Hematologic Malignancies
Conditions
Keywords
umbilical cord transplant, acute leukemia, UCBT, Hodgkin's Lymphoma, Lymphoid Leukemia, Multiple Myeloma, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Hematopoietic malignancies
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.
Interventions
DRUGRomiplostim
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.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed