Monoclonal Antibody Therapy in Treating Patients With Leukemia

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00019227

Collaborator

(none)

Location

117

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Radiation Toxicity	Drug: pentetic acid calcium Radiation: yttrium Y 90 daclizumab	Phase 1/Phase 2

Detailed Description

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 Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 1996

Actual Study Completion Date :

Jul 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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