NCT02335268: EUROPE

Validation of a Predictive Model of Response to Romiplostim in Patients With IPSS Low or Intermediate-1 Risk MDS and Thrombocytopenia

Completed Phase 2 Results posted Last updated 16 August 2023

What this trial tests

Phase 2 trial testing N-Plate / romiplostim in Myelodysplastic Syndromes in 77 participants. Completed in 1 July 2021.

Timeline

21 May 2015

Primary endpoint
1 July 2021

1 July 2021

Quick facts

Lead sponsor	Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	77
Start date	21 May 2015
Primary completion	1 July 2021
Estimated completion	1 July 2021
Sites	36 locations across France, Germany

Drugs / interventions tested

• N-Plate / romiplostim — full drug profile →

Conditions studied

• Myelodysplastic Syndromes — all drugs for Myelodysplastic Syndromes →

Sponsor

Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH — full company profile →

Who can join

18 and older, any sex, with 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.

Hematologic Improvement of Platelets (HI-P) After 4 Months on Therapy Primary · after 4 months on therapy (week 16)

The primary efficacy endpoint was the rate of HI-P defined as an absolute increase of platelet count to ≥ 30/nL for patients starting at \> 20/nL or an increase of platelets from \< 20/nL to \> 20/nL and by at least 100%, according to IWG 2006 criteria lasting for ≥ 8 weeks after at least 16 Weeks of romiplostim treatment.

Group	Value	95% CI
Model Group A	71.75	-15.5 – 342.5
Model Groups B+C	18.75	-25.0 – 161.0

Cumulative Hematologic Improvement Secondary · week 16

Cumulative rate of hematologic improvement of platelets (HI-P), erythrocytes (HI-E) and neutrophil granulocytes (HI-N). None of the patients achieved simultaneous response of HI-P, HI-E and HI-N.

Group	Value	95% CI
Model Group A	0
Model Groups B+C	0
Model Group A	51
Model Groups B+C	26

The Incidence of Disease Progression to Higher Stage MDS or AML Secondary · week 16

The incidence of disease progression to higher stage MDS or AML according to WHO (increase in blast percentage of ≥ 20 %)

yes

Group	Value	95% CI
Model Group A	6
Model Groups B+C	2

no

Group	Value	95% CI
Model Group A	45
Model Groups B+C	24

Increase of Peripheral Blasts During Therapy Secondary · week 16

< 5%

Group	Value	95% CI
Model Group A	31
Model Groups B+C	15

5%-10%

Group	Value	95% CI
Model Group A	0
Model Groups B+C	0

10%-20%

Group	Value	95% CI
Model Group A	0
Model Groups B+C	0

> 20%

Group	Value	95% CI
Model Group A	0
Model Groups B+C	0

missing

Group	Value	95% CI
Model Group A	20
Model Groups B+C	11

Association of the Presence of Certain Mutations With Disease Progression in a Retrospective Analysis Secondary · week 16

Group	Value	95% CI
Full Analysis Set	69
Full Analysis Set	8

Incidence of Bleeding Events Secondary · up to 12 months

Group	Value	95% CI
Model Group A	0.263	± 0.476
Model Groups B+C	0.249	± 0.363

Type, Incidence and Severity of All Adverse Events Including Clinically Significant Changes in Laboratory Values Secondary · up to 12 months

Group	Value	95% CI
Model Group A	499
Model Groups B+C	159

Adverse events — posted to ClinicalTrials.gov

Time frame: 16 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Model Group A

Serious: 12/51 (24%)

Deaths: 0/51

Model Groups B+C

Serious: 8/26 (31%)

Deaths: 1/26

Serious adverse events (40 terms)

Reaction	System	Model Group A	Model Groups B+C
Syncope	Nervous system disorders	—	—
Hemorrhage	Vascular disorders	—	—
Central venous catheterization	Surgical and medical procedures	—	—
AML	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Oropharyngeal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Asthenia	General disorders	—	—
Mucosal hemorrhage	General disorders	—	—
Pyrexia	General disorders	—	—
Testicular torsion	Reproductive system and breast disorders	—	—
Drug-specific antibody	Investigations	—	—
Monocyte count increased	Investigations	—	—
C-reactive protein increased	Investigations	—	—
Physical examination	Investigations	—	—
Angina unstable	Cardiac disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Lung infiltration	Respiratory, thoracic and mediastinal disorders	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Colitis	Gastrointestinal disorders	—	—
Gastrointestinal angiectasia	Gastrointestinal disorders	—	—
Hematochezia	Gastrointestinal disorders	—	—
Inguinal hernia	Gastrointestinal disorders	—	—

Other adverse events (14 terms — click to expand)

Reaction	System	Model Group A	Model Groups B+C
Leukocytosis	Blood and lymphatic system disorders	—	—
Blast cells present	Investigations	—	—
Petechiae	Skin and subcutaneous tissue disorders	—	—
Hematoma	Vascular disorders	—	—
Hypertension	Vascular disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Headache	Nervous system disorders	—	—
Chest pain	General disorders	—	—
Injection site hematoma	General disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—

Most-reported serious reactions: Syncope, Hemorrhage, Central venous catheterization, AML, Oropharyngeal cancer, Asthenia, Mucosal hemorrhage, Pyrexia.

Data from ClinicalTrials.gov NCT02335268 adverse events section.

Sponsor's own description

There are currently no licensed drugs in the EU to treat thrombocytopenia in MDS patients classified as IPSS low/int-1. Prior studies with romiplostim (a TPO receptor agonist) in MDS found that baseline concentration of TPO as well as transfusion history were predictive of subsequent response in a retrospective model. The current prospective study has the aim to explore whether both pretreatment variables (endogenous TPO, TPO-level, platelet transfusion history) can predict the response to subsequent short-term treatment with romiplostim.

Publications & conference data

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

1. Prospective validation of a biomarker-driven response prediction model to romiplostim in lower-risk myelodysplastic neoplasms - results of the EUROPE trial by EMSCO.
   Kubasch AS, Giagounidis A, Metzgeroth G, Jonasova A, et al · · 2022 · cited 8× · PMID 36071100 · DOI 10.1038/s41375-022-01669-z
2. Abstract Book for the 27th Congress of the European Hematology Association
   · 2022
3. Facing the challenge: Novel treatment options for patients with myelodysplastic syndromes
   Kubasch A, Platzbecker U. · · 2018