Leukemia, Non-Hodgkin's Lymphoma, NHL
Conditions
Brief summary
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 treatment.
Interventions
Sponsors
Cambridge Antibody Technology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * 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 immunohistochemistry * 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. PATIENTS CHARACTERISTICS Performance Status * ECOG 0-2 Life Expectancy * Life expectancy of less than 6 months, as assessed by the principal investigator Other * 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 the study
Exclusion criteria
* 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 formula Hematologic function: * 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 anti-neoplastic therapy). * 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. Pulmonary function: * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Estimate the maximum dose that can be safely administered to a patient; Characterize the toxicity profile of CAT-8015; Study the clinical pharmacology of CAT-8015; Observe anti-tumor activity, if any. | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the immunogenic potential of CAT-8015 to induce antibodies; To investigate the potential of biomarkers to predict any therapeutic or toxic response. | — |
Countries
Poland, United States
Outcome results
None listed