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

This study has been terminated.
(Due to a lack of IP supply and then terminated because they were combined into one new study with the new IP formulation.)
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00587015
First received: December 21, 2007
Last updated: November 21, 2011
Last verified: November 2011
  Purpose

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


Condition Intervention Phase
Lymphoma
Drug: CAT-8015
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Assess safety, estimate MTD, characterize toxicity profile, study pharmacology and observe anti-tumor activity at the MTD. [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess immunogenicity of CAT 8015 and potential biomarkers for therapeutic or toxicity responses. [ Time Frame: Day 0-7; 0-14 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: August 2007
Study Completion Date: October 2009
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00587015

Locations
United States, California
Tower Hematology Oncology Medical Group
Beverly Hills, California, United States, 90211-1850
United States, Maryland
NCI, National Institutes of Health
Bethesda, Maryland, United States, 20892
Poland
Kalinika Hemotologii Uniwersytetu Medycznego
Lodz, Poland, 93-510
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Robert Leechleider, M.D. MedImmune LLC
  More Information

No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00587015     History of Changes
Other Study ID Numbers: CAT-8015-1003
Study First Received: December 21, 2007
Last Updated: November 21, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on April 15, 2014