidelberg
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Köln, Germany, 50937
- Universitätsklinikum Köln (AöR)
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Ulm, Germany, 89081
- Universitatsklinikum Ulm
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Patients with relapsed CLL
Patients with relapsed CLL after at least two prior treatment regimens will receive BI 836826.
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Monotherapy with BI 836826 at escalating dose levels administered as an intravenous infusion.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With Dose-Limiting Toxicities Adverse Events (DLTs)
Time Frame: 14 days after first administration of BI836826 (MTD evaluation period)
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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.
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14 days after first administration of BI836826 (MTD evaluation period)
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Maximum Tolerated Dose (MTD)
Time Frame: 14 days after first administration of BI836826 (MTD evaluation period)
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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.
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14 days after first administration of BI836826 (MTD evaluation period)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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).
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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
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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
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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.
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≥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
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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
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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.
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≥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
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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
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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.
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≥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
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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.
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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.
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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.
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Progression-free Survival
Time Frame: Data collected up to cut-off date 26Oct2016, Up to 1809 days.
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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:
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Data collected up to cut-off date 26Oct2016, Up to 1809 days.
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Failure-free Survival
Time Frame: Data collected up to cut-off date 26Oct2016, Up to 1809 days.
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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:
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Data collected up to cut-off date 26Oct2016, Up to 1809 days.
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Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1270.1
- 2010-021488-34 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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