First line treatment of Chronic Graft versus Host Disease in patients having received a first allogeneic stem cell transplantation for a hematological disease
Conditions
Interventions
Trade Name: Trisenox
Product Name: Trioxyde d'arsenic
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Medsenic
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult patients (=18 years) who have received a first allogeneic stem cell transplantation for a hematological disease (any source of hematopoietic stem cells is authorized; any category of conditioning regimen prior to allo-SCT is authorized; any type of stem cell donors is authorized) 2. Confirmed diagnosis of a first episode of chronic GvHD requiring systemic immunosuppressive therapy (any prior GvHD prophylaxis previously used is accepted). Chronic GvHD diagnosis is defined according to the NIH Working Group Consensus. Chronic GvHD diagnosis will be based on the evaluation of the severity of the different clinical manifestations including: a/ Performance status evaluation b/ Cutaneous evaluation measured by the percentage of extension or the presence of sclerotic features. If relevant, confirmation with a biopsy should be performed whenever possible c/ Oral symptoms d/ Ocular symptoms e/ Gastro-intestinal symptoms f/ Evaluation of liver involvement (total bilirubin, transaminases and alkaline phosphatases) g/ Pulmonary function evaluation h/ Evaluation of the musculoskeletal manifestations, especially the amplitude of the relevant articulations i/ Genital tract symptoms 3. Signed informed consent 4. Absence of contra-indications to the use of ATO 5. Subjects affiliated with an appropriate social security system? 6. Women who are of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable method of contraception throughout the study and for 3 months following the end of the study 7. Patient not participating or not having participated in a clinical study in the 30 days prior to his/her inclusion in the study 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Patient developing acute GvHD (whether early or “late onset” form) 2. Patients developing overlap GvHD as defined by the 2014 NIH Working Group Consensus (presence of one or more acute GvHD manifestations in a patient with a diagnosis of chronic GvHD) 3. A “mild” form of chronic GvHD not requiring systemic immunosuppressive therapy 4. A “moderate” form of chronic GvHD limited to one organ site not requiring systemic immunosuppressive therapy 5. Patient receiving mycophenolate mofetil 6. GvHD occurring following donor lymphocytes infusion (DLI) 7. Not the first episode of chronic GvHD needing systemic immunosuppressive therapy 8. Second allogeneic stem cell transplant 9. Significant arrhythmias, electrocardiogram (EKG) abnormalities: a/ Congenital QT syndromes b/ History or presence of significant ventricular or atrial tachyarrhythmia c/ Clinically significant resting bradycardia ( 480 msec on screening EKG (using the QTcF formula) e/ Right bundle branch block plus left anterior hemiblock, bifascicular block 10. Central or peripheral neuropathy 11. Neutrophils < 0.5 × 109/L 12. Platelets < 50 × 109/L 13. Uncontrolled systemic infection which in the opinion of the investigator is associated with an increased risk of the patients’ death within 1 month after the start of therapy 14. Severe neurological or psychiatric disorders 15. Denied informed consent 16. Pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To improve the response rate (complete and partial remission) at 6 months after diagnosis of chronic graft versus host disease (GvHD) and treatment with arsenic trioxide (ATO) in combination with prednisone with or without ciclosporine as first line treatment;Secondary Objective: 1. To evaluate failure-free survival (FFS), defined as death, recurrent or progressive malignancy, or initiation of a new systemic treatment for chronic GvHD 2. To decrease non-relapse mortality (NRM) of infectious and non-infectious origin 3. To improve overall survival (OS) and progression-free survival (PFS) 4. To spare patients from long-term use of corticosteroids (and their long-term side effects) 5. To improve quality of life self-reported by patient using the Lee Symptom Scale (LSS) and Functional Assessment of Chronic Illness Therapy with Bone Marrow Transplantation subscale (FACT-BMT) 6. To evaluate tolerability and safety of ATO in combination with prednisone, with or without ciclosporine, in patients with chronic GvHD after allo-SCT ;Primary end point(s): Evaluation of response rate (complete and partial remission) of chronic GvHD at 6 months after diagnosis of chronic GvHD and treatment with arsenic trioxide (ATO) in combination with prednisone, with or without cyclosporine, as first line treatment;Timepoint(s) of evaluation of this end point: 6 months after the inclusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of patients with documented failure free survival (FFS), defined as death, recurrent or progressive malignancy, or the initiation of a new systemic treatment for chronic GvHD 2. Corticosteroids dosage and percentage of reduction in corticosteroids dosage at 6 and 12 months after diagnosis of chronic GvHD and treatment with ATO as first line treatment 3. Cumulative incidence of transplant-related mortality (TRM) of infectious and non-infectious origin at 6 and 12 months after diagnosis of chronic GvHD and treatment with ATO as first line treatment 4. OS and PFS at 6 and 12 months after diagnosis of chronic GvHD and treatment ATO as first line treatment 5. Descriptive analysis of quality of life parameters at inclusion, at 6 and 14 weeks, and at 6, 9 and 12 months after diagnosis of chronic GvHD and treatment with ATO as first line treatment 6. Tolerability and safety of ATO in combination with prednisone, with or without cyclosporine, in patients with chronic GvHD after allo-SCT ;Timepoint(s) of evaluation of this end point: At 6 and 14 weeks, and at 6, 9 and 12 months after the start of treatment with ATO | — |
Countries
France
Contacts
Public ContactFranck Sévenier
Fovea
Outcome results
None listed