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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Mundipharma Pte Ltd.
Information provided by (Responsible Party):
Arbeitsgemeinschaft medikamentoese Tumortherapie
ClinicalTrials.gov Identifier:
NCT00951457
First received: August 3, 2009
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

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 Intervention Phase
Leukemia, Lymphocytic, Chronic, B-Cell
Drug: Bendamustine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the efficacy of a bendamustine/ alemtuzumab combination therapy in terms of complete response rates [ Time Frame: 2 - 16 months ] [ Designated as safety issue: No ]
  • To evaluate the achievable cumulative doses of bendamustine and alemtuzumab in terms of maximum tolerated doses while on treatment [ Time Frame: 2 -16 months ] [ Designated as safety issue: Yes ]
  • To determine response rates in all phases by 4-colour flow cytometric MRD analysis [ Time Frame: 2 -16 months ] [ Designated as safety issue: No ]
  • To identify and characterize potential risk factors via FISH cytogenetics, CD38/ Zap-70 expression and mutational status [ Time Frame: 2 - 6 months ] [ Designated as safety issue: No ]
  • To define clonal evolution by use of longitudinal FISH cytogenetics [ Time Frame: 2 - 6 months ] [ Designated as safety issue: No ]
  • To define T cell subsets including prognostic EM T cells and Treg cells [ Time Frame: 2 - 16 months ] [ Designated as safety issue: No ]
  • To document change upon quality of life by use of a standardized QoL questionnaire [ Time Frame: 2 -16 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: March 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Bendamustine

    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

    Other Names:
    • Ribomustin
    • MabCampath
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00951457

Locations
Austria
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.
Investigators
Study Chair: Richard Greil, Prof.Dr. Arbeitsgemeinschaft medikamentoese Tumortherapie
  More Information

No publications provided

Responsible Party: Arbeitsgemeinschaft medikamentoese Tumortherapie
ClinicalTrials.gov Identifier: NCT00951457     History of Changes
Other Study ID Numbers: AGMT CLL-6 BendAlem
Study First Received: August 3, 2009
Last Updated: October 4, 2012
Health Authority: Austria: Agency for Health and Food Safety
Austria: Ethikkommission

Keywords provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:
CLL
pretreated
immune therapy
dose escalation
maintenance therapy
Bendamustine
Alemtuzumab

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Alemtuzumab
Nitrogen Mustard Compounds
Campath 1G
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014