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

October 19, 2016 updated by: Sidney Kimmel Cancer Center at Thomas Jefferson University

A Phase I/II Study of Llme Treated Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematological Malignancies

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University'

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • LLME
Drug: Fludarabine
Fludarabine 30 mg/m2 prior to HSCT infusion
Other Names:
  • Fludara
  • fludarabine phosphate
Drug: Cytarabine
Cytarabine 2gm/m2 prior to HSCT infusion
Other Names:
  • Ara-C
  • cytosine arabinoside
  • Arabinofuranosyl Cytidine
Drug: Cyclophosphamide
Cyclophosphamide 1gm/m2 prior to HSCT infusion
Other Names:
  • Cytoxan
  • Endoxan
  • Neosar
  • Revimmune
  • Procytox
  • cytophosphane
Drug: Tacrolimus
Tacrolimus given before and after HSCT infusion
Other Names:
  • Fujimycin
  • FK-506
Drug: Mesna
Mesna 1gm/m2/day given prior to HSCT infusion.
Other Names:
  • Mesnex
  • Uromitexan
Biological: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)
GM-CSF given post HSCT infusion
Other Names:
  • GM-CSF
Procedure: Hematopoietic stem cell transplantation (HSCT)
CD34 selected allogeneic stem cell infusion with 5x104/kg untreated T cells
Other Names:
  • HSCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of CD34+ Stem Cell Infusions Followed by LLME as Measured by 100-Day Mortality
Time Frame: Through 100 days post-transplant or death

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.
Through 100 days post-transplant or death

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Engraftment of Non-Myeloablative Transplants
Time Frame: Through 30 days post-transplant
Determine the engraftment rate of non-myeloablative transplants using CD34+ stem cells and LLME treated CD34- products.
Through 30 days post-transplant
Incidence of Grade II-IV Acute Graft-Versus-Host-Disease (GVHD)
Time Frame: Through 24 months post-treatment
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.
Through 24 months post-treatment
Rate of Serious Infectious Complications
Time Frame: Through 3 months post-transplant

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.
Through 3 months post-transplant
Number of Patients Who Achieve a CD4 Count > 200/Micro-liters
Time Frame: Through 60 Days Post Transplant
Determine the number of patients who achieve a CD4 count > 200/micro-liters by 60 days after transplant.
Through 60 Days Post Transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Investigators

  • Principal Investigator: John Wagner, MD, Thomas Jefferson University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2004

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

May 1, 2009

Study Registration Dates

First Submitted

January 29, 2007

First Submitted That Met QC Criteria

January 30, 2007

First Posted (Estimate)

January 31, 2007

Study Record Updates

Last Update Posted (Estimate)

November 29, 2016

Last Update Submitted That Met QC Criteria

October 19, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 04U.115
  • 2003-68 (Other Identifier: CCRRC)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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