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Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Cyclosporine

Primary Purpose

Anemia, Leukemia, T-Cell, Lymphocytosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cyclosporine
Sponsored by
National Heart, Lung, and Blood Institute (NHLBI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia focused on measuring Anemia, Chronic T Cell Lymphocytosis with Neutropenia, Immunosuppression, Neutropenia, T-LGL Leukemia

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Patients must be greater than or equal to 18 years of age. Peripheral blood absolute LGL count of greater than or equal to 300/ul (performed on a manual differential), with LGL cells having the characteristic appearance of large lymphocytes with abundant pale blue cytoplasm, with or without a perinuclear clear zone, with varying degrees of azurophilic granules. Immunophenotypic studies of peripheral blood showing an increased population of T-LGL (Staining for: CD3, CD8, and either CD16 or CD57+/- CD56). Severe neutropenia (less than or equal to 500 neutrophils/uL of peripheral blood), or severe thrombocytopenia (less than or equal to 20,000 platelets/uL, or moderate thrombocytopenia (less than or equal to 50,000 platelets/uL with active bleeding , or anemia (hemoglobin less than or equal to 9 gm/dL), or red blood cell transfusion requirement of greater than or equal to 2 units/month for two months prior to initiation of CsA treatment. Patients must not have had previous treatment with CsA or FK506. Patients must not have a reactive LGL lymphocytosis to a viral infection. Patients must not have a ECOG performance status of greater than 3. Patients must not be currently pregnant, or unwilling to take oral contraceptives unless postmenopausal. Mothers must not be breast feeding. Patients must be able to give informed consent. Patients must not be HIV positive.

Sites / Locations

  • National Heart, Lung and Blood Institute (NHLBI)

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
July 14, 2006
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00001533
Brief Title
Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Cyclosporine
Official Title
Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Cyclosporine
Study Type
Interventional

2. Study Status

Record Verification Date
October 1999
Overall Recruitment Status
Completed
Study Start Date
September 1996 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
September 2000 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

5. Study Description

Brief Summary
T Cell Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders are a heterogeneous group of uncommon diseases which may involve a polyclonal or a monoclonal T cell population, which bear characteristic surface markers corresponding to activated cytotoxic (CD3+, CD8+) lymphocytes. They are often associated with quite severe neutropenia, anemia, and thrombocytopenia which may be life-threatening. There is some evidence that the abnormal cytotoxic lymphocyte population may cause the cytopenias by suppressing hematopoiesis, although the mechanism is unclear. Case reports suggest that immunosuppressive therapy directed toward T cells may reverse the cytopenia. This pilot study involving up to 25 patients evaluates the clinical response to cyclosporine, an immunosuppressive drug, and seeks to elucidate the mechanism underlying the cytopenia.
Detailed Description
T Cell Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders are a heterogeneous group of uncommon diseases which may involve a polyclonal or a monoclonal T cell population, which bear characteristic surface markers corresponding to activated cytotoxic (CD3+, CD8+) lymphocytes. They are often associated with quite severe neutropenia, anemia, and thrombocytopenia which may be life-threatening. There is some evidence that the abnormal cytotoxic lymphocyte population may cause the cytopenias by suppressing hematopoiesis, although the mechanism is unclear. Case reports suggest that immunosuppressive therapy directed toward T cells may reverse the cytopenia. This pilot study involving up to 25 patients evaluates the clinical response to cyclosporine, an immunosuppressive drug, and seeks to elucidate the mechanism underlying the cytopenia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Leukemia, T-Cell, Lymphocytosis, Neutropenia, Thrombocytopenia
Keywords
Anemia, Chronic T Cell Lymphocytosis with Neutropenia, Immunosuppression, Neutropenia, T-LGL Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
25 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
cyclosporine

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Patients must be greater than or equal to 18 years of age. Peripheral blood absolute LGL count of greater than or equal to 300/ul (performed on a manual differential), with LGL cells having the characteristic appearance of large lymphocytes with abundant pale blue cytoplasm, with or without a perinuclear clear zone, with varying degrees of azurophilic granules. Immunophenotypic studies of peripheral blood showing an increased population of T-LGL (Staining for: CD3, CD8, and either CD16 or CD57+/- CD56). Severe neutropenia (less than or equal to 500 neutrophils/uL of peripheral blood), or severe thrombocytopenia (less than or equal to 20,000 platelets/uL, or moderate thrombocytopenia (less than or equal to 50,000 platelets/uL with active bleeding , or anemia (hemoglobin less than or equal to 9 gm/dL), or red blood cell transfusion requirement of greater than or equal to 2 units/month for two months prior to initiation of CsA treatment. Patients must not have had previous treatment with CsA or FK506. Patients must not have a reactive LGL lymphocytosis to a viral infection. Patients must not have a ECOG performance status of greater than 3. Patients must not be currently pregnant, or unwilling to take oral contraceptives unless postmenopausal. Mothers must not be breast feeding. Patients must be able to give informed consent. Patients must not be HIV positive.
Facility Information:
Facility Name
National Heart, Lung and Blood Institute (NHLBI)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8324214
Citation
Loughran TP Jr. Clonal diseases of large granular lymphocytes. Blood. 1993 Jul 1;82(1):1-14.
Results Reference
background
PubMed Identifier
7920220
Citation
Witzig TE, Weitz JJ, Lundberg JH, Tefferi A. Treatment of refractory T-cell chronic lymphocytic leukemia with purine nucleoside analogues. Leuk Lymphoma. 1994 Jun;14(1-2):137-9. doi: 10.3109/10428199409049659.
Results Reference
background
PubMed Identifier
8562948
Citation
Gabor EP, Mishalani S, Lee S. Rapid response to cyclosporine therapy and sustained remission in large granular lymphocyte leukemia. Blood. 1996 Feb 1;87(3):1199-200. No abstract available.
Results Reference
background

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Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Cyclosporine

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