Ruxolitinib for Steroid-refractory GVHD

St. Petersburg State Pavlov Medical University75 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Graft Vs Host Disease

Interventions

Ruxolitinib Oral TabletDRUG

Dose reduction criteria for acute GVHD: grade 4 neutropenia or grade 4 thrombocytopenia related to ruxolitinib administration based on the decision of attending physician. Dose reduction criteria for chronic GVHD: grade 3 neutropenia, grade 3 thrombocytopenia or anemia requiring transfusion, related to ruxolitinib administration based on the decision of attending physician. Reduced dose schedule: 5 mg bid for adults and children with body weight \> 40 kg, 0.08 mg/kg bid for children with body weight \< 40 kg. Treatment discontinuation criteria: complete response; absence of response after 28 days or progressive disease after 7 days for acute GVHD; absence of response after 84 days or progressive disease after 28 days for chronic GVHD; life-threatening complications.

Eligibility

Sex: ALLMin age: 1 YearMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (1)

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, Russia

Outcomes

Primary Outcomes

Overall response rate

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

Time frame: 84 days

Secondary Outcomes

6-month overall survival

Time from start of ruxolitinib until death or 6 months, summarized using Kaplan-Meier estimates.

Time frame: 6 months

Toxicity based NCI CTC grades

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).

Time frame: 6 months

Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

Time frame: 6 months

GVHD relapse incidence after complete response

Time from stopping ruxolitinib until recurrence of GVHD or 6 months, summarized using cumulative incidence estimates.

Time frame: 6 months

Relapse incidence of underlying hematologic malignancy

Time from starting ruxolitinib until hematologic relapse or 12 months, summarized using cumulative incidence estimates

Time frame: 12 months

Data from ClinicalTrials.gov

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