Clinical Trial: A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Participants With Chronic Leukemia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase I, Multicenter, Dose-Escalation Study of CAT-8015 in Patients With Relapsed or Refactory Chronic Lymphocytic Leukemia (CLL) Prolymphocytic Leukemia (PLL), or Small

Brief Summary: This was a multicenter, Phase 1, standard 3+3 dose-escalation study to evaluate the safety and anti-neoplastic activity of moxetumomab pasudotox in relapsed or refractory participants with chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL) or Small Lymphocytic Lymphoma (SLL).

Detailed Summary: This was a multicenter, Phase 1, standard 3+3 dose-escalation study to evaluate the safety and anti-neoplastic activity of CAT-8015 in relapsed or refractory participants with CLL, PLL, or SLL. Participants in the initial dose cohort were to receive CAT-8015 at a dose of 5 microgram per kilogram (mcg/kg) CAT-8015, increasing to 10 mcg/kg in the second dose cohort, and then increasing by 10 mcg/kg increments in subsequent cohorts (that is, to doses of 20, 30, 40, 50, 60 mcg/kg, etc) until a maximum tolerated dose (MTD) was identified. Following identification of the MTD, the MTD cohort was to be expanded to 16 participants.
Sponsor: MedImmune LLC

Current Primary Outcome:

  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: From start of study drug administration until 30 days after the last dose of study drug ]
    An adverse event (AE) events present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received moxetumomab pasudotox. Treatment-emergent were events between administration of investigational product and Day 28 that were absent before treatment or that worsened relative to pretreatment state.
  • Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From start of study drug administration until 30 days after the last dose of study drug ]
    Vital signs included parameters as heart rate, blood pressure, temperature, weight, pulse oximetry and respiratory rate. TEAEs were events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug.
  • Number of Participants With Clinically Relevant Electrocardiogram (ECG) A

    Original Primary Outcome: Assess safety, efficacy,characterize toxicity profile, study pharmacology, observe anti-tumor activity [ Time Frame: Day 28 ]

    Current Secondary Outcome:

    • Number of Participants With Positive Neutralizing Antibodies [ Time Frame: Up to end of treatment (4-6 weeks after the last dose) ]
      Participants tested for immunogenicity to moxetumomab pasudotox prior to enrollment, before each cycle and at end of study. The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of moxetumomab pasudotox to its target, cluster of differentiation 22 (CD22), coated onto enzyme linked immunosorbent assay (ELISA) plates. It was used as a direct surrogate for biological activity based on the mechanism of action of this drug. Significant level of neutralizing antibody activity defined as the capacity of test plasma to inhibit greater than (>)50 percentage (%) of the binding of CAT-8015 to CD22 using an ELISA-based method.
    • Percentage Change From Baseline in Cluster of Differentiation 22 (CD22) Expression [ Time Frame: End of treatment (4-6 weeks after the last dose) ]
      Participants demonstrated CD22 expression on malignant cells at Screening and CD22 is a regulatory molecule that prevents the over activation of the immune system and the development of autoimmune diseases.


    Original Secondary Outcome: Assess immunogenicty and potential biomarkers for response or toxicity for phase 2 dose [ Time Frame: Days 0-7; 0-14 ]

    Information By: MedImmune LLC

    Dates:
    Date Received: December 21, 2007
    Date Started: March 2007
    Date Completion:
    Last Updated: February 27, 2017
    Last Verified: February 2017