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

Primary Purpose

Leukemia, Lymphocytic, Chronic, B-Cell

Status
Completed
Phase
Phase 1
Locations
Austria
Study Type
Interventional
Intervention
Bendamustine
Alemtuzumab
Sponsored by
Arbeitsgemeinschaft medikamentoese Tumortherapie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell focused on measuring CLL, pretreated, immune therapy, dose escalation, maintenance therapy, Bendamustine, Alemtuzumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie
  • Landeskrankenhaus Feldkirch
  • A.ö. Landeskrankenhaus Leoben
  • Krankenhaus der Elisabethinen Linz
  • Krankenhaus der Stadt Linz
  • Universitaetsklinik f. Innere Medizin III
  • Klinikum Wels-Grieskirchen GmbH

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Overall study

Arm Description

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

Outcomes

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

Secondary Outcome Measures

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

Full Information

First Posted
August 3, 2009
Last Updated
February 15, 2022
Sponsor
Arbeitsgemeinschaft medikamentoese Tumortherapie
Collaborators
Mundipharma Pte Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT00951457
Brief Title
Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL)
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 Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
August 6, 2012 (Actual)
Study Completion Date
August 6, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arbeitsgemeinschaft medikamentoese Tumortherapie
Collaborators
Mundipharma Pte Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphocytic, Chronic, B-Cell
Keywords
CLL, pretreated, immune therapy, dose escalation, maintenance therapy, Bendamustine, Alemtuzumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Overall study
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Ribomustin
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
To evaluate the efficacy of a bendamustine/ alemtuzumab combination therapy in terms of complete response rates
Time Frame
2 - 16 months
Title
To evaluate the achievable cumulative doses of bendamustine and alemtuzumab in terms of maximum tolerated doses while on treatment
Time Frame
2 -16 months
Title
To determine response rates in all phases by 4-colour flow cytometric MRD analysis
Time Frame
2 -16 months
Title
To identify and characterize potential risk factors via FISH cytogenetics, CD38/ Zap-70 expression and mutational status
Time Frame
2 - 6 months
Title
To define clonal evolution by use of longitudinal FISH cytogenetics
Time Frame
2 - 6 months
Title
To define T cell subsets including prognostic EM T cells and Treg cells
Time Frame
2 - 16 months
Title
To document change upon quality of life by use of a standardized QoL questionnaire
Time Frame
2 -16 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Greil, Prof.Dr.
Organizational Affiliation
Arbeitsgemeinschaft medikamentoese Tumortherapie
Official's Role
Study Chair
Facility Information:
Facility Name
Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie
City
Innsbruck
State/Province
Tirol
ZIP/Postal Code
A-6020
Country
Austria
Facility Name
Landeskrankenhaus Feldkirch
City
Feldkirch
ZIP/Postal Code
A-6806
Country
Austria
Facility Name
A.ö. Landeskrankenhaus Leoben
City
Leoben
ZIP/Postal Code
A-8700
Country
Austria
Facility Name
Krankenhaus der Elisabethinen Linz
City
Linz
ZIP/Postal Code
A-4010
Country
Austria
Facility Name
Krankenhaus der Stadt Linz
City
Linz
ZIP/Postal Code
A-4020
Country
Austria
Facility Name
Universitaetsklinik f. Innere Medizin III
City
Salzburg
ZIP/Postal Code
A-5020
Country
Austria
Facility Name
Klinikum Wels-Grieskirchen GmbH
City
Wels
ZIP/Postal Code
A-4600
Country
Austria

12. IPD Sharing Statement

Learn more about this trial

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

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