Safety Study of CAT-8015 Immunooxin in Patients With HCL With Advance Disease

Brief Title

Safety Study of CAT-8015 Immunooxin in Patients With HCL With Advance Disease

Official Title

A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Patient With Relapsed or Refractory Hairy Cell Leukemia (HCL)

Brief Summary

      RATIONALE: The CAT-8015 immunotoxin can bind tumor cells and kill them without harming normal
      cells. This may be an effective treatment for hairy cell leukemia(HCL) that has not responded
      to chemotherapy, surgery or radiation therapy.

      PURPOSE: Phase I dose escalation study to determine the maximum tolerated dose of CAT-8015
      immunotoxin in treating patients who have hairy cell leukemia (HCL) that has not responded to
      treatment.
    

Detailed Description

      OUTLINE: Patients receive CAT-8015 IV over 30 minutes on days 1, 3, and 5 followed by rest.
      Treatment repeats every 4 weeks for up to a total of 10 courses in the absence of dose
      limiting toxicity, complete response or disease progression. Patients are followed at 1, 3,
      6,12,15,18, 21, 24 months following the start of the last treatment cycle.

      Cohorts of 3-6 patients each will receive escalating doses of recombinant CAT-8015 until the
      maximum tolerated dose (MTD) is determined. The MTD is defined as the dose proceeding that at
      which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is
      determined, between16 to 25 new patients will be added to the MTD cohort depending on how
      well the CAT-8015 is tolerated.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Estimate the maximum dose that can be safely administered to a patient

Secondary Outcome

 To assess the immunogenic potential of CAT-8015 to induce antibodies

Condition

Leukemia

Intervention

Immunotoxin therapy


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

40

Start Date

April 2007



Eligibility Criteria

        INCLUSION CRITERIA:

        DISEASE CHARACTERISTICS:

          -  Confirmed diagnosis of hairy cell leukemia

          -  Measurable 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

          -  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.

        PATIENT CHARACTERISTICS:

        Performance status • ECOG 0-2

        Life expectancy

        • Life expectancy of greater than 6 months, as assessed by the principal investigator

        Other

          -  Patients with other cancers who meet eligibility criteria and have had less than 5
             years of disease free survival will be considered on a case-by-case basis

          -  Ability to understand and sign informed consent

          -  Female and male patients agree to use an approved method of contraception during the
             study

        EXCLUSION CRITERIA:

          -  Documented and ongoing central nervous system involvement with their malignant disease
             (history of CNS involvement is not an exclusion criterion)

          -  History of bone marrow transplant

          -  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)

          -  Baseline coagulopathy > grade 3 unless due to anticoagulant 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

        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 following bronchodilator therapy.

        Recent prior therapy:

          -  Cytotoxic chemotherapy (except stable doses of prednisone), whole body electron beam
             radiation therapy, interferon, retinoids or other systemic therapy, or investigational
             therapy of the malignancy for 3 weeks prior to entry into the trial

          -  Less than or equal to < 3 months prior monoclonal antibody therapy (i.e. rituximab)

          -  Patients who have received or are receiving 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 pseudomonas-exotoxin (PE) immunotoxin administration
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

Poland

Location Countries

Poland

Administrative Informations


NCT ID

NCT00462189

Organization ID

CAT-8015-1001



Study Sponsor

Cambridge Antibody Technology


Study Sponsor

, , 


Verification Date

April 2007