Research Study to Determine if an Experimental Agent, LLME Can Decrease the Incidence and Severity of Graft-Versus-Host-Disease (GVHD) Following Blood (Hematopoietic) Stem Cell Transplantation
The purpose of this research study is to determine if an experimental agent, LLME can decrease the incidence and severity of Graft-Versus-Host-Disease (GVHD) following blood (hematopoietic) stem cell transplantation
Drug: L-leucyl-L-leucine Methyl Ester (LLME)
Biological: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)
Procedure: Hematopoietic stem cell transplantation (HSCT)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Llme Treated Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematological Malignancies|
- Safety of CD34+ Stem Cell Infusions Followed by LLME as Measured by 100-Day Mortality [ Time Frame: Through 100 days post-transplant or death ] [ Designated as safety issue: Yes ]
Determine the safety of CD34+ stem cell infusions followed by the LLME treated CD34- fraction. This includes monitoring the patients for any side effects associated with the LLME treated cell infusion or any other unexpected adverse events.
This regimen will be gauged as to its safety using 100 day mortality as the measured endpoint. Deaths from all causes will be included.
- Rate of Engraftment of Non-Myeloablative Transplants [ Time Frame: Through 30 days post-transplant ] [ Designated as safety issue: No ]Determine the engraftment rate of non-myeloablative transplants using CD34+ stem cells and LLME treated CD34- products.
- Incidence of Grade II-IV Acute Graft-Versus-Host-Disease (GVHD) [ Time Frame: Through 24 months post-treatment ] [ Designated as safety issue: Yes ]Determine the incidence of grade II-IV acute GVHD after administration of grafts when combined with Cyclosporine/Mycophenolate Mofetil for GVHD prophylaxis. GVHD assessments occur daily as an in patient and at each out patient visit.
- Rate of Serious Infectious Complications [ Time Frame: Through 3 months post-transplant ] [ Designated as safety issue: Yes ]
Determine the rate of serious infectious complications. A serious infection will be defined as any requiring hospitalization or parenteral therapy.
CD4 counts will be measured monthly for the first 3 months after transplant.
- Number of Patients Who Achieve a CD4 Count > 200/Micro-liters [ Time Frame: Through 60 Days Post Transplant ] [ Designated as safety issue: No ]Determine the number of patients who achieve a CD4 count > 200/micro-liters by 60 days after transplant.
|Study Start Date:||March 2004|
|Study Completion Date:||May 2009|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Experimental: LLME to Decrease GVHD Following HSC T
To determine if an experimental agent, LLME, can decrease the incidence and severity of Graft-Versus-Host-Disease (GVHD) following hematopoietic stem cell transplantation (HSCT).
Drug: L-leucyl-L-leucine Methyl Ester (LLME)
Infusion of L-leucyl-L-leucine methyl ester (LLME) treated donor white blood cells
Other Name: LLMEDrug: Fludarabine
Fludarabine 30 mg/m2 prior to HSCT infusion
Other Names:Drug: Cytarabine
Cytarabine 2gm/m2 prior to HSCT infusion
Other Names:Drug: Cyclophosphamide
Cyclophosphamide 1gm/m2 prior to HSCT infusion
Other Names:Drug: Tacrolimus
Tacrolimus given before and after HSCT infusion
Other Names:Drug: Mesna
Mesna 1gm/m2/day given prior to HSCT infusion.
Other Names:Biological: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)
GM-CSF given post HSCT infusion
Other Name: GM-CSFProcedure: Hematopoietic stem cell transplantation (HSCT)
CD34 selected allogeneic stem cell infusion with 5x104/kg untreated T cells
Other Name: HSCT
We believe that the risks of allogeneic transplant can be drastically reduced if the following criteria can be met: (1) consistent engraftment, (2) little or no GVHD with the ability to rapidly withdraw immune suppression, (3) rapid recovery of CD4 counts to levels greater than 200 cells/micro liter. Our prior (ongoing) trial attempts to address how LLME treated T cells given as donor lymphocyte infusion (DLI) can address points 2 and 3 above. The current study addresses how treatment of the CD34- fraction of the graft attempts to address points 1 and 2 (and to a lesser extent point 3) above. We believe that if these points can be consistently achieved that the mortality of allogeneic HSCT may be reduced to levels more akin to those of autologous HSCT. We propose to test the hypothesis that LLME-treated T cells will be safe with regard to reducing GVHD or other infusion related toxicities and that their administration as part of the transplant will facilitate engraftment. We believe that this approach will ultimately be an important step in a variety of transplant settings ranging from matched siblings to haplodisparate donors.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00429416
|United States, Pennsylvania|
|Thomas Jefferson University`|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||John Wagner, MD||Thomas Jefferson University|