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Eculizumab in Treating Patients With Paroxysmal Nocturnal Hemoglobinuria

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.
 
ClinicalTrials.gov Identifier: NCT00112983
Recruitment Status : Completed
First Posted : June 3, 2005
Last Update Posted : May 30, 2013
Sponsor:
Information provided by:
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE June 2, 2005
First Posted Date  ICMJE June 3, 2005
Last Update Posted Date May 30, 2013
Study Start Date  ICMJE November 2004
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00112983 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Eculizumab in Treating Patients With Paroxysmal Nocturnal Hemoglobinuria
Official Title  ICMJE 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
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Masking: Double
Primary Purpose: Prevention
Condition  ICMJE Leukemia
Intervention  ICMJE Biological: eculizumab
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 2005
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00112983
Other Study ID Numbers  ICMJE ALEXION-C04-001
UCLA-0406101-01
CDR0000409569 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Jonsson Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ronald Paquette, MD Jonsson Comprehensive Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date June 2005

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