Eculizumab in Treating Patients With Paroxysmal Nocturnal Hemoglobinuria

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00112983

Collaborator

(none)

Location

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: eculizumab	Phase 3

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 Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Nov 1, 2004

Actual Study Completion Date :

Jun 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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