Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors
Leukemia, Myeloid, Acute
Leukemia, Lymphocytic, Chronic, B-Cell
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial Evaluating the Safety and Efficacy of Plerixafor and Sargramostim (GM-CSF) for the Mobilization of Peripheral Blood Stem Cells (PBSC) From Normal, HLA-Matched Allogeneic Sibling Donors|
- Reduce the number of donors requiring a second collection [ Time Frame: 6 days (donor) ] [ Designated as safety issue: No ]The primary endpoint is to reduce the number of donors treated with GM-CSF who require a second collection to obtain a minimum CD34/Kg (2 x 106) necessary for allogeneic stem cell transplantation when compared to historic controls mobilized with GM-CSF or plerixafor alone. A reduction in failed first leukapheresis from 40% to less than 10% as seen with G-CSF alone would be considered clinically meaningful.
- Donor toxicity [ Time Frame: 30 days after completion of therapy ] [ Designated as safety issue: Yes ]To estimate the 95% confidence intervals of the proportion of HLA-identical sibling donors who experience grade 3-4 infusion toxicity.
- Donor stem cell collection in 1 or 2 apheresis [ Time Frame: 6 days ] [ Designated as safety issue: Yes ]To estimate the 95% confidence intervals of the proportion of HLA-identical sibling donors who mobilize ≥ 2x106 CD34+ cells/Kg recipient weight safely following one or two aphereses and to estimate the 95% confidence intervals the proportion of HLA-identical sibling donors who reach 5x106 CD34+cells/Kg recipient weight in 1 or 2 aphereses.
- Kinetics of stems cell, lymphocyte and dendritic cell mobilization [ Time Frame: Day 21 ] [ Designated as safety issue: Yes ]To determine the kinetics of stem cell, lymphocyte and dendritic cell mobilization using IV plerixafor and GM-CSF and to determine if peripheral blood stem cell products collected after mobilization with IV plerixafor can be used safely for hematopoietic cell transplantation in HLA-matched recipients as measured by neutrophil engraftment by day +21.
- Pharmacokinetics and pharmacodynamics [ Time Frame: 5 days ] [ Designated as safety issue: No ]Determine the pharmacokinetics and pharmacodynamics of GM-CSF on IV plerixafor.
- Engraftment post transplant [ Time Frame: 100 days ] [ Designated as safety issue: No ]Determine the kinetics of immune reconstitution measured by engraftment of neutrophils, platelets, lymphocyte subsets, TREC analysis, and quantitative immunoglobulins after transplantation.
- Rate of acute and chronic Graft vs. Host Disease (GvHD) [ Time Frame: 100 days ] [ Designated as safety issue: No ]Determine the rate of acute GvHD and chronic GvHD in recipients who receive GM-CSF + IV plerixafor mobilized peripheral blood stem cells.
- Transplant related mortality [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]Determine transplant related mortality at day +100
- Relapse, disease progression and death of any cause [ Time Frame: 1 year ] [ Designated as safety issue: No ]Determine relapse, disease progression and death of any cause
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm 1 - Donor
Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF
Day 5: Mobilization with 320 mcg/kg plerixafor IV
Day 5: Leukopheresis
If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.
Other Name: GM-CSF, LeukineDrug: Plerixafor
Other Name: AMD3100, Mozobil
No Intervention: Arm 2 - Recipient
Day -2 = GvHD prophylaxis
Day 0 or +1 = PBSC transplant
Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day
The main purpose of this study is to gather information about the combination the drugs plerixafor with sargramostim in donors of blood-forming cells (stem cells). Stem cells can be taken from the bone marrow of the pelvic bones or from the blood following treatment with drugs called growth factors; sargramostim is such a drug. Once stem cells leave the bone marrow and circulate in the blood, they are called peripheral blood stem cells (PBSCs). These cells can be collected through a routine procedure called apheresis, which involves placing two IVs into the arm which are connected to an apheresis machine; the machine then takes blood from the body, removes the stem cells, and returns the blood to the body.
Normally, a growth factor called filgrastim is given to donors in order to collect the stem cells used for transplantation. However, when stem cells collected using filgrastim are transplanted in patients, a possible unpredictable complication is graft versus host disease. It's thought that using a different growth factor such as sargramostim might reduce the occurrences of graft versus host disease in patients. However, sargramostim alone does not provide as many stem cells for transplantation as other growth factors. Plerixafor is another drug that can increase the number of PBSCs in a donor, but like with sargramostim, plerixafor alone does not always provide enough stem cells. This is why sargramostim and plerixafor are being combined in this study: the investigators believe that the two drugs together will provide enough stem cells for transplantation and may also reduce the risk of graft versus host disease.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01158118
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Mark Schroeder, M.D.||Washington University School of Medicine|