Monoclonal Antibody Therapy in Treating Patients With Leukemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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PHASE I/II STUDY OF TAC-EXPRESSING ADULT T-CELL LEUKEMIA (ATL) WITH YTTRIUM-90 (90Y)-RADIOLABELED HUMANIZED ANTI-TAC AND CALCIUM-DTPA

Conditions
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Lymphoma, Radiation Toxicity

Intervention / Treatment
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* Drug: pentetic acid calcium
* Radiation: yttrium Y 90 daclizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: pentetic acid calcium|nan|
|Radiation: yttrium Y 90 daclizumab|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, radiation toxicity