Overview

This trial is active, not recruiting.

Condition graft versus host disease
Treatment imatinib mesylate and nilotinib
Phase phase 2
Sponsor University Hospital, Lille
Collaborator Novartis
Start date December 2012
End date March 2017
Trial size 65 participants
Trial identifier NCT02891395, 2009_18, 2012-000770-36

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
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.

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)
time frame: Between Baseline and minimum 12 weeks of treatment

Secondary Outcomes

Measure
Best response to IM within 12 months and the duration of this response
time frame: From 12 to 52 weeks of Imatinib Mesylate treatment
Best response rate to Nilotinib within 12 months and the duration of this response
time frame: From 12 to 52 weeks of Nilotinib treatment
IM failure for intolerance
time frame: From baseline to 12 weeks of IM treatment
Nilotinib failure for intolerance
time frame: From baseline to 12 weeks of Nilotinib treatment

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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

Additional Information

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.
Principal investigator YAKOUB-AGHA Ibrahim, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by University Hospital, Lille.