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 For apheresis, blood is withdrawn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.
Background:
- 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.
Objective:
- Identify changes in gene expression patterns induced by cyclosporine therapy in
patients with LGL leukemia
- Identify differences between responding and non-responding patients
Eligibility:
-Patients with Large Granular Lymphocyte leukemia
Design:
- 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
samples.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03239392 -
A Dose-Ranging Study of IV BNZ-1 in LGL Leukemia or Refractory CTCL
|
Phase 1/Phase 2 |