Clinical trial 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)
Official title: 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 -
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Myeloid Leukemia
Keywords: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-10-14
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 12 months
Secondary outcomes:
measure: Rate of major cytogenetic response (MCyR) at 6 and 12 months
timeFrame: 12 months
measure: Rate of complete cytogenetic response (CCyR) at 6 and 12 months
timeFrame: 12 months
measure: Rate of major molecular response (MMR) at 12 months
timeFrame: 12 months
measure: Safety profile of nilotinib in combination with interferon alfa, i.e. the number of dose limiting toxicities (DLT) for each interferon alfa dose level
timeFrame: 12 months
measure: Progression-free survival (PFS)
timeFrame: 12 months
measure: Event-free survival
timeFrame: 12 months
measure: Overall survival (OS)
timeFrame: 12 months
Other outcomes:
Locations:
city: Leipzig
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Guilhot F, Roy L, Saulnier PJ, Guilhot J. Interferon in chronic myeloid leukaemia: past and future. Best Pract Res Clin Haematol. 2009 Sep;22(3):315-29. doi: 10.1016/j.beha.2009.10.005.