Protocol Number: 06-H-0190

Title:

Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders with Alemtuzumab (Campath)

Number:

06-H-0190

Summary:

This study will examine the use of alemtuzumab (Campath® (Registered Trademark)) in patients with T cell large granular lymphocytic leukemia (T-LGL). Patients with T-LGL often have reduced white blood cells, red blood cells and platelets, and increased numbers of abnormal cells called large granular lymphocytes (LGLs). Patients may have recurrent infections, anemia, or abnormal bleeding. Campath® (Registered Trademark) destroys specific parts of the abnormal LGLs, which interfere with the production of normal blood cells. This study will determine whether Campath® (Registered Trademark) can increase blood counts and reduce the number of abnormal LGLs in patients and will examine the side effects of the drug.

Patients 18 to 85 years of age with T-LGL leukemia may be eligible for this study. Participants undergo the following procedures:

Before starting Campath® (Registered Trademark) treatment

-Medical history and physical examination, blood tests, electrocardiogram (ECG).

-Echocardiogram (heart ultrasound) and 24-hour Holter monitoring (continuous ECG recording).

-Bone marrow biopsy: About a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone. The procedure is done using local anesthetic.

-Placement of central line, if needed: An intravenous line (tube) is placed into a major vein in the chest. It can stay in the body and be used for the entire treatment period. The line is used to give chemotherapy or other medications, including antibiotics and blood transfusions, and to collect blood samples. The line is usually placed under local anesthesia in the radiology department or the operating room.

-Apheresis: A catheter (plastic tube) is placed in a vein in each arm. Blood is drawn from one vein and run through a cell-separating machine, where the white blood cells are collected and saved. The remaining blood is transfused back to the patients through the vein in the other arm.

During Campath® (Registered Trademark) treatment

-Campath® (Registered Trademark) therapy: After a small test dose, patients receive10 daily infusions of Campath® (Registered Trademark), each of which lasts about 2 hours. The first few infusions are given at the NIH Clinical Center so that the patient can be monitored closely.

-Induction therapy: Aerosolized pentamadine, valacyclovir and other medicines are given to protect against or treat various infections that commonly affect patients with suppressed immune systems.

-Whole blood or platelet transfusions, if needed, and injections of growth factors, if needed.

-Blood tests and check of vital signs (temperature, pulse, blood pressure) every day during treatment. Echocardiogram and 24-hour Holter monitor after the last dose of Campath® (Registered Trademark).

Follow-up evaluations after Campath® (Registered Trademark) treatment ends

-Blood tests at home or at NIH (weekly for the first 3 months, then every other week until 6 months, then annually for 5 years

-Echocardiogram at NIH (at 3 months only)

-Bone marrow biopsy at NIH (at 6 and 12 months, then as clinically indicated)

-One repeat apheresis collection for laboratory studies.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Clinical history supportive of the diagnosis of T-LGL leukemia (i.e. a history of cytopenias with peripheral blood morphologic evidence of LGLs)

Immunophenotypic studies of peripheral blood showing an increased population of T-LGLs (suggested by staining with CD3+, CD8+ and CD16+ or CD57+) or gammadelta T cells.

Restricted or clonal rearrangement of the T-cell receptor by PCR AND one or more of the following:

Severe neutropenia (less than 500 neutrophils/microliter); OR

Severe thrombocytopenia (less than 20,000 platelets/microliter), or moderate thrombocytopenia (less than 50,000 platelets/microliter) with active bleeding; OR

Symptomatic anemia with a hemoglobin less than 9 g/dL or red blood cell transfusion requirement of greater than 2 units/month for two months prior to initiation of Campath

Ages 18-85

EXCLUSION CRITERIA:

A reactive LGL lymphocytosis to a viral infection

Serologic evidence of HIV infection

Infection not adequately responding to appropriate therapy

Previous immunosuppressive therapy with alemtuzumab

History of carcinoma that is not considered cured (excluding non-melanoma skin carcinoma)

Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the subject's ability to tolerate protocol therapy or that death within 7-10 days is likely.

Current pregnancy, or unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential

Not able to understand the investigational nature of the study or give informed consent.

Special Instructions:

Currently Not Provided

Keywords:

Neutropenia

Monoclonal Antibody Therapy

Anti-CD52

T-LGL Leukemia

LGL Leukemia

Anemia

Immunosuppression

Chronic T Cell Lymphocytosis with Neutropenia

Recruitment Keyword(s):

LGL Leukemia

T-LGL Leukemia

Leukemia

Condition(s):

Lymphoprofilerative Disorders

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Alemtuzumab (Campath)

Supporting Site:

National Heart, Lung and Blood Institute

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

McKenna RW, Parkin J, Kersey JH, Gajl-Peczalska KJ, Peterson L, Brunning RD. Chronic lymphoproliferative disorder with unusual clinical, morphologic, ultrastructural and membrane surface marker characteristics. Am J Med. 1977 Apr;62(4):588-96.

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

Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP Jr. The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood. 1997 Jan 1;89(1):256-60.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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