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| ID | Type | Description | Link |
|---|---|---|---|
| 2003-68 | Other Identifier | CCRRC |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-leucyl-L-leucine Methyl Ester (LLME) | Drug | Infusion of L-leucyl-L-leucine methyl ester (LLME) treated donor white blood cells |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Engraftment of Non-Myeloablative Transplants | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Wagner, MD | Thomas Jefferson University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Thomas Jefferson University' | Philadelphia | Pennsylvania | 19107 | United States |
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| Label | URL |
|---|---|
| Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center | View source |
| Thomas Jefferson University Hospital | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | LLME to Decrease GVHD Following HSC T | To determine if an experimental agent, L-leucyl-L-leucine Methyl Ester (LLME), can decrease the incidence and severity of Graft-Versus-Host-Disease (GVHD) following hematopoietic stem cell transplantation (HSCT). Treatment Outline: Day -6: Fludarabine 30 mg/m2 IV, Cytarabine 2 gm/m2 IV Day -5: Fludarabine 30 mg/m2 IV, Cyclophosphamide 1 gm/m2 IV, Mesna 1 gm/m2 IV Day -4: Fludarabine 30 mg/m2 IV, Cytarabine 2 gm/m2 IV, Mesna 1 gm/m2 IV Day -3: Fludarabine 30 mg/m2 IV, Cyclophosphamide 1 gm/m2 IV, Mesna 1 gm/m2 IV Day -2: Fludarabine 30 mg/m2 IV, Cytarabine 2 gm/m2 IV, Mesna 1 gm/m2 IV Day -1: Rest day Day 0: CD34 selected allogeneic stem cell infusion with 5x104/kg untreated T cells Day 1: Infusion of LLME treated donor CD34 - cells |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Fludarabine | Drug | Fludarabine 30 mg/m2 prior to HSCT infusion |
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| Cytarabine | Drug | Cytarabine 2gm/m2 prior to HSCT infusion |
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| Cyclophosphamide | Drug | Cyclophosphamide 1gm/m2 prior to HSCT infusion |
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| Tacrolimus | Drug | Tacrolimus given before and after HSCT infusion |
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| Mesna | Drug | Mesna 1gm/m2/day given prior to HSCT infusion. |
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| Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) | Biological | GM-CSF given post HSCT infusion |
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| Hematopoietic stem cell transplantation (HSCT) | Procedure | CD34 selected allogeneic stem cell infusion with 5x104/kg untreated T cells |
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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 | 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 | Determine the number of patients who achieve a CD4 count > 200/micro-liters by 60 days after transplant. | Through 60 Days Post Transplant |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | participants | Through 100 days post-transplant or death |
|
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| |||||||||||||||||||||||||||
| Secondary | Rate of Engraftment of Non-Myeloablative Transplants | Determine the engraftment rate of non-myeloablative transplants using CD34+ stem cells and LLME treated CD34- products. | Posted | Number | participants | Through 30 days post-transplant |
|
| ||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Number | participants | Through 24 months post-treatment |
|
| ||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Number | participants | Through 3 months post-transplant |
|
| ||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Number | participants | Through 60 Days Post Transplant |
|
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"Other Adverse Events" were not collected/assessed
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). | 10 | 14 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | General disorders |
| |||
| Bone marrow cellularity | General disorders |
| |||
| Infection | General disorders |
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| Pancyptopenia | General disorders |
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| Hematoma | General disorders |
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| Death | General disorders |
| |||
| Hypersensitivity | General disorders |
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| Chest pain | General disorders |
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| Progressive disease | General disorders |
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| Nausea | General disorders |
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| Vomiting | General disorders |
| |||
| Fevers | General disorders |
| |||
| Rash | General disorders |
| |||
| Prostatic obstruction | General disorders |
| |||
| Pericardial effusion | General disorders |
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| Opportunistic infection | General disorders |
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| Bladder obstruction | General disorders |
| |||
| Hepatic failure | General disorders |
| |||
| Renal insufficiency | General disorders |
| |||
| Renal failure | General disorders |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Wagner, MD | Thomas Jefferson University | 215-955-8874 | John.Wagner@jefferson.edu |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D003561 | Cytarabine |
| D003520 | Cyclophosphamide |
| D016559 | Tacrolimus |
| D015080 | Mesna |
| D003115 | Colony-Stimulating Factors |
| D016178 | Granulocyte-Macrophage Colony-Stimulating Factor |
| D018380 | Hematopoietic Stem Cell Transplantation |
| ID | Term |
|---|---|
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D018942 | Macrolides |
| D007783 | Lactones |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
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