Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cancer-Related Problem/Condition; Leukemia
Intervention: alemtuzumab (Biological); polymerase chain reaction (Genetic); flow cytometry (Other); laboratory biomarker analysis (Other); pharmacological study (Other)
Phase: Phase 1/Phase 2
Sponsored by: German CLL Study Group
Official(s) and/or principal investigator(s):
Michael Hallek, MD, Study Chair, Affiliation: Medizinische Universitaetsklinik I at the University of Cologne
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.
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
Study design: Treatment, Open Label
Maximum tolerated dose
Rate of complete minimal residual disease response
Rate of immunophenotypic remission using 4-color flow cytometry
Rate of infections (especially CMV infections and reactivations)
Rate of severe hematologic and non-hematologic side effects
Pharmacokinetics of alemtuzumab (after IV and subcutaneous administration)
Complete remission rate
- 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
Minimum age: 18 Years.
Maximum age: N/A.
- Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL)
- Disease in complete or partial remission after completion of 4-6 courses of
second-line cytoreductive therapy no less than 90 days and no more than 150 days ago
- Second-line cytoreductive therapy must comprise 1 of the following regimens:
- Fludarabine phosphate alone (F)
- Fludarabine phosphate and cyclophosphamide (FC)
- Fludarabine phosphate, cyclophosphamide, and rituximab (FCR)
- Bendamustine hydrochloride alone (B)
- Bendamustine hydrochloride and rituximab chemotherapy (BR)
- Complete minimal residual disease response defined by the following:
- At least negativity of 4-color-cytometry and/or even PCR-amplifiable clonal CDR
III rearrangement of the IgV_H
- For PCR analysis, blood sample need to be taken at beginning or during
second-line cytoreductive therapy before achievement of a clinical complete
- Disease not refractory to first-line F/FC/FCR/B/BR if received such therapy
- Presence of bulky lymph nodes (> 5 cm) after second-line F/FC/FCR/B/BR
- Clinically apparent autoimmune cytopenia (i. e., autoimmune hemolytic anemia,
autoimmune thrombocytopenia, or pure red cell aplasia)
- CNS involvement with B-CLL
- ECOG performance status 0-1
- ANC â‰¥ 1,500/ÂµL
- Platelets â‰¥ 50,000/ÂµL
- Creatinine â‰¤ 1. 5 times the upper normal limit (ULN)
- Conjugated bilirubin â‰¤ 2 times ULN
- Thyroid function normal
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Severe infection during second-line treatment with F/FC/FCR/B/BR, meeting any 1 of the
- Any episode of NCI grade 4 infection
- More than 1 episode of NCI grade 3 infection
- Medical condition requiring long-term use of oral corticosteroids for more than 1
- Active bacterial, viral, or fungal infection
- HIV, hepatitis B virus, and/or hepatitis C virus-positive serum status
- Concurrent severe diseases that exclude the administration of protocol therapy,
including any of the following:
- NYHA class III-IV heart insufficiency
- Severe chronic obstructive lung disease with hypoxemia
- Severe ischemic cardiac disease
- Active secondary malignancy other than B-CLL prior to the study
- Known hypersensitivity or anaphylactic reaction against murine proteins or one of the
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No more than 2 prior chemotherapies, including F/FC/FCR/B/BR therapy
- No more than 1 pretreatment (before second-line therapy) with chlorambucil or
- No chemotherapy or radiotherapy for any neoplastic disease other than B-CLL prior to
Locations and Contacts
III Medizinische Klinik Mannheim, Mannheim D-68305, Germany; Recruiting
Contact Person, Phone: 49-621-383-4152, Email: firstname.lastname@example.org
Klinikum Barnim GmbH, Werner Forssmann Krankenhaus, Eberswalde 16225, Germany; Recruiting
Contact Person, Phone: 49-89-595-191, Email: email@example.com
Klinikum Lippe - Lemgo, Lemgo D-32657, Germany; Recruiting
Contact Person, Phone: 49-526-126-4129, Email: firstname.lastname@example.org
Krankenhaus Barmherzige Brueder Regensburg, Regensburg D-93049, Germany; Recruiting
Contact Person, Phone: 49-941-264-129
Medizinische Universitaetsklinik I at the University of Cologne, Cologne D-50924, Germany; Recruiting
Michael Hallek, MD, Phone: 49-221-478-4400
Universitatsklinikum Heidelberg, Heidelberg D-69115, Germany; Recruiting
Contact Person, Phone: 49-622-156-8023, Email: email@example.com
Clinical trial summary from the National Cancer Institute's PDQÂ® database
Starting date: November 2003
Last updated: February 6, 2009