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

December 15, 2025 updated by: University Hospital, Lille

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.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Liège, Belgium
        • CHU Sart Tilman
  • France
      • Amiens, France
        • CHU D'amiens
      • Angers, France
        • CHU d'Angers
      • Besançon, France
        • CHU Besançon
      • Bordeaux, France
        • CHU Bordeaux
      • Brest, France
        • Hôpital Morvan
      • Caen, France
        • CHU Clemenceau
      • Clamart, France
        • HIA de Percy
      • Clermont-Ferrand, France
        • CHU de Clermont Ferrand
      • Grenoble, France
        • CHU Grenoble
      • Lille, France
        • Centre hospitalier et régional de Lille
      • Lille, France, 59037
        • Diseases of Blood Service HURIEZ hospital CHRU de LILLE
      • Lyon, France
        • CHU de Lyon
      • Marseille, France
        • Institut Paoli Calmettes
      • Montpellier, France
        • Hopital Saint Eloi
      • Nantes, France
        • Chu Hotel Dieu
      • Nice, France
        • Chu de Nice
      • Paris, France
        • Hopital Pitie Salpetriere
      • Paris, France
        • Hopital Necker
      • Rouen, France
        • Centre Henri Becquerel
      • Strasbourg, France
        • CHU de Strasbourg
      • Toulouse, France
        • CHU Purpan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best response to IM within 12 months and the duration of this response
Time Frame: From 12 to 52 weeks of Imatinib Mesylate treatment
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
From 12 to 52 weeks of Nilotinib treatment
use of systemic secondary treatment due to intolerance to IM
Time Frame: From baseline to 12 weeks of IM treatment
measure intolerance by IM failure
From baseline to 12 weeks of IM treatment
use of systemic secondary treatment due to intolerance to Nilotinib
Time Frame: From baseline to 12 weeks of Nilotinib treatment
measure intolerance by Nilotinib failure
From baseline to 12 weeks of Nilotinib treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Lille

Collaborators

Novartis

Investigators

  • Principal Investigator: YAKOUB-AGHA Ibrahim, MD, University Hospital, Lille

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 24, 2012

Primary Completion (Actual)

July 26, 2017

Study Completion (Actual)

July 26, 2017

Study Registration Dates

First Submitted

September 1, 2016

First Submitted That Met QC Criteria

September 1, 2016

First Posted (Estimated)

September 7, 2016

Study Record Updates

Last Update Posted (Estimated)

December 22, 2025

Last Update Submitted That Met QC Criteria

December 15, 2025

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009_18
  • 2012-000770-36 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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