Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors
|Leukemia, Myeloid, Acute Myelodysplastic Syndromes Lymphoma, Non-Hodgkin Hodgkin Disease Leukemia, Lymphocytic, Chronic, B-Cell Multiple Myeloma||Drug: Sargramostim Drug: Plerixafor||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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|
- Number of Donors Requiring a Second Collection to Obtain a Minimum CD34/Kg (2 x 10^6) Necessary for Allogeneic Stem Cell Transplantation [ Time Frame: Up to 6 days ]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.
- Proportion of Donors Who Experience Grade 3-4 Infusion Toxicity [ Time Frame: 30 days after completion of therapy (estimated to be 36 days) ]Infusional toxicity will be evaluated by measuring the patient's blood pressure, heart rate, respirations and temperature one hour prior to the allograft infusion and then 15 minutes, 30 minutes, one hour, 2 hours, and 4 hours, and 6 hours post infusion. Donors will have vital signs collected at each time point. EKGs will be performed immediately prior to IV AMD3100 and one hour after infusion.
- Number of Donors Who Mobilize ≥ 2x10^6 CD34+ Cells/Kg Recipient Weight Safely Following One or Two Aphereses [ Time Frame: Up to 6 days ]-The donor will undergo a leukapheresis procedure to process 20L of blood volume. After the procedure, the collection will be analyzed to look at CD34+ cell content. If it contains at least 2x10^6 CD34+ cells/kg, then the procedure will be considered successful.
- Percentage of Donors Who Reach 5x10^6 CD34+ Cells/Kg Recipient Weight in 1 or 2 Aphereses [ Time Frame: 6 days ]-The donor will undergo a leukapheresis procedure to process 20L of blood volume. After the procedure, the collection will be analyzed to look at CD34+ cell content. The percentage of donors who reach at least 5x10^6 CD34+ cells/Kg recipient weight will be analyzed for this outcome measure.
- 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 Time to Neutrophil Engraftment (Recipient Only) [ Time Frame: Up to Day 21 ]-Time to neutrophil engraftment is measured by determining the first of 3 consecutive measurements of neutrophil count ≥ 500/ul following conditioning regimen induced nadir.
- Kinetics of Immune Reconstitution as Measured by Time to Neutrophil Engraftment (Recipient Only) [ Time Frame: Up to Day 100 ]-Time to neutrophil engraftment is measured by determining the first of 3 consecutive measurements of neutrophil count ≥ 500/ul following conditioning regimen induced nadir.
- Kinetics of Immune Reconstitution as Measured by Time to Platelet Engraftment (Recipient Only) [ Time Frame: Up to Day 180 ]-Time to platelet engraftment is measured by determining the first of 3 consecutive measurements of platelet count ≥ 20,000/ul without platelet transfusion support for 7 days.
- Rate of Acute Graft vs. Host Disease (GvHD) (Recipient Only) [ Time Frame: Up through Day 100 ]-Incidence and severity of acute GVHD will be assessed based on the Seattle criteria. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).
- Rate of Chronic Graft vs. Host Disease (GvHD) (Recipient Only) [ Time Frame: Day 100-1 year ]Incidence and severity of chronic GVHD will be assessed based on the NIH consensus criteria and global severity scoring system. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).
- Transplant Related Mortality (Recipient Only) [ Time Frame: 100 days ]Death that results from a transplant procedure related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause.
- Relapse and Disease Progression Rate [ Time Frame: Up to 1 year ]-A patient will be considered relapsed (disease progressed) when there is a recurrence of the original malignant disease after transplantation.
- Death of Any Cause (Recipients Only) [ Time Frame: Up to 1 year ]
|Actual Study Start Date:||April 1, 2011|
|Study Completion Date:||December 31, 2016|
|Primary Completion Date:||January 15, 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm 1 - Donor
Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF (first 4 donors were mobilized with 10 mcg/kg GM-CSF then changed to 5 mcg/kg for remaining donors)
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|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Mark Schroeder, M.D.||Washington University School of Medicine|