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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00586924
Recruitment Status : Completed
First Posted : January 7, 2008
Last Update Posted : August 7, 2015
Cambridge Antibody Technology
Information provided by (Responsible Party):
MedImmune LLC

December 21, 2007
January 7, 2008
August 7, 2015
May 2007
May 2015   (Final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00586924 on Archive Site
Assess immunogenicity and potential biomarkers for response or toxicity for phase 2 dose [ Time Frame: Routine safety tests ]
Same as current
Not Provided
Not Provided
A Phase I, Multicenter Dose Escalation Study in Patients With Leukemia
A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Relapsed or Refractory Hairy Cell Leukemia (HCL)
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.
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).
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hairy Cell Leukemia
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.
Experimental: 1
CAT 8015
Intervention: Biological: CAT 8015 (Moxetumomab Pasudotox)
Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, FitzGerald DJ, Santiago L, Gao G, Lanasa MC, Pastan I. Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase I results and long-term follow-up. Blood. 2018 Feb 27. pii: blood-2017-09-803072. doi: 10.1182/blood-2017-09-803072. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
May 2015
May 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Poland,   United States
Not Provided
Not Provided
MedImmune LLC
MedImmune LLC
Cambridge Antibody Technology
Investigator: MedImmune MedImmune LLC
MedImmune LLC
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP