Clinical Trial: Anti-Tac for Treatment of Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Study of the Efficacy and Toxicity of Humanized Anti-Tac (Zenapax(Trademark)) in the Therapy of Tac-Expressing Adult T-Cell Leukemia

Brief Summary: The purpose of the study was to determine: (1) the toxicity and maximum tolerated dose (MTD) of humanized anti-Tac (daclizumab), (Zenapax(Registered Trademark)) in patients with adult T-cell leukemia/lymphoma (ATL); (2) to define the dose of Zenapax(Registered Trademark) required to saturate interleukin 2 receptor alpha (IL-2R) alpha in patients with ATL; (3) determine the clinical response to humanized (Hu) anti-Tac (Zenapax(Registered Trademark) of patients with Tac-expressing adult T-cell leukemia; and (4) determine the serum dieaway curve (pharmacokinetics) of infused humanized (Hu)-anti-Tac in patients who have ATL. This study represented an extension of Metabolism Branch National Cancer Institute (NCI) protocols utilizing modifications of the original murine anti-Tac monoclonal antibody (mAb) developed by our group for the treatment of ATL. The scientific basis for these therapeutic studies is that the leukemic cells of patients with ATL express abnormally high levels of the Tac antigen (IL-2R alpha) on their surface whereas resting normal cells including normal T-cells of the patients do not. One presumed mode of action of Hu-anti-Tac in the treatment of ATL involves the interruption of the interaction of interleukin 2 (IL-2) with its growth factor receptor. To be effective in this goal we must maintain saturation of the IL-2 receptors (IL-2R) with humanized anti-Tac thereby preventing IL-2 mediated proliferation and yielding cytokine deprivation and apoptotic cell death of the leukemic cells. Eligible patients with ATL were treated with escalating doses of Zenapax(Registered Trademark) between groups in the Clinical Center of the National Institutes of Health (NIH). Groups of patients received sufficient Zenapax(Registered Trademark) to yield saturation of the IL-2 receptor for a period of 17 weeks. Clinical response was evaluated using routine immunological and clinical evaluation and by monitoring the saturation of the IL-2R and the absolute number of resi

Detailed Summary:

Background:

Human T-lymphotropic virus type 1 (HTLV-1)-associated adult T cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disorder.

Chemotherapy has had limited impact on survival.

The interleukin 2 receptor alpha (IL-2R alpha) (CD25) is over expressed on ATL cells and the smoldering and chronic stages of ATL are often interleukin 2 (IL-2) dependent.

The monoclonal antibody daclizumab (Zenapax) inhibits interleukin 2 (IL-2) binding to its receptor.

It is hypothesized that daclizumab may inhibit ATL growth.

Objectives:

To determine the toxicity and maximum tolerated dose (MTD) of humanized anti-Tac (daclizumab, Zenapax) in patients with ATL.

To define the dose of Zenapax required to saturate IL-2R alpha in patients with ATL.

To determine the clinical response to humanized (Hu) anti-Tac (Zenapax) of patients with Tac-expressing smoldering and chronic stage adult T cell leukemia.

To determine the serum dieaway curve (pharmacokinetics) of infused humanized (Hu) - anti - Tac in patients who have ATL.

Eligibility:

Smoldering and chronic stage HTLV-1-associated adult T cell leukemia.

At least 5 percent of malignant cells in the peripheral blood or lymph nodes must react with the anti-Tac (CD25) antibody.

Age greater than or
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Duration of Response [ Time Frame: 21-220 weeks ]
    Duration of response was defined as the interval from the time response is first achieved to the time progression from the best response is detected. Responses are assessed by a modified World Health Organization (WHO) criteria. Partial response is a reduction of >=50% saturation in the circulating leukemic cell count; complete response is disappearance of all measurable and non-measurable disease lasting more than 1 month; stable disease is patients who did not meet the criteria; and progressive disease is a >=25% increase in leukemic cell count.
  • Overall Survival [ Time Frame: 132.6 weeks ]
    Measured from the time the patient is consented until death.
  • Percentage of Participants With an Overall Response Rate [ Time Frame: up to 220 weeks ]
    Participants overall response rate was defined as complete response (CR) + partial response (PR) from study consent until progression was measured. Responses was assessed by a modified World Health Organization (WHO) criteria. Partial response is a reduction of >=50% saturation in the circulating leukemic cell count; complete response is disappearance of all measurable and non-measurable disease lasting more than 1 month; and progressive disease is a >=25% increase in leukemic cell count
  • Number of Participants With Adverse Events [ Time Frame: 12 months ]
    Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.


Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: January 18, 2000
Date Started: December 1999
Date Completion:
Last Updated: August 13, 2012
Last Verified: August 2012