Treatment of Chronic Graft Versus Host Disease With Arsenic Trioxide

NCT ID: NCT02966301

Last Updated: 2022-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2020-06-30

Brief Summary

This study aims to evaluate the early chronic GvHD events (first line therapy), if the addition of arsenic trioxide to standard therapy with corticosteroids, with or without cyclosporine, will be effective in controlling chronic GvHD and to reduce the duration of corticosteroid therapy

Detailed Description

Graft-versus-host disease (GvHD) is the most common long-term complication in patients who underwent allogeneic transplantation.

First-line therapy for chronic GVHD is based on immunosuppressive agents (corticosteroids with or without cyclosporine) achieving satisfactory response in around 30% of patients.

This is a prospective, national, multicenter, non-randomized Phase II study that will include a total number of 24 patients in which, trioxide d'arsenic will be administrated at 0,15mg/kg/day.

Clinical response will be evaluated based on the Working Group Report 2015, published by the National Institute of Health Consensus.

Follow-up visits will be weekly for four weeks (ATO cycle), every two weeks from second to third month of ATO treatment, every month from the fourth to sixth month of ATO treatment and every 3 months, at 9 months and 12 months (final visit).

Conditions

Chronic Graft-Versus-Host Disease; Immune System Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

interventional

Single arm : Arsenic trioxide

Group Type: EXPERIMENTAL

Arsenic Trioxide Injectable Solution

Intervention Type: DRUG

Each patient will receive eleven perfusions of arsenic trioxide (0,15 mg/kg/Day - IV administration) over a 4 weeks period (one cycle).

Patients in partial response after the 1st cycle of ATO will be eligible to receive a second cycle of ATO as consolidation therapy. A delay of 8 weeks (from the first infusion of ATO) will be observed between the two cycles of ATO therapy.

The study duration will be 2 years (12 months recruitment + 12 months follow-up).

Interventions

Arsenic Trioxide Injectable Solution

Each patient will receive eleven perfusions of arsenic trioxide (0,15 mg/kg/Day - IV administration) over a 4 weeks period (one cycle).

Patients in partial response after the 1st cycle of ATO will be eligible to receive a second cycle of ATO as consolidation therapy. A delay of 8 weeks (from the first infusion of ATO) will be observed between the two cycles of ATO therapy.

The study duration will be 2 years (12 months recruitment + 12 months follow-up).

Intervention Type: DRUG

Other Intervention Names

Trisenox / Arscimed

Eligibility Criteria

Inclusion Criteria

• 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)
• 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:

• Performance status evaluation
• 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
• Oral symptoms
• Ocular symptoms
• Gastro-intestinal symptoms
• Evaluation of liver involvement (total bilirubin, transaminases and alkaline phosphatases)
• Pulmonary function evaluation
• Evaluation of the musculoskeletal manifestations, especially the amplitude of the relevant articulations
• Genital tract symptoms
• Signed informed consent
• Absence of contra-indications to the use of ATO
• Subjects affiliated with an appropriate social security system
• Men must use a medically acceptable method of contraception throughout the treatment period and for at least 4 months and 10 days following the last treatment administration
• 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
• Patient not participating or not having participated in a clinical study in the 30 days prior to his/her inclusion in the study

Exclusion Criteria

• Patient developing acute GvHD (whether early or "late onset" form)
• 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)
• A "mild" form of chronic GvHD not requiring systemic immunosuppressive therapy
• A "moderate" form of chronic GvHD limited to one organ site not requiring systemic immunosuppressive therapy
• Patient receiving mycophenolate mofetil
• Not the first episode of chronic GvHD needing systemic immunosuppressive therapy
• Second allogeneic stem cell transplant
• Severe cardiac diseases (congestive heart failure (NYHA class III), recent myocardial infarction (in the past 6 months before the inclusion), histories of unexplained syncope, ...)
• Significant arrhythmias, electrocardiogram (EKG) abnormalities:
• Congenital QT syndromes
• History or presence of significant ventricular or atrial tachyarrhythmia
• Clinically significant resting bradycardia (< 50 beats per minutes)
• QTc>450msecformenand>470msecfor women on screening EKG (using the QTcF formula)
• Right bundle branch block plus left anterior hemiblock, bifascicular block
• Central or peripheral neuropathy
• Neutrophils < 0.5 × 109/L
• Platelets < 50 × 109/L
• Potassium ≤ 4 mEq/l*
• Magnesium ≤ 1.8 mg/dl*
• Calcium ≤ 2.15 mmol/l*
• Hepatic impairment due to a suspected or proven liver damage, other than direct hepatic cGvHD involvement
• PT < 50%
• Renal impairment (creatinine ≥ 100 μmol/l)
• 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
• Severe neurological or psychiatric disorders
• Denied informed consent
• Pregnancy
• Women breastfeeding at selection and throughout the treatment period

• If abnormal at selection, to be corrected and re-validated following electrolytes infusion, before inclusion and each drug perfusion.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medsenic

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohamad Mohty, Pr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint-Antoine, AP-HP - Paris

Anne Huyhn, Dr

Role: PRINCIPAL_INVESTIGATOR

Institut Universitaire du Cancer - Oncopole - Toulouse

Sylvain Chantepie, Dr

Role: PRINCIPAL_INVESTIGATOR

Institut d'Hématologie de Basse Normandie - CHU de Caen

Patrice Chevallier, Dr

Role: PRINCIPAL_INVESTIGATOR

Hôtel Dieu - CHU Nantes

Didier Blaise, Pr

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli Calmettes - Centre de Recherche en Cancérologie de Marseille

Patrice Ceballos, Dr

Role: PRINCIPAL_INVESTIGATOR

Hôpital St Eloi - Montpellier

Patrice Turlure, Dr

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Limoges

Edouard Forcade, Dr

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

References

Rongvaux-Gaida D, Dupuis M, Poupon J, Djebrani-Oussedik N, Lemonnier C, Rieger F. High Response Rate and Corticosteroid Sparing with Arsenic Trioxide-Based First-Line Therapy in Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation. Transplant Cell Ther. 2022 Oct;28(10):679.e1-679.e11. doi: 10.1016/j.jtct.2022.07.004. Epub 2022 Jul 10.

Reference Type: DERIVED

PMID: 35830931 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GMED16-001

Identifier Type: -

Identifier Source: org_study_id