A Phase I, Multicenter Dose Escalation Study in Patients With Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cambridge Antibody Technology
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00586924
First received: December 21, 2007
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

To administer the highest dose that can safely be given to a patient and establish the safest dose based on the highest tolerated dose for clinical testing.


Condition Intervention Phase
Hairy Cell Leukemia
Biological: CAT 8015 (Moxetumomab Pasudotox)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics 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 Hairy Cell Leukemia (HCL)

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Assess safety, efficacy, characterize toxicity profile, study pharmacology and observe anti-tumor activity [ Time Frame: Disease assessment will be completed prior to the first cycle of CAT-8015 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess immunogenicity and potential biomarkers for response or toxicity for phase 2 dose [ Time Frame: Routine safety tests ] [ Designated as safety issue: Yes ]

Enrollment: 50
Study Start Date: May 2007
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
CAT 8015
Biological: CAT 8015 (Moxetumomab Pasudotox)
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 the (maximum tolerated dose) MTD, for subsequent clinical testing (Phase 2 recommended dose).

  Eligibility

Ages Eligible for Study:   18 Years and older
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 HCL
  • Measurable disease
  • Patient's must have had at least 2 prior systemic therapies. There must have been at least 2 prior courses of purine analog, or 1 if the response to this course lasted <2 years, or if the patient had unacceptable toxicity to purine analog.
  • 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 greater 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
  • Stage of Disease:

At least one of the following indications for treatment:

  • Neutropenia (ANC <1000 cells/μL),
  • Anemia (Hgb <10g/dL),
  • Thrombocytopenia (Plt <100,000/μL),
  • An absolute lymphocyte count of >20,000 cells/μL, or
  • Symptomatic splenomegaly

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
  • 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 is 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 systemic therapy, 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(PE)immunotoxin 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: NCT00586924

Locations
United States, California
Research Site
Stanford, California, United States
United States, Illinois
Research Site
Chicago, Illinois, United States
United States, Maryland
Research Site
Bethesda, Maryland, United States
Poland
Research Site
Lodz, Poland
Sponsors and Collaborators
MedImmune LLC
Cambridge Antibody Technology
Investigators
Study Director: Mark Lanasa, M.D. MedImmune LLC
  More Information

Additional Information:
No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00586924     History of Changes
Other Study ID Numbers: CAT-8015-1001
Study First Received: December 21, 2007
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Hairy Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on October 01, 2014