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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
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This is a phase III trial comparing, for newly diagnosed chronic phase CML patients, nilotinib 600 mg BID as a standard arm and nilotinib 600 mg BID combined to interferon alfa 2 a (pegylated form improving tolerance and maybe enhancing is efficacy) at increased doses for a total of 24 months of combination, in a 1:1 randomized manner. The assessment for the primary efficacy endpoint will be performed at 12 months (since nilotinib initiation) and is the rate patients obtaining MR4.5 will be measured at this time point.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Molecular response (MR) 4.5 at 12 months of nilotinib 300 mg twice a day versus a combination of low-dose Peg-Interferon (Peg-IFN) to nilotinib 300 mg twice a day in newly diagnosed CP-CML Chronic Phase Chronic Myelogenous Leukemia patients. | Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Molecular Response 4.5 at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MR4.5 during the second year of treatment (18, 24 and 36 months). | Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment. | 36 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Franck NICOLINI, MD | Hopsices Civils de Lyon | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Franck NICOLINI | Lyon | 04 78 86 22 50 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Abstract We evaluated whether adding pegylated interferon-α2a (Peg-IFNα2a) to nilotinib affected dose intensity, molecular response kinetics, and long-term outcomes in newly diagnosed chronic myeloid leukemia. Delivered nilotinib doses remained comparable between treatment arms up to 72 months, indicating no dose reduction from Peg-IFNα2a-related toxicity. At diagnosis, 8.5 % of 199 patients had additional cytogenetic abnormalities (ACAs). At 3 months, complete and partial cytogenetic response (CCyR/PCyR) rates did not differ between nilotinib alone and the combination (CCyR 72.5 % vs 76 %; PCyR 16.5 % vs 11.5 %). Molecular kinetics showed faster early BCR::ABL1 transcript decline with the combination, but cumulative incidence (CI) curves for major molecular response (MMR) converged by 36 months. Two-year CI of MMR was 80.5 % with nilotinib and 91 % with the combination; five-year CI 93 % vs 97 % (global p = 0.155). The primary endpoint, MR4.5 at 12 months, was reached in 15 % vs 24 % (p = 0.048), but long-term deep molecular response rates (MR4/MR4.5) were ultimately similar at 5 years. In exploratory analyses, female sex (HR 3.06) and higher cumulative Peg-IFNα2a dose in the first 9 months (HR 2.89) predicted early MR4.5, whereas high Sokal or ELTS scores and elevated BCR::ABL1 at month 3 were adverse. ABL1 kinase domain mutations emerged in 10 patients overall (8 nilotinib, 2 combination). Conclusion Peg-IFNα2a with nilotinib accelerated early molecular responses and increased 12-month MR4.5 rates without impairing nilotinib exposure or long-term outcomes. Female sex and Peg-IFNα2a dose intensity correlated with deep early response, supporting potential personalization of combination strategies. | ||
| 42069411 |
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| ID | Term |
|---|---|
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C498826 | nilotinib |
| C100416 | peginterferon alfa-2a |
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| Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®) | Drug |
|
|
| Major Molecular Response at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MMR during the second year of treatment (18, 24 and 36 months). |
Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment. |
| 36 months |
| Rate of patients with BCR-ABL/ABL (IS) ≥10% at 3 months. | Centralised assessment of the BCR-ABL transcripts at 3 months. | 3 months after nilotinib initiation |
| Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 12 months of nilotinib. | Local bone marrow cytogenetic assessment (on 20 metaphases) | Assessment at 3, 6 and 12 months |
| Safety of the nilotinib combined to Peg-IFN or not (hematological and non-hematological adverse events (AE) graded according to the NCI CTC AE v3). | Continuous evaluation of the AEs and SAEs reported during 36 months | 36 months |
| Quality of life of patients treated in both arms | EORTC-QLQ C30 and C24 questionnaire at months -1 (Arm B), month 0, 1, 6, 12, 24, 36. | 36 months |
| Doses-reductions/interruptions of drugs in both arms. Mean daily doses of nilotinib and Peg-IFN administered. | Continuous recording of dose intensity along the study for 24-36 months. | 24 months for Peg-IFN, and 36 months for both drugs |
| Compliance to drugs in each arms | Morisky questionnaire to be fulfilled at 1, 6, 12, 24 and 36 months after nilotinib initiation. | 36 months |
| Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5. | Local (but standardized) assessment of the BCR-ABL transcripts every months for 3 months. | 36 months |
| Event-free survival. | Survival since randomization without any event defined as loss of CHR, loss of PCyR or CCyR, death from any cause, progression towards accelerated phase or blast crisis. | 36 months |
| Progression-free survival | Survival without progression towards accelerated of blast phase, death. | 36 months |
| Overall survival. | Survival without death from any cause | 36 months |
| Derived |
| Nicolini FE, Etienne G, Huguet F, Charbonnier A, Roth-Guepin G, Escoffre-Barbe M, Dubruille V, Johnson-Ansah H, Rousselot P, Legros L, Parry A, Roy L, Coiteux V, Lenain P, Ianotto JC, Doublet C, Orvain C, Simonet-Boissard M, Chretien ML, Penot A, Meunier M, Ame S, Hermet E, Quittet P, Lapusan S, Schwiertz V, Cayuela JM, Maute C, Rea D, Morisset S, Mahon FX, Dulucq S. Final results of nilotinib versus nilotinib combined with pegylated interferon alfa-2a as first-line therapy in chronic phase chronic myeloid leukaemia in France (PETALs): an open-label, multicentre, randomised phase 3 trial. Lancet Haematol. 2026 May;13(5):e315-e326. doi: 10.1016/S2352-3026(26)00043-8. |
| D009196 |
| Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |