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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00458523
First received: April 9, 2007
Last updated: August 9, 2013
Last verified: April 2007
  Purpose

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.


Condition Intervention Phase
Leukemia
Biological: alemtuzumab
Genetic: fluorescence in situ hybridization
Genetic: mutation analysis
Other: flow cytometry
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Eradication of Minimal Residual Disease (MRD) in Patients With Chronic Lymphocytic Leukaemia (CLL) With Alemtuzumab: A Phase II Study

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Rate of undetectable minimal residual disease (MRD) after completion of alemtuzumab therapy [ Designated as safety issue: No ]
  • Rate of unacceptable toxicities [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rate of overall response (complete or partial response) [ Designated as safety issue: No ]
  • Time to MRD relapse [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Expression of CD52 on chronic lymphocytic leukemia cells [ Designated as safety issue: No ]
  • Rate of re-achievement of MRD negativity after completion of alemtuzumab therapy [ Designated as safety issue: No ]
  • Incidence of successful retreatment [ Designated as safety issue: No ]
  • Toxicity from repeated therapy [ Designated as safety issue: Yes ]
  • Length of interval between required treatments [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: December 2006
Study Completion Date: February 2008
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00458523

Locations
United Kingdom
Kent and Canterbury Hospital
Canterbury, England, United Kingdom, CT1 3NG
Leeds General Infirmary
Leeds, England, United Kingdom, LS1 3EX
Sponsors and Collaborators
Leeds Cancer Centre at St. James's University Hospital
Investigators
Study Chair: Peter Hillmen, MD Leeds General Infirmary
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00458523     History of Changes
Other Study ID Numbers: LCC-CTRU-CLL207, CDR0000538115, SPRI-LCC-CTRU-CLL207, ISRCTN23153249, EU-20715, EUDRACT-2006-000053-22
Study First Received: April 9, 2007
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasm, Residual
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Alemtuzumab
Campath 1G
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014