NCT00321711

Determination of Safe and Effective Dose of Romiplostim (AMG 531) in Subjects With Myelodysplastic Syndrome (MDS)Receiving Hypomethylating Agents

Completed Phase 2 Results posted Last updated 17 October 2018

What this trial tests

Phase 2 trial testing Placebo in MDS in 69 participants. Completed in 19 October 2009.

Timeline

1 October 2006

Primary endpoint
19 October 2009

19 October 2009

Quick facts

Lead sponsor	Amgen
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	supportive care
Enrollment	69
Start date	1 October 2006
Primary completion	19 October 2009
Estimated completion	19 October 2009

Drugs / interventions tested

• Placebo
• AMG 531 (Romiplostim) — full drug profile →
• Azacitidine (azacitidine) — full drug profile →
• Decitabine (decitabine) — 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

18 and older, 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.

Occurrence of a Clinically Significant Thrombocytopenic Event Primary · Treatment period (up to 20 weeks)

Occurrence of a clinically significant thrombocytopenic event within the participant, defined as any platelet count obtained from day 15 of cycle 1 through the end of the interim follow-up visit that was less than 50 x 10\^9/L or receipt of platelet transfusions at any time through the interim follow-up visit.

Group	Value	95% CI
Romiplostim (AMG 531) Placebo Plus Azacitidine	11
Romiplostim (AMG 531) 500 mcg Plus Azacitidine	8
Romiplostim (AMG 531) 750 mcg Plus Azacitidine	10
Romiplostim (AMG 531) Placebo Plus Decitabine	11
Romiplostim (AMG 531) 750 mcg Plus Decitabine	12

Hypomethylating Agent Dose Reduction and Delay Due to Thrombocytopenia Secondary · Treatment period (up to 20 weeks)

Occurrence of hypomethylating agent dose reduction and delay due to thrombocytopenia

Group	Value	95% CI
Romiplostim (AMG 531) Placebo Plus Azacitidine	1
Romiplostim (AMG 531) 500 mcg Plus Azacitidine	1
Romiplostim (AMG 531) 750 mcg Plus Azacitidine	0
Romiplostim (AMG 531) Placebo Plus Decitabine	0
Romiplostim (AMG 531) 750 mcg Plus Decitabine	0

Achieving an Overall Response (Complete or Partial Response, CR or PR) at the End of the Treatment Period Secondary · Treatment period (up to 20 weeks)

CR = decrease in bone marrow blast (≤5%) and improvement in peripheral blood counts (Hgb ≥ 11 g/dL, platelets ≥ 100x10\^9/L, neutrophils ≥ 1x10\^9/L, peripheral blasts=0%). PR = improvement in peripheral blood counts plus a decrease in bone marrow blasts ≥50% but not ≤5, or decrease in International Prognostic Scoring System score.

Group	Value	95% CI
Romiplostim (AMG 531) Placebo Plus Azacitidine	2
Romiplostim (AMG 531) 500 mcg Plus Azacitidine	1
Romiplostim (AMG 531) 750 mcg Plus Azacitidine	1
Romiplostim (AMG 531) Placebo Plus Decitabine	3
Romiplostim (AMG 531) 750 mcg Plus Decitabine	5

Platelet Transfusion Secondary · Study day 1 through the interim follow-up visit (up to 20 weeks)

Occurrence of one or more platelet transfusions from study day 1 through the interim follow-up visit (16 weeks)

Group	Value	95% CI
Romiplostim (AMG 531) Placebo Plus Azacitidine	9
Romiplostim (AMG 531) 500 mcg Plus Azacitidine	6
Romiplostim (AMG 531) 750 mcg Plus Azacitidine	5
Romiplostim (AMG 531) Placebo Plus Decitabine	8
Romiplostim (AMG 531) 750 mcg Plus Decitabine	7

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 20 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A Placebo

Serious: 9/13 (69%)

Deaths: —

Part A Romiplostim 500 µg

Serious: 4/13 (31%)

Deaths: —

Part A Romiplostim 750 µg

Serious: 10/14 (71%)

Deaths: —

Part B Placebo

Serious: 8/14 (57%)

Deaths: —

Part B Romiplostim 750 µg

Serious: 8/15 (53%)

Deaths: —

Serious adverse events (68 terms)

Reaction	System	Part A Placebo	Part A Romiplostim 500 µg	Part A Romiplostim 750 µg	Part B Placebo	Part B Romiplostim 750 µg
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Pancytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—
Atrial flutter	Cardiac disorders	—	—	—	—	—
Sick sinus syndrome	Cardiac disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Anal fissure	Gastrointestinal disorders	—	—	—	—	—
Caecitis	Gastrointestinal disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—
Haemorrhoidal haemorrhage	Gastrointestinal disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—
Inflammation	General disorders	—	—	—	—	—
Pain	General disorders	—	—	—	—	—
Hyperbilirubinaemia	Hepatobiliary disorders	—	—	—	—	—
Hypersensitivity	Immune system disorders	—	—	—	—	—

Other adverse events (253 terms — click to expand)

Reaction	System	Part A Placebo	Part A Romiplostim 500 µg	Part A Romiplostim 750 µg	Part B Placebo	Part B Romiplostim 750 µg
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Injection site pain	General disorders	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Ecchymosis	Skin and subcutaneous tissue disorders	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Injection site erythema	General disorders	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—
Skin laceration	Injury, poisoning and procedural complications	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Blood blister	Skin and subcutaneous tissue disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—
Atrial flutter	Cardiac disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—	—	—
Melaena	Gastrointestinal disorders	—	—	—	—	—
Oral pain	Gastrointestinal disorders	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Chills	General disorders	—	—	—	—	—
Injection site discomfort	General disorders	—	—	—	—	—

Most-reported serious reactions: Febrile neutropenia, Anaemia, Pyrexia, Pneumonia, Urinary tract infection, Hypotension, Pancytopenia, Atrial fibrillation.

Data from ClinicalTrials.gov NCT00321711 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the effect of Romiplostim (AMG 531) on the incidence of clinically significant thrombocytopenic events (grade 3 or 4 and/or receipt of platelet transfusions) in subjects with low or intermediate risk Myelodysplastic Syndrome (MDS) receiving hypomethylating agents. It is hypothesized that Romiplostim administration, at the appropriate dose and schedule, will result in reduction in the incidence of clinically significant thrombocytopenic events in low or intermediate risk MDS subjects receiving hypomethylating agents.

Publications & conference data

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

1. Trials with 'epigenetic' drugs: an update.
   Nebbioso A, Carafa V, Benedetti R, Altucci L. · · 2012 · cited 162× · PMID 23103179 · DOI 10.1016/j.molonc.2012.09.004
2. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy.
   Kantarjian HM, Giles FJ, Greenberg PL, Paquette RL, et al · · 2010 · cited 101× · PMID 20631375 · DOI 10.1182/blood-2010-03-274753
3. 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
4. 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
5. 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
6. Historical expectations with DNA methyltransferase inhibitor monotherapy in MDS: when is combination therapy truly "promising"?
   Brunner AM, Fell G, Steensma DP. · · 2022 · cited 3× · PMID 35143613 · DOI 10.1182/bloodadvances.2021006357