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

Leukemia Clinical Trial

— NHL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00515892
• Other study ID #: CAT-8015-1003
• Status: Recruiting
• Phase: Phase 1
• First received: August 10, 2007
• Last updated: August 10, 2007
• Start date: August 2007

Study information

• Verified date: August 2007
• Source: Cambridge Antibody Technology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00522483

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma, Non-Hodgkin
• NHL
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• Immunotoxin therapy

• CAT-8015 Immunotoxin

Procedure:
• Biological therapy

• Antibody Therapy

• Monoclonal Antibody Therapy

Locations

Country	Name	City	State
Poland	Klinika Hamtologii Uniwersytetu Medycznego (Medical University of Lodz)	Lodz
United States	Warren Grant Megnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland
United States	Tower Hematology Oncology Medical Group	Beverly Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
Cambridge Antibody Technology

Countries where clinical trial is conducted

United States,  Poland, 

References & Publications (1)

Kreitman RJ, Squires DR, Stetler-Stevenson M, Noel P, FitzGerald DJ, Wilson WH, Pastan I. Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. J Clin Oncol. 2005 Sep 20;23(27):6719-29. Epub 2005 Aug 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To assess the immunogenic potential of CAT-8015 to induce antibodies; To investigate the potential of biomarkers to predict any therapeutic or toxic response.