Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02201459 | Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients | PHASE3 | COMPLETED | 200 | — | — | Aug 1, 2014 | Oct 1, 2022 | Oct 2, 2025 | 1 | France |
| NCT01254188 | Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients | PHASE3 | COMPLETED | 421 | — | — | Apr 1, 2011 | Nov 1, 2014 | Mar 3, 2016 | 100 | Algeria, Argentina +17 |
| NCT01275196 | Safety and Efficacy of Nilotinib vs. Imatinib in the Treatment of Newly Diagnosed Chinese Ph+ CML-CP Patients | PHASE3 | COMPLETED | 267 | — | — | Apr 1, 2011 | Oct 1, 2014 | Apr 8, 2016 | 12 | China |
| NCT01126892 | A Study of Nilotinib in Adult Patients With Imatinib Resistant or - Intolerant Chronic Myeloid Leukemia in Blast Crisis, Accelerated Phase or Chronic Phase | PHASE3 | COMPLETED | 6 | — | — | Jan 1, 2009 | Apr 1, 2011 | Feb 28, 2017 | 2 | Colombia, Venezuela |
| NCT03874858 | A Study of Full Treatment-free Remission in Patients With Chronic Myeloid Leukemia | PHASE2 | COMPLETED | 124 | — | — | Mar 22, 2019 | Oct 15, 2025 | Apr 2, 2026 | 26 | Italy |
| NCT01698905 | Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop) | PHASE2 | COMPLETED | 163 | — | — | Dec 20, 2012 | Jan 29, 2025 | Sep 2, 2025 | 62 | United States, Argentina +16 |
| NCT02253277 | Safety and Tolerability of Combined Treatment With Nilotinib and Ruxolitinib in CML and Ph+ ALL Patients | PHASE1 | COMPLETED | 5 | — | — | Feb 18, 2015 | Apr 3, 2018 | May 1, 2019 | 4 | Germany |
| NCT01220648 | Determining the Maximum Tolerated Dose of Low Dose Interferon-alpha in Conjunction With Nilotinib in Pretreated Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP) | PHASE1 | COMPLETED | 4 | — | — | Apr 1, 2012 | Jan 1, 2014 | May 5, 2015 | 1 | Germany |
| NCT01077544 | A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL) | PHASE1 | COMPLETED | 15 | — | — | Apr 14, 2011 | Jul 1, 2015 | Dec 29, 2020 | 12 | France, Italy +2 |
| NCT01223898 | To Evaluate the Effects of Multiple Doses of Nilotinib on the Pharmacokinetics and Metabolism of Midazolam in CML Patients With Additional Extension Phase to Evaluate the Safety of Nilotinib | PHASE1 | COMPLETED | 19 | — | — | Jun 1, 2010 | Dec 1, 2013 | Dec 9, 2020 | 5 | Germany, United Kingdom |
Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation
MMR is defined as BCR-ABL ratio (%) on IS \<= 0.1% (corresponds to \>=3 log reduction of BCR-ABL transcripts from standardized baseline value). Clopper-Pearson method
Major molecular response (MMR) was defined as a value of ≤ 0.1% of BCR-ABL ratio on the IS. The minimum number of control genes for a sample to be valid was 3000. For statistical comparison purpose, MMR was considered as a binary variable with patients achieving MMR grouped as 'responders' and patients not achieving MMR, patients with missing PCR evaluations or patients with atypical transcripts at baseline grouped as 'non-responders'. This endpoint was calculated based on the 12 month analysis.
Full Treatment-Free Remission (FTFR) is defined as patients with Major Molecular Response (MMR) or better (i.e. BCR-ABL ≤ 0.1% IS), including those who have totally discontinued treatment during the Treatment-Free Remission (TFR) stage and those who are treated with half the standard dosage. Percentage of patients in full treatment-free remission 96 weeks after the start of the consolidation period of TFR1 stage is calculated by dividing the number of patients with no loss of MMR-Major Molecular Response (BCR-ABL ≤ 0.1% (IS) after 96 weeks by the number of patients who entered consolidation of TFR1 stage.
Treatment-Free Remission (TFR) is defined as patients with MMR or better (i.e. BCR-ABL ≤ 0.1% IS). Percentage of patients in TFR 48 weeks after the start of TFR2 phase during TFR2 stage is calculated by dividing the number of patients with no loss of MMR after 48 weeks by the number of patients who entered TFR2 during TFR2 stage. Patients who require re-initiation of nilotinib during TFR2 for loss of MMR, and those discontinued from the study will be considered failures.
