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)

Study Overview
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Brief Summary
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This study will assess the maximum tolerated dose of low dose interferon in conjunction with nilotinib in pretreated Philadelphia chromosome positive (Ph+) chronic myeloid leukemia patients in chronic phase (CML-CP).

Official Title
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An Open Label, Nonrandomized, Single-center, Phase I Trial of Pretreated Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP) With Nilotinib in Combination With Low Dose Interferon-alpha (IFN) - NICOLI Study -

Conditions
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Chronic Myeloid Leukemia

Intervention / Treatment
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* Drug: Nilotinib, interferon-alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with chronic myeloid leukemia in chronic phase (CML-CP) at screening Initial diagnosis of CML cytogenetically confirmed by the presence of the Ph+ metaphases from the bone marrow Patients who have been treated with nilotinib for a minimum of 6 months (1 month represents 28 days) after switch from previous CML treatments Patients who have been treated with stable dosing of 2x400mg nilotinib within the last month before start of study treatment No grade 3-4 CTC toxicities on nilotinib alone in the last month preceding the start of the study regimen Exclusion Criteria: Patients who are considered Ph- because they do not have a confirmed cytogenetic diagnosis of the t(9;22) translocation in their bone marrow metaphases Evidence of a point mutation within the BCR-ABL gene leading to a clinically relevant amino acid exchange in the kinase domain at position T315 (gatekeeper mutation T315I) Impaired cardiac function Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection). Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nilotinib in conjunction with low dose interferon alfa<br> | Drug: Nilotinib, interferon-alfa<br> <br> * Other names: AMN107;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Clinically significant adverse events or abnormal laboratory values (dose-limiting toxicities) unrelated to disease progression, intercurrent illness, or concomitant medications on the combination treatment |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major cytogenetic response (MCyR) at 6 and 12 months |  | 12 months | 
| Rate of complete cytogenetic response (CCyR) at 6 and 12 months |  | 12 months | 
| Rate of major molecular response (MMR) at 12 months |  | 12 months | 
| Safety profile of nilotinib in combination with interferon alfa, i.e. the number of dose limiting toxicities (DLT) for each interferon alfa dose level |  | 12 months | 
| Progression-free survival (PFS) |  | 12 months | 
| Event-free survival |  | 12 months | 
| Overall survival (OS) |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic myeloid leukemia, interferon alfa, nilotinib, combination, CML, Philadelphia chromosome positive (Ph+) chronic myeloid leukemia patients in chronic phase (CML-CP) after switch from previous CML treatment