NCT00614523

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

Completed Phase 2 Results posted Last updated 7 November 2022

What this trial tests

Phase 2 trial testing Placebo in MDS in 250 participants. Completed in 30 November 2015.

Timeline

21 July 2008

Primary endpoint
31 March 2011

30 November 2015

Quick facts

Lead sponsor	Amgen
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	supportive care
Enrollment	250
Start date	21 July 2008
Primary completion	31 March 2011
Estimated completion	30 November 2015

Drugs / interventions tested

• Placebo
• Romiplostim (ROMIPLOSTIM) — full drug profile →

Conditions studied

• MDS — all drugs for MDS →
• Myelodysplastic Syndromes — all drugs for Myelodysplastic Syndromes →
• Thrombocytopenia — all drugs for Thrombocytopenia →

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 90, any sex, with MDS or Myelodysplastic Syndromes. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Clinically Significant Bleeding Events Primary · Test Treatment Period (Weeks 1-26)

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 sepa

Group	Value	95% CI
Placebo	116
Romiplostim	178

Annualized Rate of Platelet Transfusion Events Secondary · Test Treatment Period (Weeks 1-26)

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 p

Group	Value	95% CI
Placebo	1013.5	905.2 – 1131.3
Romiplostim	748.9	681.3 – 821.4

Annualized Rate of Overall Bleeding Events Secondary · Test Treatment Period (Weeks 1-26)

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).

Group	Value	95% CI
Placebo	3786.4	3574.1 – 4008.0
Romiplostim	3459.9	3312.8 – 3611.9

Annualized Rate of Total Platelet Transfusion Units Secondary · Test Treatment Period (Weeks 1-26)

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.

Group	Value	95% CI
Placebo	3120.2	2927.8 – 3322.0
Romiplostim	2221.8	2104.2 – 2344.2

Number of Participants With Platelet Hematologic Improvement (HI-P) Secondary · Test Treatment Period (Weeks 1-26)

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 meas

Group	Value	95% CI
Placebo	3
Romiplostim	61

Exposure-adjusted Total Duration of Platelet Hematologic Improvement (HI-P) in the Absence of Platelet Transfusions Secondary · Test Treatment Period (Weeks 1-26)

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 to

Group	Value	95% CI
Placebo	2.57	1.85 – 3.47
Romiplostim	35.02	32.98 – 37.16

Number of Participants Who Died Secondary · From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012.

Group	Value	95% CI
Placebo	17	NA – NA
Romiplostim	30	NA – NA

Time to Death Secondary · From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012.

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).

Group	Value	95% CI
Placebo	NA	NA – NA
Romiplostim	NA	NA – NA

Kaplan-Meier Estimate of Survival at Month 12 Secondary · Month 12, with a data cut-off date of 20 July 2012.

Overall survival was calculated using Kaplan-Meier methods.

Group	Value	95% CI
Placebo	78	67 – 86
Romiplostim	83	76 – 88

Annualized Rate of Patient-reported Bleeding Events Secondary · Test Treatment Period (Weeks 1-26)

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.

Group	Value	95% CI
Placebo	1995	1840.5 – 2158.9
Romiplostim	1264	1175.1 – 1357.7

Adverse events — posted to ClinicalTrials.gov

Time frame: 58 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 22/82 (27%)

Deaths: —

Romiplostim

Serious: 67/168 (40%)

Deaths: —

Serious adverse events (106 terms)

Reaction	System	Placebo	Romiplostim
Pneumonia	Infections and infestations	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Pyrexia	General disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Head injury	Injury, poisoning and procedural complications	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Sepsis	Infections and infestations	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Splenic infarction	Blood and lymphatic system disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Bronchitis	Infections and infestations	—	—
Bronchopneumonia	Infections and infestations	—	—
Erysipelas	Infections and infestations	—	—
Neutropenic sepsis	Infections and infestations	—	—
Post procedural haemorrhage	Injury, poisoning and procedural complications	—	—
Myeloblast count increased	Investigations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Cerebral haemorrhage	Nervous system disorders	—	—
Dizziness	Nervous system disorders	—	—
Syncope	Nervous system disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (42 terms — click to expand)

Reaction	System	Placebo	Romiplostim
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Haematoma	Vascular disorders	—	—
Petechiae	Skin and subcutaneous tissue disorders	—	—
Contusion	Injury, poisoning and procedural complications	—	—
Gingival bleeding	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Oedema peripheral	General disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Blood blister	Skin and subcutaneous tissue disorders	—	—
Fatigue	General disorders	—	—
Haemorrhage	Vascular disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Mouth haemorrhage	Gastrointestinal disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Ecchymosis	Skin and subcutaneous tissue disorders	—	—
Pyrexia	General disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Dizziness	Nervous system disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Insomnia	Psychiatric disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Injection site haematoma	General disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Conjunctival haemorrhage	Eye disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Oral herpes	Infections and infestations	—	—
Vessel puncture site haematoma	General disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: Pneumonia, Anaemia, Pyrexia, Thrombocytopenia, Atrial fibrillation, Head injury, Epistaxis, Gastrointestinal haemorrhage.

Data from ClinicalTrials.gov NCT00614523 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia.
   Giagounidis A, Mufti GJ, Fenaux P, Sekeres MA, et al · · 2014 · cited 120× · PMID 24706489 · DOI 10.1002/cncr.28663
2. Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial.
   Kantarjian HM, Fenaux P, Sekeres MA, Szer J, et al · · 2018 · cited 71× · PMID 29396092 · DOI 10.1016/s2352-3026(18)30016-4
3. Development and validation of a model to predict platelet response to romiplostim in patients with lower-risk myelodysplastic syndromes.
   Sekeres MA, Giagounidis A, Kantarjian H, Mufti GJ, et al · · 2014 · cited 15× · PMID 25039607 · DOI 10.1111/bjh.13037
4. Safety and Efficacy of Eltrombopag and Romiplostim in Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis.
   Meng F, Chen X, Yu S, Ren X, et al · · 2020 · cited 14× · PMID 33324559 · DOI 10.3389/fonc.2020.582686
5. Thrombopoietin mimetics for patients with myelodysplastic syndromes.
   Dodillet H, Kreuzer KA, Monsef I, Skoetz N. · · 2017 · cited 13× · PMID 28962071 · DOI 10.1002/14651858.cd009883.pub2
6. Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation.
   Desborough M, Estcourt LJ, Doree C, Trivella M, et al · · 2016 · cited 10× · PMID 27548292 · DOI 10.1002/14651858.cd010982.pub2
7. Relationship of different platelet response criteria and patient outcomes in a romiplostim myelodysplastic syndromes trial.
   Platzbecker U, Sekeres MA, Kantarjian H, Giagounidis A, et al · · 2014 · cited 9× · PMID 25179731 · DOI 10.1038/leu.2014.253
8. Off-Label Use of Thrombopoietin Receptor Agonists: Case Series and Review of the Literature.
   Capecchi M, Serpenti F, Giannotta J, Pettine L, et al · · 2021 · cited 6× · PMID 34650908 · DOI 10.3389/fonc.2021.680411