Protocol Number: 06-C-0177

Title:

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

Number:

06-C-0177

Summary:

Background:

-Large granular lymphocyte (LGL) leukemia is a low-grade non-Hodgkin's lymphoma.

-LGL is associated with low numbers of white blood cells (leading to recurring infections), red blood cells (causing anemia) and platelets (causing abnormal bleeding).

-Cyclosporine (CSA) is an immunosuppressive drug that improves low blood cell counts in about 50 percent of patients with LGL leukemia.

Objectives:

-To identify what factors determine why cyclosporine works in some patients and not in others.

-To identify what causes low blood counts in LGL leukemia.

Eligibility: Patients 18 years of age and older with LGL leukemia.

Design:

-Patients have a medical history, physical examination blood tests, bone marrow biopsy and x-ray studies, including chest x-rays and CT scans of the chest, abdomen and pelvis. Patients with an easily accessible enlarged lymph node have a node biopsy (removal of a small piece of tissue for microscopic examination).

-Patients take cyclosporine twice a day by mouth. Blood samples are taken at least weekly to monitor drug levels.

-Patients undergo apheresis (collection of white blood cells) at a number of different time points in the study (maximum 6 times) to look at the differences in the leukemia cells before and during treatment with cyclosporine. For apheresis, blood is withdrawn through a needle in an arm vein and directed through a catheter (plastic tube) into a machine that separates it into its components. The white cells are extracted and the rest of the blood is returned through the same needle or through a second needle in the other arm.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

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.

EXCLUSION CRITERIA:

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 HIV seropositivity.

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 cyclopsorine.

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

Special Instructions:

Currently Not Provided

Keywords:

Large Granular Lymphocyte (LGL)

LGL

Leukemia

Cyclosporine

Microarray

Gene Expression

Cyclosporin

Recruitment Keyword(s):

Large Granular Lymphocyte Leukemia

LGL Leukemia

Leukemia

Condition(s):

Large Granular Lymphocytic Leukemia

LGL leukemia

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Cyclosporine

Procedure/Surgery: Apheresis

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Lamy T, Loughran TP Jr. Clinical features of large granular lymphocyte leukemia. Semin Hematol. 2003 Jul;40(3):185-95. Review.

Vie H, Chevalier S, Garand R, Moisan JP, Praloran V, Devilder MC, Moreau JF, Soulillou JP. Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder. Blood. 1989 Jul;74(1):285-90

Lamy T, Dauriac C, Le Prise PY. Long-term survival in chronic granulocytic leukaemia. Br J Haematol. 1989 Mar;71(3):337-42. Br J Haematol. 1989 Oct;73(2):279.

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