Monoclonal Antibody Therapy in Treating Patients With Leukemia

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00019227
• Other study ID #: CDR0000065240
• Secondary ID: NCI-96-C-0147K
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 11, 2001
• Last updated: June 19, 2013
• Start date: October 1996
• Est. completion date: July 2006

Study information

• Verified date: March 2003
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00001514

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoma
• Radiation Injuries
• Radiation Toxicity

Intervention

Drug:
• pentetic acid calcium

Radiation:
• yttrium Y 90 daclizumab

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,