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

NCT02201459 | Completed Phase 3 DMC

• 1 other identifier: 2013.837
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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

Keywords

Peg-IFN, nilotinib, MR4.5, CML, chronic phase, first-line

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (12)

• 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).

  36 months

• 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).

  36 months

• Rate of patients with BCR-ABL/ABL (IS) ≥10% 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.

  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).

  36 months

Study Arms (2)

Nilotinib

ACTIVE COMPARATOR

Control arm, this compound been licensed in this indication.

Drug: Nilotinib (Tasigna ®), capsules of 150 mg

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.

Drug: Nilotinib (Tasigna ®), capsules of 150 mg; Drug: Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)

Interventions

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

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.

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead
• Novartis: collaborator

Study Sites (1)

Franck NICOLINI

Lyon, 04 78 86 22 50, France

Location

Related Publications (1)

• 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.

  BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Franck NICOLINI, MD

  Hopsices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2014
• First Posted: July 28, 2014
• Study Start: August 1, 2014
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: October 2, 2025

Record last verified: 2025-09

Locations

FR (1)