Addition of Etanercept and Extracorporeal Photopheresis (ECP) to Standard Graft-Versus-Host Disease (GVHD) Prophylaxis in Stem Cell Transplant
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00639717|
Recruitment Status : Completed
First Posted : March 20, 2008
Results First Posted : September 25, 2014
Last Update Posted : August 1, 2017
This research study investigates the benefits and possible risks of adding both etanercept (Enbrel) and ECP (extracorporeal photopheresis) to the conventional preventative (or prophylactic) treatments for graft-versus-host disease (GVHD). GVHD is a common, serious, and too often fatal, complication after matched unrelated donor stem cell transplantation, regardless of the pre-transplant conditioning regimen used (full or reduced intensity).
Reduced intensity transplants which employ lower doses of chemotherapy during the conditioning phase of the transplant, are less toxic than full intensity transplants. Reduced intensity transplants may extend the unrelated donor transplant option to older patients or to patients with existing medical conditions or illness, where a full intensity transplant is not possible. To be successful, reduced intensity transplants need to offset any lower effectiveness in killing cancer cells during the conditioning phase, with the establishment of a donor cell, graft-versus-leukemia effect (GVL). The GVL effect and GVHD are associated with each other and therefore, the goal of GVHD prophylaxis for this study is not so much to prevent all GVHD, but rather to prevent serious and fatal acute GVHD.
Most GVHD-related deaths are either the direct consequence of severe GVHD or from infections associated with intense immunosuppression, a consequence of the standard treatments for acute GVHD, which almost always include high-dose steroids. A more effective prophylaxis therapy that allows for the GVL effect to develop, while limiting the exposure to high-dose steroids may reduce transplant mortality and morbidity. We also will study how key chemical and cellular factors relate to clinical outcome.
|Condition or disease||Intervention/treatment||Phase|
|Graft Versus Host Disease||Procedure: stem cell transplant Drug: tacrolimus (standard GVHD prophylaxis) Drug: mycophenolate (standard GVHD prophylaxis) Drug: etanercept Drug: methoxsalen||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Addition of Etanercept and Extracorporeal Photopheresis to Standard GVHD Prophylaxis in Patients Undergoing Reduced Intensity Unrelated Donor Hematopoietic Stem Cell Transplant|
|Study Start Date :||March 2009|
|Actual Primary Completion Date :||January 2012|
|Actual Study Completion Date :||April 2016|
Experimental: Etanercept and ECP
Etanercept and ECP (Extracorporeal Photopheresis) in addition to standard GVHD prevention:
Etanercept will be given twice weekly by subcutaneous injection starting on the day of HSCT (Hematopoietic stem cell transplantation) conditioning until 8 weeks post transplant. ECP treatments will begin at once weekly starting at 4 weeks post transplant and continue at less frequent intervals until 6 months post transplant.
GVHD prophylaxis will consist of a standard two drug regimen: mycophenolate for 4 weeks and tacrolimus (titrated to a therapeutic level) for 8 weeks, then weaned over 4 months with discontinuation by 6 months post-transplant.
Procedure: stem cell transplant
reduced intensity, matched unrelated donor stem cell transplantDrug: tacrolimus (standard GVHD prophylaxis)
Drug: mycophenolate (standard GVHD prophylaxis)
Tacrolimus(or cyclosporine when necessary)
Tacrolimus will begin on day -3, IV or oral.
Target trough level for tacrolimus is 8-12 ng/ml.
In the absence of GVHD, tacrolimus tapering will begin on day +56 post transplant
Mycophenolate will begin on day 0 at 10 mg/kg/dose (up to 1 gram per dose) every 8 hours orally or intravenously and will continue until day 28.Drug: etanercept
Etanercept will be given at a dose 0.4 mg/kg (actual weight) up to a maximum dose of 25 mg, subcutaneously, twice weekly from day 0 to day 56 (16 doses)
Other Name: EnbrelDrug: methoxsalen
Methoxsalen (UVADEX) treatments by Extracorporeal photopheresis (ECP) will be started day +28 post transplant and given weekly.
On day +70 post transplant ECP frequency will be given every other week.
On day +100 post transplant ECP will be given monthly until day +180 and stopped.
Other Name: UVADEX
- Percentage of Patients Alive at 6 Months [ Time Frame: 6 months ]Overall survival at 6 months
- Percentage of Patients Who Experienced Relapse by 6 Months [ Time Frame: 6 months ]Relapse rate at 6 months. Relapse is defined as recurrence of disease.
- The Percentage of Patients That Experienced Graft Versus Host Disease [ Time Frame: 6 Months ]Incidence of acute GVHD grades 2-4 and chronic GVHD in this study population
- Measured Level of Circulating Plasma Markers After Transplant [ Time Frame: 100 days ]
- Regulatory T Cell Numbers Post-transplant [ Time Frame: 180 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00639717
|United States, Michigan|
|University of Michigan Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Gregory Yanik, MD||University of Michigan Cancer Center|