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
18 Years
N/A
Both
Leukemia
Trial Information
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
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention
Principal Investigator
Ronald Paquette, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
ALEXION-C04-001
NCT ID:
NCT00112983
Start Date:
November 2004
Completion Date:
June 2005
Related Keywords:
- Leukemia
- adult acute lymphoblastic leukemia
- adult acute myeloid leukemia
- Hemoglobinuria
- Leukemia
- Hemoglobinuria, Paroxysmal
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center at UCLA | Los Angeles, California 90095-1781 |
