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Treatment of Chronic Graft Versus Host Disease With Arsenic Trioxide (GvHD-ATO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02966301
Recruitment Status : Active, not recruiting
First Posted : November 17, 2016
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
FOVEA - POPSICUBE
Information provided by (Responsible Party):
Medsenic

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

Condition or disease Intervention/treatment Phase
Chronic Graft-Versus-Host Disease Immune System Diseases Drug: Arsenic Trioxide Injectable Solution Phase 2

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of First Line Treatment of Chronic Graft Versus Host Disease With Arsenic Trioxide
Actual Study Start Date : December 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: interventional
Single arm : Arsenic trioxide Injectable Solution
Drug: 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).

Other Name: Trisenox / Arscimed




Primary Outcome Measures :
  1. 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 ]
    Clinical response will be evaluated based on the Working Group Report 2015, published by the National Institute of Health Consensus : Lee SJ et al. Biol Blood Marrow Transplant, 2015 (cGvHD activity assessment Clinician Form A & cGvHD assessment patient self-report Form B)


Secondary Outcome Measures :
  1. Steroid dose reduction (mg/kg/day of prednisone) [ Time Frame: 2 weeks and 3, 6, 9 & 12 months after ATO cycle treatment ]
  2. Quality of life self-reported by patient using the Lee Symptom Scale (LSS) [ Time Frame: 6 & 14 week, 6, 9 & 12 months ]
  3. Quality of life self-reported by patient using the Functional Assessment of Chronic Illness : Therapy with Bone Marrow Transplantation subscale (FACT-BMT) [ Time Frame: 6 & 14 week, 6, 9 & 12 months ]
  4. Time without relapse in case of positive response [ Time Frame: 12 months ]
  5. Progression-free survival rates [ Time Frame: 12 months ]
  6. Adverse events [ Time Frame: 12 months ]
    Follow-up throughout the study

  7. Blood test of immunoglobulins [ Time Frame: Inclusion, 6 & 14 week, 6, 9 & 12 months ]
  8. Blood test of arsenic [ Time Frame: D2, D3, D4, D5, D8, D12, D17 and D24, during arsenic trioxide treatment period ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02966301


Locations
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France
CHU de Caen - Institut d'Hématologie de Basse Normandie
Caen, France, 14033
Institut Paoli Calmettes - Département d'hématologie - Centre de Recherche en Cancérologie de Marseille
Marseille, France, 13273
CHU Hôtel Dieu - Service Hématologie Clinique
Nantes, France, 44093
Hôpital Saint Antoine - Hématologie et thérapie cellulaire - AP-HP
Paris, France, 75012
Institut Universitaire du Cancer - Oncopole - Service d'Hématologie
Toulouse, France, 31059
Sponsors and Collaborators
Medsenic
FOVEA - POPSICUBE
Investigators
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Principal Investigator: 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

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Responsible Party: Medsenic
ClinicalTrials.gov Identifier: NCT02966301     History of Changes
Other Study ID Numbers: GMED16-001
First Posted: November 17, 2016    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Medsenic:
c GvHD
Arsenic Trioxyde
Hematology
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Arsenic Trioxide
Antineoplastic Agents