BI836826 Dose Escalation in Relapsed Chronic Lymphocytic Leukaemia (CLL)
- Registration Number
- NCT01296932
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Patients with relapsed CLL BI 836826 Patients with relapsed CLL after at least two prior treatment regimens will receive BI 836826.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) 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.
Number of Patients With Dose-Limiting Toxicities Adverse Events (DLTs) 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.
- Secondary Outcome Measures
Name Time Method Number of Patients With Improved Platelet Count for at Least Two Subsequent Response Assessments ≥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 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 ≥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 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.
Number of Patients With Improved Haemoglobin Count for at Least Two Subsequent Response Assessments ≥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 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.
Best Overall Response According to 'International Workshop on Chronic Lymphocytic Leukemia' (IWCLL) Criteria 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. 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 Data collected up to cut-off date 26Oct2016, Up to 1809 days. 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.Best Percentage Change From Baseline in Number of Lymphocytes in the Peripheral Blood 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 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).
Failure-free Survival Data collected up to cut-off date 26Oct2016, Up to 1809 days. 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.
Trial Locations
- Locations (10)
UNIV UZ Gent
🇧🇪Gent, Belgium
CTR Investigation Clinique, onco, Montpellier
🇫🇷Montpellier Cedex 5, France
INS Universitaire du Cancer
🇫🇷Toulouse, France
INS Paoli-Calmettes
🇫🇷Marseille, France
Universitätsklinikum Frankfurt
🇩🇪Frankfurt am Main, Germany
Universitätsklinikum Köln (AöR)
🇩🇪Köln, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Brussels - UNIV Saint-Luc
🇧🇪Bruxelles, Belgium
Edegem - UNIV UZ Antwerpen
🇧🇪Edegem, Belgium
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany