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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

NCT ID: NCT00429416

Last Updated: 2016-11-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-03-31

Study Completion Date

2009-05-31

Brief Summary

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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

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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.

Conditions

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Hematologic Malignancies

Keywords

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Hematologic Malignancies GVHD Graft-Versus-Host-Disease LLME CD34+ stem cell infusions CD34- fraction Cyclosporine Mycophenolate Mofetil HSCT Hematopoietic stem cell transplantation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

L-leucyl-L-leucine Methyl Ester (LLME)

Intervention Type DRUG

Infusion of L-leucyl-L-leucine methyl ester (LLME) treated donor white blood cells

Fludarabine

Intervention Type DRUG

Fludarabine 30 mg/m2 prior to HSCT infusion

Cytarabine

Intervention Type DRUG

Cytarabine 2gm/m2 prior to HSCT infusion

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide 1gm/m2 prior to HSCT infusion

Tacrolimus

Intervention Type DRUG

Tacrolimus given before and after HSCT infusion

Mesna

Intervention Type DRUG

Mesna 1gm/m2/day given prior to HSCT infusion.

Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)

Intervention Type BIOLOGICAL

GM-CSF given post HSCT infusion

Hematopoietic stem cell transplantation (HSCT)

Intervention Type PROCEDURE

CD34 selected allogeneic stem cell infusion with 5x104/kg untreated T cells

Interventions

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L-leucyl-L-leucine Methyl Ester (LLME)

Infusion of L-leucyl-L-leucine methyl ester (LLME) treated donor white blood cells

Intervention Type DRUG

Fludarabine

Fludarabine 30 mg/m2 prior to HSCT infusion

Intervention Type DRUG

Cytarabine

Cytarabine 2gm/m2 prior to HSCT infusion

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide 1gm/m2 prior to HSCT infusion

Intervention Type DRUG

Tacrolimus

Tacrolimus given before and after HSCT infusion

Intervention Type DRUG

Mesna

Mesna 1gm/m2/day given prior to HSCT infusion.

Intervention Type DRUG

Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)

GM-CSF given post HSCT infusion

Intervention Type BIOLOGICAL

Hematopoietic stem cell transplantation (HSCT)

CD34 selected allogeneic stem cell infusion with 5x104/kg untreated T cells

Intervention Type PROCEDURE

Other Intervention Names

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LLME fludarabine phosphate Fludara cytosine arabinoside Ara-C Arabinofuranosyl Cytidine Endoxan Cytoxan Neosar Procytox Revimmune cytophosphane FK-506 Fujimycin Uromitexan Mesnex GM-CSF HSCT

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sidney Kimmel Cancer Center at Thomas Jefferson University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John Wagner, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

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Thomas Jefferson University'

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Related Links

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http://www.KimmelCancerCenter.org

Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center

http://www.JeffersonHospital.org/

Thomas Jefferson University Hospital

Other Identifiers

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2003-68

Identifier Type: OTHER

Identifier Source: secondary_id

04U.115

Identifier Type: -

Identifier Source: org_study_id