Sustained Treatment-free Remission in BCR-ABL+ Chronic Myeloid Leukemia (SUSTRENIM)
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|ClinicalTrials.gov Identifier: NCT02602314|
Recruitment Status : Recruiting
First Posted : November 11, 2015
Last Update Posted : October 17, 2017
|Condition or disease||Intervention/treatment||Phase|
|Chronyc Myeloid Leukemia||Drug: Imatinib Drug: Nilotinib||Phase 4|
This is a prospective, interventional, randomized, two arms, phase IV study evaluating both the depth of the molecular response and the rate of treatment free remission rate in newly diagnosed CP-CML patients treated with NIL or IM followed by switch to NIL in absence of optimal response (defined according the ELN 2013 criteria) as per clinical practice.
The enrolled patients will be randomized 1:1 between NIL and IM. Patients will be stratified according to the Sokal risk score to high versus intermediate/low risk groups. Newly diagnosed patients will be treated according to the registered dose of NIL and IM for frontline chronic phase CML (300 mg BID and 400 mg OAD, respectively). The patients intolerant to IM and the patients without optimal response to IM at 3 months, at 6 months, at 12 months (except the patients with progression to accelerated or blastic phase) will be switched to NIL second line.
The absence of optimal response is defined by at least one of the following ELN criteria: a) Absence of Complete Hematologic Response at 3 months or thereafter; b) Absence of Partial Cytogenetic Response (> 35% Ph+ metaphases) at 3 months; c) BCR-ABL transcript level > 10% according to the IS at 3 months; d) Absence of Complete Cytogenetic Response (> 1% Ph+ metaphases) at 6 months; e) BCR-ABL transcript level > 1% according to the IS at 6 months; f) Absence of Major Molecular Response (MR3.0, transcript level > 0.1% according to the IS) at 12 months.
Treatment choice for the patients with progression to advanced disease phase while on IM and for the patients intolerant to or resistant (including progressions to advanced phases) to NIL will be up to the principal investigator of the participating Center. However, information concerning the course and outcome of these patients will be collected and recorded for at least 5 years, and they could be enrolled in investigational studies promoted by GIMEMA or other sponsors.
After the induction of deep molecular remission phase of therapy, i.e. the first two years of the study, residual disease will be closely monitored (quarterly) by Q-PCR assays. All the patients who obtain a reduction greater than 4.0 logs of residual disease (MR4.0) within the first three years of treatment, and maintain this level of response in all the subsequent tests up to the end of the fourth years of therapy qualify for the discontinuation phase of the study. Therefore, all patients who are in MR4.0 after a four-year period of TKI treatment, that must include in its final part at least one years of maintained MR4.0, defined as 12-month period during which the MR4.0 never is lost in 4 consecutive MRD analyses at three-monthly intervals, will enter the treatment free remission (TFR) phase of the study. In case of loss of MR3.0, the last assumed TKI will be resumed at the same dose.
All patients, including those who do not match the criteria for discontinuation of TKI treatment, will continue the assigned treatment and will be followed for 5 years, starting from the date of enrolment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||600 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Sustained Treatment-free Remission in BCR-ABL+ Chronic Myeloid Leukemia: a Prospective Study Comparing Nilotinib Versus Imatinib With Switch to Nilotinib in Absence of Optimal Response. SUSTRENIM Study - GIMEMA CLM1415|
|Actual Study Start Date :||November 11, 2016|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||February 2024|
|Experimental: Imatinib + Nilotinib||
- Number of of patients with molecular response [ Time Frame: At 24 months from study entry ]
- Number of patients who remain in sustained treatment free remission, without molecular relapse [ Time Frame: After 12 months after entering the treatment-free-remission (TFR) phase ]
- Number of patients with molecular response [ Time Frame: 4 years after study entry ]
- Number of patiens in progression-free survival [ Time Frame: 5 years after study entry ]
- Number of patients with major molecular response [ Time Frame: At 1, 2, 3 and 4 years from study entry ]
- Number of toxic events [ Time Frame: At 5 years from study entry ]
- Number of patients who discontinue treatment [ Time Frame: At 5 years from study entry ]
- Number of patients with quality of life differences between treatment arms over time [ Time Frame: At baseline and at 3, 6, 12, 18, 24, 30, 36, 42, 48, and 60 months from study entry. ]To assess the patient-reported quality of life (QoL) and adherence to therapy at baseline and at 6, 12, 18, 24, 27, 33, 36, 39, 42, 48, 51, 54 and 60 months in the following QoL scales: Fatigue, Physical Functioning and Global Health Status/QoL (outcome measure: EORTC QLQ-C30), Impact on Daily Life and Symptom Burden (outcome measure: EORTC CML-24), Burden of Illness (outcome measure: EORTC QLQ-ELD14).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02602314
|Contact: Paola Fazifirstname.lastname@example.org|
|Contact: Enrico Creaemail@example.com|
|Study Chair:||Fabrizio Pane||Università Federico II of Naples|