A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Non-Hodgkin's Lymphoma (NHL)

Study Overview
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Brief Summary
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A dose-escalation study to estimate the maximum tolerated dose(MTD) of CAT-8015 that can be safely administered to a patient.

Detailed Description
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To estimate the maximum tolerated dose (MTD), defined as the highest dose that can be safely administered to a patient, and to establish a safe dose, based on MTD, for subsequent clinical testing.

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

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: CAT-8015


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following criteria to be eligible to participate in the study: 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 Disease characteristics: 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. 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 performance status of 0-2 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 Life expectancy of less than 6 months, as assessed by the principal investigator Must be able to understand and sign informed consent Must be at least 18 years old Female and male patients must agree to use an approved method of contraception during the study Exclusion Criteria: Subjects meeting any of the following criteria are not eligible for participation in the study: History of allogeneic 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 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 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. 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 greater than or equal to 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: Patients 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 to 1 month 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
Maximum Age: 80 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>CAT-8015 | Drug: CAT-8015<br>* The dose level of the initial cohort will be 5 μg/kg so cohorts will be dosed at 5, 10, 20, 30, 40, 50, 60…μg/kg until toxicity supervenes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess safety, estimate MTD, characterize toxicity profile, study pharmacology and observe anti-tumor activity at the MTD. |  | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess immunogenicity of CAT 8015 and potential biomarkers for therapeutic or toxicity responses. |  | Day 0-7; 0-14 |