TFR is defined as no confirmed loss of MR4 (Molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL \> 0.01% IS. Loss of MMR does not require confirmation. Percentage of patients in TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 48 weeks after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase, and multiplied by 100.
Occurrence of DLTs during cycle 1
The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.
The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.
The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.
The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.
The steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses
The steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses
The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose.
| Arm | Type | Description |
|---|---|---|
| Nilotinib | ACTIVE_COMPARATOR | Control arm, this compound been licensed in this indication. |
| Peg-IFN alfa 2a (Pegasys®) and Nilotinib | EXPERIMENTAL | Arm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients. |
| Imatinib | ACTIVE_COMPARATOR | - |
| TFR1 stage- Nilotinib | EXPERIMENTAL | During TFR1 stage, all patients will be treated with nilotinib 300 mg QD for up to 48 weeks (consolidation period). * Patients with sustained DMR at the end of the consolidation period will enter the TFR1 period and nilotinib will be discontinued. * Patients with loss of MMR will return to the standard nilotinib administration * Patients with ≥ MMR, but without sustained DMR at the end of the consolidation period will be treated with nilotinib 300 mg QD |
| TFR2 stage- Nilotinib+Asciminib | EXPERIMENTAL | During the TFR2 stage, participants will be treated with nilotinib and asciminib for up to 96 weeks (reinduction period). * Patients with sustained DMR at the end of reinduction will enter TFR2 and asciminib + nilotinib will be discontinued. * Patients with ≥ MMR, but without sustained DMR, at the end of the reinduction, will be treated with nilotinib monotherapy at 300 mg BID until the end of the TFR2 stage. * Patients with loss of MMR at any time during reinduction or during nilotinib monotherapy will be discontinued from the study. |
| Nilotinib and Ruxolitinib | EXPERIMENTAL | The study included two strata, which were to be treated in parallel. The first stratum consisted of CML-patients in CP, which had been on nilotinib treatment before entering the study. These patients did not optimally respond to the previous treatment. The second stratum consisted of patients with CML in AP or BC and patients with relapsed/refractory Ph+ ALL and Ph+ ALL patients with MRD, with or without previous nilotinib treatment. Patients were treated with 300mg nilotinib BID during the escalation phase (12 months) with increasing doses of ruxolitinib. The dose expansion phase (12 months) began following the determination of the MTD of the combination and the decision to explore the cohort for confirmation of RPIID. In this phase, safety and tolerability of the MTD and/or potential RPIID was to be further evaluated, with the purpose of establishing that this dose is suitable for use in this patient group. |
| Nilotinib in conjunction with low dose interferon alfa | EXPERIMENTAL | - |
| Group 1 | EXPERIMENTAL | 1 year to \< 10 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid. |
| Group 2 | EXPERIMENTAL | \>= 10 years to \<18 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid. |
| Name | Type | Description |
|---|---|---|
| Nilotinib (Tasigna ®), capsules of 150 mg | DRUG | Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months |
| Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®) | DRUG | * Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months and * Pegylated interferon alfa 2a subcutaneously once a week (auto-injection syringes of 135 and 90 micrograms) at 30 micrograms/week the first month alone (= priming procedure), then at 30 micrograms/2weeks the first month of combination to nilotinib and then at 45 micrograms/week thereafter until month 24 after nilotinib initiation. |
| Nilotinib | DRUG | This was an open-label, single-arm, prospective, multi-center, Phase IIIb clinical study with nilotinib 300 mg bid treatment in newly diagnosed CML-CP patients not previously treated with imatinib therapy and diagnosed within 6 months of study entry. For patients insufficiently responding to nilotinib 300 mg bid, the dose may have been increased to 400 mg bid. Among patients with adverse events who had dose reduction, this study also allowed a possible re-escalation to 300 mg bid. |
| Imatinib | DRUG | - |
| Asciminib | DRUG | Asciminib orally at a dose of 40 mg BID film-coated tablets (FCT) |
| Ruxolitinib | DRUG | Ruxolitinib was supplied by Novartis as 5 mg, 15 mg, and 20 mg tablets. Medication labels were in German and complied with the legal requirements of Germany. They included storage conditions for the drug but no information about the patient. The investigator emphasized compliance and instructed the patient to take ruxolitinib exactly as prescribed. |
| Nilotinib, interferon-alfa | DRUG | - |
| Tasigna | DRUG | - |
Inclusion Criteria: * Male and female patients * CP-CML, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript), diagnosed less than 3 months prior to study entry * Age of at least 18 years-old and less than 65 years * Patient for whom treatment with Nilotinib is expected * No othe...