Treatment of Chronic Graft Versus Host Disease With Arsenic Trioxide

NCT02966301 | Completed Phase 2 Results DMC

• 1 other identifier: GMED16-001
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

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

Conditions

Chronic Graft-Versus-Host Disease; Immune System Diseases

Keywords

cGvHD; Arsenic Trioxide; Hematology

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Complete or Partial Remission of Chronic Graft Versus Host Disease After a First Line Treatment With Arsenic Trioxide

  Clinical response will be evaluated based on the Working Group Report 2015, published by the National Institute of Health Consensus. Response definition is as follows: * Complete remission (CR) is defined as complete disappearance of any sign of chronic GvHD. * Partial remission (PR) is defined as a significant improvement as defined by the organ or site specific measurement scale without progression in any other organ or site.

  six months

Secondary Outcomes (4)

• Average Dose of Corticosteroids

  Average dose of Prednisone at 6 months after the first infusion of ATO

• Failure Free Survival

  6 months after first ATO infusion

• Number of Adverse Events

  12 months after the first infusion of ATO for each patient

• Cumulative Incidence for Non-relapse Mortality (NRM)

  12 months after first ATO infusion

Study Arms (1)

interventional

EXPERIMENTAL

Single arm : Arsenic trioxide

Drug: Arsenic Trioxide Injectable Solution

Interventions

Arsenic Trioxide Injectable Solution 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).

Also known as: Trisenox / Arscimed

interventional

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Medsenic: lead

Related Publications (1)

• 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.

  PMID: 35830931 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Immune System Diseases

Interventions

Arsenic Trioxide

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds

Results Point of Contact

• Title: RIEGER François - CEO - Scientific Director
• Organization: MEDSENIC

fr@medsenic.org

+33671733159

Study Officials

• Mohamad Mohty, Pr

  Hôpital Saint-Antoine, AP-HP - Paris

  PRINCIPAL INVESTIGATOR

• Anne Huyhn, Dr

  Institut Universitaire du Cancer - Oncopole - Toulouse

  PRINCIPAL INVESTIGATOR

• Sylvain Chantepie, Dr

  Institut d'Hématologie de Basse Normandie - CHU de Caen

  PRINCIPAL INVESTIGATOR

• Patrice Chevallier, Dr

  Hôtel Dieu - CHU Nantes

  PRINCIPAL INVESTIGATOR

• Didier Blaise, Pr

  Institut Paoli Calmettes - Centre de Recherche en Cancérologie de Marseille

  PRINCIPAL INVESTIGATOR

• Patrice Ceballos, Dr

  Hôpital St Eloi - Montpellier

  PRINCIPAL INVESTIGATOR

• Patrice Turlure, Dr

  University Hospital, Limoges

  PRINCIPAL INVESTIGATOR

• Edouard Forcade, Dr

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2016
• First Posted: November 17, 2016
• Study Start: December 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: May 9, 2022
• Results First Posted: May 9, 2022

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share