Treatment for patients whith graft-versus-host disease after bone marrow transplantation.

Phase 1

• Conditions: Chronic graft-versus-host disease .; MedDRA version: 14.1Level: LLTClassification code 10008907Term: Chronic GVH diseaseSystem Organ Class: 100000004870; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-000770-36-BE
• Lead Sponsor: CHU-ULg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-12-10
• Last Update Posted: 18 January 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

Induction phase (imatinib)
- Age: = 18 and <75 years.
- Patients who underwent allogeneic hematopoietic stem cell transplantation for a hematological disease.
- Body weight = 40 kg.
- Confirmed diagnosis of an extensive cGVH resistant to at least one systemic immunosuppressive therapy.
- Any source of hematopoietic stem cells is authorized.
- Myeloablative and non-myeloablative regimes are allowed.
- No contra-indication to the use of IM or nilotinib.

Salvage Phase (nilotinib):
Patients enrolled in the first phase who did not respond to IM:
- Patients who discontinued IM after 3 months du to a lack of response.
(stable disease = no response)
- Patients who experienced disease progression at any time.
- Patients who relapsed after an initial response at any time.
- Patients who discontinued treatment due to toxicity at any time.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion Criteria

- Appearance of acute GVHD ( early form or late onset ).
- First episode of cGVHD or cGVHD not requiring systemic treatment.
- Patient treated with IM or nilotinib , a tyrosine kinase inhibitor given after transplantation within 3 months before enrollment.
- Patients treated with ITK for GVHD.
- Contra-indication to IM or nilotinib.
- Neutropenia < 0,5.10E9 / l.
- Uncontrolled systemic infection which the investigator may associate to an increased death risk during the first month of treatment .
- Severe neurological or psychiatric disorders .
- Pregnant or breastfeeding women .
- Known uncontrolled arrhythmias or symptomatic heart disease or ventricular ejection fraction < 45% (cardiac tests according to clinical indication).
- Performance index: WHO = 3 unrelated to chronic GVHD.
- Relapse of the blood disease for which transplantation was performed except presence of minimal residual disease confirmed by PCR.
- Appearance of a secondary cancer = 2 years before enrollment, subject to the following exceptions :
-cutaneous basal cell carcinoma.
-squamous cell carcinoma of skin.
-carcinoma in situ of the cervix.
-carcinoma in situ of the breast.
-prostate cancer (Stage TNM [ Tumor , Node , Metastasis ] T1a or T1b) .
- Refusal to sign the consent form .
- Patients in an emergency situation or unable to consent .

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Response rate at 3 months of extensive cGVH (complete or partial remission ) in nilotinib-treated patients who have not responded to imatinib mesylate.;Secondary Objective: * For Imatinib mesylate (IM):<br>- To confirm the effectiveness of IM in patients with extensive cGVH requiring treatment and resistant to at least one therapeutic line.<br><br>* For Nilotinib:<br>- Evaluate the effectiveness of nilotinib in patients with a resistance or intolerance to IM.<br>- Avoid long-term use of immunosuppresive drugs, including corticosteroids (and their long-term adverse effects).<br>- Reduce non-relapse mortality (NRM) of infectious or non-infectious origin.<br>- Improve quality-of-life parameters.<br><br><br><br><br><br><br>;Primary end point(s): Response rate at 3 months (complete and partial remission) after salvage therapy by nilotinib in patients with a cGVHD who did not respond to imatinib mesylate (IM).