Safety and Efficacy of POL6326 for Mobilization/Transplant of Sibling Donor in Patients With Hematologic Malignancies
Acute Myeloid Leukemia in Remission
Adult Acute Lymphoblastic Leukemia in Remission
Chronic Myelogenous Leukemia (CML)
Non-Hodgkin's Lymphoma (NHL) or Hodgkin's Disease (HD) in 2nd or Greater Complete Remission, Partial Remission
Chronic Lymphocytic Leukemia (CLL)
Multiple Myeloma (MM)
Myelodysplastic Syndrome (MDS)
Procedure: PBSC Transplant
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study Evaluating the Safety and Efficacy of Intravenous POL6326 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies|
- Phase I Study - safety and tolerability of POL6326 as a mobilization agent. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
- Phase II Study - determine the number of allogeneic donors who require a second leukapheresis [ Time Frame: 2 days ] [ Designated as safety issue: No ]Determine the number of allogeneic donors which collect >= 2 mill CD34+ cells with one or two leukapheresis procedures treated with IV POL6326. Comparison with historic group of donors who were mobilized with 240 µg/kg SC plerixafor.
- Phase I Study - define maximum tolerated dose of POL6326 [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
- Phase II Study - the proportion of HLA-identical sibling donors who experience grade 3-4 infusional toxicity and the proportion who are safely mobilized [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]To estimate the proportion of HLA-identical sibling donors who experience grade 3-4 infusional toxicity and the proportion from whom > 2 mill CD34+ cells/kg recipient weight are safely mobilized following one or two leukapheresis procedures
- Phase II Study - pharmacokinetics and pharmacodynamics of IV POL6326 [ Time Frame: Day 1-3 ] [ Designated as safety issue: No ]Stem cell and T-cell phenotyping
- Phase II Study - rate of acute GVHD and chronic GVHD in patients who receive IV POL6326 mobilized peripheral blood stem cells. [ Time Frame: Day 100 (+/- 7 days) or Day 365 (+/-14 days) ] [ Designated as safety issue: Yes ]Acute GVHD - Day 100 (+/- 7 days) Chronic GVHD - Day 365 (+/- 14 days)
- Phase II Study - kinetics of neutrophil and platelet engraftment in recipients of POL6326 mobilized peripheral blood stem cells. [ Time Frame: Day 365 (+/- 14 days) ] [ Designated as safety issue: No ]
|Study Start Date:||April 2012|
|Study Completion Date:||December 2015|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Experimental: Donor (Phase I and Phase II)
On Day 1 (and possibly Day 2) POL6326 IV Infusion with increasing dose levels in Phase I or with random dose assignment (from the 2 selected from Phase I) in phase II
Leukapheresis collection on Day 1 (and possibly Day 2)
|Drug: POL6326 Procedure: Leukapheresis|
Day 0 - PBSC transplant with stem cells mobilized with IV POL6326
|Procedure: PBSC Transplant|
Current protocols use G-CSF to mobilize hematopoietic progenitor cells from matched sibling donors. This process requires from four to six days of G-CSF injection and is associated with significant morbidity, most notably bone pain. POL6326 is associated with few side effects and collection of cells occurs on the same day as POL6326 administration.
This study will evaluate the safety and efficacy of this novel agent for hematopoietic progenitor cell mobilization and allogeneic transplantation based on the following hypotheses:
- Donors mobilized with intravenous POL6326 will require fewer collections than have previously been seen for donors mobilized with subcutaneous plerixafor.
- Healthy HLA-matched donors receiving one or two infusions of POL6326 will mobilize sufficient CD34+ cells (at least 2.0 x 106 CD34+ cells/kg recipient weights) following leukapheresis to support a hematopoietic cell transplant.
- IV POL6326 will result in more rapid kinetics and a higher maximum (peak) of human CD34+ stem cells mobilized from human normal allogeneic donors compared to previous donors who were mobilized with plerixafor.
- The hematopoietic cells mobilized by IV POL6326 will be functional and will result in prompt and durable hematopoietic engraftment following transplantation into HLA-identical siblings with advanced hematological malignancies using various non-myeloablative and myeloablative conditioning regimens and regimens for routine GVHD prophylaxis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01413568
|United States, Kansas|
|University of Kansas Cancer Center|
|Kansas City, Kansas, United States, 66205|
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Daniel Couriel, M.D.||University of Utah|