Trial of 2 Step ATG for Prevention of Acute GVHD Post Allogeneic Stem Cell Transplant
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorUniversity of Alabama at Birmingham
About this trial
In an effort to reduce graft versus host disease (GVHD) and enhance graft versus leukemia (GVL) effect post allogenic hematopoietic stem cell transplantation (AHSCT), recent research has focused on host immune cell depletion. Frame shifting anti-thymocyte globulin (ATG) backwards to earlier days before days 0 can result in deeper host and less graft T-cell depletion, leading to better immune reconstitution. Preliminary data where 80% of the ATG dose is given on days -6,-5,-4 and 20% given on day -1, showed effective prevention of severe acute GVHD, chronic GVHD and favorable early immune reconstitution. We hypothesize that our 2 step ATG dosing platform when combined with standard tacrolimus and mini methotrexate can prevent grade III-IV acute GVHD and chronic GVHD, resulting in improvement of GVHD/relapse free survival at one year post transplant.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adult male or female, age 18-75 years
Patients must have a related or unrelated peripheral blood stem cell donor. Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation. Unrelated donor must be 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to NMDP criteria.
A candidate for reduced intensity preparative regimen, based on age≥60, or HCT-CI of ≥4, or considered by the treating physician to have high risk for toxicity with myeloablative preparative regimen.
Cardiac function: Ejection fraction >40%
Disqualifiers
Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.
Patients with florid residual AML with > 5% blast in the marrow or circulating blast in the peripheral blood are not eligible for this study.
Previous allogeneic stem cell transplant.
Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.
Trial design
Design model
Single group
Treatments tested in this trial
ATG dosing platform when combined with standard tacrolimus and mini methotrexate
DrugOn Day -8, you will be admitted to the hospital and receive a dose of prednisone at 1 mg/kg (ATG premedication). You will receive a steroids 3 hours before every ATG infusion. On day -7, you will receive a small dose of ATG as an intravenous (IV) infusion. ATG will be repeated on days -6, -5 and -1. Routine transplant chemotherapy agent fludarabine will be given on days -7 to -3 as daily IV infusions. Melphalan, another routine transplant chemotherapy will be given on day -4 as IV infusion. Tacrolimus (standard immune suppression agent) will start on day -3 as continuous IV infusion and switched to oral after engraftment. Methotrexate is another standard immune suppression medication which is given IV on day +1, +3, +6, and +11 post-transplant. We plan to draw blood on days -4,, -1, +3, +7, and +14 to measure ATG levels.
Treatment groups
56 Participants
are divided into 1 treatment groupGroup A: phase II single arm study of 2 step ATG dosing in prevention of aGVHDExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Rate of GRFS (graft versus host disease GVHD, relapse free survival) at one year post transplant.
Rate of GRFS is defined as the time from date of first dose of fludarabine until occurrence of grade III-IV aGVHD, and or cGVHD requiring systemic immune suppression, and or disease progression or death whichever comes first.
Time frame
1 year post transplantSponsors and contacts
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Source ClinicalTrials.gov