Trial Outcomes & Findings for 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 NCT00429416)

Last Updated: 2016-11-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Through 100 days post-transplant or death

Results posted on

2016-11-29

Participant Flow

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	14
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Death	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LLME to Decrease GVHD Following HSC T n=14 Participants 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).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	54.65 years STANDARD_DEVIATION 9.74 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants

PRIMARY outcome

Timeframe: Through 100 days post-transplant or death

Outcome measures

Outcome measures
Measure	LLME to Decrease GVHD Following HSC T n=13 Participants 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).
Safety of CD34+ Stem Cell Infusions Followed by LLME as Measured by 100-Day Mortality	1 participants

SECONDARY outcome

Timeframe: Through 30 days post-transplant

Determine the engraftment rate of non-myeloablative transplants using CD34+ stem cells and LLME treated CD34- products.

Outcome measures

Outcome measures
Measure	LLME to Decrease GVHD Following HSC T n=13 Participants 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).
Rate of Engraftment of Non-Myeloablative Transplants	13 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	LLME to Decrease GVHD Following HSC T n=13 Participants 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).
Incidence of Grade II-IV Acute Graft-Versus-Host-Disease (GVHD) Developed grade II-IV GVHD	3 participants
Incidence of Grade II-IV Acute Graft-Versus-Host-Disease (GVHD) Developed cGVHD (Chronic GVHD)	1 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	LLME to Decrease GVHD Following HSC T n=13 Participants 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).
Rate of Serious Infectious Complications	2 participants

SECONDARY outcome

Timeframe: Through 60 Days Post Transplant

Determine the number of patients who achieve a CD4 count \> 200/micro-liters by 60 days after transplant.

Outcome measures

Outcome measures
Measure	LLME to Decrease GVHD Following HSC T n=13 Participants 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).
Number of Patients Who Achieve a CD4 Count > 200/Micro-liters	13 participants

Adverse Events

LLME to Decrease GVHD Following HSC T

Serious events: 10 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LLME to Decrease GVHD Following HSC T n=14 participants at risk 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).
General disorders Diarrhea	14.3% 2/14 • Number of events 2 "Other Adverse Events" were not collected/assessed
General disorders Bone marrow cellularity	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Infection	21.4% 3/14 • Number of events 7 "Other Adverse Events" were not collected/assessed
General disorders Pancyptopenia	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Hematoma	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Death	50.0% 7/14 • Number of events 7 "Other Adverse Events" were not collected/assessed
General disorders Hypersensitivity	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Chest pain	14.3% 2/14 • Number of events 2 "Other Adverse Events" were not collected/assessed
General disorders Progressive disease	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Nausea	21.4% 3/14 • Number of events 3 "Other Adverse Events" were not collected/assessed
General disorders Vomiting	14.3% 2/14 • Number of events 2 "Other Adverse Events" were not collected/assessed
General disorders Fevers	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Rash	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Prostatic obstruction	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Pericardial effusion	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Opportunistic infection	21.4% 3/14 • Number of events 3 "Other Adverse Events" were not collected/assessed
General disorders Bladder obstruction	7.1% 1/14 • Number of events 2 "Other Adverse Events" were not collected/assessed
General disorders Hepatic failure	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Renal insufficiency	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed
General disorders Renal failure	7.1% 1/14 • Number of events 1 "Other Adverse Events" were not collected/assessed

Other adverse events

Adverse event data not reported

Additional Information

John Wagner, MD

Thomas Jefferson University

Phone: 215-955-8874

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place