Monoclonal Antibody Therapy in Treating Patients With Leukemia

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00019227
First received: July 11, 2001
Last updated: June 19, 2013
Last verified: March 2003
  Purpose

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 Intervention Phase
Lymphoma
Radiation Toxicity
Drug: pentetic acid calcium
Radiation: yttrium Y 90 daclizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: October 1996
Study Completion Date: July 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019227

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Thomas A. Waldmann, MD NCI - Metabolism Branch;MET
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00019227     History of Changes
Obsolete Identifiers: NCT00001514
Other Study ID Numbers: CDR0000065240, NCI-96-C-0147K
Study First Received: July 11, 2001
Last Updated: June 19, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Radiation Injuries
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Wounds and Injuries
Daclizumab
Pentetic Acid
Edetic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antidotes
Protective Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Iron Chelating Agents
Anticoagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014