Efficacy and Safety of Nilotinib in Patients With a Chronic Disease of the Graft Against the Host

NCT ID: NCT02891395

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-24
• Study Completion Date: 2017-07-26

Brief Summary

Open label non-randomized multicenter phase 2 trial with direct individual benefice

Detailed Description

Induction phase: Imatinib mesylate - starting with 100 mg/day with increase of 100 mg/day each other week up to maximum tolerable dose or 400 mg/day whichever occurred first. For the responders and in absence of toxicity, the treatment will be maintained up to one year. Patients, who discontinue imatinib mesylate at 3 months for lack of response (no response = stable disease), those who experience progression at any time, those who relapse after an initial response at any time or those who discontinue for toxicity at any time, will go to the salvage phase.

Salvage phase:

Nilotinib - starting with 200 mg/day with increase of 200 mg/day each other week up to maximum tolerable dose or 800 mg/day whichever occurred first. In absence of toxicity, the treatment will be maintained up to one year.

Conditions

Graft Versus Host Disease

Keywords

allogeneic stem cell transplantation; imatinib Mesylate; Nilotinib

Study Design

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

Study Groups

open-label

Induction phase: Imatinib mesylate - starting with 100 mg/day with increase of 100 mg/day each other week up to maximum tolerable dose or 400 mg/day whichever occurred first. For the responders and in absence of toxicity, the treatment will be maintained up to one year.

Salvage phase:

Nilotinib - starting with 200 mg/day with increase of 200 mg/day each other week up to maximum tolerable dose or 800 mg/day whichever occurred first. In absence of toxicity, the treatment will be maintained up to one year.

Group Type: EXPERIMENTAL

Imatinib Mesylate and Nilotinib

Intervention Type: DRUG

For patients under Imatinib Mesylate: the total length of follow up period for those patients will be for 52 weeks following IM treatment, with a follow up at weeks IM4, IM8, IM12, IM26, IM38 and IM52.

For patients requiring a salvage phase: after the switch for nilotinib, the total length of follow up period for this phase will be for 52 weeks following nilotinib treatment, with a follow up at weeks nilo4, nilo8, nilo12, nilo26, nilo38 and nilo52.

Interventions

Imatinib Mesylate and Nilotinib

For patients under Imatinib Mesylate: the total length of follow up period for those patients will be for 52 weeks following IM treatment, with a follow up at weeks IM4, IM8, IM12, IM26, IM38 and IM52.

For patients requiring a salvage phase: after the switch for nilotinib, the total length of follow up period for this phase will be for 52 weeks following nilotinib treatment, with a follow up at weeks nilo4, nilo8, nilo12, nilo26, nilo38 and nilo52.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Induction phase (IM):

• Patients aged ≥18 years to 75 years
• Patients who underwent allo-SCT for a hematological disorder
• Body weight ≥ 40 Kg.
• Confirmed diagnosis of cGVHD resistant to at least one systemic immunosuppressive therapy. The diagnosis of cGHVD should be based on the NIH Working Group Consensus (www.asbmt.org/gvhd/index.htm). Grading of cGVHD will be based on clinical manifestations including:

1. ocular, oral and mucosal symptoms;

2. performance status;

3. evaluation of pulmonary functions;

4. cutaneous evaluation;

5. evaluation of musculo-skeletal manifestations;

6. evaluation of liver involvement;

• Any source of hematopoietic stem cell is allowed
• Both myeloablative and nonmyeloablative conditioning regimens are authorized.
• Absence of contra-indications to the use of IM or Nilotinib
• Patient having French health care coverage
• Female patients of childbearing potential must have before initiation of study drug and agree to have efficient contraceptive precautions throughout the trial and for 3 months after the end of the trial.
• Signed informed consent.

Salvage phase (Nilotinib) :

Patients enrolled in the first phase and who failed to IM:

• Patients, who discontinue imatinib mesylate at 3 months for lack of response (no response = stable disease),
• those who experience progression at any time,
• those who relapse after an initial response at any time
• or those who discontinue for toxicity at any time.

Exclusion Criteria

• Patient developing acute GVHD (whether early or "late onset" form)
• First episode of cGVHD
• Patient who received IM or Nilotinib treatment or any other TKI after transplant 3 months before the inclusion on the study
• Patient treated by TKI for a GVHD
• Contra-indication to IM or Nilotinib
• Neutropenia < 0.5 G/L
• Uncontrolled systemic infection which can be associated, according to the investigator, to an enhanced risk of patient's death during the first month of treatment
• Severe neurological or psychiatric disorders
• Pregnancy or lactation
• Known uncontrolled arrhythmias or symptomatic heart disease or left ventricular ejection fraction < 40% (cardiac tests as clinically indicated)
• Recurrence of cancer for which the transplant was done except for presence of minimal residual disease by PCR
• Patients with secondary malignancy ≤ 2 years prior study-entry except:

• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Prostate cancer (Tumor, Node, Metastasis [TNM] stage T1a or T1b)
• Patients in emergency situation
• Patients kept in detention
• Patients unable or unwilling to comply with the protocol requirements

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

YAKOUB-AGHA Ibrahim, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Lille

Locations

CHU Sart Tilman

Liège, , Belgium

CHU d'Amiens

Amiens, , France

CHU d'Angers

Angers, , France

CHU Besançon

Besançon, , France

CHU Bordeaux

Bordeaux, , France

Hopital Morvan

Brest, , France

CHU Clémenceau

Caen, , France

HIA de Percy

Clamart, , France

CHU de Clermont Ferrand

Clermont-Ferrand, , France

CHU Grenoble

Grenoble, , France

Diseases of Blood Service HURIEZ hospital CHRU de LILLE

Lille, , France

Centre hospitalier et régional de Lille

Lille, , France

CHU de Lyon

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

Hôpital Saint Eloi

Montpellier, , France

CHU Hotel Dieu

Nantes, , France

CHU de Nice

Nice, , France

Hopital NECKER

Paris, , France

Hôpital pitié Salpetrière

Paris, , France

Centre Henri Becquerel

Rouen, , France

CHU de STRASBOURG

Strasbourg, , France

CHU Purpan

Toulouse, , France

Countries

Belgium; France

References

Srour M, Alsuliman T, Labreuche J, Bulabois CE, Chevallier P, Daguindau E, Forcade E, Francois S, Guillerm G, Coiteux V, Turlure P, Beguin Y, Yakoub-Agha I, Magro L. Nilotinib efficacy and safety as salvage treatment following imatinib intolerance and/or inefficacy in steroid refractory chronic graft-versus-host-disease (SR-cGVHD): a prospective, multicenter, phase II study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Bone Marrow Transplant. 2023 Apr;58(4):401-406. doi: 10.1038/s41409-022-01898-x. Epub 2023 Jan 9.

Reference Type: RESULT

PMID: 36624161 (View on PubMed)

Other Identifiers

2012-000770-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2009_18

Identifier Type: -

Identifier Source: org_study_id