Expired Study
This study is not currently recruiting Study Participants on ClinicalConnection.com. If you would like to find active studies please search for clinical trials.

Bethesda, Maryland 20892


Purpose:

RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. PURPOSE: This phase I trial is studying the side effects and best dose of a monoclonal antibody in treating patients with T-cell large granular lymphocyte leukemia.


Study summary:

OBJECTIVES: Primary - Determine the adverse effects, dose-limiting toxicity, and maximum tolerated dose of humanized monoclonal antibody MiK-beta-1 in patients with T-cell large granular lymphocyte leukemia. - Determine the dose of this drug that is required to saturate and maintain saturation of the IL-2R/IL-15Rβ receptor antibody binding sites in these patients. - Determine the IL-2/IL-15Rβ saturation/desaturation kinetics on circulating T-cell large granular lymphocytes after a single dose of this drug in these patients. - Determine the tolerability of this drug in these patients. Secondary - Determine the pharmacokinetics of this drug in these patients. - Determine the immunogenicity of this drug in these patients. - Determine, preliminarily, the antileukemic activity of this drug, in terms of response rate, time to progression, and overall survival, in these patients. - Determine the effect of this drug on the number of polymorphonuclear leukocytes, red blood cells, and platelets in these patients. OUTLINE: This is an open-label, dose-escalation study. Patients receive a single dose of humanized monoclonal antibody MiK-beta-1 IV over 90 minutes on day 1. Cohorts of 3-6 patients receive escalating doses of humanized monoclonal antibody MiK-beta-1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed at 2, 3, 4, and 6 weeks and then every 3 months for 9 months. PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within 2.5-3 years.


Criteria:

DISEASE CHARACTERISTICS: - Histologically or cytologically confirmed T-cell large granular lymphocyte leukemia (T-LGL) as defined by the following: - Peripheral blood smear or bone marrow biopsy/aspirate with morphological findings consistent with LGL - Absolute CD3+, CD8+, and usually CD57+ cell (T-LGL) count ≥ 1,000/mm^3 in the peripheral blood or bone marrow by flow cytometry - At least 50% of the CD3+/CD8+ cells must also express CD122 - T-LGL-associated hemocytopenia, defined by at least 1 of the following: - Absolute granulocyte count < 1,000/mm^3 - Platelet count < 100,000/mm^3 - Hemoglobin < 9.0 g/dL - Received at least 3 red blood cell product transfusions within the past 6 months - No symptomatic CNS involvement by leukemia PATIENT CHARACTERISTICS: Age - Over 18 Performance status - Karnofsky 70-100% Life expectancy - More than 2 months Hematopoietic - See Disease Characteristics - Platelet count ≥ 10,000/mm^3 (no transfusion) Hepatic - Bilirubin < 2.0 mg/dL - SGOT and SGPT ≤ 2.5 times upper limit of normal - Hepatitis B surface antigen negative - Hepatitis C antibody negative Renal - Creatinine < 1.5 mg/dL Cardiovascular - No acute myocardial infarction within the past 6 months - No unstable angina - No New York Heart Association class III or IV congestive heart failure - No uncontrolled hypertension - No symptomatic cerebrovascular disease - No stroke within the past 6 months Pulmonary - No respiratory insufficiency requiring oxygen therapy Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after study participation - HIV negative - Human T cell lymphotrophic virus I/II negative - No prior grade III or greater toxicity or allergic reaction attributed to humanized monoclonal antibodies or study drug - No other serious medical condition that would preclude study participation - No other malignancy within the past 5 years requiring treatment except basal cell skin cancer, curatively treated carcinoma in situ of the cervix, or any other prior malignancy with a ≤ 10% probability of recurrence - No serious active infection requiring systemic anti-infective therapy - No other physical or psychological condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy - Prior humanized monoclonal antibody MiK-beta-1 allowed provided patient has not developed human anti-mouse or human anti-human antibodies - Prior epoetin alfa, interleukin-11 (IL-11), filgrastim (G-CSF), or sargramostim (GM-CSF) - At least 4 weeks since prior interferon - Concurrent epoetin alfa, G-CSF, GM-CSF, or IL-11 allowed provided dose has been stable for more than 4 weeks before study entry - No other concurrent monoclonal antibody therapy - No concurrent interferon Chemotherapy - At least 4 weeks since prior chemotherapy - No concurrent chemotherapy Endocrine therapy - Prior corticosteroids allowed - Concurrent steroids allowed provided dose has been stable (< 25 mg/day of prednisone or equivalent) for at least 3 weeks before study entry Radiotherapy - Not specified Surgery - Prior splenectomy allowed Other - At least 4 weeks since prior cyclosporine - No concurrent immunosuppression for an organ graft - No other concurrent investigational agents


NCT ID:

NCT00079196


Primary Contact:

Study Chair
Thomas A. Waldmann, MD
NCI - Metabolism Branch;MET


Backup Contact:

N/A


Location Contact:

Bethesda, Maryland 20892
United States



There is no listed contact information for this specific location.

Site Status: N/A


Data Source: ClinicalTrials.gov

Date Processed: June 25, 2018

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


Click to view Full Listing

This study is not currently recruiting Study Participants on ClinicalConnection.com. The form below is not enabled.