A phase II multicentre, randomized, controlled open-label study on the use of anti-thymocyte globulin and rituximab for immunomodulation of graft-versus-host disease in allogeneic matched transplants for non malignancies

INTERVENTION: Trade Name: ATG Fresenius S Pharmaceutical Form: Infusion INN or Proposed INN: NA CAS Number: NA Current Sponsor code: DB00098 Other descriptive name: NA Concentration unit: mg/kg milligram(s)/kilogram Concentration type: range Concentration number: 10‐15 Trade Name: MABTHERA*EV 2F 10ML 100MG Pharmaceutical Form: Solution for infusion INN or Proposed INN: RITUXIMAB CAS Number: 174722‐31‐7 Current Sponsor code: NA Other descriptive name: NA Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 200‐ Trade Name: Treosulfan Pharmaceutical Form: Powder for injection INN or Proposed INN: TREOSULFAN CAS Number: 299‐75‐2 Current Sponsor code: 9296 Other descriptive name: NA Concentration unit: gm/m2 gram(s)/square meter Concentration type: range Concentration number: 3‐8 Pharmaceutical Form: Powder for injection INN or Proposed INN: FLUDARABINE PHOSPHATE CAS Number: 75607‐67‐9 Current Sponsor code: 657237 Other descriptive name: NA Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 25‐ Trade Name: tepadina Pharmaceutical Form: Powder for infusion INN or Proposed INN: THIOTEPA CAS Number: 52‐24‐4 Current Sponsor code: DB04572 Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 100‐ CONDITION: graft‐versus‐host disease ; MedDRA version: 14.1 Level: SOC Classification code 10021428 Term: Immune system disorders System Organ Class: 10021428 ‐ Immune system disorders Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: Assess in a randomized fashion the benefit on standard graft‐versus‐host disease (GVHD) prophylaxis of the addition of ATG‐Fresenius S in transplants from matched related donors (MRD) and of anti‐CD20 rituximab in transplants from matched unrelated donors (MUD) Primary end point(s): For patients transplanted from a MRD; ; The primary end‐point is the cumulative incidence of a combined end‐point defined as the time from randomization to:; ‐ primary and secondary graft failure, ; ‐ aGVHD II‐IV, ; ‐ cGVHD, ; ‐ death, ; whichever occurs first.; For patients transplanted from a MUD; ; The primary end‐point is the cumulative incidence of a combined end‐point defined as the time from randomization to:; ‐ aGVHD II‐IV, ; ‐ EBV viremia, ; whichever occurs first. Secondary Objective: For patients transplanted from a MUD; ; Reduced incidence and severity of cGVHD after transplantation using rituximab Timepoint(s) of evaluation of this end point: NA SECONDARY OUTCOME: Secondary end point(s): 1. the cumulative incidence and severity of cGVHD after randomization ; 2. the incidence of TRM after randomization ; 3. the overall survival after randomization Timepoint(s) of evaluation of this end point: NA INCLUSION CRITERIA: ? Availability of a matched related donor (MRD) or Matched Unrelated Donor (MUD) ? Lansky or Karnofsky Index = 60 ? Inherited metabolic disorders: DQ =70 (+ MRI Loes score = 9 for adrenoleukodystrophy) ? Adequate cardiac, renal, hepatic and pulmonary functions as evidenced by: ? Serum creatinine =1.5 × upper limit of normal (ULN) ? Heart shortening fraction (left‐ventricle) > 28 % or LVEF > 55% ? Serum bilirubin =1.5 × ULN (except for Wolman disease), ? AST and ALT = 2.5 × ULN (except for thalassemic syndromes and Wolman disease) ? Pulmonary function: if cooperative: FEV1 and FVC on pulmonary function testing > 60 %; if non cooperative: pulse oximetry > 95 % in room air ? Availability of autologous back up marrow (> 2 x 108 TNC+ cells/kg or > 2 x 106 CD34+ cells/kg) for MUD ? Adequate contraception in female patients of child‐bearing potential ? Signed informed consent Are the trial subjects under 18? yes<