Hu-Mik-beta1 to Treat T-Cell Large Granular Lymphocytic Leukemia
This study will examine the use of the humanized Mik-beta-1 (Hu-Mik-beta1) antibody 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. Hu-Mik-beta1 attaches to LGL cells and blocks the action of growth factors called interleukins that stimulate LGL growth. Blocking these interleukins may stop T-LGL leukemia cells from growing. This study will determine the dose and frequency of treatment with Hu-Mik-(SqrRoot) 1 that can safely be given to patients to coat the surface of their leukemic cells with antibody, determine how long the antibody lasts in the blood after injection, and examine the side effects and possible benefits of the drug in these patients.
Patients age 18 or older with T-LGL may be eligible for this study. Candidates will be screened with a medical history and physical examination, review of pathology studies, skin biopsy, evaluation of rheumatoid arthritis if present, chest x-ray, computerized tomography (CT) scans and other imaging studies as needed, bone marrow biopsy, and blood and urine tests.
Participants will receive a single dose of Hu-Mik-beta1 by a 90-minute infusion through a vein. Groups of patients will be treated with increasing doses (0.5, 1.0, and 1.5 mg/kg) of the antibody. Patients who develop serious drug side effects are taken off the study. The treatment requires a 3- to 4-day hospital stay. In addition to Hu-Mik-(SqrRoot) 1 treatment, patients will undergo the following tests and procedures:
- Collection of blood for 8 days following the dose of Hu-Mik-beta1 to measure blood levels of the antibody.
- Follow-up visits of 1 to 2 days at 22, 29, and 43 days after the dose of the antibody and then every 3 months for a total of 9 months.
- Bone marrow aspirate and biopsy if one has not been done within 6 weeks before entering the study, and a repeat biopsy if complete remission of T-LGL is achieved after completing treatment. For the biopsy, an area of the hip is numbed and a special needle is used to draw bone marrow from the hipbone.
- Imaging studies, such as chest x-ray and CT scan of the body after completing treatment if the screening scans showed abnormalities due to the T-LGL leukemia.
- Lymph node biopsy in individuals with enlarged superficial lymph nodes due to T-LGL leukemia to see if the treatment is reaching the leukemia in the lymph nodes.
There may or may not be a direct benefit from participating in this study. However, the results may help in the treatment of future patients.
|T-Cell Large Granular Lymphocytic Leukemia Leukemia, T-Cell Large Granular Lymphocytic||Biological: Hu-MiK-Beta-1||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase I Open-Label Single-Dose Study of Humanized Mik-Beta-1 Monoclonal Antibody Directed Toward the IL-2R/IL-15R-Beta Subunit (CD122) in T Cell Large Granular Lymphocytic Leukemia|
- DLT and MTD of Hu MIK Beta 1 [ Time Frame: 21 days ]
|Study Start Date:||January 6, 2004|
|Study Completion Date:||November 12, 2010|
|Primary Completion Date:||November 12, 2010 (Final data collection date for primary outcome measure)|
One dose of Hu-MiK Beta-1
Hu-MiK-Beta-1 administered as an intravenous infusion over 90- minutes.
- T cell large granular lymphocyte (T-LGL) leukemia is a chronic lymphoproliferative disorder associated with granulocytopenia, anemia and/or thrombocytopenia.
- Although agents such as cyclosporine and methotrexate have shown activity in T-LGL, treatment of T-LGL has remained largely undefined and symptomatic.
- The shared IL-2R/Il-15R Beta receptor (CD122) is over expressed on T-LGL cells and may stimulate growth T-LGL cells through its interaction with IL-15.
- Hu-Mik-Beta1 is a humanized monoclonal antibody that binds to IL-2R/IL-15R Beta
- Hu-Mik-Beta1 may inhibit the growth and exert cytotoxic activity against T-LGL cells.
- To determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of Hu-Mik-Beta1 when administered to patients with T-LGL.
- To determine the dose of Hu-Mik-Beta1 required to saturate IL-2R/IL-15R Beta (CD122) on -T-LGL cells in the peripheral blood.
- To determine the pharmacokinetics and serum die-away curve of Hu-Mik-Beta1.
- To provide preliminary information on the clinical response following single dose administration of Hu-MiK-Beta1 in patients with CD122 expressing T-LGL leukemia.
--T cell large granular lymphocyte leukemia (T-LGL).
Patients must have a granulocyte count of less than 1000/microL, or hemoglobin less than 10 gm/dL, or be transfusion dependent, or platelets less than 100,000/ microL, or any combination of these unless receiving a hematopoietic growth factor.
- T-LGL cell count greater than or equal to 1000/microL (CD3 plus/CD8 plus/usually CD57 plus) by flow cytometry.
- Patients may be receiving a stable dose of a hematopoietic growth factor.
- Cohorts of 3 patients each will be treated with a single intravenous dose of Hu-Mik-Beta1 at 0.5, 1.0 or 1.5 mg/kg.
- Patients will be observed for adverse events for 6-weeks.
- Detailed pharmacokinetic studies and determination of CD122 receptor saturation will be performed.
- Response will be evaluated using hematological, flow cytometry, molecular and clinical evaluations.
- An additional 3 patients will be accrued at the highest dose or MTD to aid in design of a Phase II trial.
- Patients participating in Phase I will also be eligible to participate in Phase II.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00076180
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Thomas A Waldmann, M.D.||National Cancer Institute (NCI)|