Safety of Romiplostim (Nplate®) Following UCBT

University of Minnesota (UMN)

Status and phase: Completed; Phase 1

Conditions: Hematologic Malignancies

Treatments: Drug: Romiplostim

Study type: Interventional

Funder types: Other

Identifiers

NCT02046291

2012LS089

MT2012-17R (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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21 participants in 1 patient group

Romiplostim treatment

Experimental group

Description:

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.

Treatment:

Drug: Romiplostim