Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence

Celgene267 enrolled

Overview

The objective of this study is to determine whether pomalidomide is safe and effective in reversing red blood cell (RBC)-transfusion-dependence in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis (global study) and in reversing anemia in Chinese with MPN-associated myelofibrosis and severe anemia not receiving RBC-transfusions (China extension study only)

The multicenter global study was conducted in 15 countries including Australia, Austria, Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Russia, Spain, Sweden, the United Kingdom, and the United States. The global study enrolled participants with myeloproliferative neoplasm (MPN)-associated myelofibrosis and RBC-transfusion-dependence. Participants were randomly assigned to receive pomalidomide or placebo in a blinded fashion. In most countries participating in the global study, RBC-transfusions are typically given for a hemoglobin level \<80-90 g/L. In China, RBC-transfusions are rarely given unless the hemoglobin level is \<60 g/L. Consequently, few Chinese with MPN-associated myelofibrosis meet RBC-transfusion-dependence criteria of the global study. A China-specific extension was developed to test the ability of pomalidomide to improve severe anemia (defined as a hemoglobin \< 80 g/L for ≥ 84 days in persons not receiving RBC-transfusions). The China-specific extension study consisted of a single-arm, open-label study in adults with MPN-associated myelofibrosis and severe anemia not receiving RBC transfusions with the objective of describing the frequency of anemia response. The Global (intent-to-treat \[ITT\] and safety) population in the main study and the China extension (ITT and safety) population are mutually exclusive.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

267

Conditions

Primary Myelofibrosis MPN-associated Myelofibrosis

Interventions

Pomalidomide 0.5 mgDRUG

Pomalidomide 0.5 mg capsule taken by mouth once daily. Immunomodulatory agent with demonstrated efficacy in the treatment of subjects with RBC-transfusion-dependence associated with MNP-associated myelofibrosis.

PlaceboDRUG

Placebo Comparator to active drug; Placebo capsule taken by mouth once daily

PomalidomideDRUG

Pomalidomide 0.5 mg capsule taken by mouth once daily.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years * Myeloproliferative-neoplasm (MPN)-associated myelofibrosis * RBC-transfusion-dependence (global study): * Average RBC-transfusion frequency ≥ 2 units/28 days over at least the 84 days immediately prior to randomization. There must be no interval \> 42 days without ≥ 1 RBC-transfusion. * Only RBC-transfusions given when the hemoglobin ≤ 90 g/L³ are scored in determining eligibility. * RBC-transfusions due to bleeding are not scored in determining eligibility. * RBC-transfusions due to chemotherapy-induced anemia are not scored in determining eligibility. * Severe anemia (China-specific extension): * ≥ 2 hemoglobin concentrations ≤ 80 g/L for ≥ 84 days immediately before the day of enrollment. * No RBC-transfusion within 6 months prior to enrollment. * Hemoglobin ≤ 130 g/L at randomization (global study); ≤ 80 g/L at enrollment in the China-specific extension. * Bone marrow biopsy within 6 months (global study only). * Inappropriate to receive blood cell or bone marrow allotransplant, erythropoietin and androgenic steroids * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. * Agree to follow pregnancy precautions as required by the protocol. * Agree to receive counseling related to teratogenic and other risks of pomalidomide. * Agree not to donate blood or semen. Exclusion Criteria: * Prior blood cell or bone marrow allotransplant. * Use of drugs to treat MPN-associated myelofibrosis ≤ 30 days before starting study drug. * Treatment with erythropoietin or androgenic steroids ≤ 84 days before starting study drug. * Anemia due to reasons other than MPN-associated myelofibrosis. * Pregnant or lactating females. * More than 10% blasts by bone marrow examination or more than 10% blasts in blood in consecutive measurements spanning at least 8 weeks * Prior history of malignancies,other than the disease being studied, unless the subject has been free of the malignancy for ≥ 5 years with the following exceptions: * Carcinoma in situ of the cervix * Carcinoma in situ of the breast * Incidental histologic finding of prostate cancer (T 1a or T 1b using TNM \[tumor, nodes, metastasis\] clinical staging system) * Human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. * Prior treatment with pomalidomide. * Allergic reaction or rash after treatment with thalidomide or lenalidomide * Any of the following laboratory abnormalities: * Neutrophils \< 0.5x10\^9 /L * Platelets \< 25 x 10\^9 /L * Estimated glomerular filtration rate (kidney function) \< 30 mL/min/1.73 m² * Aspartate aminotransferase (AST) and alanine transaminase (ALT) \> 3.0 x upper limit of normal (ULN) * Total bilirubin ≥ 4 x ULN; * Uncontrolled hyperthyroidism or hypothyroidism. * Deep venous thrombosis (DVT) or pulmonary embolus (PE) \< 6 months before starting study drug * Clinically-important heart disease within the past 6 months

Locations (87)

Outcomes

Primary Outcomes

Percentage of Participants Who Achieved RBC-Transfusion Independence

RBC-transfusion independence was defined as the absence of RBC transfusions for any consecutive 84-day interval.

Time frame: 168 days

China Extension: Number of Participants Achieving a Hemoglobin Increase of ≥ 15 g/L Compared to Baseline for ≥ 84 Consecutive Days

A response in the China extension study was defined as an increase in hemoglobin ≥ 15 g/L above baseline value (in the absence of RBC transfusion) for ≥ 84 consecutive days.

Time frame: From the first dose of study drug until treatment discontinuation; median treatment duration was 24.0 weeks.

Secondary Outcomes

Overall Survival

The time from randomization to the death or to the latest date when participants are known to be alive. Overall survival was analyzed using Kaplan-Meier method; participants who were alive or lost to follow-up were censored at the latest date they were known to be alive.

Time frame: From first dose of study drug up to end of study; median follow-up time was 19.1 months in the pomalidomide 0.5 mg arm and 17.6 months in the placebo arm.

Duration of RBC-Transfusion Independence

The duration of RBC-transfusion independence is the time from the date at which the first RBC-transfusion independence started to the date of another RBC-transfusion given at least 84 days after the time the transfusion independence started. The duration of the RBC-transfusion independence was analyzed using the Kaplan-Meier method. Data were censored at the end of the treatment phase for participants who had not received another RBC-transfusion after the start of transfusion independence by the end of treatment phase.

Time frame: From first dose of study drug up to 28 days after last dose, as of the data cut-off date of 16 Jan 2013; median treatment duration was 23.6 weeks in the pomalidomide arm and 23.9 weeks in the placebo arm.

Data from ClinicalTrials.gov

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