Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients

NCT ID: NCT02201459

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2022-10-31

Brief Summary

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.

Conditions

Chronic Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nilotinib

Control arm, this compound been licensed in this indication.

Group Type: ACTIVE_COMPARATOR

Nilotinib (Tasigna ®), capsules of 150 mg

Intervention Type: 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

Peg-IFN alfa 2a (Pegasys®) and Nilotinib

Arm testing the efficacy of a combination of nilotinib and Peg-IFN alfa 2a as frontline therapy for first line chronic phase CML patients.

Group Type: EXPERIMENTAL

Nilotinib (Tasigna ®), capsules of 150 mg

Intervention Type: 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®)

Intervention Type: 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.

Interventions

Nilotinib (Tasigna ®), capsules of 150 mg

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

Intervention Type: DRUG

Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)

• 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.

Intervention Type: DRUG

Eligibility Criteria

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 other CML treatment except for hydroxyurea and/or anagrelide
• No previous TKI treatment.
• No previous treatment with IFN even for other purposes.
• SGOT and SGPT < 2.5 UNL
• Serum creatinine < 2 UNL
• No planned allogeneic stem cell transplantation
• Signed informed consent
• ECOG score 0 to 2

Exclusion Criteria

• Contra-indication to IFN
• Transcripts other than M-Bcr
• Pregnancy, lactation
• HIV positivity, chronic hepatitis B or C.
• Prior or concurrent malignancy other than CML (exceptions to be mentioned)
• History of arterial occlusive disease or (peripheral, carotids or severe coronary heart disease).
• Permanent elevation of total cholesterol and triglycerides despite treatment
• Severe psychiatric/neurological disease (previous or ongoing)
• Concomitant auto-immune disease
• Other investigational product ongoing
• Ongoing immunosuppressive treatment
• Ongoing treatment at risk for inducing torsades de pointes
• QTcF > 450ms despite correction of predisposing factors (i.e electrolytes…)
• Congenital long QTcF
• Unstabilised thyroid disorder
• No health insurance coverage

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Franck NICOLINI, MD

Role: PRINCIPAL_INVESTIGATOR

Hopsices Civils de Lyon

Locations

Franck NICOLINI

Lyon, , France

Countries

France

References

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.

Reference Type: BACKGROUND

Other Identifiers

2013.837

Identifier Type: -

Identifier Source: org_study_id