Safety of Romiplostim (Nplate®) Following UCBT

Study Overview
=================
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.

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

Conditions
-----------------
Hematologic Malignancies

Intervention / Treatment
-----------------
* Drug: Romiplostim


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romiplostim treatment<br>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<br>* 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.<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
umbilical cord transplant, acute leukemia, UCBT, Hodgkin's Lymphoma, Lymphoid Leukemia, Multiple Myeloma, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Hematopoietic malignancies