Pre-treated chronic lymphocytic leukaemia (B-CLL) MedDRA version: 14.0 Level: LLT Classification code 10003946 Term: B-Lymphocytic, CLL (Kiel Classification) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Ribomustin
Product Name: Bendamustin
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: BENDAMUSTINE HYDROCHLORIDE
CAS Number: 3543757
Concentration uni
Sponsors
Arbeitsgemeinschaft medikamentöse Tumortherapie gemeinnützige GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male or female patients with CD23+, CD5+, CD19+ light chain monoclonal B-CLL with treatment indication according to IWCLL criteria (Appendix 4) •1st or greater relapse after fludarabine or any other primary treatment regimen OR Refractory to any previous treatment and simultaneous indication for treatment according to IWCLL criteria (Appendix 4) •Age 18 years and older •ECOG status 0 – 2 •Life expectancy > 6 months •Written informed consent given by the patient •Patient using a reliable means of contraception (e.g. physical barrier, contraceptive pill or patch, spermicide and barrier, or IUD) for the duration of the study. Male patients have to use an adequate contraception method for the duration of study treatment and for 6 months following completion of study treatment. Women of childbearing potential have to use an effective method of contraception for the duration of study participation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: •HIV positive or positive for Hepatitis B or C •Active uncontrolled infection •Hypersensitivity with anaphylactic reaction to humanised monoclonal antibodies or to the excipients of any of the applied drugs (e.g. Bendamustine hydrochloride or mannitol) •Previous treatment with bendamustine •Treatment with an experimental drug within the previous 2 months •Patients with a history of other malignancies within 2 years prior to study entry, except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent. •Transformation to aggressive B-cell malignancy (e.g. large B-cell lymphoma, Richter's syndrome, or prolymphocytic leukemia (PLL) •Decreased kidney function with creatinine clearance < 30 ml/min •Patients with severe co-morbidities or major organ dysfunctions (e.g. known severe liver damage, jaundice) •Patients with a history of severe cardiac disease; e.g. NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, or unstable angina •Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent, or patients unable to comply with requirements of study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the percentage of patients achieving a response, defined as the percentage of patients achieving complete response, partial response and stable disease/ no change upon treatment with the combination therapy according to NCI response criteria (also established according to IWCLL guidelines) upon treatment with a combination of bendamustine and alemtuzumab;Secondary Objective: Secondary objectives of this study are •To determine the safety profile of bendamustine/ alemtuzumab combination therapy in terms of observed toxicities according to NCI CTCAE v3 •To evaluate the efficacy of a bendamustine/ alemtuzumab combination therapy in terms of complete response rates •To evaluate the achievable cumulative doses of bendamustine and alemtuzumab in terms of maximum tolerated doses while on treatment •To determine response rates in all phases by 4-colour flow cytometric MRD analysis •To identify and characterize potential risk factors via FISH cytogenetics, CD38/ Zap-70 expression and mutational status •To define clonal evolution by use of longitudinal FISH cytogenetics •To define T cell subsets including prognostic EM T cells and Treg cells •To document change upon quality of life by use of a standardized QoL questionnaire ;Primary end point(s): Effucacy - Overall Response Rate;Timepoint(s) of evaluation of this end point: The primary objective of this study is to determine the percentage of patients achieving a response, defined as the percentage of patients achieving complete response, partial response and stable disease/ no change upon treatment with the combination therapy according to NCI response criteria (also established according to IWCLL guidelines) upon treatment with a combination of bendamustine and alemtuzumab. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety profile of the Bendamustin – Alemtuzumab combination CR rate Achieveable cumulative doses of Bendamustine and Alemtuzumab Response rates in all phases by 4-colour flow cytometric MRD analysis Risk factor analysis (FISH cytogenetics, CD-38/ Zap-70 expression, mutation status) Longitudinal FISH cytogenetics for definition of clonal evolution Longitudinal definition of T-cell subsets (including prognostic EM T-cells and T-reg cells) QoL evaluation;Timepoint(s) of evaluation of this end point: end of the study | — |
Countries
Austria
Contacts
Public ContactDaniela Wolkersdorfer
AGMT gemeinnützige GmbH
Outcome results
None listed