Clinical trial NCT00587015: A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Non-Hodgkin's Lymphoma (NHL)
Official title: A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphoma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2008-01-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Assess safety, estimate MTD, characterize toxicity profile, study pharmacology and observe anti-tumor activity at the MTD.
timeFrame: Day 28
Secondary outcomes:
measure: Assess immunogenicity of CAT 8015 and potential biomarkers for therapeutic or toxicity responses.
timeFrame: Day 0-7; 0-14
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Hematology Oncology Medical Group
state: California
city: Bethesda
country: United States
facility: NCI, National Institutes of Health
state: Maryland
city: Lodz
country: Poland
facility: Kalinika Hemotologii Uniwersytetu Medycznego
Study officials:
affiliation: MedImmune LLC
name: Robert Leechleider, M.D.
role: STUDY_DIRECTOR
References: