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

Graft Versus Host Disease Clinical Trial

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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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02891395
• Other study ID #: 2009_18
• Secondary ID: 2012-000770-36
• Status: Completed
• Phase: Phase 2
• Start date: December 24, 2012
• Est. completion date: July 26, 2017

Study information

• Verified date: July 2019
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: July 26, 2017
• Est. primary completion date: July 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Disease
• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Belgium	CHU Sart Tilman	Liège
France	CHU d'Amiens	Amiens
France	CHU d'Angers	Angers
France	CHU Besançon	Besancon
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	Centre hospitalier et régional de Lille	Lille
France	Diseases of Blood Service HURIEZ hospital CHRU 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

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	Novartis

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate at 3 months (complete and partial remission) after salvage treatment with Nilotinib in patients with chronic GVHD who failed Imatinib Mesylate (IM)	Response rate at 3 months (complete and partial remission) after salvage treatment with Nilotinib in patients with chronic GVHD who failed Imatinib Mesylate (IM)	Between Baseline and minimum 12 weeks of treatment
Secondary	Best response to IM within 12 months and the duration of this response		From 12 to 52 weeks of Imatinib Mesylate treatment
Secondary	Best response rate to Nilotinib within 12 months and the duration of this response		From 12 to 52 weeks of Nilotinib treatment
Secondary	use of systemic secondary treatment due to intolerance to IM	measure intolerance by IM failure	From baseline to 12 weeks of IM treatment
Secondary	use of systemic secondary treatment due to intolerance to Nilotinib	measure intolerance by Nilotinib failure	From baseline to 12 weeks of Nilotinib treatment