Clinical Trial Result Information

Title of Study:
Phase II Randomized Multicenter Comparative Study of Peginterferon alfa-2a vs. Roferon-A for the Treatment of Patients with Recently Diagnosed Chronic Phase Myelogenous Leukemia (CML) not Previously Treated with Interferon.

Fast Facts:

Protocol number:	NO16006
Sponsor:	Hoffman-La Roche Inc
Company division:	Pharmaceutical
Product name:	PEGASYS
Generic name:	peginterferon alfa-2a (40KD)
Phase of development:	III
Therapeutic area, approved indication:	Myelogenous Leukemia Chronic
Date of report:	4/1/2008

Clinical study summary:
This was a randomized, open-label, parallel arm multicenter study to compare treatment with PEGASYS (peginterferon alfa-2a (40KD)) and Roferon-A in patients with recently diagnosed chronic myelogenous leukemia (CML).

Study center(s) :
74 centers in Austria, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, India, Israel, Italy, Mexico, Poland, Russian Federation, Slovakia, South Africa, Spain, Taiwan, Thailand, United Kingdom and USA.

Objectives:
Primary: To compare the efficacy of subcutaneous administration (s.c.) of PEGASYS once weekly to that of once daily Roferon-A 9 MIU in patients with CML.
Secondary: To compare safety and tolerability.

Methodology:
Patients were randomized to receive PEGASYS, 450 micrograms once weekly or Roferon-A, 9 MIU once daily titrated upwards from a starting dose of 3 MIU daily. If the patient had no evidence of hematological response within the first 6 months, treatment could be discontinued and the patient counted as a non-responder or treatment could be continued until 12 months, at the discretion of the investigator. If the patient exhibited a complete or partial cytogenetic response within the first 12 months, treatment could be continued for a further 12 months providing there was no evidence of progressive disease. This period was termed the maintenance phase. If the cytogenetic response was not complete at 18 months, treatment could be discontinued at the discretion of the investigator. Patients who had achieved a complete cytogenetic response at 24 months could be considered for continuing maintenance treatment. Survival status was determined at 24 months after the last patient was randomized.
Clinical and laboratory assessments were performed at baseline and weekly for the first 4 weeks of treatment, then once every 4 weeks until 12 months. Two follow-up assessments were performed at weeks 1 and 4 after the last dose of the study drug except in patients continuing into the maintenance phase.

Number of patients (planned/analyzed):
144 patients

Diagnosis and main criteria for inclusion:
Male or female patients ≥18 years old with Philadelphia chromosome positive CML, diagnosed within 12 months prior to start of study drug and not previously treated with interferon, STI-571 or Ara-C.

Test product, dose and mode of administration or test procedure:
PEGASYS (peginterferon alfa-2a (40KD)) 450μg/sc/once-weekly.

Duration of treatment:
1 year

Reference therapy, dose and mode of administration or reference procedure:
Roferon-A: up to 9 MIU/sc/once-daily.

Criteria for evaluation (efficacy, safety):
Efficacy: Cytogenetic response, hematologic response.
Safety: Adverse events, clinical laboratory tests.

Statistical methods:
Cytogenetic and hematologic response rates were compared between the treatment groups using the Cochran-Maentel-Haenszel test (CMH). Overall survival and progression-free survival were calculated by the method of Kaplan-Meier.
The number and percentage of patients alive at the 2-year follow-up time are reported.

Summary (efficacy, safety, other results):
Efficacy: During the study, more patients receiving PEGASYS achieved a major (complete or partial) cytogenetic response (25/71, 35.2%) compared with those who received Roferon-A (14/73, 19.2%). In addition, more patients receiving PEGASYS achieved a major (complete or partial) hematologic response (60/71, 84.5%) during the study compared with those who received Roferon-A (51/73, 69.9%). When the hematological response was measured over the first six months of treatment, more patients receiving PEGASYS achieved a major (complete or partial) response (51/71, 71.8%) compared with those who received Roferon-A (41/73, 56.1%).

Safety: The types of clinical adverse events were generally similar between treatments, although some differences in incidence were noted. The most commonly reported AEs across both groups were pyrexia (64% Roferon-A, 61% PEGASYS), myalgia (31% Roferon-A, 37% PEGASYS), fatigue (28% Roferon-A, 32% PEGASYS), anorexia (32% Roferon-A, 21% PEGASYS), headache (20% Roferon-A, 34% PEGASYS), asthenia (28% Roferon-A, 24% PEGASYS) and diarrhea (30% Roferon-A, 21% PEGASYS). More than half of all AEs in both groups were mild in intensity. The commonly noted severe AEs in the Roferon-A group were pyrexia (six patients), asthenia (six patients), myalgia (four patients), diarrhea (three patients), and depression (three patients). In the PEGASYS group, commonly noted severe AEs included thrombocytopenia (five patients), pyrexia (three patients), and fatigue (three patients).
A total of 18 patients died during the study and of these patients 11/74 were from the Roferon-A group and 7/71 were from the PEGASYS group. Overall 27 patients were reported with at least one SAE during the study. Of these 15/74 were in the Roferon-A group and 12/71 were in the PEGASYS group. During the treatment phase, more patients were withdrawn from the Roferon-A group (39/74) than the PEGASYS group (21/71). The main reasons for withdrawal were adverse events or an insufficient therapeutic response. No patients were withdrawn during the maintenance phase. During the follow-up phase, a further 10/74 (14%) patients were withdrawn from the Roferon-A group (for safety and non-safety reasons) and 2/71 (3%) were withdrawn from the PEGASYS group (for non-safety reasons only).

Conclusions:
PEGASYS 450μg administered once weekly in the treatment of chronic myelogenous leukemia was well tolerated and had a safety profile similar to that observed with Roferon-A therapy.

Click here for the protocol registry listing of this trial.