Clinical trial NCT00458523: Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia in Partial Remission or Complete Remission
Official title: Eradication of Minimal Residual Disease (MRD) in Patients With Chronic Lymphocytic Leukaemia (CLL) With Alemtuzumab: A Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-04-11
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Rate of undetectable minimal residual disease (MRD) after completion of alemtuzumab therapy
measure: Rate of unacceptable toxicities
Secondary outcomes:
measure: Rate of overall response (complete or partial response)
measure: Time to MRD relapse
measure: Overall survival
measure: Expression of CD52 on chronic lymphocytic leukemia cells
measure: Rate of re-achievement of MRD negativity after completion of alemtuzumab therapy
measure: Incidence of successful retreatment
measure: Toxicity from repeated therapy
measure: Length of interval between required treatments
Other outcomes:
Locations:
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: England
Study officials:
affiliation: Leeds General Infirmary
name: Peter Hillmen, MD
role: STUDY_CHAIR
References: