Donor Enhancement With Plerixafor Post Myeloablative Allogeneic Transplant
This phase I/II clinical trial will test the safety and the efficacy of post transplant administration of plerixafor in enhancing hematological recovery in humans. Patients who are appropriate candidates for myeloablative allogeneic stem cell transplantation from an HLA-matched sibling, matched unrelated donor or umbilical cord blood are eligible for enrollment. The investigators plan to enroll a total of 50 patients for this study (30 patients with HLA-matched sibling or matched unrelated donor transplant, and 20 patients with umbilical cord blood transplant). During phase I study, a small number of patients (3-6 patients from each group) will be enrolled to determine the safety of post transplant administration of plerixafor. Patients will receive plerixafor given at 240 µg/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment. Limiting toxicities are defined as primary or secondary graft failure, plerixafor-related severe premature ventricular arrhythmia or death. If safety criteria are met from the investigators phase I study, the investigators will proceed with phase II study to determine the efficacy of post transplant administration of plerixafor in enhancing haematological recovery. The experimental aspect of this study is the use of plerixafor and all other aspects of care will be in line with the standard of care. Both Phase I and Phase II patients will be combined for efficacy analysis, and data collected from this study will be compared with the investigators historical control. The results from this study will set the stage and provide the justification for a larger phase 3 trial.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study: Enhancing Donor Hematopoietic Cell Engraftment With Plerixafor in Myeloablative Allogeneic Hematopoietic Cell Transplantation|
- Time to neutrophil recovery [ Time Frame: 100 Days post Transplant ] [ Designated as safety issue: Yes ]leukocytes > 500/ul on 2 consecutive days
- Time to platelet recovery [ Time Frame: 100 Days Post Transplant ] [ Designated as safety issue: Yes ]platelet > 20,000/ul on 2 consecutive days
- Plerixafor-associated adverse events [ Time Frame: 100 Days Post Transplant ] [ Designated as safety issue: Yes ]
- Overall survival at day +100 [ Time Frame: 100 Days Post Transplant ] [ Designated as safety issue: Yes ]
- Immunological reconstitution [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]As determined by CD4 count, CD8 count, NK cells, B cells and Immunloglobulin level on day +30, 60+, and +90
- Plasma cytokines/chemokines [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]As determined by IL-12, IFN-gamma, TNF-alpha and macrophage inhibitory protein-1 measured at day +7, +14 and +30.
- Incidence of grade II/IV acute graft versus host disease [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]Weekly through Day 100 post transplant
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||February 2018|
|Estimated Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
Experimental: Matched sibling or Dual Cord Donor
This arm will be stratified into transplant recipients from 30 matched sibling donors and 20 dual cord blood donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Matched sibling or Dual Cord donor subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Recruitment to this trial will be stratified by donor type as HLA matched sibling, matched unrelated donor or umbilical cord blood. Patients will be conditioned with a myeloablative regimen such as, but not limited to, total body irradiation and cyclophosphamide. The donor stem cell grafts will come from mobilized peripheral blood of 8/8 or 7/8 HLA-identical family members, 8/8 (HLA A, B, C, DRBeta1) allele-level matched unrelated donors, or dual umbilical cord blood grafts with at least 4 of 6 HLA matching at HLA A and B (low resolution) and DRBeta1 (at high resolution). The target CD34+ cell dose will be 5 X 10(6)/kg recipient ideal body weight. For HLA matched sibling or matched unrelated donor (MUD) transplants, all patients will receive a minimum of 2 X 10(6) CD 24+ cells/kg. For cord blood transplants, each unit will contain a minimum total nucleated cell count of of 1.5 X 10(7)/kg. Post-transplant GVHD prophylaxis will be given per institutional standard.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01280955
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27705|
|United States, South Carolina|
|Medical University of South Carolina|
|Charleston, South Carolina, United States, 29425|
|Principal Investigator:||Mitchell Horwitz, MD||Duke University|
|Principal Investigator:||Saurabh Chhabra, MD||Medical University of South Carolina|