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

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

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

Study Overview

• Status: Terminated
• Conditions: Lymphoma
• Intervention / Treatment: Drug: CAT-8015

Detailed Description

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.

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

Contacts and Locations

Study Locations

• Poland
  • Lodz, Poland, 93-510
    • Kalinika Hemotologii Uniwersytetu Medycznego
• United States
  • California
    • Beverly Hills, California, United States, 90211-1850
      • Tower Hematology Oncology Medical Group
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • NCI, National Institutes of Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; CAT-8015	Drug: CAT-8015; 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.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Robert Leechleider, M.D., MedImmune LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimate): January 7, 2008

Study Record Updates

• Last Update Posted (Estimate): November 22, 2011
• Last Update Submitted That Met QC Criteria: November 21, 2011
• Last Verified: November 1, 2011

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; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Immunotoxin HA22
• Other Study ID Numbers: CAT-8015-1003