Clinical trial NCT02891395: Efficacy and Safety of Nilotinib in Patients With a Chronic Disease of the Graft Against the Host
Official title: Efficacy and Safety of Nilotinib in Patients With a Chronic Disease of the Graft Against the Host (Graft Versus Host, GVH) Did Not Respond to Imatinib Mesylate.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Versus Host Disease
Keywords: allogeneic stem cell transplantation
imatinib Mesylate
Nilotinib
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2016-09-07
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Response rate at 3 months (complete and partial remission) after salvage treatment with Nilotinib in patients with chronic GVHD who failed Imatinib Mesylate (IM)
timeFrame: Between Baseline and minimum 12 weeks of treatment
Secondary outcomes:
measure: Best response to IM within 12 months and the duration of this response
timeFrame: From 12 to 52 weeks of Imatinib Mesylate treatment
measure: Best response rate to Nilotinib within 12 months and the duration of this response
timeFrame: From 12 to 52 weeks of Nilotinib treatment
measure: use of systemic secondary treatment due to intolerance to IM
timeFrame: From baseline to 12 weeks of IM treatment
measure: use of systemic secondary treatment due to intolerance to Nilotinib
timeFrame: From baseline to 12 weeks of Nilotinib treatment
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: CHU Sart Tilman
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU d'Angers
city: Besancon
country: France
facility: CHU Besançon
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Brest
country: France
facility: Hopital Morvan
city: Caen
country: France
facility: CHU Clémenceau
city: Clamart
country: France
facility: HIA de Percy
city: Clermont Ferrand
country: France
facility: CHU de Clermont Ferrand
city: Grenoble
country: France
facility: CHU Grenoble
city: LIlle
country: France
facility: Diseases of Blood Service HURIEZ hospital CHRU de LILLE
city: Lille
country: France
facility: Centre hospitalier et régional de Lille
city: Lyon
country: France
facility: CHU de Lyon
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Hôpital Saint Eloi
city: Nantes
country: France
facility: CHU Hotel Dieu
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: Hopital NECKER
city: Paris
country: France
facility: Hôpital pitié Salpetrière
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Strasbourg
country: France
facility: CHU de STRASBOURG
city: Toulouse
country: France
facility: CHU Purpan
Study officials:
affiliation: University Hospital, Lille
name: YAKOUB-AGHA Ibrahim, MD
role: PRINCIPAL_INVESTIGATOR
References: