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

Sponsor

Cambridge Antibody Technology (Other)

Overall Status

Unknown status

CT.gov ID

NCT00515892

Collaborator

(none)

Enrollment

Locations

16.7

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Non-Hodgkin's Lymphoma NHL	Drug: Immunotoxin therapy Drug: CAT-8015 Immunotoxin Procedure: Biological therapy Procedure: Antibody Therapy Procedure: Monoclonal Antibody Therapy	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2007

Outcome Measures

Primary Outcome Measures

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

To assess the immunogenic potential of CAT-8015 to induce antibodies; To investigate the potential of biomarkers to predict any therapeutic or toxic response. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tower Hematology Oncology Medical Group	Beverly Hills	California	United States	90211
2	Warren Grant Megnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892
3	Klinika Hamtologii Uniwersytetu Medycznego (Medical University of Lodz)	Lodz		Poland