Leukemia, Myelogenous, Chronic, BCR-ABL Positive Clinical Trial
— NiloPost-STIMOfficial title:
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)
Verified date | August 2022 |
Source | University Hospital, Bordeaux |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 31 |
Est. completion date | December 21, 2020 |
Est. primary completion date | December 21, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 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 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 |
Country | Name | City | State |
---|---|---|---|
France | CHU Angers | Angers | |
France | Institut Bergonié | Bordeaux | |
France | Centre Hospitalier de Versailles - Hôpital André Mignot - Service de Médecine B | Le Chesnay | |
France | CHU de Nice, Service Hématologie Clinique | Nice | |
France | Hôpital Haut Lévêque, Service Hématologie | Pessac | |
France | Centre Hospitalier Lyon Sud, Service Hématologie | Pierre Benite | |
France | CH d'Annecy | Pringy | |
France | Hôpital Pontchaillou | Rennes | |
France | CHU de Toulouse, Service d'Hématologie | Toulouse | |
France | CH Valence | Valence |
Lead Sponsor | Collaborator |
---|---|
University Hospital, Bordeaux |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Rate and kinetics of CMR while on treatment with nilotinib | Same definition of CMR as above | at 6 and 12 months of treatment with nilotinib | |
Secondary | Duration of CMR while on treatment with nilotinib | Defined as the time from the date of first documented CMR to the date of first confirmed molecular relapse defined as positivity of Bcr-Abl transcripts in quantitative RT-PCR with a ratio of bcr-abl to Abl = 10-5, as confirmed by a second analysis point at two successive assessments | Any time | |
Secondary | Event free survival (EFS) | Events include loss of major molecular response (MMR) , loss of complete cytogenetic response (CCyR) loss of complete hematologic response (CHR), progression to accelerated phase and blst crisis (AP-BC), death whatever the cause, adverse-event leading to premature discontinuation of nilotinib | Any time | |
Secondary | Safety tolerability of nilotinib and compliance | Haematological and non-haematological adverse events (AE) graded will be according to the NCI CTC AE v4. Compliance will be estimated using the 4 items Morisky scale | Any time | |
Secondary | Duration of CMR after nilotinib discontinuation | Measured from the start of nilotinib discontinuation to the date of first confirmed molecular relapse as defined above | ||
Secondary | Event free survival (EFS) | Same events as for EFS described above | Overall and after nilotinib discontinuation | |
Secondary | Predictive factors of maintained CMR after nilotinib discontinuation: sex, Sokal risk score at diagnosis, duration of previous treatment with imatinib, CMR duration before and after discontinuation of imatinib | Parameters will be recorded before and after both sequences of treatment imatinib and nilotinib | After discontinuation of nilotinib |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01437202 -
Pharmacogenomics Validation for Imatinib in Chronic Myeloid Leukemia
|
N/A | |
Completed |
NCT02896842 -
A Prospective Randomized Phase II Study Evaluating the Monitoring of Imatinib Mesylate Plasmatic Through Level in Patients Newly Diagnosed With CP-CML
|
Phase 2 | |
Withdrawn |
NCT02421926 -
Extension Study of IDEAL (Imatinib) for Chronic Myelgenous Leukemia (CML)
|
||
Completed |
NCT01768689 -
Interventional Study to Improve Adherence to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
|
N/A | |
Not yet recruiting |
NCT02903277 -
National Observatory of Chronic Myeloid Leukemia Adolescent and Young Adults Treated With Tyrosine Kinase Inhibitors in First Intent
|
N/A | |
Completed |
NCT03090477 -
Impact of a Pharmaceutical Care Model in the Management of Chronic Myeloid Leukemia Patients
|
N/A | |
Active, not recruiting |
NCT02885766 -
Study to Evaluate Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of PF-114 for Oral Administration in Adults With Ph+ Chronic Myeloid Leukemia, Which is Resistant to the 2-nd Generation Bcr-Abl Inhibitors or Has T315I Mutation in the BCR-ABL Gene
|
Phase 1/Phase 2 | |
Recruiting |
NCT01464411 -
Dasatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia in Japan
|
N/A | |
Completed |
NCT01602952 -
Philadelphia Chromosome Positive CML Patients Without Optimal Response or Tolerance to Bcr-Abl TKI
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT02687425 -
Safety and Efficiency Study of Pioglitazone in Combination With Imatinib Mesylate to Treat Chronic Myelogenous Leukemia
|
Phase 2 | |
Completed |
NCT00171223 -
An Extension Study to Determine the Efficacy and Safety of STI571 in Participants With Chronic Myeloid Leukemia Who Are Refractory to or Intolerant of Interferon-Alpha
|
Phase 2 | |
Recruiting |
NCT04877522 -
Asciminib Roll-over Study
|
Phase 4 | |
Completed |
NCT01511289 -
Radotinib Versus Imatinib in Newly Diagnosed Philadelphia Chromosome and Chronic Myeloid Leukemia Chronic Phase Patients
|
Phase 3 | |
Completed |
NCT02480608 -
Treatment of CML Patients With Imatinib and Hydroxyurea (CML2004)
|
Phase 1/Phase 2 | |
Completed |
NCT02389972 -
Effectiveness of Dasatinib in Adult Patients With Chronic Myeloid Leukemia in China: A Multicenter, Registry Study
|
N/A |