Safety of Romiplostim (Nplate®) Following UCBT

• ClinicalTrials.gov Identifier: NCT02046291
• Recruitment Status: Completed
• First Posted: January 27, 2014
• Last Update Posted: June 8, 2021
• Sponsor: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

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 (Clinical Trial)
• 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: April 10, 2015
• Actual Primary Completion Date: December 12, 2020
• Actual Study Completion Date: June 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 Name: Nplate

Outcome Measures

Primary Outcome Measures :

1. Maximum tolerated dose of romiplostim [ Time Frame: 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 :

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

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Minnesota

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Margaret MacMillan, MD, MSc, FRCPC; University of Minnesota

More Information

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT02046291
• Other Study ID Numbers: 2012LS089; MT2012-17R ( Other Identifier: University of Minnesota Blood and Marrow Transplant Program )
• First Posted: January 27, 2014
• Last Update Posted: June 8, 2021
• Last Verified: June 2021

Keywords provided by Masonic Cancer Center, University of Minnesota:

umbilical cord transplant; acute leukemia; UCBT; Hodgkin's Lymphoma; Lymphoid Leukemia; Multiple Myeloma; Myeloid and Monocytic Leukemia; Non-Hodgkin's Lymphoma; Hematopoietic malignancies

Additional relevant MeSH terms:

Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Hematologic Diseases