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 trial to study the effectiveness of monoclonal antibody therapy in treating
patients who have relapsed or refractory chronic lymphocytic leukemia or small lymphocytic
- Determine a recommended phase II dose of IDEC-152 monoclonal antibody in patients with
relapsed or recurrent chronic lymphocytic leukemia.
- Determine the safety profile of this drug in these patients.
- Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
- Determine the efficacy of this drug in these patients.
OUTLINE: This is an open-label, multicenter, dose-escalation study.
Patients receive IDEC-152 monoclonal antibody IV over at least 2 hours on days 1, 2, 8, 15,
Cohorts of 3-10 patients receive escalating doses of IDEC-152 monoclonal antibody until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which at least 2 of 3, 2 of 6, or 3 of 10 patients experience dose-limiting toxicity.
Patients are followed every 3 months for 2 years and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 15-50 patients will be accrued for this study within 6 months.
- Histologically confirmed chronic lymphocytic leukemia OR small lymphocytic lymphoma
- Stage III-IV OR
- Stage I-II, if determined to have disease progression evidenced by 1 of the
- Rapid doubling of peripheral lymphocyte count
- Progressive lymphadenopathy
- Progressive splenomegaly
- B symptoms
- Grade 2 or 3 fatigue
- CD23+ disease
- Progressive disease after at least 1 prior chemotherapy course
- 18 and over
- WHO 0-2
- At least 6 months
- Platelet count at least 50,000/mm^3
- Bilirubin no greater than 2.0 mg/dL
- AST/ALT no greater than 1.5 times upper limit of normal (ULN)
- Creatinine no greater than 1.5 times ULN
- No New York Heart Association class III or IV cardiac disease
- No myocardial infarction within the past 6 months
- No unstable arrhythmia
- No evidence of ischemia on EKG within the past 14 days
- FEV_1 at least 60% of predicted
- DLCO at least 55% of predicted
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study
- HIV negative
- No secondary malignancy requiring active treatment (except hormonal therapy)
- No serious nonmalignant disease that would preclude study participation
- No active uncontrolled bacterial, viral, or fungal infection
- No clinically active autoimmune disease
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior anticancer biologic therapy
- More than 4 weeks since prior anticancer radioimmunotherapy
- No prior exposure to IDEC-152 or anti-CD23 antibodies
- See Disease Characteristics
- More than 4 weeks since prior anticancer chemotherapy
- Concurrent hormonal therapy allowed for second malignancy
- More than 4 weeks since prior anticancer radiotherapy
- More than 4 weeks since prior major surgery (except for diagnostic surgery)
- More than 4 weeks since prior anticancer investigational therapy
- No other concurrent anticancer therapy