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)

NCT01774630 | Completed Phase 2 DMC

• 2 other identifiers: CHUBX 2012/182012-004048-31
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 10

Brief Summary

Chronic myeloid leukemia (CML) is a hematopoietic neoplasm characterized by the reciprocal translocation t(9;22). The resulting oncoprotein, bcr-abl is an essential trigger for growth and survival of leukemic cells. In the past decade, the bcr-abl tyrosine kinase inhibitor (TKI) imatinib (IM or Glivec©) has been the standard of care for patients with CML, inducing durable responses. However, requiring continuing IM indefinitely and the ability of IM to eradicate the CML clone was uncertain. In a small proportion of patients, IM can induce complete molecular response (CMR) defined by the disappearance of the bcr-abl transcript in conventional quantitative RT-PCR. The question whether or not these patients are cured and can discontinue drug therapy has been assessed by Mahon and coll, in the STIM study. He demonstrates that IM can be safely discontinued in patient with a CMR of at least 2 year duration and all patients who relapsed after IM discontinuation mainly did it in the first 6 months and responded to reintroduction of imatinib. Nilotinib is a rationally designed second generation tyrosine kinase inhibitor with improved target specificity over imatinib. Its efficacy and safety in the treatment of patients who are resistant or intolerant to imatinib as well as patients with newly diagnosed CML-CP led to the registration in second and first line treatment of CML-CP patients. Nilotinib produces even faster and deeper responses with more occurrence of CMR than does Imatinib. Consequently, one can assume that a more potent drug such nilotinib could induce deeper and sustained CMR allowing longer period off treatment than IM. The objective of this pilot trial is 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.

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Keywords

Treatment, relapse, complete molecular response

Outcome Measures

Primary Outcomes (1)

• Estimated survival rate of patients without molecular relapse 3 years after enrollment

  CMR is defined as \>5 log reduction in Bcr-Abl and Abl levels and undetectable transcripts on quantitative RTq-PCR

  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

Secondary Outcomes (7)

• Rate and kinetics of CMR while on treatment with nilotinib

  at 6 and 12 months of treatment with nilotinib

• Duration of CMR while on treatment with nilotinib

  Any time

• Event free survival (EFS)

  Any time

• Safety tolerability of nilotinib and compliance

  Any time

• Duration of CMR after nilotinib discontinuation

  Measured from the start of nilotinib discontinuation to the date of first confirmed molecular relapse as defined above

Study Arms (1)

Nilotinib

EXPERIMENTAL

300 mg/twice a day

Drug: Nilotinib

Interventions

Nilotinib DRUG

300 mg/twice a day

Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients
• Patient participating to the STIM trials (including STIM, STIM2 et EURO-SKI) 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (10)

CHU Angers

Angers, 49033, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Hospitalier de Versailles - Hôpital André Mignot - Service de Médecine B

Le Chesnay, 78157, France

Location

CHU de Nice, Service Hématologie Clinique

Nice, 06202, France

Location

Hôpital Haut Lévêque, Service Hématologie

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud, Service Hématologie

Pierre-Bénite, 69495, France

Location

CH d'Annecy

Pringy, 74374, France

Location

Hôpital Pontchaillou

Rennes, 35033, France

Location

CHU de Toulouse, Service d'Hématologie

Toulouse, 31059, France

Location

CH Valence

Valence, 26953, France

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Recurrence

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Viviane DUBRUILLE

  Nantes University Hospital

  STUDY CHAIR

• Gabriel ETIENNE

  University Hospital Bordeaux, France

  STUDY CHAIR

• Franck NICOLINI

  Hospices Civils de Lyon

  STUDY CHAIR

• Delphine REA

  APHP, St Louis Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2013
• First Posted: January 24, 2013
• Study Start: April 10, 2013
• Primary Completion: December 21, 2020
• Study Completion: December 21, 2020
• Last Updated: May 19, 2026

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10)