RATIONALE: BL22 immunotoxin can find tumor cells and kill them without harming normal cells.
PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin
in treating patients with refractory B-cell chronic lymphocytic leukemia, prolymphocytic
leukemia, or non-Hodgkin's lymphoma.
- Determine the maximum tolerated dose of recombinant BL22 immunotoxin in patients with
CD22-positive refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia,
or indolent non-Hodgkin's lymphoma.
- Determine the safety and efficacy of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the immunogenicity of this drug in these patients.
- Determine the effect of this drug on various components of the circulating cellular
immune system in these patients.
OUTLINE: This is a nonrandomized, dose-escalation study. Patients are stratified according
to disease type (chronic lymphocytic leukemia vs non-Hodgkin's lymphoma).
Patients receive recombinant BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5.
Treatment repeats ≥ every 27 days for up to 6 courses in the absence of neutralizing
antibodies to BL22 or PE38, disease progression, or unacceptable toxicity. Patients
achieving a complete response (CR) receive 2 additional courses beyond CR. Patients who
relapse from a CR lasting ≥ 6 months may receive additional courses.
Cohorts of 3-6 patients per stratum receive escalating doses of recombinant BL22 immunotoxin
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.
PROJECTED ACCRUAL: A total of 24 patients (12 per stratum) will be accrued for this study
within 1-2 years.
- Diagnosis of B-cell leukemia or lymphoma of 1 of the following types:
- Chronic lymphocytic leukemia
- Failed standard chemotherapy
- Prolymphocytic leukemia
- Failed standard chemotherapy
- Indolent non-Hodgkin's lymphoma, including mantle cell lymphoma
- Stage III or IV disease
- Failed ≥ 1 prior doxorubicin- or fludarabine-containing standard therapy
- CD22-positive disease, as evidenced by 1 of the following:
- More than 15% malignant cells react with anti-CD22 by immunohistochemistry
- More than 30% malignant cells are CD22-positive by fluorescence-activated cell
- More than 400 CD22 sites per malignant cell (average) by radiolabeled anti-CD22
- Treatment is medically indicated, as evidenced by any of the following:
- Progressive disease-related symptoms
- Progressive cytopenias due to marrow involvement
- Progressive or painful splenomegaly or adenopathy
- Rapidly increasing lymphocytosis
- Autoimmune hemolytic anemia or thrombocytopenia
- Increased frequency of infections
- No neutralizing anti-toxin or anti-mouse immunoglobulin G (IgG) antibodies to BL22 or
- No serum neutralization of > 75% of the activity of 1 μg/mL of BL22
- No CNS disease requiring treatment
- No hairy cell leukemia
- 18 and over
- ECOG 0-2
- More than 6 months
- Absolute neutrophil count > 1,000/mm^3*
- Platelet count > 40,000/mm^3 NOTE: *Patients with leukemia are eligible regardless of
absolute neutrophil count; Grade III-IV pancytopenia or growth factor dependence
allowed if due to disease
- Bilirubin < 1.5 times upper limit of normal (ULN)
- ALT and AST < 2.5 times ULN
- Creatinine ≤ 1.5 mg/dL
- FEV1 ≥ 60% of predicted
- DLCO ≥ 55% of predicted
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
PRIOR CONCURRENT THERAPY:
- Prior bone marrow transplantation allowed
- More than 3 weeks since prior biologic therapy, including interferon, denileukin
diftitox, or LMB-2 immunotoxin
- More than 3 months since prior monoclonal antibody therapy (e.g., rituximab)
- See Disease Characteristics
- More than 3 weeks since prior cytotoxic chemotherapy
- More than 1 week since prior steriods
- Less than 5 doses for non-treatment reasons (e.g., allergy prophylaxis)
- No evidence of disease response
- More than 3 weeks since prior whole-body electron beam radiotherapy
- Radiotherapy within the past 3 weeks allowed provided the volume of bone marrow
treated is < 10% AND the patient has measurable disease located outside the
- Not specified
- More than 3 weeks since prior retinoids
- More than 3 weeks since other prior systemic therapy for this malignancy