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

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

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.

Study Overview

• Status: Unknown
• Conditions: Leukemia; Non-Hodgkin's Lymphoma; NHL
• Intervention / Treatment: Drug: Immunotoxin therapy; Drug: CAT-8015 Immunotoxin; Procedure: Biological therapy; Procedure: Antibody Therapy; Procedure: Monoclonal Antibody Therapy

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Lodz, Poland
    • Not yet recruiting
    • Klinika Hamtologii Uniwersytetu Medycznego (Medical University of Lodz)
    • Contact: Krzysztof Jamroziak, MD; Phone Number: (48) 42 689-5191
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Tower Hematology Oncology Medical Group
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • Warren Grant Megnuson Clinical Center - NCI Clinical Trials Referral Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Cambridge Antibody Technology

Publications and helpful links

General Publications

• 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. doi: 10.1200/JCO.2005.11.437. Epub 2005 Aug 1.

Study record dates

Study Major Dates

• Study Start: August 1, 2007

Study Registration Dates

• First Submitted: August 10, 2007
• First Submitted That Met QC Criteria: August 10, 2007
• First Posted (Estimate): August 14, 2007

Study Record Updates

• Last Update Posted (Estimate): August 14, 2007
• Last Update Submitted That Met QC Criteria: August 10, 2007
• Last Verified: August 1, 2007

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunotoxins; Immunotoxin HA22
• Other Study ID Numbers: CAT-8015-1003