Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia in Partial Remission or Complete Remission

NCT ID: NCT00458523

Last Updated: 2013-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2008-02-29

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 II trial is studying the side effects and how well alemtuzumab works in treating patients with B-cell chronic lymphocytic leukemia in partial remission or complete remission.

Detailed Description

OBJECTIVES:

Primary

• Determine the rate of achieving minimum residual disease (MRD) negativity after treatment with alemtuzumab in patients with B-cell chronic lymphocytic leukemia (B-CLL) who have low levels of MRD after conventional therapy or who relapse at an MRD level after a prior MRD-negative remission.
• Determine the safety of alemtuzumab in patients treated in the MRD-positive setting.

Secondary

• Determine the clinical response in patients treated with this drug.
• Determine the time to MRD relapse in patients treated with this drug.
• Determine the overall survival of patients treated with this drug.
• Determine the effect of this drug when administered as consolidation/maintenance therapy on CD52 expression on CLL cells.
• Determine the safety and efficacy of repeated drug dosing required to achieve sustained MRD negativity in these patients.

OUTLINE: This is a multicenter study.

• Observation: Patients with minimal residual disease (MRD)-negative status are observed every 4 weeks for 12 weeks and then every 12 weeks thereafter. If they become MRD-positive, then they are eligible for treatment.
• Treatment: Patients with MRD-positive status receive alemtuzumab subcutaneously or IV over 2 hours three times weekly for up to 12 weeks in the absence of disease progression or unacceptable toxicity. After completion of 6 weeks of study therapy, patients are evaluated for response. Patients who remain MRD-positive and are responding to study therapy receive an additional 6 weeks of treatment. Patients who remain MRD-positive and show no significant improvement in the level of leukemic cells detected in their peripheral blood or bone marrow are removed from the study. Patients achieving MRD-negative remission are removed from study therapy and monitored for disease recurrence at an MRD level. If MRD-level relapse is confirmed in these patients, they may be retreated with alemtuzumab provided their initial response to therapy lasted for at least 6 months.

Patients undergo collection of peripheral blood and bone marrow periodically during study for assessment of MRD by MRD flow cytometry, fluorescent in situ hybridization (FISH) analysis, somatic mutation analysis, and B-cell selection.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

Conditions

Leukemia

Keywords

B-cell chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage 0 chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

alemtuzumab

Intervention Type: BIOLOGICAL

fluorescence in situ hybridization

Intervention Type: GENETIC

mutation analysis

Intervention Type: GENETIC

flow cytometry

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) meeting the following criterion:

• Confirmed by characteristic immunophenotype on peripheral blood flow cytometry
• In complete or partial remission after prior therapy for B-CLL

• No treatment failure after receiving prior alemtuzumab therapy
• Minimal residual disease (MRD) status meeting 1 of the following criteria:

• Detectable B-CLL MRD (i.e., MRD-positive) as shown by peripheral blood or bone marrow involvement
• Undetectable B-CLL MRD (i.e., MRD-negative remission)
• Lymph nodes < 2 cm in maximum diameter
• No persisting severe pancytopenia due to prior therapy rather than disease, as defined by the following criteria:

• Neutrophil count < 5,000/mm^3
• Platelet count < 50,000/mm^3
• No clinically progressive disease (i.e., peripheral blood B-cell count ≥ 5,000/mm³)
• No mantle cell lymphoma
• No CNS involvement with B-CLL

PATIENT CHARACTERISTICS:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study therapy
• Creatinine < 2 times upper limit of normal (ULN)*
• Bilirubin < 2 times ULN*
• No known HIV positivity
• No concurrent active infection
• No history of anaphylaxis after exposure to rat or mouse-derived, complementary-determining region-grafted humanized monoclonal antibodies
• No other concurrent severe diseases or mental disorders
• No concurrent active secondary malignancy NOTE: *Unless secondary to direct infiltration of the liver by B-CLL or hemolysis

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior allogeneic stem cell transplantation

• Any other prior therapy allowed
• At least 6 months since completion of last therapy for B-CLL
• More than 6 weeks since prior investigational agents
• No other concurrent cytotoxic agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leeds Cancer Centre at St. James's University Hospital

OTHER

Sponsor Role: lead

Principal Investigators

Peter Hillmen, MD

Role: STUDY_CHAIR

Leeds General Infirmary

Locations

Kent and Canterbury Hospital

Canterbury, England, United Kingdom

Leeds General Infirmary

Leeds, England, United Kingdom

Countries

United Kingdom

Other Identifiers

CDR0000538115

Identifier Type: REGISTRY

Identifier Source: secondary_id

SPRI-LCC-CTRU-CLL207

Identifier Type: -

Identifier Source: secondary_id

ISRCTN23153249

Identifier Type: -

Identifier Source: secondary_id

EU-20715

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2006-000053-22

Identifier Type: -

Identifier Source: secondary_id

LCC-CTRU-CLL207

Identifier Type: -

Identifier Source: org_study_id