Know Cancer

forgot password

Eradication of Minimal Residual Disease (MRD) in Patients With Chronic Lymphocytic Leukaemia (CLL) With Alemtuzumab: A Phase II Study

Phase 2
18 Years
Open (Enrolling)

Thank you

Trial Information

Eradication of Minimal Residual Disease (MRD) in Patients With Chronic Lymphocytic Leukaemia (CLL) With Alemtuzumab: A Phase II Study



- 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.


- 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.

Inclusion Criteria


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

- 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


- 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


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Rate of undetectable minimal residual disease (MRD) after completion of alemtuzumab therapy

Safety Issue:


Principal Investigator

Peter Hillmen, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Leeds General Infirmary



Study ID:




Start Date:

December 2006

Completion Date:

Related Keywords:

  • Leukemia
  • 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
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Neoplasm, Residual