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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


Phase 3
18 Years
N/A
Not Enrolling
Both
Leukemia

Thank you

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 UCLALos Angeles, California  90095-1781