Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Biological: Alemtuzumab s.c.Biological: Alemtuzumab i.v.
- Registration Number
- NCT00634881
- Lead Sponsor
- German CLL Study Group
- Brief Summary
RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.
PURPOSE: This phase I/II trial is studying the side effects and best dose of alemtuzumab in treating patients with B-cell chronic lymphocytic leukemia.
- Detailed Description
OBJECTIVES:
* To determine the safest dose of alemtuzumab as consolidation therapy in patients in second remission after fludarabine phosphate alone; fludarabine phosphate and cyclophosphamide; fludarabine phosphate, cyclophosphamide, and rituximab; bendamustine hydrochloride alone; or bendamustine hydrochloride and rituximab.
* To determine the frequency of cytomegalovirus reactivations or infections during or after alemtuzumab treatment.
* To determine which dose of alemtuzumab is efficient to eliminate minimal residual disease in peripheral blood and bone marrow (i.e., to turn a clinical partial remission into a clinical complete remission \[CR\], to turn a flow cytometry-positive CR into a flow cytometry-negative CR, or to turn a PCR-positive CR into a PCR-negative CR).
* To determine the pharmacokinetic profile of alemtuzumab.
* To compare the pharmacokinetic profile between intravenous versus subcutaneous administration of alemtuzumab.
OUTLINE: This is a multicenter, dose-escalation study of alemtuzumab.
* Group 1: Patients receive escalating doses of alemtuzumab IV over 2 hours once weekly for 8 weeks until the maximum tolerated dose (MTD) is determined.
* Group 2: Patients receive escalating doses of alemtuzumab subcutaneously once weekly for 8 weeks, beginning with the MTD determined in group 1 until a second MTD is determined.
Patients undergo bone marrow and blood sample collection periodically for laboratory and pharmacokinetic studies. Samples are analyzed for minimal residual disease and T-cell subsets (i.e., CD4 and CD8) via quantitative-PCR analysis and flow cytometry and cytomegalovirus antigens via PCR.
After completion of study treatment, patients are followed at 3, 6, 9, 12, 18, and 24 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 13
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort B: Alemtuzumab s.c. Alemtuzumab s.c. After i.v. MTD (maximum tolerable dosage) has been determined, subcutaneous dose escalation is performed according to the same escalation rules as for cohort A, starting with the recommended dose level of i.v. application. Cohort A: Alemtuzumab i.v. Alemtuzumab i.v. Intravenous administration of alemtuzumab according to the 3 + 3 dose escalation design.
- Primary Outcome Measures
Name Time Method Dose-limiting toxicity 28 days after the last dose of study medication • Dose-limiting toxicity (DLT) and maximal tolerable dose (MTD) DLT is defined as a) all grade III/IV non-hematologic toxicity and b) all grade IV hematologic toxicity lasting for more than 2 weeks (excluding lymphopenia) occuring during or within 4 weeks after end of consolidation therapy.
Maximum tolerated dose 28 days after the last dose of study medication • Dose-limiting toxicity (DLT) and maximal tolerable dose (MTD) DLT is defined as a) all grade III/IV non-hematologic toxicity and b) all grade IV hematologic toxicity lasting for more than 2 weeks (excluding lymphopenia) occuring during or within 4 weeks after end of consolidation therapy.
- Secondary Outcome Measures
Name Time Method Rate of complete minimal residual disease response will be tested repeatedly, first time 3 months after the last dose of study medication, last time point 24 months after last dose of study medication • Rate of molecular responses (defined by negativity of 4- colour- cytometry in BOTH peripheral blood AND bone marrow in patients in clinical CR) The approved laboratory diagnostics for detection of MRD response is 4-colour flow cytometry. Collaterally, it is possible to take samples for potential PCR- analysis for confirmation if available.
Rate of infections (especially CMV infections and reactivations) upt to 24 months after last dose of study medication (end of study) Rate of immunophenotypic remission using 4-color flow cytometry will be tested repeatedly, first time 3 months after the last dose of study medication, Rate of severe hematologic and non-hematologic side effects 28 days after the last dose of study medication Overall survival upt to 24 months after last dose of study medication (end of study) Progression-free survival upt to 24 months after last dose of study medication (end of study) Complete remission rate 28 days after the last dose of study medication Pharmacokinetics of alemtuzumab (after IV and subcutaneous administration) up to 8 weeks during the alemtuzumab treatment Pharmacokinetic samples will be taken at week 4 and 8 during alemtuzumab treatment at the following time points: 0, 4, 8, 24, 48, 96, 168 h
Trial Locations
- Locations (6)
Medizinische Universitaetsklinik I at the University of Cologne
🇩🇪Cologne, Germany
Universitatsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Klinikum Barnim GmbH, Werner Forssmann Krankenhaus
🇩🇪Eberswalde, Germany
III Medizinische Klinik Mannheim
🇩🇪Mannheim, Germany
Krankenhaus Barmherzige Brueder Regensburg
🇩🇪Regensburg, Germany
Klinikum Lippe - Lemgo
🇩🇪Lemgo, Germany