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Chronic Graft-Versus-Host DiseasePhase 2GvHD-ATONCT02966301

Treatment of Chronic Graft Versus Host Disease With Arsenic Trioxide

A Phase 2 study testing Arsenic Trioxide Injectable Solution in people with Chronic Graft-Versus-Host Disease and Immune System Diseases, run by Medsenic.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Arsenic Trioxide Injectable Solution
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
No sites listed yet
Study dates
Dec 2016to Jun 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 17Show fewer
  • 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

Who cannot join

  • 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
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  • 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.

About this study

Official title: Phase II Study of First Line Treatment of Chronic Graft Versus Host Disease With Arsenic Trioxide

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

Read the 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).

Being tested
Arsenic Trioxide Injectable Solution
Keywords
cGvHD, Arsenic Trioxide, Hematology
Medical subject headings
Bronchiolitis Obliterans Syndrome, Immune System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Arsenic Trioxide Injectable SolutionDrug

    Also called Trisenox / Arscimed

    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).

Study groups in NCT02966301
Study groupRoleWhat they receive
interventionalExperimentalSingle arm : Arsenic trioxide
Receives: Drug: Arsenic Trioxide Injectable Solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: six months

Secondary outcomes (4)

  1. Average Dose of Corticosteroids

    Average dose in mg/kg/day of prednisone or prednisone equivalent

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

  2. Failure Free Survival

    Treatment failure were defined by:

    • Initiation of a new systemic treatment for chronic GvHD;
    • Recurrent or progressive malignancy;
    • Death

    Measured: 6 months after first ATO infusion

  3. Number of Adverse Events

    Tolerability and safety of ATO in combination with Prednisone, with or without Ciclosporine, in patients with chronic GvHD after allo-SCT.

    Adverse events follow-up for all patients throughout the study

    Measured: 12 months after the first infusion of ATO for each patient

  4. Cumulative Incidence for Non-relapse Mortality (NRM)

    Non-Relapse Mortality (NRM) of infectious and non-infectious origin

    Measured: 12 months after first ATO infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2016 (estimated)
  2. Study startDec 2016
  3. Primary completionJun 2020
  4. Study completionJun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02966301
Sponsor's protocol ID
GMED16-001
Acronym
GvHD-ATO
Status last verified
Jul 2020
First submitted
28 Oct 2016
Last updated
9 May 2022
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 35830931

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Arsenic Trioxide Injectable Solution in people with Chronic Graft-Versus-Host Disease and Immune System Diseases, run by Medsenic.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 May 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Complete or Partial Remission of Chronic Graft Versus Host Disease After a First Line Treatment With Arsenic Trioxide (time frame: six months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02966301, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2022.

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