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

Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001533
• Other study ID #: 960142
• Secondary ID: 96-H-0142
• Status: Completed
• Phase: Phase 1
• First received: November 3, 1999
• Last updated: July 14, 2006
• Start date: September 1996
• Est. completion date: September 2000

Study information

• Verified date: October 1999
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: September 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Leukemia, T-Cell
• Lymphocytosis
• Lymphoproliferative Disorders
• Neutropenia
• Thrombocytopenia
• Thrombocytosis

Intervention

Drug:
• cyclosporine

Locations

Country	Name	City	State
United States	National Heart, Lung and Blood Institute (NHLBI)	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

Loughran TP Jr. Clonal diseases of large granular lymphocytes. Blood. 1993 Jul 1;82(1):1-14. Review. — View 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. — View Citation