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

NCT00429416 | Completed Phase 1 Results DMC

• 2 other identifiers: 04U.1152003-68
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Through 100 days post-transplant or death

Secondary Outcomes (4)

• Rate of Engraftment of Non-Myeloablative Transplants

  Through 30 days post-transplant

• Incidence of Grade II-IV Acute Graft-Versus-Host-Disease (GVHD)

  Through 24 months post-treatment

• Rate of Serious Infectious Complications

  Through 3 months post-transplant

• Number of Patients Who Achieve a CD4 Count > 200/Micro-liters

  Through 60 Days Post Transplant

Study Arms (1)

LLME to Decrease GVHD Following HSC T

EXPERIMENTAL

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); Drug: Fludarabine; Drug: Cytarabine; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mesna; Biological: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF); Procedure: Hematopoietic stem cell transplantation (HSCT)

Interventions

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

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

Also known as: LLME

LLME to Decrease GVHD Following HSC T

Fludarabine DRUG

Fludarabine 30 mg/m2 prior to HSCT infusion

Also known as: fludarabine phosphate, Fludara

LLME to Decrease GVHD Following HSC T

Cytarabine DRUG

Cytarabine 2gm/m2 prior to HSCT infusion

Also known as: cytosine arabinoside, Ara-C, Arabinofuranosyl Cytidine

LLME to Decrease GVHD Following HSC T

Cyclophosphamide DRUG

Cyclophosphamide 1gm/m2 prior to HSCT infusion

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

LLME to Decrease GVHD Following HSC T

Tacrolimus DRUG

Tacrolimus given before and after HSCT infusion

Also known as: FK-506, Fujimycin

LLME to Decrease GVHD Following HSC T

Mesna DRUG

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

Also known as: Uromitexan, Mesnex

LLME to Decrease GVHD Following HSC T

Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) BIOLOGICAL

GM-CSF given post HSCT infusion

Also known as: GM-CSF

LLME to Decrease GVHD Following HSC T

Hematopoietic stem cell transplantation (HSCT) PROCEDURE

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

Also known as: HSCT

LLME to Decrease GVHD Following HSC T

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University'

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

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

MeSH Terms

Conditions

Hematologic Neoplasms; Graft vs Host Disease

Interventions

fludarabine; fludarabine phosphate; Cytarabine; Cyclophosphamide; Tacrolimus; Mesna; Colony-Stimulating Factors; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: John Wagner, MD
• Organization: Thomas Jefferson University

John.Wagner@jefferson.edu

215-955-8874

Study Officials

• John Wagner, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2007
• First Posted: January 31, 2007
• Study Start: March 1, 2004
• Primary Completion: December 1, 2008
• Study Completion: May 1, 2009
• Last Updated: November 29, 2016
• Results First Posted: December 10, 2013

Record last verified: 2016-10

Locations

US (1)