Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation
|Graft Versus Host Disease||Drug: Visilizumab Drug: Tacrolimus Drug: Methotrexate Drug: Antithymocyte globulin (ATG)||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
|Official Title:||A Phase II Study of Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation|
- Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days [ Time Frame: 100 days ]
Cumulative Incidence of Grade II-IV Acute GVHD Score at 100 Days. Investigators had planned to assess whether the grade of acute GVHD was decreased by visilizumab in combination with tacrolimus/methotrexate compared to standard treatment with thymoglobulin/tacrolimus/methotrexate after transplantation from unrelated mismatched donors, from day of transplant up to one year. Study was closed during the first treatment stage and did not proceed to the second stage treatment comparison to ATG in combination with tacrolimus/methotrexate as originally planned.
Overall GVHD Grade: From Filipovich AH, Weisdorf D, Pavletic S, etal: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 11:945-955 (2005). Grade I: Skin Stage 1-2, Liver Stage 0, Gut State 0; Grade II: Skin Stage 3 or, Liver Stage 1 or, Gut Stage 1; Grade II
- Incidence of Epstein-Barr Virus (EBV) Reactivation [ Time Frame: 3 months ]Number of participants who reactivated EBV. Patients had their plasma tested once weekly using the TaqMan polymerase chain reaction (PCR) for quantitative determination of EBV-DNA for 6 weeks. Plasma levels > 1000 copies per ml plasma were scored as positive.
- Incidence of Rituximab Response to Reactivated EBV Without PTLD [ Time Frame: 100 days ]
Participants who developed plasma EBV-DNA of >1000 copies/mL on any tests received rituximab.
Incidence of Rituximab Response: Reactivated EBV participants whose plasma titers cleared after rituximab, without post-transplant lymphoproliferative disorder (PTLD).
- Overall Survival (OS) [ Time Frame: At 2 years and 5 years ]Median OS in days. Survival was measured from the time of transplant to the time of death.
- Pharmacodynamics of Visilizumab - Test 1 [ Time Frame: At 1 - 2 hours ]Mean Cmax (±SD)
- Pharmacodynamics of Visilizumab - Test 2 [ Time Frame: Up to 205 hours ]Mean terminal half-life (±SD)
|Study Start Date:||December 2007|
|Study Completion Date:||December 2013|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: First Study Stage: Study Treatment
Visilizumab, Tacrolimus and Methotrexate.
3 mg/m^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).Drug: Tacrolimus
0.02 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 4 after transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.Drug: Methotrexate
15 mg/m^2 intravenously (IV) on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
Active Comparator: Second Study Stage: Standard Treatment
Second Stage: Antithymocyte-globulin (ATG), Tacrolimus and Methotrexate. The study was closed during first stage and did not proceed to the second stage comparison to ATG in combination with tacrolimus/methotrexate as originally planned.
Drug: Antithymocyte globulin (ATG)
1 mg/kg IV over 6 hours on Day 3 before transplant; 3.25 mg/kg IV over 4 hours on days 2 and 1 before transplant.
Other Name: Thymoglobulin-ATGDrug: Tacrolimus
0.03 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 3 before transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.Drug: Methotrexate
15 mg/m^2 IV on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
The protocol plan was a two stage, controlled, phase II study to assess safety and compare the grade of acute graft-versus-host disease (GVHD) with visilizumab, or Anti-thymocyte Globulin (ATG) in combination with tacrolimus + methotrexate in patients at high risk of GVHD after transplant from unrelated donors mismatched for 1-2 alleles of any type at human leukocyte antigen (HLA) A, B, C and DRB1.
The study design included two stages. The first stage of the trial was to enroll 15 patients on a single arm to be treated with "study treatment" (visilizumab, tacrolimus and methotrexate) to assess for treatment safety and exclude intolerable GVHD. The second stage of the trial was to include a random control group of patients treated with the current "standard treatment" (ATG, tacrolimus, and methotrexate) or "study treatment". The purpose of this comparison was to determine if the "study treatment" visilizumab causes less severe side effects and if it is more potent in reducing graft-versus-host disease symptoms than the "standard treatment".
Please refer to this study by its ClinicalTrials.gov identifier: NCT00720629
|United States, Florida|
|H. Lee Moffitt Cancer Center & Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Lia Perez, MD||H. Lee Moffitt Cancer Center and Research Institute|