Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia
Recruitment status was Recruiting
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.
Genetic: polymerase chain reaction
Other: flow cytometry
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Consolidation Therapy With Alemtuzumab (MabCampath®) in Patients With Chronic Lymphocytic Leukemia Who Are in Complete or Partial 2nd Remission After Cytoreduction With Fludarabine or Fludarabine Plus Cyclophosphamide or Fludarabine Plus Cyclophosphamide Plus Rituximab or Bendamustine or Bendamustine Plus Rituximab - a Phase I/II Study|
- Dose-limiting toxicity [ Designated as safety issue: Yes ]
- Maximum tolerated dose [ Designated as safety issue: Yes ]
- Rate of complete minimal residual disease response [ Designated as safety issue: Yes ]
- Rate of immunophenotypic remission using 4-color flow cytometry [ Designated as safety issue: No ]
- Rate of infections (especially CMV infections and reactivations) [ Designated as safety issue: Yes ]
- Rate of severe hematologic and non-hematologic side effects [ Designated as safety issue: Yes ]
- Pharmacokinetics of alemtuzumab (after IV and subcutaneous administration) [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: Yes ]
- Overall survival [ Designated as safety issue: Yes ]
- Complete remission rate [ Designated as safety issue: No ]
|Study Start Date:||November 2003|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
- 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.
|Medizinische Universitaetsklinik I at the University of Cologne||Recruiting|
|Cologne, Germany, D-50924|
|Contact: Michael Hallek, MD 49-221-478-4400|
|Klinikum Barnim GmbH, Werner Forssmann Krankenhaus||Recruiting|
|Eberswalde, Germany, 16225|
|Contact: Contact Person 49-89-595-191 firstname.lastname@example.org|
|Heidelberg, Germany, D-69115|
|Contact: Contact Person 49-622-156-8023 email@example.com|
|Klinikum Lippe - Lemgo||Recruiting|
|Lemgo, Germany, D-32657|
|Contact: Contact Person 49-526-126-4129 firstname.lastname@example.org|
|III Medizinische Klinik Mannheim||Recruiting|
|Mannheim, Germany, D-68305|
|Contact: Contact Person 49-621-383-4152 email@example.com|
|Krankenhaus Barmherzige Brueder Regensburg||Recruiting|
|Regensburg, Germany, D-93049|
|Contact: Contact Person 49-941-264-129|
|Study Chair:||Michael Hallek, MD||Medizinische Universitaetsklinik I at the University of Cologne|