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

• Status: Completed
• Trial end date: 2017-07-26
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Lille
• Collaborator: Novartis
• Treatments: Imatinib Mesylate

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