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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00951457
Recruitment Status : Completed
First Posted : August 4, 2009
Last Update Posted : December 7, 2017
Mundipharma Pte Ltd.
Information provided by (Responsible Party):
Arbeitsgemeinschaft medikamentoese Tumortherapie

Brief 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.

Condition or disease Intervention/treatment Phase
Leukemia, Lymphocytic, Chronic, B-Cell Drug: Bendamustine Phase 1 Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL) - A Phase I/II Trial With Concomitant Evaluation of Safety and Efficacy
Study Start Date : March 2009
Actual Primary Completion Date : August 6, 2012
Actual Study Completion Date : August 6, 2012

Arm Intervention/treatment
Experimental: Overall study

Dose escalation phase:

Days -3, -2, -1: 3 - 10 - 30 mg Alemtuzumab s.c.

Treatment phase:

Bendamustine 70 mg/m2 i.v. on d1 + d2 repeat every 28 days for 4 cycles

Alemtuzumab 30 mg s.c. 3x per week (days 1, 3, 5) continuously in parallel with chemotherapy cycles for a maximum of 16 weeks

Drug: Bendamustine
Other Name: Ribomustin

Primary Outcome Measures :
  1. 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 [ Time Frame: 2 -16 months ]

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00951457

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Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie
Innsbruck, Tirol, Austria, A-6020
Landeskrankenhaus Feldkirch
Feldkirch, Austria, A-6806
A.ö. Landeskrankenhaus Leoben
Leoben, Austria, A-8700
Krankenhaus der Elisabethinen Linz
Linz, Austria, A-4010
Krankenhaus der Stadt Linz
Linz, Austria, A-4020
Universitaetsklinik f. Innere Medizin III
Salzburg, Austria, A-5020
Klinikum Wels-Grieskirchen GmbH
Wels, Austria, A-4600
Sponsors and Collaborators
Arbeitsgemeinschaft medikamentoese Tumortherapie
Mundipharma Pte Ltd.
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Study Chair: Richard Greil, Prof.Dr. Arbeitsgemeinschaft medikamentoese Tumortherapie

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Responsible Party: Arbeitsgemeinschaft medikamentoese Tumortherapie Identifier: NCT00951457     History of Changes
Other Study ID Numbers: AGMT CLL-6 BendAlem
First Posted: August 4, 2009    Key Record Dates
Last Update Posted: December 7, 2017
Last Verified: December 2017
Keywords provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:
immune therapy
dose escalation
maintenance therapy
Additional relevant MeSH terms:
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Bendamustine Hydrochloride
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological