Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

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

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.


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.

Relevance to patient case: not relevant