Clinical Trial Result Information

Protocol number
ML17616

Title of Study
Multicenter, open label study of NeoRecormon treatment for anemia in adult patients with Multiple Myeloma, Low Grade Non-Hodgkin’s Lymphoma or Chronic Lymphocytic Leukemia who have a relatively Erythropoietin Deficiency and are Receiving anti-tumor Chemotherapy.

Sponsor
Shanghai Roche Pharmaceuticals Ltd

Company division
Pharmaceutical

Product name
NeoRecormon

Generic name
epoetin beta

Therapeutic area
Anemia

Clinical study summary
This was a multicenter, open-label, two-arm study to investigate the effect of NeoRecormon in patients with hematologic malignancies who have a relative erythropoietin deficiency and are receiving anti-tumor chemotherapy. NeoRecormon treatment was compared with standard treatment for anemia.

Study center(s)
11 sites in China.

Phase of development
III

Objectives
To determine the efficacy and safety of NeoRecormon (epoetin beta) in the treatment of anemia in adult patients with hematological malignancies who have a relative erythropoietin deficiency and are receiving anti-tumor chemotherapy.

Methodology
Eligible patients were randomized to receive either NeoRecormon treatment, at a starting dose of 150 IU/kg s.c. tiw, or standard treatment (supported blood transfusion and iron supplements, as necessary). The number and volume of blood transfusions were documented during the study, laboratory parameters and blood pressure were measured at regular intervals, and AEs were recorded continuously.

Number of patients (planned/analyzed)
60 patients enrolled.

Diagnosis and main criteria for inclusion
Men and women >18 years old who had anemia with multiple myeloma, low grade non-Hodgkin’s Lymphoma or chronic lymphocytic leukemia who were transfusion dependent and had a relative erythropoietin deficiency (serum erythropoietin level <100mU at a Hb>9 to<10g/dL, <180mU at a Hb >8 to ≤9g/dL, <300mU at a Hb ≤8g/dL) and were receiving chemotherapy.

Test product, dose and mode of administration or test procedure
NeoRecormon (epoetin beta). Starting dose: 150 IU/kg body weight s.c. tiw.

Duration of treatment
12 weeks

Criteria for evaluation (efficacy, safety)
Efficacy: Primary: The percentage of patients with increase in hemoglobin values by >2g/dL compared to baseline without blood transfusion in the previous 6 weeks (defined as response rate). Secondary: Increase in hemoglobin; number and volume of blood transfusion per patient; hematocrit; red cell count; reticulocyte count; iron, ferritin, transferrin. Safety: AEs, laboratory parameters, blood pressure.

Statistical methods
Efficacy: The 2 arms were compared for response rate and other efficacy parameters at the end of the study. The primary and all secondary efficacy parameters were analyzed using the intent-to-treat population (all randomized patients) and the per protocol population (patients who completed ≥8 weeks of study, with no protocol violations).
Safety: All patients who have received at least one dose of the study medication whether withdrawn prematurely or not were included in the safety analysis.

Summary (efficacy, safety, other results)
Efficacy: The response rate of NeoRecormon was 68.4% in the ITT population and 73.5% in the PP population, while the response rate in the control group was 36.1% in the ITT population and 46.4% in the PP population. Hemoglobin levels in the NeoRecormon group were elevated when compared with the baseline value after week 1, and the hemoglobin increase was consistently higher in the NeoRecormon group than in the control group after week 3. At the end of treatment, the hemoglobin increase in the NeoRecormon group was 30.93±20.77 g/L in the ITT population and 31.42±21.02 g/L in the PP population, while the increase was 17.63±22.76 g/L in both the ITT and PP populations in the control group. At the end of treatment, the increase in hematocrit in the NeoRecormon group was 9.07±7.40 % in the ITT population and 9.26±7.49 % in the PP population; both were higher than in the control group. The increase in red cell count was also higher in the NeoRecormon group than in the control group (1.10±0.80x1012/L in the ITT and 1.12±0.81x1012/L in the PP population, respectively). There were no differences in the number and volume of blood transfusions, reticulocyte counts and serum iron, ferritin and transferrin between the two groups.

Safety: Safety data revealed that the overall incidence of adverse events was comparable between the two groups. A total of 2 patients in the NeoRecormon group experienced SAEs during the study, including 1 death which was unrelated to the study drug. The second SAE, upper gastrointestinal bleeding, was considered remotely related to study drug. Two patients in the NeoRecormon group experienced 6 AEs which were judged as possibly related to the study drug: fatigue (2), drowsiness, hiccough, vomiting and shivering. These AEs were mild in intensity and resolved without treatment. There were no differences between the groups in safety laboratory parameters, and no abnormal laboratory parameters related to the study drug. Blood pressure in both groups of patients remained stable during the entire treatment period.

Conclusions
In this study, NeoRecormon steadily and consistently increased the hemoglobin level in anemic patients with multiple myeloma, low malignancy non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, with good tolerability. It can be concluded that NeoRecormon is an effective and safe drug for anemia in Chinese adult patients with these hematological malignancies and relative erythropoietin deficiency and receiving anti-tumor chemotherapy.

Date of report
12/18/2006

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