Monoclonal Antibody Therapy in Treating Patients With Leukemia

June 19, 2013 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 1996

Study Completion (Actual)

July 1, 2006

Study Registration Dates

First Submitted

July 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 20, 2013

Last Update Submitted That Met QC Criteria

June 19, 2013

Last Verified

March 1, 2003

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000065240
  • NCI-96-C-0147K

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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