METHOXSALEN for Acute graft-versus-host disease (Grade II)

Inclusion criteria

• {"criterion_text":"- Age > 18 years\n- An individual who has received full information about how the clinical trial will be conducted and has signed an informed consent form\n- An individual who has undergone clinical screening adapted to the clinical trial,\n- allogeneic hematopoietic stem cell transplantation received (from any type of graft and donor) after malignant or non malignant disease\n- patient suffering from Grade II acute GVHD with skin +/- upper Gastrointestinal tract involvement (stage 2-3 skin + stage 1 upper gastrointestinal tract or isolated skin stage 3) in the 3 months following stem cell transplantation\n- patient requiring first line therapy to treat acute GVHD,\n- patient able to start ECP therapy in the 3 days after randomization\n- validation of the presence of a peripheral or central venous access (its type should be conform to the recommendations described in the Therakos Cellex operator manual, Annex 3), allowing to perform PCE sessions weekly during 3 months. In the absence of appropriate preexisting central line at inclusion, peripheral access will be preferred.\n- Leukocytes > 1.5 G/L based on the last available blood testing results,\n- Platelets > 30 G/L, hematocrit > 27% (blood transfusion are permitted), based on the last available blood testing results,\n- An individual affiliated to a social security scheme or beneficiary of such a scheme"}

Exclusion criteria

• {"criterion_text":"- Grade 1 acute GVHD,\n- Patient with contraindications to posaconazole (NOXAFIL®): 1/Hypersensitivity to active ingredient or excipients,2/Ongoing treatment with ergot alkaloids, 3/Ongoing treatment with one CYP3A4 substrate which could lead to increased plasma concentration of these drugs, and so can result in QTc interval prolongation and rare cases of Torsade de Pointe (terfenadine, astemizole, cisapride, pimozide, halofantrin, quinidine), 4/Ongoing treatment with inhibitors of the HMG-CoA reductase (simvastatin, lovastatin, atorvastatin) due to greater risk of rhabdomyolysis, 5/Ongoing or scheduled treatment with venetoclax\n- Ongoing or scheduled treatment on short-term perspective with vinca-alkaloids\n- Patients with medical history corresponding to contra-indications to photopheresis:1/ aphakia, 2/photosensitive disease (e.g., porphyria, systemic lupus erythematosus, albinism), 3/cardiac insufficiency, 4/previous splenectomy, 5/coagulation abnormalities, 6/heparin-induced thrombocytopenia, 7/uncontrolled digestive bleeding\n- Patients with contra-indication to steroids:1/Allergy to prednisone or methylprednisolone, 2/Uncontrolled psychotic disease\n- patient with previous deep vein thrombosis in the last 5 years,\n- Patient with ongoing psychiatric cares as described in act L.3212-1 et L.3213-1 of the French Public Health code:1/Individuals referred to in Articles 10, 31, 32, 33 and 34 of Regulation (EU) No 536/2014, 2/Minor (not emancipated), 3/Adult subject to a legal protection measure (such as guardianship, conservatorship), 4/Adult who is unable to give consent\n- Included in another prospective study of acute GVH treatment\n- Acute GVHD grade > II or acute GVH with lower tract gastrointestinal tract or with liver involvement,\n- Hematologic disease relapse at time of acute GVHD,\n- uncontrolled ongoing infection at time of inclusion: bacterial or fungal infections, CMV reactivation with increasing CMV viral load\n- HIV positivity or replicative HBV or HCV infection (based on pre-transplant assessment),\n- Pregnant or breast feeding female\n- Women of childbearing age without effective contraception\n- Patient with allergy or contraindications to UVADEX : 1/ Known 8 MOP allergy 2/ Melanoma, basal cell, or squamous cell skin carcinoma, 3/ Phenytoin treatment"}

