PHASE I STUDY OF T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA USING THE MIK-BETA 1 MONOCLONAL ANTIBODY DIRECTED TOWARD THE IL-2R BETA SUBUNIT
18 Years
N/A
Both
Leukemia
Trial Information
PHASE I STUDY OF T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA USING THE MIK-BETA 1 MONOCLONAL ANTIBODY DIRECTED TOWARD THE IL-2R BETA SUBUNIT
OBJECTIVES:
- Evaluate the toxicity of murine monoclonal antibody Mik-beta-1 (MOAB Mik-beta-1) in
patients with T-cell large granular lymphocytic leukemia associated with
granulocytopenia, anemia, or thrombocytopenia.
- Determine the clinical response in patients treated with this drug.
- Assess the effect of this drug on the number of circulating CD3+, CD8+ expressing
granular lymphocytes and the number of polymorphonuclear leukocytes, red blood cells,
and platelets in this patient population.
- Monitor patients for the time course of decline in circulating infused MOAB Mik-beta-1
and for the production of human antibodies to IV infused murine MOAB Mik-beta-1.
OUTLINE: This is a dose-escalation study.
Patients receive monoclonal antibody Mik-beta-1 (MOAB Mik-beta-1) IV over 2 hours on days 1,
4, 7, and 10. Patients achieving a complete response (CR) or partial response (PR) may
receive 1 additional course beginning no sooner than 4 weeks after completion of the first
course, in the absence of antibodies to MOAB Mik-beta-1. Treatment continues in the absence
of disease progression, unacceptable toxicity, or severe allergic reaction.
Cohorts of 3-6 patients receive escalating doses of MOAB Mik-beta-1 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 toxicity.
Patients are followed at 6-10 days and at 4-6 weeks after therapy. Patients with a PR or CR
may be followed every 6 months for 2 years or until relapse. All patients are followed for
survival.
PROJECTED ACCRUAL: A maximum of 25 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed T-cell large granular lymphocytic (T-LGL) leukemia
associated with clinically significant hematocytopenia demonstrated by one of the
following values while off growth factor support:
- Absolute neutrophil count less than 1,000/mm^3
- Hemoglobin less than 8 g/dL
- Platelet count less than 50,000/mm^3
- Clinically evaluable disease with peripheral blood T-LGL leukemia cells expressing
the CD3+, CD8+ phenotype detectable by FACS
- Monoclonal T-cell population in peripheral blood (circulating mononuclear cells)
demonstrated by TCR beta or gamma chain gene rearrangement
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 50-100%
Life expectancy:
- More than 2 months
Hematopoietic:
- See Disease Characteristics
- No active major bleeding episode within the past 4 weeks
Hepatic:
- Direct bilirubin less than 1.5 mg/dL
Renal:
- Creatinine less than 2.0 mg/dL
Other:
- No concurrent serious active infection
- Patients with fever without apparent site of infection may begin study while on
antibiotics as long as the following are true:
- No pathogenic organism in culture
- Afebrile (maximum temperature less than 38°C) for at least 5 days
- HIV negative
- No other primary cancer other than basal cell skin cancer
- Not pregnant or nursing
- Negative pregnancy test
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 4 weeks since prior interferon
- Concurrent filgrastim (G-CSF), sargramostim (GM-CSF), interleukin-11, or similar
sustained-release/long-acting product (e.g., pegylated G-CSF) allowed if dose
established at least 4 weeks prior to study participation
- No concurrent interferon
Chemotherapy:
- At least 4 weeks since prior chemotherapy
- No concurrent chemotherapy
Endocrine therapy:
- Concurrent corticosteroids allowed if dose established at least 3 weeks prior to
study participation
Radiotherapy:
- Not specified
Surgery:
- Not specified
Other:
- At least 1 week since completion of prior antibiotic regimen for serious infectious
episode
- No other concurrent investigational drugs
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Thomas A. Waldmann, MD
Investigator Role:
Study Chair
Investigator Affiliation:
NCI - Metabolism Branch;MET
Authority:
United States: Federal Government
Study ID:
CDR0000064038
NCT ID:
NCT00019032
Start Date:
March 1996
Completion Date:
Related Keywords:
- Leukemia
- refractory chronic lymphocytic leukemia
- T-cell large granular lymphocyte leukemia
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Leukemia, Large Granular Lymphocytic
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
