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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00587015
• Date of registration: 21/12/2007
• Prospective Registration: No
• Primary sponsor: MedImmune LLC
• Public title: A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Non-Hodgkin's Lymphoma (NHL)
• Scientific title: A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)
• Date of first enrolment: August 2007
• Target sample size: 50
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT00587015
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Poland, United States

Contacts

• Name: Robert Leechleider, M.D.
• Affiliation: MedImmune LLC

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Lymphoma

Intervention(s)

Drug: CAT-8015

Primary Outcome(s)

Assess safety, estimate MTD, characterize toxicity profile, study pharmacology and observe anti-tumor activity at the MTD. [Time Frame: Day 28]

Secondary Outcome(s)

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

Secondary ID(s)

CAT-8015-1003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors