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

NCT00951457 | Completed Phase 1 DMC

• 1 other identifier: AGMT CLL-6 BendAlem
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

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.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Keywords

CLL; pretreated; immune therapy; dose escalation; maintenance therapy; Bendamustine; Alemtuzumab

Outcome Measures

Primary Outcomes (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

  2 -16 months

Secondary Outcomes (7)

• To evaluate the efficacy of a bendamustine/ alemtuzumab combination therapy in terms of complete response rates

  2 - 16 months

• To evaluate the achievable cumulative doses of bendamustine and alemtuzumab in terms of maximum tolerated doses while on treatment

  2 -16 months

• To determine response rates in all phases by 4-colour flow cytometric MRD analysis

  2 -16 months

• To identify and characterize potential risk factors via FISH cytogenetics, CD38/ Zap-70 expression and mutational status

  2 - 6 months

• To define clonal evolution by use of longitudinal FISH cytogenetics

  2 - 6 months

Study Arms (1)

Overall study

EXPERIMENTAL

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; Drug: Alemtuzumab

Interventions

Bendamustine DRUG

Also known as: Ribomustin

Overall study

Alemtuzumab DRUG

Overall study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with CD23+, CD5+, CD19+ light chain monoclonal B-CLL with treatment indication according to IWCLL criteria (Appendix 4)
• st 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Arbeitsgemeinschaft medikamentoese Tumortherapie: lead
• Mundipharma Pte Ltd.: collaborator

Study Sites (7)

Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie

Innsbruck, Tyrol, A-6020, Austria

Location

Landeskrankenhaus Feldkirch

Feldkirch, A-6806, Austria

Location

A.ö. Landeskrankenhaus Leoben

Leoben, A-8700, Austria

Location

Krankenhaus der Elisabethinen Linz

Linz, A-4010, Austria

Location

Krankenhaus der Stadt Linz

Linz, A-4020, Austria

Location

Universitaetsklinik f. Innere Medizin III

Salzburg, A-5020, Austria

Location

Klinikum Wels-Grieskirchen GmbH

Wels, A-4600, Austria

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Bendamustine Hydrochloride; Alemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Richard Greil, Prof.Dr.

  Arbeitsgemeinschaft medikamentoese Tumortherapie

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2009
• First Posted: August 4, 2009
• Study Start: March 1, 2009
• Primary Completion: August 6, 2012
• Study Completion: August 6, 2012
• Last Updated: March 3, 2022

Record last verified: 2017-12

Locations

AU (7)