search
Back to results

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

Primary Purpose

Hematologic Malignancies

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
L-leucyl-L-leucine Methyl Ester (LLME)
Fludarabine
Cytarabine
Cyclophosphamide
Tacrolimus
Mesna
Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)
Hematopoietic stem cell transplantation (HSCT)
Sponsored by
Sidney Kimmel Cancer Center at Thomas Jefferson University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring Hematologic Malignancies, GVHD, Graft-Versus-Host-Disease, LLME, CD34+ stem cell infusions, CD34- fraction, Cyclosporine, Mycophenolate Mofetil, HSCT, Hematopoietic stem cell transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must be > 18 years of age, with no upper age limit.
  • Patients must have an ECOG performance status of 0 or 1.
  • Any patient with a hematologic malignancy which is unlikely to be cured by conventional treatment is eligible for this study.
  • Patients for whom a disease specific protocol exists will be transplanted on those protocols as discussed in the introduction.
  • Patients who have had prior autografts may be treated on this protocol.
  • Patients must have adequate physical function as measured by the following criteria:
  • Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be >40%.
  • Hepatic: Aspartate transaminase (AST) micro 3x the upper limits of normal and total serum bilirubin < 2.5 mg/dL. Patients with a higher bilirubin from "benign conditions" such as Gilbert's disease may still be eligible for the study.
  • Renal: Serum creatinine within the normal range or if creatinine outside normal range then creatinine clearance > 60 ml/min/1.73m2. Serum creatinine must be less than or equal to 2.0 mg/dl.
  • Pulmonary: Asymptomatic or, if symptomatic, DLCO (diffusion capacity) > 45% of predicted (corrected for hemoglobin)
  • The patient or guardian(s) must be able to give informed consent to the study.
  • Patient must have a suitable donor who is identical for HLA (human leukocyte antigens) -A, -B, -C, -DR. Single antigen mismatches for HLA-A, -B, -C, -DR are also permitted. Donors obtained through the National Marrow Donor Program (NMDP) will follow NMDP guidelines.

Exclusion Criteria:

  • Patients who are eligible for a standard myeloablative transplant and for whom a standard myeloablative transplant is preferable will not be treated on this protocol.

Sites / Locations

  • Thomas Jefferson University'

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LLME to Decrease GVHD Following HSC T

Arm Description

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).

Outcomes

Primary Outcome Measures

Safety of CD34+ Stem Cell Infusions Followed by LLME as Measured by 100-Day Mortality
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.

Secondary Outcome Measures

Rate of Engraftment of Non-Myeloablative Transplants
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)
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
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
Determine the number of patients who achieve a CD4 count > 200/micro-liters by 60 days after transplant.

Full Information

First Posted
January 29, 2007
Last Updated
October 19, 2016
Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
search

1. Study Identification

Unique Protocol Identification Number
NCT00429416
Brief Title
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
Official Title
A Phase I/II Study of Llme Treated Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
March 2004 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancies
Keywords
Hematologic Malignancies, GVHD, Graft-Versus-Host-Disease, LLME, CD34+ stem cell infusions, CD34- fraction, Cyclosporine, Mycophenolate Mofetil, HSCT, Hematopoietic stem cell transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LLME to Decrease GVHD Following HSC T
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
L-leucyl-L-leucine Methyl Ester (LLME)
Other Intervention Name(s)
LLME
Intervention Description
Infusion of L-leucyl-L-leucine methyl ester (LLME) treated donor white blood cells
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
fludarabine phosphate, Fludara
Intervention Description
Fludarabine 30 mg/m2 prior to HSCT infusion
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
cytosine arabinoside, Ara-C, Arabinofuranosyl Cytidine
Intervention Description
Cytarabine 2gm/m2 prior to HSCT infusion
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane
Intervention Description
Cyclophosphamide 1gm/m2 prior to HSCT infusion
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK-506, Fujimycin
Intervention Description
Tacrolimus given before and after HSCT infusion
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Uromitexan, Mesnex
Intervention Description
Mesna 1gm/m2/day given prior to HSCT infusion.
Intervention Type
Biological
Intervention Name(s)
Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)
Other Intervention Name(s)
GM-CSF
Intervention Description
GM-CSF given post HSCT infusion
Intervention Type
Procedure
Intervention Name(s)
Hematopoietic stem cell transplantation (HSCT)
Other Intervention Name(s)
HSCT
Intervention Description
CD34 selected allogeneic stem cell infusion with 5x104/kg untreated T cells
Primary Outcome Measure Information:
Title
Safety of CD34+ Stem Cell Infusions Followed by LLME as Measured by 100-Day Mortality
Description
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.
Time Frame
Through 100 days post-transplant or death
Secondary Outcome Measure Information:
Title
Rate of Engraftment of Non-Myeloablative Transplants
Description
Determine the engraftment rate of non-myeloablative transplants using CD34+ stem cells and LLME treated CD34- products.
Time Frame
Through 30 days post-transplant
Title
Incidence of Grade II-IV Acute Graft-Versus-Host-Disease (GVHD)
Description
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.
Time Frame
Through 24 months post-treatment
Title
Rate of Serious Infectious Complications
Description
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.
Time Frame
Through 3 months post-transplant
Title
Number of Patients Who Achieve a CD4 Count > 200/Micro-liters
Description
Determine the number of patients who achieve a CD4 count > 200/micro-liters by 60 days after transplant.
Time Frame
Through 60 Days Post Transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must be > 18 years of age, with no upper age limit. Patients must have an ECOG performance status of 0 or 1. Any patient with a hematologic malignancy which is unlikely to be cured by conventional treatment is eligible for this study. Patients for whom a disease specific protocol exists will be transplanted on those protocols as discussed in the introduction. Patients who have had prior autografts may be treated on this protocol. Patients must have adequate physical function as measured by the following criteria: Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be >40%. Hepatic: Aspartate transaminase (AST) micro 3x the upper limits of normal and total serum bilirubin < 2.5 mg/dL. Patients with a higher bilirubin from "benign conditions" such as Gilbert's disease may still be eligible for the study. Renal: Serum creatinine within the normal range or if creatinine outside normal range then creatinine clearance > 60 ml/min/1.73m2. Serum creatinine must be less than or equal to 2.0 mg/dl. Pulmonary: Asymptomatic or, if symptomatic, DLCO (diffusion capacity) > 45% of predicted (corrected for hemoglobin) The patient or guardian(s) must be able to give informed consent to the study. Patient must have a suitable donor who is identical for HLA (human leukocyte antigens) -A, -B, -C, -DR. Single antigen mismatches for HLA-A, -B, -C, -DR are also permitted. Donors obtained through the National Marrow Donor Program (NMDP) will follow NMDP guidelines. Exclusion Criteria: Patients who are eligible for a standard myeloablative transplant and for whom a standard myeloablative transplant is preferable will not be treated on this protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Wagner, MD
Organizational Affiliation
Thomas Jefferson University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Thomas Jefferson University'
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.JeffersonHospital.org/
Description
Thomas Jefferson University Hospital

Learn more about this trial

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

We'll reach out to this number within 24 hrs