Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL)

Leukemia, Lymphocytic, Chronic, B-Cell Clinical Trial

Official title:

Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL) - A Phase I/II Trial With Concomitant Evaluation of Safety and Efficacy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00951457
• Other study ID #: AGMT CLL-6 BendAlem
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2009
• Est. completion date: August 6, 2012

Study information

• Verified date: December 2017
• Source: Arbeitsgemeinschaft medikamentoese Tumortherapie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

This is a non-randomized, multicenter, open-label, single-arm Phase I/II study to evaluate the safety and efficacy of bendamustine combined with alemtuzumab in patients with pretreated CD20-positive CLL (according to the revised NCI/ IWCLL criteria).

Eligible patients will receive bendamustine as 4 courses of 70 mg/m2 on days 1 and 2 every 28 days and 30 mg alemtuzumab s.c. continuously on days 1, 3 and 5 of every week, for a maximum of 16 weeks. Safety assessments will be conducted weekly; efficacy assessments including imaging will be performed at months 2, 4, 6, 10 and 16. Bone marrow biopsies will be performed upon CR (according to the 2008 IWCLL response criteria) or fixed at 6 and 16 months.

Following recruitment of the first 3 and 7 patients safety evaluations will be performed by a data safety monitoring board. An interim analysis for response and safety as well as maximum tolerated dose levels will occur after the first 7 patients have completed treatment (Gehan timepoint). If the treatment is deemed clinically safe a further 13 patients will be enrolled.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 6, 2012
• Est. primary completion date: August 6, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Exclusion Criteria:

• HIV positive or positive for Hepatitis B or C

• Active uncontrolled infection

• Pregnant or lactating women

• 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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Bendamustine

• Alemtuzumab

Locations

Country	Name	City	State
Austria	Landeskrankenhaus Feldkirch	Feldkirch
Austria	Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie	Innsbruck	Tirol
Austria	A.ö. Landeskrankenhaus Leoben	Leoben
Austria	Krankenhaus der Elisabethinen Linz	Linz
Austria	Krankenhaus der Stadt Linz	Linz
Austria	Universitaetsklinik f. Innere Medizin III	Salzburg
Austria	Klinikum Wels-Grieskirchen GmbH	Wels

Sponsors (2)

Lead Sponsor	Collaborator
Arbeitsgemeinschaft medikamentoese Tumortherapie	Mundipharma Pte Ltd.

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		2 -16 months
Secondary	To evaluate the efficacy of a bendamustine/ alemtuzumab combination therapy in terms of complete response rates		2 - 16 months
Secondary	To evaluate the achievable cumulative doses of bendamustine and alemtuzumab in terms of maximum tolerated doses while on treatment		2 -16 months
Secondary	To determine response rates in all phases by 4-colour flow cytometric MRD analysis		2 -16 months
Secondary	To identify and characterize potential risk factors via FISH cytogenetics, CD38/ Zap-70 expression and mutational status		2 - 6 months
Secondary	To define clonal evolution by use of longitudinal FISH cytogenetics		2 - 6 months
Secondary	To define T cell subsets including prognostic EM T cells and Treg cells		2 - 16 months
Secondary	To document change upon quality of life by use of a standardized QoL questionnaire		2 -16 months