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Large Granular Lymphocytic LeukemiaPhase 2NCT00363779

Effect of Cyclosporine Therapy on Gene Expression in Patients With Large Granular Lymphocyte Leukemia

A Phase 2 study testing Cyclosporine, Gene expression analysis and Microarray analysis in people with Large Granular Lymphocytic Leukemia and LGL Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclosporine, Gene expression analysis and Microarray analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
Jun 2006to Nov 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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.
  • Patients must have measurable or evaluable disease
  • Patients must have a creatinine of less than 2.0 mg/dl.
  • Omission of cytotoxic chemotherapy for 3 weeks prior to entry into the trial is required. However, patients receiving stable corticosteroids will be eligible.
  • Age greater than 18 years
Show all 10Show fewer
  • Karnofsky performance greater than 70%
  • Patients must have a life expectancy of greater than 3 months.
  • Patients must be able to understand and sign an Informed Consent form.
  • All female patients must use adequate contraception during participation in this trial and for three months after completing therapy.

Who cannot join

  • Patients with uncontrolled hypertension
  • 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.
  • Underlying immunodeficiency state including human immunodeficiency virus (HIV) seropositivity.
  • Positive for antibodies to hepatitis C or positive for hepatitis B surface antigen,
  • 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.
  • Patients who received cyclosporine for LGL leukemia previously and failed to respond.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.
Read more

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.
Read the detailed description

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.
Being tested
Cyclosporine, Gene expression analysis, Microarray analysis, Laboratory biomarker analysis
Keywords
Large Granular Lymphocyte (LGL), LGL, Leukemia, Cyclosporine, Microarray, Gene Expression, Cyclosporin, Large Granular Lymphocyte Leukemia, LGL Leukemia
Medical subject headings
Leukemia, Large Granular Lymphocytic, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclosporineDrug

    Also called Ciclosporin

    An oral preparation given every 12 hours, 5-10 mg/kg/day in divided doses. Doses are adjusted to maintain a therapeutic level between 200-400 ng/ml. Levels will be checked twice weekly and once the patient has achieved steady state levels they shall be monitored once every 2 weeks. These therapeutic levels shall be maintained for 3 months.

  • Gene expression analysisGenetic

    A permutation test will be performed to examine whether the overall expression profile changes due to treatment. This will be done by comparing the number of significant genes to the distribution of this number if in fact there is no difference between pre-treatment and post-treatment gene expression.

  • Microarray analysisGenetic

    Gene expression profiling will be carried out on Affymetrix microarrays to compare pretreatment and posttreatment samples.

  • Laboratory biomarker analysisOther

    Analysis of differential gene expression profiles in patients with LGL leukemia treated with cyclosporine.

Study groups in NCT00363779
Study groupRoleWhat they receive
LGL Patients administered cyclosporineExperimentalLarge Granular Lymphocyte Leukemia (LGL) is a low grade non-Hodgkins lymphoma characterized by tissue invasion of the marrow, spleen, and liver. Cyclosporine 5-10 mg/kg/day was administered as an oral preparation given every 12 hours. Doses are adjusted to maintain a therapeutic level between 200-400 ng/ml.
Receives: Drug: Cyclosporine; Genetic: Gene expression analysis; Genetic: Microarray analysis; Other: Laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and 12 weeks

Secondary outcomes (1)

  1. 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.

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2006 (estimated)
  2. Study startJun 2006
  3. Primary completionNov 2010
  4. Study completionNov 2010

Why it stopped: Study terminated due to low accrual and the investigator left the NIH.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00363779
Sponsor's protocol ID
060177
Other IDs
06-C-0177
Status last verified
Jun 2015
First submitted
10 Aug 2006
Last updated
21 Jul 2015
Data monitoring committee
No

Publications

  • Lamy T, Loughran TP Jr. Clinical features of large granular lymphocyte leukemia. Semin Hematol. 2003 Jul;40(3):185-95. doi: 10.1016/s0037-1963(03)00133-1.

    PubMed 12876667

  • 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.

    PubMed 2546620

  • Lamy T, Dauriac C, Le Prise PY. Long-term survival in chronic granulocytic leukaemia. Br J Haematol. 1989 Oct;73(2):279. doi: 10.1111/j.1365-2141.1989.tb00270.x. No abstract available.

    PubMed 2818949

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclosporine, Gene expression analysis and Microarray analysis in people with Large Granular Lymphocytic Leukemia and LGL Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in Gene Expression Patterns (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00363779, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2015.

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