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Microarray Analysis of the Effect of Cyclosporine Therapy on Gene Expression Patterns in Large Granular Lymphocytic Leukemia

Phase 2
18 Years
Not Enrolling
Large Granular Lymphocytic Leukemia, LGL Leukemia

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Trial Information

Microarray Analysis of the Effect of Cyclosporine Therapy on Gene Expression Patterns in Large Granular Lymphocytic Leukemia


- LGL leukemia is a low grade non-Hodgkins Lymphoma characterized by tissue invasion of
the marrow, spleen and liver

- Recurrent infections due to chronic neutropenia and transfusion-dependent anemia are
the principal causes for initiation of therapy

- Approximately 50% of patients treated with cyclosporine (CSA) respond to treatment. CSA
appears to correct the associated cytopenia without decreasing LGL numbers, suggesting
it may inhibit LGL secretion of yet unidentified mediators of neutropenia and anemia.

- Analysis of differential gene expression profiles in patients with LGL leukemia treated
with cyclosporine has the potential to detect as yet unidentified, therapeutic targets
and possibly provide predictors of CSA responsiveness.


- Identify changes in gene expression patterns induced by cyclosporine therapy in
patients with LGL leukemia

- Identify differences between responding and non-responding patients


-Patients with Large Granular Lymphocyte leukemia


- Patients will be treated with cyclosporine at a dose of 5-10mg/kg/day in divided doses,
with doses adjusted to maintain a therapeutic serum level between 200-400ng/ml. These
therapeutic levels shall be maintained for 3 months.

- Tumor response will be evaluated after 3 months therapy, the dose of CsA may then be
tapered to that required to sustain a response or discontinued if no evidence of
response, or after relapse.

- Blood sampling or Lymphapheresis for collection of circulating malignant cells will be
performed at a number of different time points. Gene expression profiling will be
carried out on Affymetrix microarrays to compare pretreatment and post-treatment

Inclusion Criteria


1. All patients must have a histologic or cytologic diagnosis of T-cell LGL
leukemia as determined by the Laboratory of Pathology or Hematology at the
Clinical Center, National Institutes of Health

2. All patients must have hemocytopenias such as granulocyte count less than
1,200/ul, platelet count less than 100,000/ul or hemoglobin less than 10 g/dl,
or require hematopoietic support (transfusion or colony stimulating factors) to
maintain counts at these or higher levels.

3. Patients must have measurable or evaluable disease

4. Patients must have a creatinine of less than 2.0 mg/dl.

5. Omission of cytotoxic chemotherapy for 3 weeks prior to entry into the trial is
required. However, patients receiving stable corticosteroids will be eligible.

6. Age greater than 18 years

7. Karnofsky performance greater than 70%

8. Patients must have a life expectancy of greater than 3 months.

9. Patients must be able to understand and sign an Informed Consent form.

10. All female patients must use adequate contraception during participation in this
trial and for three months after completing therapy.


1. Patients with uncontrolled hypertension

2. Pregnant and nursing patients are not eligible for the study as CSA crosses the
placenta. Based on clinical use, premature births and low birth weight were
consistently observed. Breast-feeding is contraindicated because CSA enters the blood
milk and may possibly be administered to the child.

3. Underlying immunodeficiency state including human immunodeficiency virus (HIV)

4. Positive for antibodies to hepatitis C or positive for hepatitis B surface antigen,

5. Patients with serious intercurrent illnesses, concurrent hepatic, renal, cardiac,
neurologic, pulmonary, infectious or metabolic disease of such severity that it would
preclude the patients' ability to tolerate cyclosporine.

6. Patients who received cyclosporine for LGL leukemia previously and failed to respond.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Changes in Gene Expression Patterns

Outcome Description:

Differences (2 fold) in mean gene expression between pre-treatment and post treatment.

Outcome Time Frame:

Baseline and 12 weeks

Safety Issue:


Principal Investigator

Thomas Waldmann, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health


United States: Federal Government

Study ID:




Start Date:

June 2006

Completion Date:

November 2010

Related Keywords:

  • Large Granular Lymphocytic Leukemia
  • LGL Leukemia
  • Large Granular Lymphocyte (LGL)
  • LGL
  • Leukemia
  • Cyclosporine
  • Microarray
  • Gene Expression
  • Cyclosporin
  • Large Granular Lymphocyte Leukemia
  • LGL Leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Leukemia, Large Granular Lymphocytic



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892