Safety Study of CAT-8015 Immunoxin in Patients With NHL With Advance Disease

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Relapsed or Refractory Non-Hodgkin'd Lymphoma (NHL)

Conditions
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Leukemia, Non-Hodgkin's Lymphoma, NHL

Intervention / Treatment
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* Drug: Immunotoxin therapy
* Drug: CAT-8015 Immunotoxin
* Procedure: Biological therapy
* Procedure: Antibody Therapy
* Procedure: Monoclonal Antibody Therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Immunotoxin therapy|nan|
|Drug: CAT-8015 Immunotoxin|nan|
|Procedure: Biological therapy|nan|
|Procedure: Antibody Therapy|nan|
|Procedure: Monoclonal Antibody Therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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. |  |  |