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Clinical Trials (PDQ®)

Phase I Study of Humanized Monoclonal Antibody MiK-beta-1 in Patients With T-Cell Large Granular Lymphocyte Leukemia

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Monoclonal Antibody Therapy in Treating Patients With T-Cell Large Granular Lymphocyte Leukemia

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase ITreatmentClosedOver 18NCINCI-04-C-0089
NCT00079196

Special Category: NCI Web site featured trial

Objectives

Primary

  1. Determine the adverse effects, dose-limiting toxicity, and maximum tolerated dose of humanized monoclonal antibody MiK-beta-1 in patients with T-cell large granular lymphocyte leukemia.
  2. Determine the dose of this drug that is required to saturate and maintain saturation of the IL-2R/IL-15Rβ receptor antibody binding sites in these patients.
  3. Determine the IL-2/IL-15Rβ saturation/desaturation kinetics on circulating T-cell large granular lymphocytes after a single dose of this drug in these patients.
  4. Determine the tolerability of this drug in these patients.

Secondary

  1. Determine the pharmacokinetics of this drug in these patients.
  2. Determine the immunogenicity of this drug in these patients.
  3. Determine, preliminarily, the antileukemic activity of this drug, in terms of response rate, time to progression, and overall survival, in these patients.
  4. Determine the effect of this drug on the number of polymorphonuclear leukocytes, red blood cells, and platelets in these patients.

Entry Criteria

Disease Characteristics:

  • Histologically or cytologically confirmed T-cell large granular lymphocyte leukemia (T-LGL) as defined by the following:
    • Peripheral blood smear or bone marrow biopsy/aspirate with morphological findings consistent with LGL
    • Absolute CD3+, CD8+, and usually CD57+ cell (T-LGL) count ≥ 1,000/mm3 in the peripheral blood or bone marrow by flow cytometry
    • At least 50% of the CD3+/CD8+ cells must also express CD122

  • T-LGL-associated hemocytopenia, defined by at least 1 of the following:
    • Absolute granulocyte count < 1,000/mm3
    • Platelet count < 100,000/mm3
    • Hemoglobin < 9.0 g/dL
    • Received at least 3 red blood cell product transfusions within the past 6 months

  • No symptomatic CNS involvement by leukemia

Prior/Concurrent Therapy:

Biologic therapy

  • Prior humanized monoclonal antibody MiK-beta-1 allowed provided patient has not developed human anti-mouse or human anti-human antibodies
  • Prior epoetin alfa, interleukin-11 (IL-11), filgrastim (G-CSF), or sargramostim (GM-CSF)
  • At least 4 weeks since prior interferon
  • Concurrent epoetin alfa, G-CSF, GM-CSF, or IL-11 allowed provided dose has been stable for more than 4 weeks before study entry
  • No other concurrent monoclonal antibody therapy
  • No concurrent interferon

Chemotherapy

  • At least 4 weeks since prior chemotherapy
  • No concurrent chemotherapy

Endocrine therapy

  • Prior corticosteroids allowed
  • Concurrent steroids allowed provided dose has been stable (< 25 mg/day of prednisone or equivalent) for at least 3 weeks before study entry

Radiotherapy

  • Not specified

Surgery

  • Prior splenectomy allowed

Other

  • At least 4 weeks since prior cyclosporine
  • No concurrent immunosuppression for an organ graft
  • No other concurrent investigational agents

Patient Characteristics:

Age

  • Over 18

Performance status

  • Karnofsky 70-100%

Life expectancy

  • More than 2 months

Hematopoietic

  • See Disease Characteristics
  • Platelet count ≥ 10,000/mm3 (no transfusion)

Hepatic

  • Bilirubin < 2.0 mg/dL
  • SGOT and SGPT ≤ 2.5 times upper limit of normal
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative

Renal

  • Creatinine < 1.5 mg/dL

Cardiovascular

  • No acute myocardial infarction within the past 6 months
  • No unstable angina
  • No New York Heart Association class III or IV congestive heart failure
  • No uncontrolled hypertension
  • No symptomatic cerebrovascular disease
  • No stroke within the past 6 months

Pulmonary

  • No respiratory insufficiency requiring oxygen therapy

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • HIV negative
  • Human T cell lymphotrophic virus I/II negative
  • No prior grade III or greater toxicity or allergic reaction attributed to humanized monoclonal antibodies or study drug
  • No other serious medical condition that would preclude study participation
  • No other malignancy within the past 5 years requiring treatment except basal cell skin cancer, curatively treated carcinoma in situ of the cervix, or any other prior malignancy with a ≤ 10% probability of recurrence
  • No serious active infection requiring systemic anti-infective therapy
  • No other physical or psychological condition that would preclude study participation

Expected Enrollment

18

A total of 3-18 patients will be accrued for this study within 2.5-3 years.

Outcomes

Primary Outcome(s)

Response rate at 9 months

Outline

This is an open-label, dose-escalation study.

Patients receive a single dose of humanized monoclonal antibody MiK-beta-1 IV over 90 minutes on day 1.

Cohorts of 3-6 patients receive escalating doses of humanized monoclonal antibody MiK-beta-1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 2, 3, 4, and 6 weeks and then every 3 months for 9 months.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Thomas Waldmann, MD, Protocol chair
Ph: 301-496-6656
Email: tawald@helix.nih.gov
John Morris, MD, Principal investigator
Ph: 301-402-2912
Email: jmorris@mail.nih.gov

Related Information

Featured trial article
Web site for additional information

Registry Information
Official Title Phase I Open-Lable Single-Dose Study of Humanized MIK-BETA-1 Monoclonal Antibody Directed Toward the IL-2R/IL-15R Beta Subunit (CD122) in T Cell Large Granular Lymphocytic Leukemia
Trial Start Date 2004-12-28
Trial Completion Date 2009-07-01 (estimated)
Registered in ClinicalTrials.gov NCT00079196
Date Submitted to PDQ 2004-01-28
Information Last Verified 2009-07-05

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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