Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft vs Host Disease Following Unrelated Stem Cell Transplant
|ClinicalTrials.gov Identifier: NCT01790568|
Recruitment Status : Completed
First Posted : February 13, 2013
Results First Posted : January 2, 2018
Last Update Posted : August 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Graft vs Host Disease Hematologic Neoplasms Non-Neoplastic Hematologic and Lymphocytic Disorder||Drug: Vorinostat Drug: Tacrolimus Drug: Methotrexate||Phase 2|
This trial is investigating the use of vorinostat (Merck) for standard graft versus-host disease (GVHD) prophylaxis after unrelated donor allogeneic hematopoietic cell transplantation (HCT). A major limitation of the increased utilization of allogeneic HCT (Hematopoietic Cell Transplantation) is the inferior outcomes when donors other than HLA (HumanLeukocyte Antigen)-matched siblings are used. Compared to matched related donors, recipients of matched unrelated donor transplants are at a significantly increased risk of death and transplant-related mortality (TRM). Acute GVHD remains a significant contributor to TRM, which develops in approximately 50-70% of recipients receiving these type of grafts despite standard immunosuppressive prophylaxis. Thus, novel GVHD prophylaxis strategies which successfully attenuate acute GVHD-related complications without increasing other causes of TRM or relapse are needed.
The historical experience of day 100 grade 2-4 acute GVHD in 154 comparable patients treated at the University of Michigan (2005 - 2011) receiving standard GVHD prophylaxis after unrelated donor allogeneic transplant is 48%. At Washington University, the cumulative incidence of acute grade 2-4 GVHD in patients following unrelated donor transplant is 62%.
Research data collectively suggests, that reducing lethal acute GVHD should improve long-term survival for patients undergoing unrelated donor transplant.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Trial of Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft Versus Host Disease Following Unrelated Donor Allogeneic Transplant|
|Study Start Date :||December 2014|
|Actual Primary Completion Date :||January 1, 2017|
|Actual Study Completion Date :||October 31, 2017|
Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant.
administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Other Name: Zolinza
- Percentage of Patients That Experience Grade 2-4 GVHD Within 100 Days of Transplant [ Time Frame: 100 Days ]
Grade 2: (Skin) Maculopapular rash 25-50% BSA, (Liver) bilirubin 3.1-6mg/dl, (Gut) 1000-1500 ml/day for adult and 20-30ml/kg/day for child.
Grade 3: (Skin) Maculopapular rash >50% BSA, (Liver) 6.1-15mg/dl, (Gut) >1500mg/day for adult and >30ml/kg/day for child.
Grade 4: (Skin) Generalized erythroderma plus bullous formation and desquamation >5% BSA, (Liver) >15mg/dl, (Gut) Severe abdominal pain with or without ileus, or grossly bloody stool.
- Percentage of Patients Alive at 1 Year [ Time Frame: 1 Year ]Overall survival at 1 Year.
- Non-Relapse Mortality Incidence [ Time Frame: 1 year ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01790568
|United States, Michigan|
|University of Michigan Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Pavan Reddy, MD||University of Michigan Rogel Cancer Center|