Clinical trial NCT01296932: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-02-16
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

1. Diagnosis of relapsed or refractory chronic lymphocytic leukaemia.
2. At least two prior treatment regimens for chronic lymphocytic leukaemia.
3. At least one criterion for active disease as defined by the International Workshop on CLL.
4. Absolute lymphocyte count lower than 200 x 10\^9/l .
5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2.
6. Age 18 years or older.
7. Written informed consent which is consistent with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines and local legislation.

Exclusion criteria:

1. 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.
2. Prior allogeneic stem cell transplantation.
3. Active autoimmune haemolytic anemia.
4. Active autoimmune thrombocytopenia.
5. Known transformation to an aggressive B-cell malignancy.
6. Concurrent treatment with relevant doses of systemic glucocorticosteroids.
7. Prior history of malignancy other than chronic lymphocytic leukaemia (exceptions to this rule are defined in the clinical trial protocol).
8. Aspartate aminotransferase or alanine aminotransferase \> 2.5 x upper limit of normal.
9. Total bilirubin \> 1.5 x upper limit of normal.
10. Absolute Neutrophil Count \< 1.000/µl.
11. Platelets \< 25.000/µL.
12. Estimated Glomerular Filtration Rate \<45 mL/min.
13. Proteinuria Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher.
14. Significant concurrent disease.
15. Any infectious disease requiring treatment at the time of enrolment or within the previous 2 weeks.
16. Hepatitis B or C.
17. Human Immunodeficiency Virus (HIV) infection.
18. Cytomegalovirus (CMV) viremia.
19. Women of childbearing potential not using a highly effective method of birth control during the trial until one year after the last dose.
20. Pregnancy or breast feeding.
21. Known or suspected active alcohol or drug abuse.
22. Treatment with another investigational drug within the past four weeks before start of therapy or concomitantly with this trial.
23. Prior treatment with BI 836826.
24. Patients unable to comply with the protocol

Primary outcomes:
measure: Number of Patients With Dose-Limiting Toxicities Adverse Events (DLTs)
timeFrame: 14 days after first administration of BI836826 (MTD evaluation period)
measure: Maximum Tolerated Dose (MTD)
timeFrame: 14 days after first administration of BI836826 (MTD evaluation period)
Secondary outcomes:
measure: Best Percentage Change From Baseline in Number of Lymphocytes in the Peripheral Blood
timeFrame: 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
measure: Number of Patients With Improved Haemoglobin Count for at Least Two Subsequent Response Assessments
timeFrame: ≥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
measure: Number of Patients With Improved Platelet Count for at Least Two Subsequent Response Assessments
timeFrame: ≥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
measure: Number of Patients With Improved Neutrophil Count for at Least Two Subsequent Response Assessments
timeFrame: ≥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
measure: Best Overall Response According to 'International Workshop on Chronic Lymphocytic Leukemia' (IWCLL) Criteria
timeFrame: 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.
measure: Progression-free Survival
timeFrame: Data collected up to cut-off date 26Oct2016, Up to 1809 days.
measure: Failure-free Survival
timeFrame: Data collected up to cut-off date 26Oct2016, Up to 1809 days.
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Edegem
country: Belgium
facility: Edegem - UNIV UZ Antwerpen
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Marseille
country: France
facility: INS Paoli-Calmettes
city: Montpellier Cedex 5
country: France
facility: CTR Investigation Clinique, onco, Montpellier
city: Toulouse
country: France
facility: INS Universitaire du Cancer
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Köln
country: Germany
facility: Universitätsklinikum Köln (AöR)
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: