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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 23, 2014