LGL Leukemia Clinical Trial
Official title:
Microarray Analysis of the Effect of Cyclosporine Therapy on Gene Expression Patterns in Large Granular Lymphocytic Leukemia
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 computed tomography (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 adjust the cyclosporine dosing to maintain therapeutic serum 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 For apheresis, blood is withdrawn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.
| Status | Terminated |
| Enrollment | 5 |
| Est. completion date | November 2010 |
| Est. primary completion date | November 2010 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
- 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 human immunodeficiency virus (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 cyclosporine. 6. Patients who received cyclosporine for LGL leukemia previously and failed to respond. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute (NCI) |
United States,
Lamy T, Dauriac C, Le Prise PY. Long-term survival in chronic granulocytic leukaemia. Br J Haematol. 1989 Oct;73(2):279. — View Citation
Lamy T, Loughran TP Jr. Clinical features of large granular lymphocyte leukemia. Semin Hematol. 2003 Jul;40(3):185-95. Review. — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Changes in Gene Expression Patterns | The goal was to examine which genes had a 2-fold gene expression between pre-treatment (baseline) and post treatment (12 weeks). Genes significant at the 0.001 level will be considered as differentially expressed due to treatment. | Baseline and 12 weeks | No |
| Secondary | Number of Participants With Adverse Events | Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module. | 3 months | Yes |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03239392 -
A Dose-Ranging Study of IV BNZ-1 in LGL Leukemia or Refractory CTCL
|
Phase 1/Phase 2 |