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Completed

NCT Number: NCT02997280

Ruxolitinib for Steroid-refractory GVHD

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.

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Key information

Conditions

Graft vs Host Disease Bronchial Diseases Bronchiolitis Bronchiolitis Obliterans Bronchiolitis Obliterans Syndrome Bronchitis Immune System Diseases Lung Diseases Lung Diseases, Obstructive Organizing Pneumonia Respiratory Tract Diseases

Age range

1 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197089, Russia

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ruxolitinib Oral Tablet

Drug

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.

Primary outcomes

  1. Overall response rate

    Time frame: 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 outcomes

  1. 6-month overall survival

    Time frame: 6 months

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

  2. Toxicity based NCI CTC grades

    Time frame: 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).

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

    Time frame: 6 months

  4. GVHD relapse incidence after complete response

    Time frame: 6 months

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

  5. Relapse incidence of underlying hematologic malignancy

    Time frame: 12 months

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

  6. Quality of life measured by FACT BMT ver. 4 questionnaire in adults

    Time frame: 6 months

  7. Quality of life measured by PedQL Stem Cell transplant module ver.1.0 questionnaire in children

    Time frame: 6 months

Sponsors and collaborators

Lead sponsor

St. Petersburg State Pavlov Medical University

Other

Collaborators

  • Ministry of Health, Russian Federation

Registry information

Official study title

Treatment of Steroid-refractory Acute and Chronic Graft-versus-host Disease With Inhibitor of Janus Kinases

Important dates

Study start
2016
Primary completion
2018
Study completion
2019
First posted
Dec 20, 2016
Registry last updated
Apr 5, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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