RATIONALE: The CAT-8015 immunotoxin can bind tumor cells and kill them without harming normal
cells. This may be effective treatment for Non-Hodgkin's lymphoma (NHL) that has not
responded to chemotherapy, surgery or radiation therapy.
PURPOSE: Phase 1 dose escalation study to determine the maximum tolerated dose of CAT-8015
immunotoxin in treating patients who have Non-Hodgkin's lymphoma and do not respond to
- Confirmed diagnosis of B-cell non-Hodgkin's lymphoma
- Measurable disease
- Evidence of CD22-positive malignancy by the following criteria,
- > 30% of malignant cells from a disease site CD22+ by FACS analysis or,
- > 15% of malignant cells from a disease site must react with anti-CD22 by
- Patients with indolent subtypes of CD22+ B-cell non-Hodgkin's lymphoma, including, but
not limited to mantle cell lymphoma, follicular lymphoma and Waldenström's
macroglobulinemia, are eligible if stage III-IV.
- Patients must have failed at least two or more courses of prior standard chemotherapy
and/or biologic therapy (e.g. Rituxan). Patients with progressive mantle cell lymphoma
may be eligible if they have failed one prior standard therapeutic regimen.
- ECOG 0-2
- Life expectancy of less than 6 months, as assessed by the principal investigator
- Patients with other cancers who meet eligibility criteria and have less than 5 years
of disease free survival will be considered on a case-by-case basis
- Must be able to understand and sign informed consent
- Female and male patients must agree to use an approved method of contraception during
- History of bone marrow transplant
- Documented and ongoing central nervous system involvement with their malignant disease
(history of CNS involvement is not an exclusion criterion)
- Pregnant or breast-feeding females
- Patients whose plasma contains either a significant level of antibody to CAT-8015 as
measured by ELISA, or antibody that neutralizes the binding of CAT-8015 to CD22 as
measured by a competition ELISA.
- HIV positive serology (due to increased risk of severe infection and unknown
interaction of CAT-8015 with antiretroviral drugs)
- Hepatitis B surface antigen positive
- Uncontrolled, symptomatic, intercurrent illness including but not limited to:
infections requiring systemic antibiotics, congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would
limit compliance with study requirements
Hepatic function: serum transaminases (either ALT or AST) or bilirubin
- ≥ Grade 2, unless bilirubin is due to Gilbert's disease
Renal function: Serum creatinine clearance ≤ 60mL/min as estimated by Cockroft-Gault
- The ANC < 1000/cmm, or platelet count <50,000/cmm, if these cytopenias are not judged
by the investigator to be due to underlying disease (i.e. potentially reversible with
- A patient will not be excluded because of pancytopenia ≥ Grade 3, or erythropoietin
dependence, if it is due to disease, based on the results of bone marrow studies
- Baseline coagulopathy > Grade 3 unless due to anticoagulant therapy.
- Patients with < 50% of predicted forced expiratory volume (FEV1) or <50% of predicted
diffusing capacity for carbon monoxide (DLCO), corrected for hemoglobin concentration
and alveolar volume. Note: Patient with no prior history of pulmonary illness are not
required to have PFTs. FEV1 will be assessed after bronchodilator therapy.
Recent prior therapy:
- Cytotoxic chemotherapy, corticosteroids (except stable doses of prednisone), whole
body electron beam radiation therapy, hormonal, biologic or other standard or any
investigational therapy of the malignancy for 3 weeks prior to entry into the trial
- Less than or equal < 3 months prior monoclonal antibody therapy (i.e. rituximab)
- Patients who are receiving or have received radiation therapy less than 3 weeks prior
to study entry will be not be excluded providing the volume of bone marrow treated is
less than 10% and also the patient has measurable disease outside the radiation port
- Any history of prior pseudomonas-exotoxin immunotoxin (PE) administration.