Multicenter Single-arm Pilot Study Evaluating Efficacy of Nilotinib in CML Patients With Molecular Relapse After Glivec Discontinuation Within the Context of the STIM Trials (STIM and STIM2)
18 Years
N/A
Both
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Trial Information
Multicenter Single-arm Pilot Study Evaluating Efficacy of Nilotinib in CML Patients With Molecular Relapse After Glivec Discontinuation Within the Context of the STIM Trials (STIM and STIM2)
Patients with CML included in STIM trials, stopped their treatment by imatinib because the
signal was not detectable. In case of reappearance of this transcript Bcr-Abl, the patient
relapses. The trial Nilo Post STIM is suggested to the patient to assess if Nilotinib can
rescue STIM patients in molecular relapse after IM discontinuation and to provide an
estimation about duration of CMR after nilotinib discontinuation in 2nd line therapy among
patients experiencing 2 years of stable CMR with nilotinib.
The treatment/strategy for this study:
- Screening
- Inclusion/exclusion criteria
- CML history
- Confirm molecular relapse after discontinuation of imatinib (quantitative RT-PCR
on two consecutive assessments from peripheral blood samples)
- Treatment
• Nilotinib 300mg BID for 2 years
- Premature treatment discontinuation while on study: primary or secondary
resistance progression to accelerated phase or blast crisis, AE (to be defined
later).
- In case of unsatisfactory response: transcript stability or increase on two
consecutive PCR: nilotinib blood monitoring, and nilotinib dose escalation up to
400mg BID will be proposed
- Discontinuation at 2 years for patients who resumed confirmed CMR
- Follow-up while on treatment with nilotinib:
- Physical exam, basic laboratory parameters, monthly during the first 3 months then
every 3 months.
- Centralized quantitative RT-PCR for Bcr-Abl monthly for 6 months then every 3
months for 24 months
- Follow AE management guidelines for nilotinib reduction/interruptions
- Follow-up after nilotinib discontinuation
- Patients in confirmed molecular relapse
- Physical exam, event collection, basic laboratory parameters (including
glycemic and lipid profile) every 2 months during the first year then every 3
months
- Hematology and centralized quantitative RT-PCR monthly the first year then
every 3 months for 12 months
- Patients without confirmed molecular relapse will take another treatment
(dasatinib for example) and will stop their follow-up in the trial
Inclusion Criteria:
- Male and female patients
- Patient participating to the STIM trial and with confirmed molecular relapse on two
consecutive RQ PCR, after imatinib discontinuation
- Still in chronic phase
- Not yet treated for this relapse
- At least 18 years old (no upper age limit)
- SGOT and SGPT < 2.5 UNL
- Serum creatinin < 2 UNL
- No planned allogeneic stem cell transplantation
- Signed informed consent
- ECOG score 0 to 2
Exclusion Criteria:
- Pregnancy, lactation
- Prior or concurrent malignancy other than CML (exceptions to be mentioned)
- Serious uncontrolled cardiovascular disease
- Severe psychiatric/neurological disease (previous or ongoing)
- Ongoing treatment at risk for inducing "torsades de pointe"
- QTcF > 450ms despite correction of predisposing factors (i.e electrolytes…)
- Congenital long QTcF
- No health insurance coverage
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Estimated survival rate of patients without molecular relapse 3 years after enrollment
Outcome Description:
CMR is defined as >5 log reduction in Bcr-Abl and Abl levels and undetectable transcripts on quantitative RTq-PCR
Outcome Time Frame:
Evaluation by RTq-PCR monthly the first year of treatment with nilotinib then every 3 months until 24 months, date of discontinuation of Nilotinib for patients in sustained complete molecular response (CMR). After discontinuation of Nilotinib patie
Safety Issue:
Yes
Principal Investigator
Viviane DUBRUILLE
Investigator Role:
Study Chair
Investigator Affiliation:
Nantes University Hospital
Authority:
France: Ministry of Health
Study ID:
CHUBX 2012/18
NCT ID:
NCT01774630
Start Date:
January 2013
Completion Date:
January 2017
Related Keywords:
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Treatment, relapse, complete molecular response
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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