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
Overview
- Phase
- Phase 2
- Intervention
- Sargramostim
- Conditions
- Leukemia, Myeloid, Acute
- Sponsor
- Washington University School of Medicine
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Number of Donors Requiring a Second Collection to Obtain a Minimum CD34/Kg (2 x 10^6) Necessary for Allogeneic Stem Cell Transplantation
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This study will gather information about the combination the drugs plerixafor with sargramostim in donors of blood-forming cells (stem cells). These stem cells will be collected from the donor and transplanted into their sibling. 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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Donor Eligibility
- •Donor is 18 to 65 years of age inclusive.
- •If female and of child-bearing age, donor must be non-pregnant, not breastfeeding, and agree to use adequate contraception.
- •Donor is a 6/6 HLA-matched sibling willing to donate PBSC for transplant.
- •Donor has adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia.
- •Donor has adequate renal function as defined by a calculated serum creatinine clearance of ≥56 ml/min for females and ≥64 ml/min for males.
- •Donor has adequate hepatic function as defined by a total bilirubin \<2x normal or absence of hepatic fibrosis/cirrhosis.
- •Donor has adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality. No history of cerebrovascular accident or seizure disorder requiring anticonvulsant medication.
- •Donor must be HIV-1\&2 antibody and HTLV-I\&II antibody sero-negative, by FDA licensed test.
- •Donor must have an ECOG performance status of 0 or
Exclusion Criteria
- •Donor Exclusion Criteria in addition to that stated above
- •Donor may not be receiving any other investigational agents.
- •Donor may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to plerixafor or GM-CSF, or known hypersensitivity to yeast-derived products or any component of the product.
Arms & Interventions
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.
Intervention: Sargramostim
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.
Intervention: Plerixafor
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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)(Up to Day 21)
- Kinetics of Immune Reconstitution as Measured by Time to Neutrophil Engraftment (Recipient Only)(Up to Day 100)
- Rate of Acute Graft vs. Host Disease (GvHD) (Recipient Only)(Up through Day 100)
- Proportion of Donors Who Experience Grade 3-4 Infusion Toxicity(30 days after completion of therapy (estimated to be 36 days))
- Number of Donors Who Mobilize ≥ 2x10^6 CD34+ Cells/Kg Recipient Weight Safely Following One or Two Aphereses(Up to 6 days)
- Percentage of Donors Who Reach 5x10^6 CD34+ Cells/Kg Recipient Weight in 1 or 2 Aphereses(6 days)
- Kinetics of Immune Reconstitution as Measured by Time to Platelet Engraftment (Recipient Only)(Up to Day 180)
- Rate of Chronic Graft vs. Host Disease (GvHD) (Recipient Only)(Day 100-1 year)
- Transplant Related Mortality (Recipient Only)(100 days)
- Relapse and Disease Progression Rate(Up to 1 year)
- Death of Any Cause (Recipients Only)(Up to 1 year)