Ruxolitinib for Steroid-refractory GVHD
- Registration Number
- NCT02997280
- Lead Sponsor
- St. Petersburg State Pavlov Medical University
- Brief Summary
Steroid-refractory acute GVHD (srGVHD) is one of the causes of mortality after allogeneic stem cell transplantation, while steroid-refractory chronic GVHD significantly increases morbidity, aggravates quality of life and may also impact survival. Currently there is no standard treatment of srGVHD. One of the most promising agents is Janus kinase (JAK) inhibitor ruxolitinib, which in the retrospective study demonstrated excellent response rate and survival of patients with either acute or chronic srGVHD. This study prospectively evaluates the efficacy of ruxolitinib in srGVHD patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
- Diagnosis of graft-versus-host disease established based on tissue biopsy
- Steroid-refractory acute or chronic graft-versus-host disease according to EBMT/ELN criteria (T. Ruutu et al, 2014)
- Age 1 to 70 years
- Karnofsky index >30%.
- Ability for oral drug intake
- Life expectancy > 1 month
- Signed informed consent
- Severe organ dysfunction: AST or ALT >5 upper normal limits (excluding cases related to liver GVHD), creatinine >2 upper normal limits
- Requirement for vasopressor support at the time of enrollment
- Uncontrolled bacterial or fungal infection at the time of enrollment
- Pregnancy
- Somatic or psychiatric disorder making the patient (or legal guardian) unable to sign informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ruxolitinib treatment Ruxolitinib Oral Tablet Ruxolitinib 10 mg bid for adults and children with body weight \> 40 kg, 0.15 mg/kg bid for children with body weight \< 40 kg.
- Primary Outcome Measures
Name Time Method Overall response rate 84 days Partial response for acute GVHD is defined as the improvement of at least one stage in the severity of aGVHD in one organ without deterioration in any other organ. A response had to last for at least 3 weeks. Partial response for chronic GVHD was defined as reduction in GVHD National Institute of Health (NIH) severity score at east for one organ without deterioration in any other organ. A complete response was defined as the absence of any symptoms related to GVHD. Overall response is defined as presence of partial or complete response
- Secondary Outcome Measures
Name Time Method 6-month overall survival 6 months Time from start of ruxolitinib until death or 6 months, summarized using Kaplan-Meier estimates.
Toxicity based NCI CTC grades 6 months Toxicity parameters based on NCI CTCAE 4.03 grades: nasea, vomiting, anemia, thrombocytopenia, leukopenia, neutropenia, hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), hemorrhagic cystitis (attending physician assessment).
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence 6 months GVHD relapse incidence after complete response 6 months Time from stopping ruxolitinib until recurrence of GVHD or 6 months, summarized using cumulative incidence estimates.
Relapse incidence of underlying hematologic malignancy 12 months Time from starting ruxolitinib until hematologic relapse or 12 months, summarized using cumulative incidence estimates
Quality of life measured by FACT BMT ver. 4 questionnaire in adults 6 months Quality of life measured by PedQL Stem Cell transplant module ver.1.0 questionnaire in children 6 months
Trial Locations
- Locations (1)
First Pavlov State Medical University of St. Petersburg
🇷🇺Saint-Petersburg, Russian Federation