Bethesda, Maryland 20892

  • Thrombocytopenia

Purpose:

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.


Study 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.


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.


Study is Available At:


Original ID:

960142


NCT ID:

NCT00001533


Secondary ID:

96-H-0142


Study Acronym:


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


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

Both


Minimum Age:

N/A


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institutes of Health Clinical Center (CC)


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety Study, Primary Pu


Number of Arms:

0


Number of Groups:

0


Total Enrollment:

25


Enrollment Type:


Study Dates

Start Date:September 1996
Completion Date:September 2000
Verification Date:October 1999
Last Changed Date:July 14, 2006
First Received Date:November 3, 1999

Study Outcomes

There are no available Study Outcomes

Study Interventions

Intervention Type:Drug
Name:cyclosporine

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Heart, Lung, and Blood Institute (NHLBI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Loughran TP Jr. Clonal diseases of large granular lymphocytes. Blood. 1993 Jul 1;82(1):1-14. Review.
PMID:8324214
Reference Type:Reference
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.
PMID:7920220
Reference Type:Reference
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.
PMID:8562948

Data Source: ClinicalTrials.gov

Date Processed: July 29, 2021

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