Salvage therapy of acute GVHD patients with gastrointestinal involvement, refractory to ruxolitinib. MedDRA version: 27.0 Level: PT Classification code 10066264 Term: Acute graft versus host disease in intestine System Organ Class: 10021428 - Immune system disorders
Conditions
Sponsors
MaaT Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Age = 18 years old •Allo-HSCT with any type of donor, stem cell source, GVHD prophylaxis or conditioning regimen. •Acute GvHD episode with GI involvement per MAGIC guidelines (= grades II to IV), with or without involvement of other organs (Harris, Young, et al. 2016). •Patients resistant to steroids AND either resistant to OR with intolerance to ruxolitinib (intolerant patients: who had grade 3 or higher treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib): Resistance to steroids is defined as any of the following: Lack of improvement (i.e., no decrease in stage in at least 1 involved organ system) after = 5 days of treatment with CS at 2mg/kg/d methylprednisolone equivalent dose, Progression (i.e., increase in any organ system or any new organ involvement) after = 3 days of treatment with CS at 2 mg/kg/d methylprednisolone equivalent dose, Patients treated with 1 mg/kg/d of CS because the physician deemed they would not tolerate 2 mg/kg/d and who correspond to the definition of SR patients, Patients who previously began CS therapy at a lower dose (at least 1 mg/kg/d methylprednisolone equivalent) for skin or upper GI GvHD but develop new GVHD in another organ system, Patients who cannot tolerate corticosteroid tapering, i.e., begin of CS at 2.0 mg/kg/d, demonstrate response, but show disease progress before a 50% decrease from the initial starting dose of CS is achieved. Resistance to ruxolitinib is defined as any of the following (Mohty et al. 2020): Progression of GvHD compared to baseline after at least 5 days of treatment with ruxolitinib, based either on objective increase in stage/grade, or new organ involvement; Lack of improvement in GvHD (partial response or better) compared to baseline after at least 14 days of treatment with ruxolitinib; Loss of response, defined as objective worsening of GvHD determined by increase in stage, grade or new organ involvement at any time after initial improvement Absence of complete response or very good partial response at day 28 after ruxolitinib Intolerance to ruxolitinib is defined as: GvHD manifestations that persist without improvement in patients who had grade 3 or higher treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib •Signature of informed and written consent by the subject or by the subject’s legally acceptable representative for patients under guardianship or trusteeship. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: •Patients with known hypersensitivity to vancomycin or to any of the excipients listed in the corresponding SmPC •Patients with active CMV colitis •Patients who had previously received other lines of systemic aGvHD treatment other than CS and ruxolitinib. •Grade II-IV hyper-acute GvHD as defined by the MD Anderson’s criteria (Saliba et al. 2007) (aGvHD onset within 14 days after allo-HSCT) •Overlap chronic GvHD as defined by the NIH Consensus Criteria (Jagasia et al. 2015) •Relapsed/persistent malignancy requiring rapid immune suppression withdrawal •Active uncontrolled infection according to the attending physician •Severe organ dysfunction unrelated to underlying GvHD, including: -Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GvHD and ongoing organ dysfunction, with the exception of Gilbert syndrome). -Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months before Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support that requires therapy. -Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen. •Current or past (1 year. •Other ongoing interventional protocol that might interfere with the current study’s primary endpoint.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of the Overall Response Rate (ORR: Complete Response +Very Good Partial Response + Partial Response) of gastrointestinal- acute graft-versus-host disease (aGvHD) at Day 28.;Secondary Objective: •To evaluate MaaT013 safety •To evaluate ORR for GI at D56 •To evaluate ORR for all organs at D28 and D56 •To evaluate the best ORR (for GI and all organs) achieved between D0 and D28 •To assess duration of response •To assess overall survival (OS) •To assess progression-free survival (PFS) •To assess time to progression •To assess steroid-free survival •To evaluate the frequency of patients that tapered off CS •To measure the incidence of chronic GvHD •To evaluate changes in patient reported outcomes (PROs) •To evaluate MaaT013 activity on immune markers;Primary end point(s): To evaluate the efficacy of MaaT013 assessed by the overall response rate (ORR) of gastrointestinal (GI) acute graft-versus-host disease (aGVHD) response at day 28 (D28);Timepoint(s) of evaluation of this end point: ORR at D28 after first dosing The patient fails to achieve at least GI-PR at D28 The patient stops treatment sequence and receives salvage aGvHD therapy before D28 The patient dies before D28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate MaaT013 safety To evaluate ORR for GI at D56 and M3 To evaluate ORR for all organs at D28, D56 and M3 To evaluate the best ORR (for GI and all organs) achieved between D0 and D28 To assess duration of response To assess overall survival (OS) To assess progression-free survival (PFS) To assess time to progression To assess steroid-free survival To evaluate the frequency of patients that tapered off CS To measure the incidence of chronic GvHD To evaluate changes in patient reported outcomes (PROs) ;Timepoint(s) of evaluation of this end point: From inclusion to Month 6 From Month 6 to Month 12 Proportion of patients achieving CR, VGPR and PR of GI symptoms at D56 and M3 Proportion of patients achieving CR, VGPR and PR for all organs at D28, D56 and M3 at any timepoint up to and including D28 and before the start of any salvage therapy for aGVHD the time from first response (at least PR) until aGvHD progression or the starting date of additional systemic therapies for aGvHD | — |
Countries
Austria, Belgium, France, Germany, Italy, Spain
Contacts
Public ContactMélanie Tilte
Maat Pharma
Outcome results
None listed