Intravenous (IV) AMD3100 for Mobilization and Matched Related Transplant for Advanced Hematological Malignancies
Procedure: Stem cell transplant
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study Evaluating the Safety and Efficacy of Intravenous AMD3100 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies|
- Number of Donors Treated With IV AMD3100 Who Required a Second Collection to Obtain the Minimum CD34/kg (2 X 106) Necessary for Allogeneic Stem Cell Transplant [ Time Frame: Completion of enrollment of all donors (17 months) ] [ Designated as safety issue: Yes ]
- Number of Donors Who Experience Grade 3-4 Infusional Toxicity [ Time Frame: Up to Day 2 ] [ Designated as safety issue: Yes ]
- Number of Recipients Who Have Neutrophil Engraftment [ Time Frame: Day 21 ] [ Designated as safety issue: Yes ]
- Pharmacokinetics of IV AMD3100 as Measured by the Mean Maximum Plasma Concentration (Cmax) [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
- Pharmacokinetics of IV AMD3100 as Measured by Half Life [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
- Pharmacodynamics of IV AMD3100 on Stem Cell and T-cell Phenotyping and on Immune Reconstitution After Transplantation. [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
- Rate of Acute GVHD (Grade II-IV) in Recipients [ Time Frame: Day 0-Day 100 (acute) ] [ Designated as safety issue: Yes ]
- Rate of Acute GVHD (Grade III-IV) in Recipients [ Time Frame: Day 0-Day 100 (acute) ] [ Designated as safety issue: Yes ]
- Time to Neutrophil Engraftment for Recipients [ Time Frame: Up through Day 100 ] [ Designated as safety issue: No ]Measured by determine the first 3 consecutive measurement of neutrophil count = 500/ul following conditioning regimen induced nadir.
- Time to Platelet Engraftment for Recipients [ Time Frame: Up to Day 100 ] [ Designated as safety issue: No ]Measured by determining the first of 3 consecutive measurements of platelet count = 20,000/ul without platelet transfusion support for 7 days.
- Transplant Related Mortality Rate for Recipients [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]Death that results from a transplant procedure related complication rather than from relapse of the underlying disease or unrelated cause.
- Grade 3-4 Toxicity for Recipients [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]Assessed and graded according to NCI Common Terminology for Adverse Events Version 3.0.
- Rate of Chronic GVHD in Recipients [ Time Frame: Day 101-1 year ] [ Designated as safety issue: Yes ]
- Number of Donors Who Experience Grade 3-4 Mobilization Toxicity Due to Pheresis Procedure [ Time Frame: Up to Day 2 ] [ Designated as safety issue: No ]
|Study Start Date:||August 2009|
|Study Completion Date:||February 2012|
|Primary Completion Date:||January 2011 (Final data collection date for primary outcome measure)|
Experimental: Arm 1 - Donor
Other Names:Procedure: Leukopheresis
Experimental: Arm 2 - Recipient
Standard of care and physician choice myeloablative or non-myeloablative chemotherapy with or without total body irradiation (permitted = cyclophosphamide and single dose total body irradiation (TBI) / fludarabine and busulfan / fractionated TBI and cyclophosphamide / fractionated TBI, etoposide, and cyclophosphamide / busulfan and cyclophosphamide / fludarabine, busulfan, and ATGAM
Day 0 = Stem Cell Transplant
|Procedure: Stem cell transplant|
- To reduce the number of donors treated with intravenous (IV) AMD3100 who require a second collection to obtain the minimum CD34/kg (2 X 106) necessary for allogeneic stem cell transplantation when compared to our historic group who received 240ug SC AMD3100 from 33% (8 in 24) to 11% (3 in 27).
- To estimate with 95% confidence intervals the proportion of human leukocyte antigen (HLA)-identical sibling donors who experience grade 3-4 infusional toxicity and the proportion from whom ≥ 2.0 x 10e6 CD34+ cells/kg recipient weight are safely mobilized following one or two intravenous infusions.
- To determine the kinetics of stem cell and lymphocyte mobilization using IV AMD3100 and to determine if peripheral blood stem cell products collected after mobilization with IV AMD3100 can be used safely for hematopoietic cell transplantation in HLA-matched recipients as measured by neutrophil engraftment by day +21.
- To determine the pharmacokinetics and pharmacodynamics of IV AMD3100 on stem cell and T-cell phenotyping and on immune reconstitution after transplantation.
- To determine the rate of acute graft-versus-host disease (GVHD) and chronic GVHD in patients who receive IV AMD3100 mobilized peripheral blood stem cells.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00914849
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||John DiPersio, M.D., Ph.D.||Washington University School of Medicine|