Primary endpoints

• {"endpoint_text":"- Percentage of patients without treatment failure at 6 months in each arm. Absence of treatment failure is defined by meeting all the following 4 conditions at 6 months from randomization:1/to be alive, 2/without relapse of the hematological disease, 3/without having required a new line of treatment for acute GVHD,4/without initiating a systemic treatment for chronic GVHD","definition_or_measurement_approach":"Absence of treatment failure is defined by meeting all the following 4 conditions at 6 months from randomization: 1) to be alive, 2) without relapse of the hematological disease, 3) without having required a new line of treatment for acute GVHD, 4) without initiating a systemic treatment for chronic GVHD. Measured at 6 months from randomization (binary outcome per patient)."}

Secondary endpoints

• {"endpoint_text":"- The mean of the cumulative dose of steroids over time (randomization-1 month, 1-2 month, 2-3 month, 3-6 month and 6-12 month periods),","definition_or_measurement_approach":"Mean cumulative steroid dose measured over defined time windows after randomization (randomization–1 month; 1–2 months; 2–3 months; 3–6 months; 6–12 months)."}
• {"endpoint_text":"- The cumulative incidence rate of infections at 6 and 12 months (bacteremia, septicemia, fungal infection and virus reactivation),","definition_or_measurement_approach":"Cumulative incidence of specified infections (bacteremia, septicemia, fungal infection, viral reactivation) assessed at 6 and 12 months."}
• {"endpoint_text":"- The cumulative incidence of thromboembolic complications at 3 months (diagnosed with Doppler ultrasound exam and/or CT coronary angiogram performed in case of indicative clinical symptoms)","definition_or_measurement_approach":"Cumulative incidence of thromboembolic events up to 3 months, diagnosed by Doppler ultrasound and/or CT angiogram where clinically indicated."}
• {"endpoint_text":"- the incidence and severity of chronic GVHD (according to NIH criteria19) at 6 and 12 months after randomization (see Annex 4),","definition_or_measurement_approach":"Incidence and severity of chronic GVHD assessed at 6 and 12 months using NIH criteria."}
• {"endpoint_text":"- the non-relapse mortality rate at 6 and 12 months (death due to any cause except underlying disease relapse)","definition_or_measurement_approach":"Non-relapse mortality (death from causes other than disease relapse) measured at 6 and 12 months."}
• {"endpoint_text":"- the incidence of underlying disease relapse at 6 and 12 months after randomization (relapse is defined on the basis of morphological evidence of leukemic or lymphoma cells in the bone marrow or other sites),","definition_or_measurement_approach":"Incidence of disease relapse at 6 and 12 months; relapse defined by morphological evidence of leukemic or lymphoma cells in marrow or other sites."}
• {"endpoint_text":"- the disease-free survival at 6 and 12 months after randomization (time from randomization date to either first relapse or death from any cause),","definition_or_measurement_approach":"Disease-free survival measured as time from randomization to first relapse or death; assessed at 6 and 12 months."}
• {"endpoint_text":"- the overall survival at 6 and 12 months after randomization (time from randomization date to either first relapse or death from any cause)","definition_or_measurement_approach":"Overall survival measured as time from randomization to death (or last follow-up); reported at 6 and 12 months."}
• {"endpoint_text":"- the mean scores of health-related quality of life using the French validated FACT-BMT (version 4.0, see Annex 5) at 3, 6 and 12 months after transplant,","definition_or_measurement_approach":"Mean FACT-BMT (v4.0) QoL scores assessed at 3, 6 and 12 months after transplant."}
• {"endpoint_text":"- immune reconstitution based on peripheral blood testing (rate of total T lymphocytes, CD4 and CD8 T cells, B cells, NK cells, gamma globulins) at 3, 6 and 12 months after randomization (depending on usual practices in each center).","definition_or_measurement_approach":"Peripheral blood immune cell counts (total T, CD4, CD8, B cells, NK cells) and gamma globulins measured at 3, 6 and 12 months according to center practice."}

France

Earliest CTIS Part Ii Submission Date

15-01-2024

Latest Decision Or Authorization Date

07-10-2025

Processing Time Days

631

Number Of Sites

11

Number Of Participants

78

Primary sponsor

Full Name

CHRU De Nancy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France