Monoclonal Antibody Therapy in Treating Patients With Leukemia

Phase 2CompletedNCT00019227

National Cancer Institute (NCI)

Overview

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I/II trial to study the effectiveness of radiolabeled monoclonal antibody plus pentetic acid calcium in patients with leukemia.

OBJECTIVES: * Determine the maximum tolerated dose of yttrium Y 90 daclizumab (90Y daclizumab) when combined with pentetic acid calcium in adults with Tac-expressing T-cell leukemia. * Determine the therapeutic efficacy and toxicity of this regimen in these patients. * Monitor patients treated on this regimen for circulating infused antibody (free and labeled) and for the serum concentration of soluble interleukin-2 receptor. * Evaluate, in a preliminary manner, the immunogenicity of daclizumab. * Determine the effect of 90Y daclizumab on various components of the circulating cellular immune system. * Determine whether there is additional urinary excretion of yttrium Y 90 when compared to that observed previously in patients treated without pentetic acid calcium. OUTLINE: This is a dose escalation study of yttrium Y 90 daclizumab (90Y daclizumab). Patients receive 90Y daclizumab IV over 2 hours on day 1 and a fixed dose of pentetic acid calcium IV over 5 hours for 3 days. Treatment repeats every 6 weeks for a maximum of 9 courses in the absence of disease progression or circulating antibodies to humanized anti-Tac. Cohorts of 3-6 patients receive escalating doses of 90Y daclizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Additional patients are treated at the MTD. Patients are followed at 4-6 weeks. PROJECTED ACCRUAL: Up to 15 patients will be accrued for the phase I portion of the study. A total of 30 patients will be accrued for the phase II portion of the study.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Conditions

Lymphoma Radiation Toxicity

Interventions

pentetic acid calciumDRUG

yttrium Y 90 daclizumabRADIATION

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Histologically confirmed adult T-cell leukemia or lymphoma (ATL) of any stage * Tac expression of malignant cells confirmed by one of the following: * At least 10% of peripheral blood, lymph node, or dermal malignant cells reactive with anti-Tac by immunofluorescent staining * Soluble interleukin-2 receptor levels greater than 1,000 U/mL (normal geometric mean = 235; 95% confidence intervals = 112-502 U/mL) * Measurable disease required * More than 10% (i.e., strongly Tac-expressing) abnormal cells in peripheral blood considered measurable disease * All stages of Tac-expressing adult T-cell leukemia are eligible * Smoldering ATL patients are eligible only if the symptoms and sites of involvement by ATL are such that there is a medical indication to treat * Smoldering ATL, defined as: * Lymphocyte count less than 4,000/mm\^3 * Less than 5% abnormal lymphocytes on morphologic exam of peripheral blood * No hypercalcemia * Lactate dehydrogenase no greater than 1.5 times normal * No lymphadenopathy * No involvement of extranodal organs except skin or lung * No malignant pleural effusion or ascites * No symptomatic CNS disease due to ATL * Concurrent diagnosis of tropical spastic paraparesis allowed * No detectable levels (i.e., greater than 250 ng/mL) of antibody to study drug as assessed by ELISA PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * Not specified Life expectancy: * Greater than 2 months Hematopoietic: * Absolute granulocyte count at least 1,000/mm\^3 * Platelet count at least 75,000/mm\^3 Hepatic: * Bilirubin less than 2.0 mg/dL (unless directly due to ATL) * AST/ALT less than 2.5 times normal Renal: * Creatinine less than 1.5 mg/dL OR * Creatinine clearance greater than 35 mL/min Cardiovascular: * No clinical cardiac failure Pulmonary: * No symptomatic pulmonary dysfunction unless due to underlying malignancy Other: * HIV negative * Not pregnant or nursing * Negative pregnancy test PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * At least 4 weeks since prior cytotoxic chemotherapy Endocrine therapy * Concurrent corticosteroids allowed Radiotherapy * Not specified Surgery * Not specified Other * Not specified

Locations (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Data from ClinicalTrials.gov

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