Safety of Romiplostim (Nplate®) Following UCBT

Safety of Romiplostim (Nplate®) in Patients Who Have Failed to Achieve Platelet Engraftment Following Umbilical Cord Blood Transplant

This is a single institution, phase I dose escalation study of weekly romiplostim post umbilical cord blood transplantation in patients who fail to achieve platelet engraftment by day +30. Engraftment is defined as a platelet count ≥ 20 x 109/L on 3 consecutive measurements without transfusion for 7 days. Romiplostim is administered at the assigned dose as 6 weekly injections beginning by day +42 post transplant. Up to 4 dose levels (4, 6, 8, and 10 mcg/kg/dose) will be evaluated with the maximum tolerated dose (MTD) of romiplostim determined by using the Continual Reassessment Method (CRM). The goal of this CRM will be to identify 1 of the 4 dose levels which corresponds to the desired maximum toxicity rate of 20% or less.

Study Overview

• Status: Completed
• Conditions: Hematologic Malignancies
• Intervention / Treatment: Drug: Romiplostim

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Masonic Cancer Center

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:

• Any patient who has undergone a single or double umbilical cord blood transplant (UCBT) except those with primary myelofibrosis.

  • Those with acute leukemia must be in remission at the time of transplant
• Must have achieved neutrophil engraftment (defined as an ANC >500 for three consecutive days) and be off daily G-CSF prior to starting romiplostim. Intermittent G-CSF is allowed.
• Failure to achieve platelet engraftment (defined as platelet count ≥20x10^9/L on 3 consecutive measurements without transfusion for 7 days) by day +28 post UCBT
• Between day +28 and day +42 status post myeloablative or nonmyeloablative UCBT (single or double cord blood transplant)
• Age ≥ 18 years

• Adequate organ function within 7 days of enrollment defined as:

  • Creatinine: ≤ 2.0 mg/dL
  • Hepatic: SGOT and SGPT < 5 x upper limit of institutional normal (ULN)
• Women of child bearing potential agree to use effective contraception during therapy and for 4 months after completion of therapy
• Voluntary written consent

Exclusion Criteria:

• Known pregnancy - Pregnancy Category C: there are no adequate and well-controlled studies of romiplostim in pregnancy
• Recurrence of AML or myelodysplastic syndrome on bone marrow evaluation done within 21 days of enrollment
• Presence of clinically significant bone marrow fibrosis on the bone marrow examination immediately prior to UCBT
• Patients requiring more than one platelet transfusion per day
• History of an allergy to romiplostim

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• 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 treatment; Romiplostim at the assigned dose will be administered subcutaneously (SQ) once a week for 6 weeks (i.e. 6 doses) unless platelet count exceeds 100 x 10^9/L and at least 4 doses of therapy were given.After the initial dose, subsequent doses will be administered within a window of +/- 3 days.	Drug: Romiplostim; Romiplostim at the assigned dose will be administered subcutaneously (SQ) once a week for 6 weeks. The dose will be assigned at the time of subject registration. This is a dose escalation to determine the maximum tolerated dose. The doses include 4 mcg/kg/dose, 6 mcg/kg/dose, 8 mcg/kg/dose, and 10 mcg/kg/dose.; Other Names: Nplate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose of romiplostim	Measured by number of patients who have failed to achieve platelet engraftment by day +28 after a myeloablative or nonmyeloablative umbilical cord blood transplant (UCBT)	Day +28 blood transplant (UCBT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet recovery	Average speed of platelet recovery in patients who have failed to achieve platelet engraftment.	Day +28
Thrombocytopenia	Incidence of clinically significant bleeding episodes and number of platelet transfusions.	Day +28
Bone marrow fibrosis	Incidence of bone marrow fibrosis.	Day 100 post transplant

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Margaret MacMillan, MD, MSc, FRCPC, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2015
• Primary Completion (Actual): December 12, 2020
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: January 23, 2014
• First Submitted That Met QC Criteria: January 23, 2014
• First Posted (Estimate): January 27, 2014

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 5, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; umbilical cord transplant; acute leukemia; UCBT; Lymphoid Leukemia; Myeloid and Monocytic Leukemia; Hematopoietic malignancies
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: 2012LS089; MT2012-17R (Other Identifier: University of Minnesota Blood and Marrow Transplant Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No