Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Neoplasms

Rare Diseases

Thrombocytopenia

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Blood Platelet Disorders

Cytopenia

Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg.

Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period.

Placebo is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.

Placebo

Romiplostim is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.

Romiplostim

The Data Monitoring Committee (DMC) for study 20060198 recommended that all subjects discontinue treatment of study drug and continue to be followed for long term follow-up. Amgen adopted the DMC recommendation.

This is a Phase 2, multicenter, randomized, double blind, placebo controlled study designed to assess the efficacy and safety of romiplostim (formerly, AMG 531) treatment in thrombocytopenic MDS patients. The study is composed of a 26-week placebo controlled test treatment period (romiplostim versus Placebo), a 4 week interim wash-out period, a 24-week placebo controlled extended treatment period, and a 4-week follow-up period followed by an End of Study (EOS) visit. During the interim wash-out period, a bone marrow biopsy will be performed in the absence of growth factor to assess changes in the marrow. In the extended treatment period, safety assessments will continue and participants will be allowed to receive any standard of care treatments for MDS. Patients will be followed for survival for an additional 60 months following the End of Study (EOS) visit.

Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

A clinically significant bleeding event is defined as any bleeding event of grade ≥ 2 per the modified World Health Organization (WHO) bleeding scale: • Grade 0 = no bleeding • Grade 1 = petechia or mucosal or retinal bleeding not requiring intervention • Grade 2 = melena, hematemesis, hematuria, hemoptysis • Grade 3 = bleeding required red cell transfusion • Grade 4 = retinal bleeding with visual impairment • Grade 5 = non-fatal cerebral bleeding • Grade 6 = fatal cerebral bleeding • Grade 7 = fatal non-cerebral bleeding. Bleeding events that continue for more than 7 days were counted as separate events every eighth day. Multiple events that arose from one organ system on one day were collapsed into one single event. Bleeding events with a start date between the first dose date and the last dose date of the test treatment period+7 days are included.

A discrete platelet transfusion is any number of platelet transfusion administered within a 3-day period. Transfusions administered more than 3 days apart are counted as separate events. Transfusion given in the absence of any bleeding, when platelet count is \>10x10\^9/L, is not counted as a platelet transfusion event. Events with start date between the first dose date and the last dose date of the test treatment period +7 days are included. Exposure adjusted event rate per 100 patient-years = (events / patient-years \* 100). Patient Year = total patient years of exposure to investigational product during 26 weeks test treatment period.

The time from first dose of study drug to the last dose of 26-week test treatment period. A bleeding event is defined as any bleeding event reported during the test treatment period. Bleeding events that continue for more than 7 days are counted as separate events every eighth day. Multiple events that arose from one organ system on one day are collapsed into one single event. Exposure adjusted event rate per 100 patient-years = events / patient-year \* 100).

The time from first dose of study drug to the last dose of 26-week test treatment period. A unit of platelets is defined as a single pack of pooled platelet-rich plasma comprised of 6 to 8 individual platelet concentrate packs (200 to 400 mL), a single pack of pooled buffy-coat concentrate, or 1 apheresis (single donor) concentrate. Exposure adjusted event rate per 100 patient-years = events / patient-years \* 100.

Platelet Hematologic Improvemen defined by the international working group (IWG) as: an absolute increase in platelet count of ≥ 30 x 10\^9/L for a patient starting with a platelet count of ≥ 20 x 10\^9/L or an increase in platelet count from \< 20 x 10\^9/L to ≥ 20 x 10\^9/L and by at least 100% in a patient that started with a platelet count \< 20 x 10\^9/L. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint.

Duration for participants who did not report HI-P during the period is 0. A platelet hematologic improvement (HI-P) is defined by an MDS International Working criteria as patients with a baseline platelet count of ≥ 20 x 10\^9/L achieving an absolute increase of ≥ 30 x 10\^9/L or increasing the platelet count to above 20 x 10\^9/L and by at least 100% in patients with a baseline of \< 20 x 10\^9/L for at least 8 consecutive weeks. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint. The durations of HI-P are cumulative if more than one incidence occurred. Exposure adjusted event rate per 100 patient-weeks = total number of weeks / patient-weeks \* 100.

Overall survival was calculated using Kaplan-Meier methods. For patients who discontinued early, additional information from the long term follow-up are added (closest available follow-up information up to 58 weeks).

Overall survival was calculated using Kaplan-Meier methods.

The number of bleeding events was obtained from the thrombocytopenia symptoms (Th-symptoms) survey. Patients reported spontaneous bleeding to have occurred 0, 1 or 2, 3 or 4, 5 or 6, or 7 or more times in the past week. The lower threshold of bleeding counts is used for conservative purposes (i.e., the "3" is used for the response option of "3 or 4 times"). Exposure adjusted event rate per 100 patient-years = number of events / patient-year \* 100.

Amgen

The safety analysis set consisted of 250 patients including 168 in the romiplostim group and 82 in the placebo group. One patient enrolled in the placebo group received 1 dose of romiplostim at week 4 of the extended treatment period. Results for this patient were analyzed as part of the romiplostim group in the Safety Analysis Set.

Total

Age, Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

Other

Race/Ethnicity, Customized

RARS

RAEB-1

RAEB-2

RCMD

RCMD-RS

MDS-U

MDS associated with isolated del 5Q

RA: Refractory Anemia RAEB-1: Refractory Anemia with Excess Blasts-1 RAEB-2: Refractory Anemia with Excess Blasts-2 RARS: Refractory Anemia with Ringed Sideroblasts RCMD: Refractory cytopenia with multilineage dysplasia RCMD-RS: Refractory cytopenia with multilineage dysplasia and ringed sideroblasts MDS-U: Myelodysplastic syndrome - unclassified MDS associated with isolated del(5q).

Myelodysplastic Syndromes World Health Organization Classification

Had received MDS therapy prior to enter the study

Prior MDS Therapy

Baseline Platelet Counts

Missing

The IPSS uses three "prognostic indicators" to develop a "score" which may be useful in understanding how the MDS may progress:

* the proportion of blast cells in the marrow;
* the type of chromosomal changes, if any, in the marrow cells;
* the presence of one or more low blood cell counts (cytopenias). Scores are sorted into one of four risk categories: 0 = low risk; 0.5-1.0 = intermediate-1; 1.5-2.0 = intermediate-2; \>2.5 = high risk.

International Prognostic Scoring System (IPSS) Total Score

Study Director

Full analysis set includes all randomized patients.

Number of Clinically Significant Bleeding Events

Annualized Rate of Platelet Transfusion Events

Annualized Rate of Overall Bleeding Events

Full analysis set includes all randomized subjects

Annualized Rate of Total Platelet Transfusion Units

Number of Participants With Platelet Hematologic Improvement (HI-P)

Exposure-adjusted Total Duration of Platelet Hematologic Improvement (HI-P) in the Absence of Platelet Transfusions

Number of Participants Who Died

Time to Death

Kaplan-Meier Estimate of Survival at Month 12

The Patient Reported Outcomes (PRO) analysis set consists of patients in the full analysis set who also completed the baseline and at least one post-baseline assessment for any PRO measure.

Spots Global Cancer Trial Database for Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial