Safety of Romiplostim (Nplate®) Following UCBT

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Completed

CT.gov ID

NCT02046291

Collaborator

(none)

Enrollment

Location

Arm

73.7

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies	Drug: Romiplostim	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Apr 10, 2015

Actual Primary Completion Date :

Dec 12, 2020

Actual Study Completion Date :

Jun 1, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of romiplostim [Day +28 blood transplant (UCBT)]
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)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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