Hematologic MalignanciesPhase 1/2NCT00429416
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
A Phase 1/2 study testing L-leucyl-L-leucine Methyl Ester (LLME), Fludarabine and Cytarabine in people with Hematologic Malignancies, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancies
- What is being tested?
- L-leucyl-L-leucine Methyl Ester (LLME), Fludarabine and Cytarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to May 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University'
Philadelphia, Pennsylvania, 19107
About this study
Official title: 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
Read the 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.
- Conditions
- Hematologic Malignancies
- Being tested
- L-leucyl-L-leucine Methyl Ester (LLME), Fludarabine, Cytarabine, Cyclophosphamide, Tacrolimus
- Keywords
- Hematologic Malignancies, GVHD, Graft-Versus-Host-Disease, LLME, CD34+ stem cell infusions, CD34- fraction, Cyclosporine, Mycophenolate Mofetil, HSCT, Hematopoietic stem cell transplantation
- Medical subject headings
- Hematologic Neoplasms, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-leucyl-L-leucine Methyl Ester (LLME)Drug
Also called LLME
Infusion of L-leucyl-L-leucine methyl ester (LLME) treated donor white blood cells
FludarabineDrug
Also called fludarabine phosphate, Fludara
Fludarabine 30 mg/m2 prior to HSCT infusion
CytarabineDrug
Also called cytosine arabinoside, Ara-C, Arabinofuranosyl Cytidine
Cytarabine 2gm/m2 prior to HSCT infusion
CyclophosphamideDrug
Also called Endoxan, Cytoxan, Neosar, Procytox
Cyclophosphamide 1gm/m2 prior to HSCT infusion
TacrolimusDrug
Also called FK-506, Fujimycin
Tacrolimus given before and after HSCT infusion
MesnaDrug
Also called Uromitexan, Mesnex
Mesna 1gm/m2/day given prior to HSCT infusion.
Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)Biological
Also called GM-CSF
GM-CSF given post HSCT infusion
Hematopoietic stem cell transplantation (HSCT)Procedure or surgery
Also called HSCT
CD34 selected allogeneic stem cell infusion with 5x104/kg untreated T cells
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through 100 days post-transplant or death
Secondary outcomes (4)
Rate of Engraftment of Non-Myeloablative Transplants
Determine the engraftment rate of non-myeloablative transplants using CD34+ stem cells and LLME treated CD34- products.
Measured: Through 30 days post-transplant
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.
Measured: 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.
Measured: 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.
Measured: Through 60 Days Post Transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2007 (estimated)
- Study startMar 2004
- Primary completionDec 2008
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John Wagner, MD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00429416
- Sponsor's protocol ID
- 04U.115
- Other IDs
- 2003-68
- Status last verified
- Oct 2016
- First submitted
- 29 Jan 2007
- Last updated
- 29 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Llme Treated Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematological Malignancies
- ClinicalTrials.gov ID
- NCT00429416
- Acronym / sponsor ID
- 04U.115
- Conditions
- Hematologic Malignancies
- Keywords
- Hematologic Malignancies, GVHD, Graft-Versus-Host-Disease, LLME, CD34+ stem cell infusions, CD34- fraction, Cyclosporine, Mycophenolate Mofetil
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- Mar 2004
- Primary completion
- Dec 2008 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 31 Jan 2007 (estimated)
- Results
- Posted 10 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LLME to Decrease GVHD Following HSC T | Experimental | 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)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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-leucyl-L-leucine Methyl Ester (LLME)Also: LLMEInfusion of L-leucyl-L-leucine methyl ester (LLME) treated donor white blood cells | Drug | LLME to Decrease GVHD Following HSC T |
| FludarabineAlso: fludarabine phosphate, FludaraFludarabine 30 mg/m2 prior to HSCT infusion | Drug | LLME to Decrease GVHD Following HSC T |
| CytarabineAlso: cytosine arabinoside, Ara-C, Arabinofuranosyl CytidineCytarabine 2gm/m2 prior to HSCT infusion | Drug | LLME to Decrease GVHD Following HSC T |
| CyclophosphamideAlso: Endoxan, Cytoxan, Neosar, ProcytoxCyclophosphamide 1gm/m2 prior to HSCT infusion | Drug | LLME to Decrease GVHD Following HSC T |
| TacrolimusAlso: FK-506, FujimycinTacrolimus given before and after HSCT infusion | Drug | LLME to Decrease GVHD Following HSC T |
| MesnaAlso: Uromitexan, MesnexMesna 1gm/m2/day given prior to HSCT infusion. | Drug | LLME to Decrease GVHD Following HSC T |
| Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF)Also: GM-CSFGM-CSF given post HSCT infusion | Biological | LLME to Decrease GVHD Following HSC T |
| Hematopoietic stem cell transplantation (HSCT)Also: HSCTCD34 selected allogeneic stem cell infusion with 5x104/kg untreated T cells | Procedure or surgery | LLME to Decrease GVHD Following HSC T |
Primary outcome
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.
4 secondary outcomes
Rate of Engraftment of Non-Myeloablative Transplants
Time frame: Through 30 days post-transplant
Incidence of Grade II-IV Acute Graft-Versus-Host-Disease (GVHD)
Time frame: Through 24 months post-treatment
Rate of Serious Infectious Complications
Time frame: Through 3 months post-transplant
Number of Patients Who Achieve a CD4 Count > 200/Micro-liters
Time frame: Through 60 Days Post Transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer CenterLink provided by the sponsor.
- Thomas Jefferson University HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Wagner, MD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing L-leucyl-L-leucine Methyl Ester (LLME), Fludarabine and Cytarabine in people with Hematologic Malignancies, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of CD34+ Stem Cell Infusions Followed by LLME as Measured by 100-Day Mortality (time frame: Through 100 days post-transplant or death). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2016.