Alemtuzumab (Campath(Registered Trademark)) to Treat T-Large Granular Lymphocyte Leukemia - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00345345

Purpose

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Bone marrow biopsy: About a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone.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.

Condition	Intervention	Phase
Lymphoprofilerative Disorders	Drug: Alemtuzumab (Campath)	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Alemtuzumab (Campath)

Resource links provided by NLM:

MedlinePlus related topics: Anemia Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Campath Alemtuzumab

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

The primary end point of the study is the response rate at three months, defined as improvement in cytopenia(s) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Secondary endpoints will include relapse-free survival, response at 6 months, life threatening toxicity, reduction in the number of abnormal T-LGL clone, and overall survival. [ Time Frame: Months/years ] [ Designated as safety issue: No ]

Estimated Enrollment:	39
Study Start Date:	June 2006
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Intervention Details:

N/A

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. Immunosuppressive therapy has been shown to improve the cytopenias of T-LGL leukemia, however the long term use of the commonly used agents often lead to significant toxicity in the older patients which are affected by this disease.

Alemtuzumab (Campath[R]) is currently approved as second line agent in patients with chronic lymphocytic leukemia (CLL) and has been used successfully in the treatment of certain autoimmune disorders. In the Hematology Branch, Campath is currently being investigated in two bone marrow failure syndromes: aplastic anemia and myelodysplasia.

Cytopenia(s) is an important characteristic of patients with T-LGL leukemia, often being the indication for immunosuppressive therapy. Our preliminary experience with Campath indicates that it is well tolerated, in particular among the elderly patients.

Therefore, we propose this pilot, Phase II, single agent, study which will evaluate the efficacy and safety of alemtuzumab (Campath[R]), an immunosuppressive drug, in subjects with T-LGL leukemia. Commercially available alemtuzumab (Campath[R]) will be administered off label at 10 mg per day by intravenous infusion for 10 days total. Subjects who do not show a response to initial Campath or relapse may receive a second cycle of drug after the 3 month time point.

The primary end point of the study is the response rate at three months, defined as improvement in cytopenia(s).

Secondary endpoints will include relapse-free survival, response at 6 months, life threatening toxicity, reduction in the number of abnormal T-LGL clone, response to second cycle of Campath, and overall survival.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00345345

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	National Institutes of Health ( Phillip Scheinberg, M.D./National Heart, Lung, and Blood Institute )
Study ID Numbers:	060190, 06-H-0190
Study First Received:	June 27, 2006
Last Updated:	September 3, 2009
ClinicalTrials.gov Identifier:	NCT00345345 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Neutropenia
Monoclonal Antibody Therapy
Anti-CD52
T-LGL Leukemia
LGL Leukemia
Anemia

Immunosuppression
Chronic T Cell Lymphocytosis with Neutropenia
LGL Leukemia
T-LGL Leukemia
Leukemia

Study placed in the following topic categories:

Immunoproliferative Disorders
Large Granular Lymphocyte Leukemia
Anemia
Antibodies, Monoclonal
Leukemia
Neutropenia
Lymphatic Diseases

Antibodies
Lymphocytosis
Alemtuzumab
Lymphoproliferative Disorders
Leukemia, Large Granular Lymphocytic
Immunoglobulins

Additional relevant MeSH terms:

Lymphatic Diseases
Immunoproliferative Disorders
Pathologic Processes
Disease
Immune System Diseases

Antineoplastic Agents
Therapeutic Uses
Alemtuzumab
Lymphoproliferative Disorders
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2009