Clinical Trial: Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Pivotal Multicenter Trial of Moxetumomab Pasudotox in Relapsed/ Refractory Hairy Cell Leukemia

Brief Summary:

Background:

- Moxetumomab pasudotox is an experimental non-chemotherapy cancer treatment drug. It targets CD22, a molecule on the surface of essentially all hairy cell leukemia cells. Moxetumomab pasudotox binds to CD22, goes into the cell, and releases a toxin which kills the cell. In a phase I trial it had activity in relapsed/refractory hairy cell leukemia with safety profile supporting further clinical study (http://ncbi.nlm.nih.gov/pubmed/22355053). This is a phase III multicenter trial designed to confirm these results.


Detailed Summary:

Background:

  • Hairy cell leukemia is an indolent B-cell leukemia comprising 2% of all leukemias, or approximately 900 of the 44,000 new cases of leukemia/year in the US
  • Over the last two decades, immunotoxin research has accumulated to support a role for CD22-targeted therapy in the treatment of HCL.
  • Moxetumomab pasudotox is a recombinant immunotoxin containing an Fv fragment of an anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin.
  • Moxetumomab pasudotox has demonstrated a high complete response (CR) rate in patients with chemoresistant hairy cell leukemia (HCL) and has shown activity in pediatric acute lymphoblastic leukemia as well.
  • Modification of the structure of moxetumomab pasudotox has greatly improved binding and cytotoxicity toward CD22 expressing malignant cells compared to the precursor molecule. Preclinical and clinical studies have demonstrated that this increase in binding affinity results in improved antitumor activity and tolerability
  • Currently there are no approved agents with significant efficacy for HCL patients after failure of standard therapy

Design:

  • This is a multicenter, single-arm study of moxetumomab pasudotox in patients with relapsed/refractory hairy cell leukemia.
  • 77 patients will be enrolled to receive moxetumomab pasudotox IV on days 1, 3 and 5 of each 28 day cycle for a maximum of 6 cycles or until disease progression, unacceptable toxicity occurs, the subject begins alternate therapy, or documented CR (for subjects who have no assessable minimal residual
    Sponsor: MedImmune LLC

    Current Primary Outcome: Rate of CR in patients treated with study drug [ Time Frame: Every 4 weeks ]

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Overall response rate [ Time Frame: every 4 weeks. ]
    • Relapse free survival [ Time Frame: Once patients have a Complete Response (CR), they will be followed with monthly blood work for 6 months then every 3 months for 2 years, then yearly thereafter. Bone marrow examinations at 6 months. ]
    • Progression free survival [ Time Frame: Once patients have a Complete Response (CR), they will be followed with monthly blood work for 6 months then every 3 months for 2 years, then yearly thereafter. Bone marrow examinations at 6 months. ]
    • Time to Response [ Time Frame: Duration of Study ]
      TTR will be measured from start of administartion to the first documentation of response (CR or PR)
    • Safety [ Time Frame: 1st Administration through 30 Days after Last Dose ]
      Occurence of AEs, abnormal laboratory values, and SAEs reported from 1st administration of moxetumomab pasudotox through 30 days after last dose
    • Pharmacokinetic [ Time Frame: Duration of Treatment ]
    • Immunogenic Potential [ Time Frame: Duration of Treatment ]


    Original Secondary Outcome:

    • Overall response rate [ Time Frame: every 4 weeks. ]
    • Relapse free survival [ Time Frame: Once patients have a Complete Response (CR), they will be followed with monthly blood work for 6 months then every 3 months for 2 years, then every 6 months. Bone marrow examinations at 6 months then yearly for 2 years, then every 2 years. ]
    • Progression free survival [ Time Frame: Once patients have a Complete Response (CR), Patients will be followed with monthly blood work for 6 months then every 3 months for 2 years, then every 6 months. Bone marrow examinations at 6 months then yearly for 2 years, then every 2 years. ]


    Information By: MedImmune LLC

    Dates:
    Date Received: April 9, 2013
    Date Started: April 29, 2013
    Date Completion: May 17, 2017
    Last Updated: March 30, 2017
    Last Verified: March 2017