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Phase 2 Trial to determine the safety and efficacy of simultaneous treatment with ruxolitinib and extracorporeal photopheresis for patients with steroid-refractory chronic Graft-versus-Host-Disease (SR-cGvHD) - RUX-ECP
EU CTIS ID: 2023-507754-33-00
What this study is testing
The primary objective of this phase 2 trial is a first evaluation of the efficacy of combined treatment of ruxolitinib and ECP for patients with SR-cGvHD as assessed by Overall Response Rate (ORR) at the week 25 (Cycle 7 Day 1) visit.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Male and female patients aged ≥18 years
- Patients have undergone alloSCT from any donor source (matched unrelated donor sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible.
- Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines.
- SR-cGvHD diagnosis: Patients with clinically diagnosed moderate to severe cGvHD according to NIH Consensus Criteria (Jagasia 2015). Moderate: - at least one organ (not lung) with a score of 2-3 or more organs with score 1 or - lung score 1 Severe: - at least one organ with a score of 3 or - lung score 2
- Patients who have received systemic glucocorticoids for the treatment of chronic graft-versus-host disease for a duration of < 6 months prior to cycle 1 day 1 and have a confirmed diagnosis of steroid refractory cGvHD defined per 2014 NIH consensus criteria (Martin 2015) irrespective of the concomitant use of a calcineurin inhibitor, as follows: A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for ≥1 week (or equivalent) or Disease persistence without improvement despite continued treatment with prednisone at >0.5 mg/kg/day or 1 mg/kg/every other day for ≥4 weeks (or equivalent) or Increase to prednisone dose to >0.25 mg/kg/day after two unsuccessful attempts to taper the dose (or equivalent)
- Evident myeloid and platelet engraftment: absolute neutrophil count >1x109/L and platelet count >25x109/L
You likely can't join if
- Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment (acute to chronic GvHD overlap syndrome). Patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed.
- Impairment of gastrointestinal (GI) function (unrelated to GvHD) or GI disease (unrelated to GvHD) that may significantly alter the absorption of oral ruxolitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- Any corticosteroid therapy for indications other than cGvHD at doses >1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1.
- Prior treatment with ruxolitinib or ECP except if the treatment was for acute GvHD.
- Patient is receiving treatment with medications that interfere with coagulation or platelet function including, but not limited to, heparin or warfarin sodium (Coumadin®). Use of low molecular weight heparin is allowed. In patients in whom aspirin is indicated for secondary cardiovascular disease prevention, aspirin daily dose must not exceed 150 mg/day.
- Patient is receiving fluconazole at daily doses higher than 200 mg.
See the full eligibility criteria
Who can join
- Male and female patients aged ≥18 years
- Patients have undergone alloSCT from any donor source (matched unrelated donor sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible.
- Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines.
- SR-cGvHD diagnosis: Patients with clinically diagnosed moderate to severe cGvHD according to NIH Consensus Criteria (Jagasia 2015). Moderate: - at least one organ (not lung) with a score of 2-3 or more organs with score 1 or - lung score 1 Severe: - at least one organ with a score of 3 or - lung score 2
- Patients who have received systemic glucocorticoids for the treatment of chronic graft-versus-host disease for a duration of < 6 months prior to cycle 1 day 1 and have a confirmed diagnosis of steroid refractory cGvHD defined per 2014 NIH consensus criteria (Martin 2015) irrespective of the concomitant use of a calcineurin inhibitor, as follows: A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for ≥1 week (or equivalent) or Disease persistence without improvement despite continued treatment with prednisone at >0.5 mg/kg/day or 1 mg/kg/every other day for ≥4 weeks (or equivalent) or Increase to prednisone dose to >0.25 mg/kg/day after two unsuccessful attempts to taper the dose (or equivalent)
- Evident myeloid and platelet engraftment: absolute neutrophil count >1x109/L and platelet count >25x109/L
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
What rules you out
- Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment (acute to chronic GvHD overlap syndrome). Patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed.
- Impairment of gastrointestinal (GI) function (unrelated to GvHD) or GI disease (unrelated to GvHD) that may significantly alter the absorption of oral ruxolitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- Any corticosteroid therapy for indications other than cGvHD at doses >1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1.
- Prior treatment with ruxolitinib or ECP except if the treatment was for acute GvHD.
- Patient is receiving treatment with medications that interfere with coagulation or platelet function including, but not limited to, heparin or warfarin sodium (Coumadin®). Use of low molecular weight heparin is allowed. In patients in whom aspirin is indicated for secondary cardiovascular disease prevention, aspirin daily dose must not exceed 150 mg/day.
- Patient is receiving fluconazole at daily doses higher than 200 mg.
- Patient is receiving and does not agree to stop herbal preparations/medications. These herbal medications include, but are not limited to, St. John’s Wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Patients must stop using herbal medications at least 7 days prior to first dose of study treatment.
- Known allergies, hypersensitivity, or intolerance of ruxolitinib or any of its excipients or similar compounds, methoxypsoralen or psoralen compounds
- Photosensitive disease
- Aphakia
- Failed prior alloSCT within the past 6 months from Cycle 1 Day 1 (relapsed original disease).
- History of tuberculosis infection that developed after alloSCT.
- Patients with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed.
- SR-cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Patients who have received a scheduled DLI as part of their transplant procedure (up to day 120) and not for management of malignancy relapse are eligible.
- History of progressive multifocal leuko-encephalopathy (PML).
- Active treatment in a clinical study of any investigational agent within 30 days prior to Cycle 1 Day1, or within 5 half-lives of the study treatment, whichever is longer.
- Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Positive result for HIV at screening.
- Inability to tolerate extracorporeal volume loss
- Sexually active men and female patients of child-bearing potential who are not willing to use highly effective methods of contraception during the trial and at least 5 months after the last ECP procedure
- Pregnancy and lactation
- Previous splenectomy
- Evidence of active viral disease including CMV, EBV, HHV-6, HBV, HCV, or BK virus (e.g. CMV pneumonia, not just CMV copy number increase). Patients with pre-transplant positive serology results must have negative viral load results for HBV and HCV within 28 days prior to Cycle 1 Day 1. Patients with unknown viral testing results prior to transplant must have viral load results confirming no evidence of active viral disease within 28 days prior to Cycle 1 Day 1.
- Coagulation disorder
- Leucocytes > 25x109/L
- Current Melanoma, basal cell carcinoma or squamous cell carcinoma of the skin requiring treatment
- Mechanical ventilation or patients who have resting O2 saturation <90% by pulse-oximetry.
- History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study including any of the following: recent myocardial infarction (within last 6 months prior to Cycle 1 Day 1) New York Heart Association Class III or IV congestive heart failure unstable angina (within last 6 months prior to Cycle 1 Day 1 clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker); ventricular arrhythmias uncontrolled hypertension
- Patients requiring vasopressors.
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration and contraindications of study drug/study procedure and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
- Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (> 176.8μmol/L), renal dialysis requirement, or have estimated creatinine clearance <30 ml/min measured or calculated by Cockroft Gault equation (confirmed within 48 hours prior to study treatment start).
- Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to cGvHD and ongoing organ dysfunction) OR total bilirubin >2mg/dL not attributable to GvHD.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.