Eculizumab in Treating Patients With Paroxysmal Nocturnal Hemoglobinuria

May 29, 2013 updated by: Jonsson Comprehensive Cancer Center

TRIUMPH: A Hemoglobin Stabilization and Transfusion Reduction Efficacy and Safety Clinical Investigation, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Using Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of eculizumab may prevent leukemia and stop the destruction of red blood cells in patients with paroxysmal nocturnal hemoglobinuria.

PURPOSE: This randomized phase III trial is studying how well eculizumab works in treating patients with paroxysmal nocturnal hemoglobinuria.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the safety of eculizumab in patients with transfusion-dependent hemolytic paroxysmal nocturnal hemoglobinuria.
  • Determine the efficacy of this drug, in terms of hemoglobin stabilization and the number of packed red blood cell units transfused during the 26-week treatment period, in these patients.

Secondary

  • Compare the occurrence of transfusion avoidance, hemolysis (measured by lactate dehydrogenase [LDH] area under the curve), and the changes in fatigue during the 26-week treatment period in patients treated with this drug vs placebo.
  • Compare LDH changes, quality of life changes, thrombosis, platelet activity, nitric oxide, and free hemoglobin measures during the 26-week treatment period in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to the number of packed red blood cell (PRBC) units transfused 1 year prior to screening (< 15 units vs 15-25 units vs > 25 units). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Within 10 days after PRBC transfusion (administered during the study observation period), patients receive placebo IV over 30 minutes once a week for 5 weeks and then once every 2 weeks for 21 weeks.
  • Arm II: Within 10 days after PRBC transfusion (administered during the study observation period), patients receive eculizumab IV over 30 minutes once a week for 5 weeks and then once every 2 weeks for 21 weeks.

Quality of life is assessed at baseline; at weeks 0-4, 12, 20, and 26 during study treatment; then at weeks 1, 2, 4, and 8 after completion of study treatment.

After completion of study treatment, patients are followed at weeks 1, 2, 4, and 8.

PROJECTED ACCRUAL: Approximately 75 patients (37 per treatment arm) will be accrued for this study.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095-1678
        • Jonsson Comprehensive Cancer Center at UCLA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of paroxysmal nocturnal hemoglobinuria

  • Must have required ≥ 4 episodes of transfusions for anemia or anemia-related symptoms within the past year

    • Mean pre-transfusion hemoglobin ≤ 10. 5 g/dL over the past year
  • Glycosylphosphatidylinositol (GPI)-deficient red blood cell clone (type III cells) of ≥ 10% by flow cytometry

  • Must have received 1 packed red blood cell transfusion during the study observation period (within 48 hours of the hemoglobin level that precipitated the transfusion) and within 1.5 g/dL of the mean pre-transfusion hemoglobin level over the past year

    • Pre-transfusion hemoglobin ≤ 9 g/dL with symptoms
    • Pre-transfusion hemoglobin ≤ 7 g/dL without symptoms
  • Received Neisseria meningitidis vaccination at least 2 weeks before initiation of study therapy

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics
  • Absolute neutrophil count > 500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Lactate dehydrogenase ≥ 1.5 times upper limit of normal

Renal

  • Not specified

Immunologic

  • No known or suspected active bacterial infection
  • No recurrent bacterial infections
  • No history of meningococcal disease

Other

  • No known or suspected hereditary complement deficiency
  • No other condition that would increase the patient's risk or confound the outcome of the study
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • No prior bone marrow transplantation
  • Concurrent epoetin alfa allowed*

Chemotherapy

  • Not specified

Endocrine therapy

  • Concurrent corticosteroids allowed**

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • More than 30 days since prior participation in another investigational drug trial
  • More than 30 days since prior investigational agents, devices, or procedures
  • Concurrent immunosuppressants allowed*
  • Concurrent warfarin allowed provided INR level is stable for the past 4 weeks and expected to remain stable during observation and study treatment
  • Concurrent iron supplements or folic acid allowed**
  • Concurrent low-molecular weight heparin allowed** NOTE: *Provided dose is stable for the past 26 weeks and during study observation and treatment

NOTE: **Provided dose is stable for the past 4 weeks and expected to remain stable (or decrease for corticosteroids) during study observation and treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Masking: DOUBLE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jonsson Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2004

Study Completion (ACTUAL)

June 1, 2005

Study Registration Dates

First Submitted

June 2, 2005

First Submitted That Met QC Criteria

June 2, 2005

First Posted (ESTIMATE)

June 3, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

May 30, 2013

Last Update Submitted That Met QC Criteria

May 29, 2013

Last Verified

June 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALEXION-C04-001
  • UCLA-0406101-01
  • CDR0000409569 (REGISTRY: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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