Using ROMIPLOSTINE for Persistent Thrombocytopenia With Transfusion-dependent Patients Who Received Allogeneic Hematopoietic Stem Cell (AGRAH003)

This is a Phase I/II multicenter study which aims to assess the toxicity profile of Romiplostim in patients with transfusion-dependent thrombocytopenia after allogeneic HSCT.

A total of 24 patients with transfusion-dependent thrombocytopenia after allogeneic HSCT will be included.

The main endpoint is the incidence and severity of adverse events.

Study Overview

• Status: Completed
• Conditions: Persistent Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
• Intervention / Treatment: Drug: Romiplostim

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Ile De France
    • Paris, Ile De France, France, 75010
      • Saint Louis Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must be ≥ 18 years, willing and able to sign informed consent
• Patients could have been transplanted for hematological disorder (malignant or non-malignant) excepted myelodysplastic syndromes patients and had received either a myeloablative or a reduced intensity conditioning. All sources of allogeneic stem cells are allowed.
• Prolonged (> 2 months) transfusion-dependent thrombocytopenia
• Screenings mean platelet count≤ 20 x giga/L or screenings mean platelet count ≤ 50 x giga/L with a history of bleeding.
• (ECOG) performance status of 0-2
• Adequate liver function
• Serum creatinine ≤ 176.8 μmol/L
• Bone marrow aspirate with cytogenetics within 6 days of the first dose of romiplostim
• Written informed consent

Exclusion Criteria:

• Relapse/progression of hematological malignancy (marrow examination required)
• Non-controlled acute and/or chronic graft versus host disease (GvHD)
• Active or uncontrolled infections
• Cardiac pathology - Thrombosis
• Pregnancy or breast feeding
• Received interleukin-11 (IL-11) within 4 weeks of screening or previously received any thrombopoietic growth factor
• Patients on anticoagulant therapy
• Receipt or planned receipt of Pegylated Granulocyte Colony Stimulating Factor (PEG-G-CSF), or Granulocyte macrophage-colony stimulating factor (GM-CSF) within 4 weeks of the first dose of investigational product
• Subject not using adequate contraceptive precautions, in the judgment of the investigator
• Sensitivity to any Escherichia coli-derived product
• Inability to comply with study procedures.
• Subject currently is enrolled in or has not yet completed 30 days since ending other investigational device or drug study
• No medical insurance in the French Health system

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Romiplostim; Weekly Romiplostim for 12 weeks with intra-patient weekly dose escalation from 1µg/Kg to a maximum dose of 10 µg/Kg with a dose reduction schema in case of platelet overshoot	Drug: Romiplostim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Incidence and severity of all adverse events	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse rate		12 months
Dose of Romiplostim	Dose of Romiplostim required to reach a platelet count above 50 x 109/L in absence of platelet transfusion	12 months
Durable platelet response after transplant:	platelet count above 50 x 109/L on 8 consecutive weeks independent of platelet transfusions	12 months
Graft versus host disease (GVHD)		12 months
Non relapse mortality rate		12 months
number of platelet transfusions		12 months
Overall number of bleeding events		12 months
platelet hematological improvements	Incidence and duration of platelet hematological improvements above 20 x 109/L and above 50 x 109/L , respectively	12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: November 4, 2013
• First Submitted That Met QC Criteria: November 4, 2013
• First Posted (Estimate): November 8, 2013

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: P110204